Name (Synonyms) | Correlation | |
---|---|---|
drug360 | Hydroxychloroquine Wiki | 0.20 |
drug616 | Placebo Wiki | 0.18 |
drug650 | Presatovir Wiki | 0.16 |
drug1008 | pregnant women with laboratory-confirmed 2019-n-CoV Wiki | 0.15 |
drug304 | Favipiravir Wiki | 0.13 |
drug361 | Hydroxychloroquine (HCQ) Wiki | 0.13 |
drug60 | Ascorbic Acid Wiki | 0.13 |
drug46 | Anakinra Wiki | 0.12 |
drug627 | Placebo oral tablet Wiki | 0.12 |
drug93 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.11 |
drug166 | CYNK-001 Wiki | 0.11 |
drug700 | Risk of MERS infection Wiki | 0.11 |
drug667 | Quality of Life Wiki | 0.11 |
drug188 | Chest computed tomography (CT) Wiki | 0.11 |
drug836 | Thalidomide Wiki | 0.11 |
drug806 | Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki | 0.11 |
drug679 | Random Donor Plasma Wiki | 0.11 |
drug800 | Supportive Care Wiki | 0.11 |
drug1037 | trimethoprim/sulfamethoxazole Wiki | 0.11 |
drug858 | Toraymyxin PMX-20R (PMX Cartridge) Wiki | 0.11 |
drug976 | mRNA-1273 Wiki | 0.11 |
drug149 | COVID-19 IgM/IgG Rapid Testing, mobile device image capture and telemedicine support Wiki | 0.11 |
drug326 | Group A HCQ Wiki | 0.11 |
drug62 | Ascorbic Acid and Zinc Gluconate Wiki | 0.11 |
drug493 | Matched Placebo Wiki | 0.11 |
drug448 | Ivermectin plus Nitazoxanide Wiki | 0.11 |
drug704 | RoActemra iv Wiki | 0.11 |
drug770 | Standard medical care Wiki | 0.11 |
drug604 | Peginterferon Lambda-1a Wiki | 0.11 |
drug684 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.11 |
drug57 | Apo-Hydroxychloroquine Wiki | 0.11 |
drug845 | Thrombin Generation Assay (TGA) Wiki | 0.11 |
drug590 | PD-1 blocking antibody+standard treatment Wiki | 0.11 |
drug351 | Hospital anxiety and depression scale Wiki | 0.11 |
drug763 | Standard Donor Plasma Wiki | 0.11 |
drug841 | There is no intervention in this study Wiki | 0.11 |
drug79 | Awake Proning Wiki | 0.11 |
drug847 | Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) Wiki | 0.11 |
drug140 | Burnout Wiki | 0.11 |
drug910 | XPro1595 Wiki | 0.11 |
drug705 | RoActemra sc Wiki | 0.11 |
drug1029 | standard treatment Wiki | 0.11 |
drug1013 | rapid salivary test Wiki | 0.11 |
drug915 | Zinc Wiki | 0.11 |
drug154 | COVID-19 convalescent plasma Wiki | 0.11 |
drug373 | Hydroxychloroquine Pre-Exposure Prophylaxis Wiki | 0.11 |
drug227 | Convalescent Plasma Transfusion Wiki | 0.11 |
drug956 | high flow nasal cannula (HFNC) Wiki | 0.11 |
drug419 | Indomethacin Wiki | 0.11 |
drug318 | GO2 PEEP MOUTHPIECE Wiki | 0.11 |
drug916 | Zinc Gluconate Wiki | 0.11 |
drug80 | Ayurveda Wiki | 0.11 |
drug85 | Azithromycin 500 milligram (mg) oral Tablet Wiki | 0.11 |
drug581 | Oral placebo Wiki | 0.11 |
drug416 | Impact Event Score Wiki | 0.11 |
drug70 | Association of diltiazem and niclosamide Wiki | 0.11 |
drug918 | Zithromax Oral Product Wiki | 0.11 |
drug677 | Radiological Detection Wiki | 0.11 |
drug327 | Group B Control Wiki | 0.11 |
drug285 | Enoxaparin Prefilled Syringe [Lovenox] Wiki | 0.11 |
drug926 | artus Influenza A/B RT-PCR Test Wiki | 0.11 |
drug928 | bacTRL-Spike Wiki | 0.11 |
drug412 | Imatinib Wiki | 0.11 |
drug158 | COVID-19 test, polymerase chain reaction for SARS-CoV-2 Wiki | 0.11 |
drug985 | muscle ultrasound Wiki | 0.11 |
drug250 | Data collection and rhinopharyngeal swab Wiki | 0.11 |
drug830 | Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. Wiki | 0.11 |
drug657 | Prone positioning (PP) Wiki | 0.11 |
drug971 | laboratory biomarkers Wiki | 0.11 |
drug168 | Cambridge Validated Viral Detection Method Wiki | 0.11 |
drug377 | Hydroxychloroquine Sulfate + Azithromycin Wiki | 0.11 |
drug651 | Presatovir placebo Wiki | 0.11 |
drug959 | hospitalized children with Covid19 Wiki | 0.11 |
drug804 | Survey and Questionnaire Wiki | 0.11 |
drug426 | Injective placebo Wiki | 0.11 |
drug852 | To assess for development of IgG antibodies against SARS-CoV2 Wiki | 0.11 |
drug122 | Biological: COVID-19 convalescent plasma Wiki | 0.11 |
drug902 | Vitamins Wiki | 0.11 |
drug252 | Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Wiki | 0.11 |
drug454 | Kevzara sc Wiki | 0.11 |
drug835 | Tetrandrine Wiki | 0.11 |
drug450 | JNJ-53718678 Wiki | 0.11 |
drug422 | Inhaled beclomethasone Wiki | 0.11 |
drug468 | Loop mediated isothermal amplification COVID-19 Wiki | 0.11 |
drug352 | Huaier Granule Wiki | 0.11 |
drug676 | REGN3051 Wiki | 0.11 |
drug931 | biological samples collection Wiki | 0.11 |
drug849 | Thymosin+standard treatment Wiki | 0.11 |
drug733 | Sarilumab SAR153191 Wiki | 0.11 |
drug675 | REGN3048 Wiki | 0.11 |
drug237 | Covid-19 Antibody testing (IgG and IgM) Wiki | 0.11 |
drug744 | Serum test Wiki | 0.11 |
drug619 | Placebo 250 cc 24 hours continuous infusion for 15 days Wiki | 0.11 |
drug741 | Serological test Wiki | 0.11 |
drug680 | Rapid diagnostics using Anyplex TMII RV16 Detection Wiki | 0.11 |
drug987 | nasopharyngeal swab Wiki | 0.11 |
drug240 | Cytokine profile Wiki | 0.11 |
drug229 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.11 |
drug696 | Retrospective data collection Wiki | 0.11 |
drug37 | Allogeneic NK transfer Wiki | 0.11 |
drug532 | NO intervention planned due to the observational study design only a diagnostic testing Wiki | 0.11 |
drug776 | Standard of care (SOC) Wiki | 0.11 |
drug596 | PTSD Wiki | 0.11 |
drug598 | Pacebo: Calcium citrate Wiki | 0.11 |
drug290 | Ergoferon Wiki | 0.11 |
drug242 | DAS181 Wiki | 0.11 |
drug697 | Reverse-transcription polymerase chain reaction (RT-PCR) Wiki | 0.11 |
drug22 | ACE inhibitor, angiotensin receptor blocker Wiki | 0.11 |
drug339 | Halo Oral Spray Wiki | 0.11 |
drug342 | Helmet non-invasive ventilation (NIV) Wiki | 0.11 |
drug712 | SAMBA II (Diagnostic for the Real World) Wiki | 0.11 |
drug661 | Public Health England Gold Standard Wiki | 0.11 |
drug376 | Hydroxychloroquine Sulfate (HCQ) Wiki | 0.11 |
drug553 | Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki | 0.11 |
drug993 | nosocomial infection/hospital acquired infection Wiki | 0.11 |
drug727 | Saline containing 1% Human serum albumin(solution of MSC) Wiki | 0.11 |
drug340 | Halo Placebo Wiki | 0.11 |
drug379 | Hydroxychloroquine Sulfate 200 MG Wiki | 0.11 |
drug333 | HCQ & AZ Wiki | 0.11 |
drug254 | Delayed diagnostics Anyplex TMII RV16 Detection Wiki | 0.11 |
drug375 | Hydroxychloroquine Sulfate Wiki | 0.10 |
drug691 | Remdesivir Wiki | 0.10 |
drug208 | Colchicine Wiki | 0.10 |
drug900 | Vitamin C Wiki | 0.10 |
drug732 | Sarilumab Wiki | 0.09 |
drug671 | Questionnaires Wiki | 0.08 |
drug533 | NORS (Nitric Oxide Releasing Solution) Wiki | 0.08 |
drug107 | Baricitinib Wiki | 0.08 |
drug946 | convalescent plasma Wiki | 0.08 |
drug828 | Telmisartan Wiki | 0.08 |
drug995 | observational Wiki | 0.08 |
drug762 | Standard Care Wiki | 0.08 |
drug558 | No intervention Wiki | 0.08 |
drug486 | MSCs Wiki | 0.08 |
drug1018 | self-administered questionnaire Wiki | 0.08 |
drug130 | Blood draw Wiki | 0.08 |
drug771 | Standard of Care Wiki | 0.07 |
drug925 | anti-SARS-CoV-2 convalescent plasma Wiki | 0.06 |
drug92 | BCG Vaccine Wiki | 0.06 |
drug901 | Vitamin D Wiki | 0.06 |
drug823 | Telemedicine Wiki | 0.06 |
drug788 | Standard treatment Wiki | 0.06 |
drug169 | Camostat Mesilate Wiki | 0.06 |
drug429 | Interferon Beta-1B Wiki | 0.06 |
drug428 | Interferon Beta-1A Wiki | 0.06 |
drug632 | Placebos Wiki | 0.06 |
drug230 | Convalescent plasma Wiki | 0.05 |
drug854 | Tocilizumab Wiki | 0.05 |
drug883 | Usual Care Wiki | 0.05 |
drug668 | Questionnaire Wiki | 0.05 |
drug480 | Losartan Wiki | 0.04 |
drug1003 | placebo Wiki | 0.04 |
drug225 | Convalescent Plasma Wiki | 0.04 |
drug775 | Standard of care Wiki | 0.04 |
drug478 | Lopinavir/ritonavir Wiki | 0.03 |
drug82 | Azithromycin Wiki | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
D045169 | Severe Acute Respiratory Syndrome NIH | 0.41 |
D018352 | Coronavirus Infections NIH | 0.35 |
D007239 | Infection NIH | 0.32 |
D003141 | Communicable Diseases NIH | 0.31 |
D018357 | Respiratory Syncytial Virus Infections NIH | 0.22 |
D003333 | Coronaviridae Infections NIH | 0.19 |
D012327 | RNA Virus Infections NIH | 0.15 |
D005335 | Fever of Unknown Origin NIH | 0.11 |
D003384 | Coxsackievirus Infections NIH | 0.11 |
D012772 | Shock, Septic NIH | 0.11 |
D007154 | Immune System Diseases NIH | 0.11 |
D019446 | Endotoxemia NIH | 0.11 |
D040921 | Stress Disorders, Traumatic NIH | 0.11 |
D018805 | Sepsis NIH | 0.11 |
D000208 | Acute Disease NIH | 0.11 |
D002637 | Chest Pain NIH | 0.11 |
D055501 | Macrophage Activation Syndrome NIH | 0.11 |
D009220 | Myositis NIH | 0.11 |
D001987 | Bronchiectasis NIH | 0.11 |
D009205 | Myocarditis NIH | 0.11 |
D012141 | Respiratory Tract Infections NIH | 0.08 |
D016638 | Critical Illness NIH | 0.08 |
D012140 | Respiratory Tract Diseases NIH | 0.08 |
D007251 | Influenza, Human NIH | 0.08 |
D030341 | Nidovirales Infections NIH | 0.08 |
D058070 | Asymptomatic Diseases NIH | 0.08 |
D004630 | Emergencies NIH | 0.08 |
D013313 | Stress Disorders, Post-Traumatic NIH | 0.08 |
D000257 | Adenoviridae Infections NIH | 0.08 |
D004211 | Disseminated Intravascular Coagulation NIH | 0.06 |
D004417 | Dyspnea NIH | 0.06 |
D018184 | Paramyxoviridae Infections NIH | 0.06 |
D020246 | Venous Thrombosis NIH | 0.06 |
D011024 | Pneumonia, Viral NIH | 0.06 |
D011014 | Pneumonia NIH | 0.06 |
D012769 | Shock, NIH | 0.05 |
D020141 | Hemostatic Disorders NIH | 0.05 |
D001778 | Blood Coagulation Disorders NIH | 0.05 |
D008171 | Lung Diseases, NIH | 0.05 |
D058186 | Acute Kidney Injury NIH | 0.05 |
D013927 | Thrombosis NIH | 0.04 |
D055371 | Acute Lung Injury NIH | 0.03 |
D013577 | Syndrome NIH | 0.03 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.03 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002110 | Bronchiectasis HPO | 0.11 |
HP:0100749 | Chest pain HPO | 0.11 |
HP:0002098 | Respiratory distress HPO | 0.08 |
HP:0002090 | Pneumonia HPO | 0.02 |
There are 84 clinical trials
Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to estimate rates of morbidity and mortality and to examine predictors of severity among participants with 2009 H1N1 infection. In 2011, as surveillance indicated that 2009 H1N1 virus was co-circulating with other seasonal influenza A and B viruses worldwide, the protocol was expanded to include other influenza A subtypes and influenza B viruses. The current version of the protocol (released in August 2013) further broadens the scope of this observational study. With the recognition that novel respiratory viruses other than novel influenza A viruses, e.g., Middle East Respiratory Syndrome Coronavirus (MERS-CoV), could become prevalent and of major public health importance, the objectives of this protocol have been expanded.
The study will be conducted using nasopharyngeal swab specimens collected prospectively from individuals suspected of having the signs and symptoms of an acute respiratory tract infection caused by a respiratory virus. A series of standard viral culture tests validated for routine use in the clinical laboratory, and/or a series of PCR-based Laboratory Developed Tests (PCR-LDT) validated by a central reference laboratory will be used to verify the performance of the investigational artus Influenza A/B RT-PCR test and the QIAGEN ResPlex II Advanced Panel test. From each specimen five (5) aliquots will be prepared: (a) one aliquot will be tested in real-time using the assigned viral culture reference methods; (b) one aliquot will be used to extract nucleic acid in real-time for investigational testing; (c) one aliquot of the specimen will be stored at --70C for subsequent shipment to the reference laboratory for PCR-LDT testing, (d) one aliquot will be archived at -70C for subsequent follow-up by the reference laboratory (e.g., bi-directional sequencing of positive specimens), and (e) any remaining specimen will be stored for the Fresh vs. Frozen Study. The extracted nucleic acid generated from the second aliquot (i.e., "b" above) will be split and subjected to testing by both the artus Influenza A/B RT-PCR test and the ResPlex II Advanced Panel test.
Description: The presence of Influenza A or Influenza B virus.
Measure: Detection of Respiratory Viruses Time: Specimens will be taken within 5 days of the appearance of symptoms.This study will be conducted in a 208-bed nursing home in Maribor. The investigators will observe a group of a 100 nursing-home residents and 50 health care workers- employees in the nursing home- in a six months period.Influenza vaccination status will be recorded in all participants at the beginning. At the beginning and at the end of the study the blood samples for vitamin D concentration determination and nasopharyngeal swabs for molecular detection of respiratory viruses will taken in all of the participants. The study will observe number of viral respiratory tract infection in participants and identify the viral etiology of infections during 6 months observational period.Nasopharyngeal swab and blood sample will be taken in each of the participant who will suffer an acute respiratory tract infection (upper or lower respiratory tract infection) and viral agents of respiratory tract diseases will be searched for. The investigators will try to detect different viral agents of respiratory tract infection: human rhinoviruses, enteroviruses, influenza A, B, parainfluenza 1-4, respiratory syncytial virus, human coronaviruses, human metapneumovirus, adenoviruses and human bocavirus with newer molecular methods (real-time polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction) in nasopharyngeal swab and in blood sample of the participants. During the study period the investigators will monitor the daily number of visitors (adults, preschool children and pupils) in each nursing home room. The epidemiological aspect of respiratory viral infection will be assessed. Our study hypothesis is that lower respiratory tract infections in elderly can be caused by viruses other than influenza. The investigators would like to know if hypovitaminosis D is a risk factor for respiratory tract infections in nursing home residents and employees. The investigators would also like to know if the number of respiratory tract infections in elderly correlates with the number of visitors in nursing home, small children in particular.
Description: Number of participants with upper and lower respiratory tract infection will be detected and etiology of viral infection will be identified
Measure: Number of viral respiratory tract infection in participants according to etiology Time: 6 monthsDescription: Serum concentration of vitamine D will be measured retrospectively from the blood samples taken at the beginning of the study and correlation between vitamine D concentration and the frequency of respiratory tract infection in participants will be made
Measure: Serum vitamine D concentration in participants Time: 6 monthsDescription: Daily number of visitors in each nursing home room will be counted and correlate with the number of respiratory tract infection in participants.
Measure: Daily number of visitors in nursing home in correlation with the number of respiratory tract infection in residents Time: 6 monthsBronchiectasis is clinically characterized by irreversible dilation of the bronchi and bronchioles leading to persistent cough, purulent sputum, and airway flow limitation, which may be accompanied by recurrent exacerbations.It has been increasingly recognized that respiratory viruses are mainly responsible for acute exacerbation of chronic pulmonary diseases, i.e. asthma, chronic obstructive pulmonary disease and cystic fibrosis. However,little is known about the roles of viral infection in driving exacerbations of bronchiectasis.This study aims to identify the frequency of common viral infections and determine the roles that viruses play in acute exacerbations of bronchiectasis.
Description: Respiratory viruses in the nasal swab and sputum will be identified using the polymerase chain reaction(PCR)technique when clinically stable and during exacerbation.The following viruses will be tested for:influenza A,B(including influenza A H1N1),respiratory syncytial virus(RSV),Enterovirus,Parainfluenza 1-4,Rhinovirus,human Coronaviruses(subtypes OC43、229E、HKU1),human metapneumovirus,adenovirus, human bocavirus,chlamydia,mycoplasma.
Measure: The prevalence of respiratory virus infection in adults with bronchiectasis during a pulmonary exacerbation and when clinically stable. Time: 1 yearDescription: Systemic and airway inflammatory cytokines including IL-1β、IL-6、IL-8、TNF-a were measured using a commercial multiplex bead-based assay.
Measure: The effect of respiratory virus infection on systemic and pulmonary inflammatory markers. Time: 1 yearDescription: Spirometric indices in the present study is referred to as forced expiratory vilume in 1s(FEV1),forced vital capacity(FVC).Spirometry tests are carried out using a spirometer (COSMED, QUARK PFT, Italy). All operation procedures meet the joint recommendation by ATS and ERS. A total of at least 3 (not more than 8) spirometric maneuvers are performed, with the variation between the best two maneuvers of <5% or 200ml in FVC and FEV1. The maximal values of FVC and FEV1 are reported.
Measure: The effect of respiratory virus on lung function Time: 1 yearDescription: Type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter
Measure: The effect of respiratory virus infection on the bacterial load in bronchiectasis. Time: 1 yearDescription: The time from exacerbation onset by which a 3-d moving average was equal to or exceeded the baseline value
Measure: Time to recovery of respective symptom Time: 1 yearDescription: Quality of life in patients with bronchiectasis were measured by St.George Respiratory Questionnaire、Leicester Cough Questionnaire and COPD assessment test during exacerbations,and then compared between virus-postive and virus-negative patients
Measure: The effect of respiratory virus on quality of life in patients with bronchiectasis Time: 1 yearThe primary objective of this study is to evaluate the effects of presatovir on respiratory syncytial virus (RSV) viral load in RSV-positive adults who have been hospitalized with acute respiratory infectious symptoms. Participants will receive 1 dose of presatovir on Day 1 and followed for 27 days postdose. Nasal swabs will be collected at each study visit (excluding Day 28) and assayed for change in viral load as the primary endpoint.
Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.
Measure: Time-Weighted Average Change in Respiratory Syncytial Viral (RSV) Load From Baseline to Day 5 Time: Baseline to Day 5Description: The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms). The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.
Measure: Time-weighted Average Change in the Flu-PRO Score From Baseline to Day 5 Time: Baseline to Day 5Description: The adjusted rate of unplanned medical encounters (clinic visits, emergency room visits, urgent care visits, and rehospitalizations) related to a respiratory illness after initial hospital discharge through Day 28 will be assessed. Event rate was calculated as the total number of unplanned medical encounters divided by the total number of participants. The mean values presented were adjusted for stratification factor.
Measure: Rate of Unplanned Medical Encounters Time: Up to Day 28The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV lower respiratory tract infection (LRTI).
Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factors.
Measure: Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9 Time: Baseline to Day 9The purpose of this study is to determine if the use of inhaled beclomethasone after a community-acquired respiratory viral infection in a lung transplant recipient decreases the risk of the subsequent development of chronic lung allograft dysfunction.
The primary objective of this study is to evaluate the effect of presatovir on nasal respiratory syncytial virus (RSV) viral load in RSV-positive lung transplant (LT) recipients with acute respiratory symptoms.
Description: The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms) for the 5-point severity scale and 0 (never) to 4 or more times (always) for the 5-point frequency scale. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.
Measure: Time-Weighted Average Change in FLU-PRO Score From Day 1/Baseline Through Day 7 Time: Up to 7 daysDescription: FEV1 is defined as forced expiratory volume in the first second.
Measure: Percent Change From Study Baseline in FEV1% Predicted Value Time: Baseline; Day 28Viral respiratory infections are common and often require use of health care resources. Patients receive inappropriate bacterial antibiotics, which has many problems including side-effects, development of resistance and costs. A small portion of the infections leads to severe clinical manifestations including hospitalisations and deaths. The significance of influenza virus is well known and it is actively detected in all age groups. However, the benefits of detecting other respiratory viruses have mainly been studied among children but not among adults. The development of multiplex PCR technique has provided a new and sensitive method for diagnosing a large panel of viruses. To convince the economical benefits of the rapid viral diagnostic in adult infectious patient, more evidence is needed. In our randomized study, nasal and pharyngeal samples from the patients evaluated at the emergency clinic of internal medicine in the University Hospital of Oulu because of any respiratory symptom, chest pain or fever, will be collected. The samples will be tested for 16 different respiratory viruses by using Anyplex TMII RV16 Detection. The adult participants will be randomized in two groups. In one group the results of the testing will be reported for the attending physician as soon as possible, and in the other group 7 days after sampling. The effect of this delay to patient care is monitored. Also the results of children and adults are compared as well as results of men and women. The hypothesis is that rapid viral diagnostics shortens the length of admission and diminishes the use of bacterial antibiotics. New information on the viral epidemiology among children and adults is provided and clinical manifestations of specific viral infections in adults are described. The estimated 1500 samples are also tested for 5 different respiratory bacteria by Anyplex TM II RB5 Detection. These results will be examined after completion of the study period. The benefits of rapid bacterial detection are evaluated in respect to the clinical course of the disease and considering the infection control aspects as well.
Description: The number of days in hospital within one month after randomization
Measure: Duration of hospitalization Time: One monthDescription: Number of days on antimicrobials within one month after randomization
Measure: Antimicrobial consumption Time: One monthDescription: Defined daily doses of antimicrobial agents within one month after randomization
Measure: Antimicrobial consumption Time: One monthThis study aimed to analysis the characteristics of MERS transmission and the effect of our institutional personal protective equipment on the controlling the MERS at a tertiary Korean Hospital.
The international multicenter double-blind placebo-controlled randomized clinical study in parallel groups.The objective of this study is to obtain additional data on the efficacy and safety of Ergoferon in the treatment of acute respiratory viral infections (ARVI) in children aged from 6 months to 6 years old.
Description: Based on patient diary data. Criteria of alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom).
Measure: Time to Alleviation of All ARVI Symptoms. Time: 14 days of observation.Description: Based on patient diary data. Oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period).
Measure: Time to Normalization of Body Temperature. Time: 14 days of observation.Description: Based on patient diary data. Absence of flu-like nonspecific symptoms/presence of one mild flu-like nonspecific symptom.
Measure: Time to Alleviation of Flu-like Nonspecific Symptoms. Time: 14 days of observation.Description: Based on patient diary data. Absence of respiratory symptoms/presence of one mild respiratory symptom.
Measure: Time to Alleviation of Respiratory Symptoms. Time: 14 days of observation.Description: Based on patient diary data. The total score (TS) ranges from 0 to 30 consisting of 4 flu-like nonspecific (decreased activity/weakness, poor appetite/refusal to eat, sick appearance, sleep disturbance) and 6 respiratory (runny nose, stuffy nose/nasal congestion, sneezing, hoarseness, sore throat, cough) symptoms according to the 4-point scale for each symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). The higher values represent a worse outcome.
Measure: Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Time: On days 2-6 of the observation period.Description: Based on the area under the curve of TS for days 2-6, according to the patient diary. The total score (TS) will be calculated based on the severity of each ARVI symptom (sum of 11 symptoms = body temperature, flu-like nonspecific symptoms (4 symptoms) and respiratory symptoms (6 symptoms) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TS the absolute oral temperature values, measured in degrees Celsius, will be converted into relative units (or points), given the following gradations: ≤37.5С = 0 point; 37.6-38.1C = 1 point; 38.2-38.8C = 2 points; ≥38.90С = 3 points. For total score minimum and maximum scores are 0 and 33, where higher values represent worse outcome.
Measure: ARVI Severity. Time: On days 2-6 of the observation period.Description: Based on patient diary data. Criteria of recovery/alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale for each flu-like nonspecific and respiratory symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom).
Measure: Percentage of Recovered Patients. Time: On days 2-6 of the observation period.Description: Based on patient diary data. The number of intakes of prescribed antipyretics.
Measure: Rates of Antipyretics Use Per Patient. Time: On days 1- 5 of the treatment period.Description: Based on patient diary data. The disease worsening: ARVI complications, including those requiring antibiotics; hospitalization).
Measure: Percentage of Patients With Worsening of Illness. Time: 14 days of observation peiod.This is a Phase 1, first-in-human (FIH), single site, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a co-administered (1:1, w/w) combination of REGN3048 and REGN3051 mAb's, administered IV in healthy adult volunteers. Study duration of approximately 16 months. Approximately 48 evaluable subjects will be enrolled in the study, eight (8) subjects in each one of 6 sequential ascending IV dose cohorts. In each cohort, subjects will be randomized to receive mAb's REGN3048 and REGN3051 (6 subjects) or placebo (2 subjects). Primary Objective: To assess the safety and tolerability of REGN3048 and REGN3051 following co-administration of single, ascending IV doses of 1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's.
Non tuberculous mycobacteria (NTM), Burkholdria spp, Aspergillus in the lung are almost impossible to eradicate with conventional antibiotics. In addition COVID-19 has know current treatment. These patients have few options to treat their lung infection. Nitric oxide has broad bactericidal and virucidal properties. It has been shown that nitric oxide was safe to be inhaled for similar cystic fibrosis patients and reduced drug resistant bacteria in the lungs. Further, research indicates that clinical isolates of NTM, Burkholderia spp, Aspergillus spp and Corona-like viruses can be eradicated by 160ppm NO exposure in the laboratory petri dish. This is not the first time inhaled NO treatment has been used in patients with difficult lung infections. This study will provide more data to see if NO therapy can reduce the bacterial load in the lungs, help the patients breath better; and in the case of COVID-19 act as a anti-viral agent resulting in the reduction of incidence of oxygen therapy, mechanical assistance of BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Description: Measure the number of unanticipated adverse events over the duration of the study protocol
Measure: Measure the safety of 160ppm inhaled nitric oxide delivery in NTM subjects Time: 26 DaysDescription: Measure the change in absolute FEV1.0 change from baseline during 160 ppm inhalation therapy
Measure: Measure the effect of 160ppm inhaled nitric oxide delivery on lung spirometry in NTM subjects Time: Day 5,12,19 and 26Description: Measure the difference from baseline NTM species bacterial load (0 to +4) in sputum during 160ppm nitric oxide inhalation therapy
Measure: Measure the antimicrobial effect of 160ppm inhaled nitric oxide on lung NTM bacterial load in the sputum Time: Day 19 and 26Description: Measure the difference from baseline CRISS (0-100) during 160ppm nitric oxide inhalation therapy (lower score represents higher quality of life)
Measure: Measure the effect of 160ppm inhaled nitric oxide on Quality of Life (CRISS) Score Time: Day 19 and 26Description: Measuring reduction in the incidence of mechanical assistance including oxygen therapy, BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Measure: Sub-Study Primary Endpoint(s): Efficacy to reduce respiratory interventions Time: Day 26Description: Measured by death from all causes
Measure: Efficacy in reduction of mortality Time: Day 26Description: Assessed by time to negative conversion of COVID-19 RT-PCR from upper respiratory tract
Measure: Antiviral effect Time: Day 26Description: Time to clinical recovery as measured by resolution of clinical signs
Measure: Efficacy on clinical improvement Time: Day 26Description: Measured by change in the Modified Jackson Cold Score
Measure: Efficacy on the respiratory symptoms Time: Day 26The purpose of this study is to evaluate the effect of JNJ-53718678 on the development of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper RTI.
Description: The proportion of participants who develop RSV LRTI through Visit Day 28 per the Endpoint Adjudication Committee (EAC) assessment will be reported.
Measure: Proportion of Participants who Develop Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) Time: Up to Day 28Description: The proportion of participants who develop RSV-associated LRTC through Visit Day 28 per the EAC's assessment will be reported.
Measure: Proportion of Participants who Develop RSV-associated Lower Respiratory Tract Complication (LRTC) Time: Up to Day 28Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Measure: Number of Participants with Adverse Events (AEs) Time: Up to 49 DaysDescription: Percentage of participants with abnormal clinical laboratory findings will be reported.
Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal ECGs findings will be reported.
Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal vital signs findings will be reported.
Measure: Percentage of Participants with Abnormal Vital Signs Findings Time: Up to 49 daysDescription: The proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, (all-cause mortality) will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, (all-cause Mortality) Time: Up to 49 daysDescription: Proportion of participants progressing to death (all-cause mortality), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Proportion of Participants Progressing to Death (All-cause Mortality), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Proportion of participants progressing to death (all-cause mortality) will be reported.
Measure: Proportion of Participants Progressing to Death (All-cause Mortality) Time: Up to 49 daysDescription: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) Time: Up to 49 daysDescription: Number of supplemental O2 free days will be reported.
Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28 Time: Through Day 28Description: Incidence of supplemental oxygen requirement in participants will be reported.
Measure: Incidence of Supplemental Oxygen Requirement Time: Up to 28 daysDescription: Duration of supplemental oxygen requirement in participants will be reported.
Measure: Duration of Supplemental Oxygen Time: Up to 28 daysDescription: Change from baseline in respiratory rate as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Respiratory Rate Time: Baseline up to 49 daysDescription: Change from baseline in heart rate as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Heart Rate Time: Baseline up to 49 daysDescription: Change from baseline in SpO2 as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2) Time: Baseline up to 49 daysDescription: Change from baseline in body temperature as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Body Temperature Time: Baseline up to 49 daysDescription: Proportion of participants hospitalized (of participants who were not hospitalized at baseline) will be reported.
Measure: Proportion of Participants Hospitalized (of Participants who Were not Hospitalized at Baseline) Time: Up to 49 daysDescription: Proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study) will be reported.
Measure: Proportion of Participants Re-hospitalized Time: Up to 49 daysDescription: Total length of hospital stay (time in hospital from first dosing) will be reported.
Measure: Total Length of Hospital Stay Time: Up to 49 daysDescription: Total time in the ICU (time in ICU from first dosing) will be reported.
Measure: Total Time in the Intensive Care Unit (ICU) Time: Up to 49 daysDescription: Incidence of Grade 3 and Grade 4 AEs will be assessed by system organ class where Grade 3: Severe and Grade 4: Life-threatening.
Measure: Incidence of Grade 3 and Grade 4 Adverse Events (AEs) Time: Up to 49 daysDescription: Incidence of respiratory AEs will be reported.
Measure: Incidence of Respiratory AEs Time: Up to 49 daysDescription: Incidence of thoracic-related AEs will be reported.
Measure: Incidence of Thoracic-related AEs Time: Up to 49 daysDescription: Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Incidence of Antibiotic use in Participants who Develop and in Those who do not Develop RSV LRTI or RSV-Associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Time to resolution of symptoms, assessed through an instrument for participant-reported symptoms (RiiQ Symptom Scale) will be reported.
Measure: Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Time: Up to 49 daysDescription: Change from baseline in severity of symptoms reported by participants in the RiiQ symptom scale through Day 28 will be reported.
Measure: Change from Baseline in Severity of Symptoms Reported by Participants in the RiiQ Symptom Scale Through Day 28 Time: Baseline up to Day 28Description: Time to resolution of respiratory illness, through the PGI-S Scale, will be reported.
Measure: Time to Resolution of Respiratory Illness as Assessed by Patient Global Impression of Severity (PGI-S) Scale Time: Up to 49 daysDescription: Change from baseline in PGI-H scale through Day 28 will be reported.
Measure: Change from Baseline in Patient Global Impression of Health (PGI-H) Scale Through Day 28 Time: Baseline up to Day 28Description: Change from baseline in PGI-C scale through Day 28 will be reported.
Measure: Change from Baseline in Patient Global Impression of Change (PGI-C) Scale Through Day 28 Time: Baseline up to Day 28Description: AUC (0-24h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose.
Measure: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours Postdose (AUC [0-24]) of JNJ-53718678 Time: Up to 24 hours postdose (on Days 1 and 8)Description: Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.
Measure: Trough Plasma Concentration (Ctrough) of JNJ-53718678 Time: Predose on Days 1 and 8Description: Cmax is defined as the maximum observed plasma concentration of JNJ-53718678 in the dosing interval.
Measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 Time: Predose; 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose (on Days 1 and 8)Description: The potential association of plasma concentration-time data of JNJ-53718678 with antiviral activity (RSV viral kinetics) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral Activity Time: Up to 49 daysDescription: The potential association of plasma concentration-time data of JNJ-53718678 with selected safety (including AEs and laboratory abnormalities) parameters will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Safety Parameters Time: Up to 49 daysDescription: The potential association of plasma concentration-time data of JNJ-53718678 with clinical outcomes (proportion of participants developing LRTI) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical Outcomes Time: Up to 49 daysDescription: RSV viral load and change from baseline over time will be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in the mid-turbinate nasal swab specimens.
Measure: RSV Viral Load and Change from Baseline Over Time Time: Baseline up to Day 28Description: RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.
Measure: RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 8, 11, 15, 22 and 28 Time: Baseline up to Days 8, 11, 15, 22 and 28Description: Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.
Measure: Time to Undetectable RSV Viral Load Time: Up to 49 daysDescription: Proportion of participants with undetectable RSV viral load at each time point throughout the study will be reported.
Measure: Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint Time: Up to 49 daysDescription: Change from baseline for the HRQOL assessment as assessed through the EQ-5D-5L through Day 28 will be reported.
Measure: Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed by 5-level EuroQol 5-Dimension (EQ-5D-5L) Through Day 28 Time: Baseline up to Day 28Description: Change from baseline for the HRQOL assessment as assessed through RiiQ impact scales through Day 28 will be reported.
Measure: Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through Day 28 Time: Baseline up to Day 28Description: Change from baseline in the RSV F gene sequence will be reported.
Measure: Change from Baseline in the RSV F Gene Sequence Time: Baseline up to 49 daysThis study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to recovery Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Change in National Early Warning Score (NEWS) from baseline Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 3 through Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Cumulative incidence of serious adverse events (SAEs) Time: Day 1 through Day 29Description: For any reason.
Measure: Discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Mean change in the ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8-point ordinal scale Time: Day 15Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 29-day mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Time to discharge or to a National Early Warning Score (NEWS) of = 2 and maintained for 24 hours, whichever occurs first Time: Day 1 through Day 29This is a phase I, open-label, dose ranging clinical trial in males and non-pregnant females, 18 to 55 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at one domestic site. Forty-five subjects will be enrolled into one of three cohorts and will receive an intramuscular (IM) injection of mRNA-1273 on Days 1 and 29 in the deltoid muscle. Subjects will be followed through 12 months post second vaccination (Day 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults.
Description: Seroconversion is defined as a 4-fold change in antibody titer from baseline
Measure: Percentage of subjects who seroconverted Time: Day 1 to Day 57COVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. No specific anti-viral treatment exists. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Cellular therapy, using mesenchymal stem cells has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. This clinical trial is to inspect the safety and efficiency of mesenchymal stem cells (MSCs) therapy for severe COVID-19.
Description: Evaluation of Pneumonia Improvement
Measure: Size of lesion area and severity of pulmonary fibrosis by chest CT Time: At Baseline , Day 6, Day 10, Day 14, Day 28 and Day 90Description: Evaluation of Pneumonia Improvement No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6.
Measure: mMRC (Modified Medical Research Council) dyspnea scale Time: Baseline , Day 7, Day 14, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Oxygenation index( PaO2/FiO2) Time: Baseline , Day 7, Day 14, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Duration of oxygen therapy(days) Time: Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Duration of hospitalization(days) Time: Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Blood oxygen saturation Time: Baseline , Day 7, Day 14, Day 28, Day 90Description: Marker of Immunological function
Measure: CD4+ T cell count and cytokine level Time: Baseline , Day 6, Day 10, Day 14, Day 21, Day 28, Day 90Description: Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measure: Side effects in the MSCs treatment group Time: Baseline , Day 3, Day 6,Day 10, Day 14, Day 21, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: 6-minute walk test Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Maximum vital capacity (VCmax) Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Diffusing Capacity (DLCO) Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90Infection with the SARS-CoV-2 coronavirus strain is associated with severe morbidity and mortality estimated today from 2% to 4%. Elderly patients or patients with serious chronic conditions justifying hospitalization are particularly at risk. The risk of infection with SARS-CoV-2 during hospitalization is also substantial and increased in fragile patients. Several cases of infection among Healthcare Professionals had been reported. The hypothesis is that similar to the corona virus agent responsible for SRAS and the influenza virus, nosocomial outbreaks of SARS-CoV-2 to be feared. Health care professionals and caregivers are populations-at-risk as they are exposed in the community and can transmit SARS-CoV-2 to hospitalized patients, and are also exposed to hospitalized patients infected with SARS-CoV-2. Describing hospital-acquired cases and SARS-CoV-2 infection transmission chains in healthcare settings is vitally essential to achieve control of this epidemic. To improve the quality of care and patient safety, this data must be accompanied by an analysis of the impact of infection control measures. In addition, an effective infection control program is urgently required to control the spread of the virus and protect both uninfected patients who require care for other medical or surgical conditions as well as health care professionals. The main objective of this prospective, non-interventional - observational, hospital based study in adults and children is to describe and document suspected or confirmed cases of nosocomial SARS-CoV-2 infection, the clinical spectrum and the determinants (risk factors/protective factors) at participating hospitals. Characterization of the clinical features of the SARS-CoV-2 infection will help to identify potential sources of virus transmission as rapidly as possible and enable implementation of appropriate hygiene practices in hospitals.
Description: The primary outcome criteria will be the proportion of patients, caregivers and health care professionals with confirmed or suspected SARS-CoV-2 nosocomial infection relative to all patients, caregivers and health care professionals with syndromes suggestive of SARS-CoV-2 infection during the study period. The infection control measures will be reported and describe according the nosocomial cases.
Measure: nosocomial infection Time: At inclusionThe study is expected to treat patients with mild and severe neo-coronary pneumonia through standard treatment regimens in combination with tetrandrine tablets, thereby reducing the clinical progress of some patients, improving prognosis, reducing the incidence of pulmonary fibrosis during rehabilitation, and improving patients' quality of life.
Description: Death event
Measure: Survival rate Time: 12 weeksDescription: inflammatory indicator
Measure: body temperature Time: 2 weeksThe Novel Coronavirus (2019-nCoV), also known as Wuhan coronavirus, causes the 2019-nCoV acute respiratory disease. The number of patients infected by 2019-nCoV in Italy closely followed an exponential trend, and Italy reported the highest number of infected patients and deaths in the world excluding China.
Description: different maternal and perinatal outcomes were evaluated including: admission to ICU, use of mechanical ventilation, maternal death, early pregnany loss, perinatal death, intrauterine growth restriction (IUGR), preterm birth, mode of delivery, LBW, admission to neonatal ICU (NICU), and clinical or serologic evidence of vertical trasmission
Measure: Maternal and perinatal outcomes Time: during gestation and at the time of delivery of the babyThis study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC + Lopinavir/Ritonavir plus interferon ß-1a versus SoC + Hydroxychloroquine. Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is the subject clinical status (on a 7-point ordinal scale) at day 15.
Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
Measure: Percentage of subjects reporting each severity rating on a 7-point ordinal scale Time: Day 15Description: Time to an improvement of one category from admission on an ordinal scale. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.
Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale Time: Days 3, 5, 8, 11, 15 and 29Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.
Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Time: Days 3, 5, 8, 11, 15 and 29Description: • Duration of hospitalization (days).
Measure: Hospitalization Time: 29 daysDescription: Rate of mortality
Measure: Mortality Time: In hospital, Day 28, Day 90Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of lopinavir Time: Days 1, 3, 5, 8 and 11Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of hydroxychloroquine Time: Days 1, 3, 5, 8 and 11In the current proposal, the investigators aim to investigate the virological and clinical effects of chloroquine treatment in patients with established COVID-19 in need of hospital admission. Patients will be randomized in a 1:1 fashion to standard of care or standard of care with the addition of therapy with chloroquine.
Description: Viral load assessed by real time polymerase chain reaction in nasopharyngeal samples
Measure: Rate of decline in SARS-CoV-2 viral load Time: Baseline (at randomization) and at 96 hoursDescription: National Early Warning Score score determines the degree of illness of a patient. Scores range from 0-20, with a higher score representing further removal from normal physiology and a higher risk of morbidity and mortality.
Measure: Change in National Early Warning Score score Time: Baseline (at randomization) and at 96 hoursDescription: Transfer from regular ward to intensive care unit during index admission
Measure: Admission to intensive care unit Time: At all times after randomization during index admission (between admission and discharge, approximately 21 days)Description: All-cause mortality during index admission
Measure: In-hospital mortality Time: At all times after randomization during index admission (between admission and discharge, approximately 21 days)Description: Total days admitted to the hospital (difference between admission date and discharge date of index admission)
Measure: Duration of hospital admission Time: During index admission (between admission and discharge, approximately 21 days)Description: All-cause mortality assessed at 30 and 90 days
Measure: Mortality at 30 and 90 days Time: At follow-up 30 and 90 daysDescription: Percentage of subjects reporting each severity rating on a 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Clinical status Time: 14 days after randomizationThe purpose of this study is to test the hypothesis that post-exposure prophylaxis with hydroxychloroquine will reduce the symptomatic secondary attack rate among household contacts of known or suspected COVID-19 patients.
Description: This is defined as either 1. COVID-19 infection confirmed within 14 days of enrollment, following self-report of COVID-19 symptoms to the research study; OR, 2. COVID-19 infection confirmed within 14 days of enrollment, with self-report of COVID-19 symptoms to a treating physician.
Measure: Number of participants with symptomatic, lab-confirmed COVID-19. Time: Date of enrollment to 14 days post-enrollment dateThe Novel Coronavirus (2019-nCoV), also known as Wuhan coronavirus, causes the 2019-nCoV acute respiratory disease.
Description: different maternal and perinatal outcomes were evaluated including: admission to ICU, use of mechanical ventilation, maternal death, early pregnany loss, perinatal death, intrauterine growth restriction (IUGR), preterm birth, mode of delivery, LBW, admission to neonatal ICU (NICU), and clinical or serologic evidence of vertical trasmission
Measure: Maternal and perinatal outcomes Time: at the time of deliverySARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease presentation which has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of 18 March 2020, there are 198,193 number of confirmed cases with an estimated case-fatality of 3%. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment. SARS-CoV-2 exploits the cell entry receptor protein angiotensin converting enzyme II (ACE-2) to access and infect human cells. The interaction between ACE2 and the spike protein is not in the active site. This process requires the serine protease TMPRSS2. Camostat Mesilate is a potent serine protease inhibitor. Utilizing research on severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 cell entry mechanism, it has been demonstrated that SARS-CoV-2 cellular entry can be blocked by camostat mesilate. In mice, camostat mesilate dosed at concentrations similar to the clinically achievable concentration in humans reduced mortality following SARS-CoV infection from 100% to 30-35%.
Description: Clinical improvement defined as live hospital discharge OR a 2 point improvement (from time of enrolment) in disease severity rating on the 7-point ordinal scale
Measure: Cohort 1: Days to clinical improvement from study enrolment Time: 30 daysDescription: Days to clinical improvement from study enrolment defined no fever for at least 48 hrs AND improvement in other symptoms (e.g. cough, expectoration, myalgia, fatigue, or head ache)
Measure: Cohort 2: Days to clinical improvement from study enrolment Time: 30 daysDescription: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Cohort 1: Clinical status as assessed by the 7-point ordinal scale at day 7, 14 and 30 Time: 30 daysDescription: Mortality
Measure: Cohort 1: Day 30 mortality Time: 30 daysDescription: NEWS2
Measure: Cohort 1: Change in NEW(2) score from baseline to day 30 Time: 30 daysDescription: ICU
Measure: Cohort 1: Admission to ICU Time: 30 daysDescription: invasive mechanical ventilation or ECMO
Measure: Cohort 1: Use of invasive mechanical ventilation or ECMO Time: 30 daysDescription: Nasal or high-flow oxygen
Measure: Cohort 1: Duration of supplemental oxygen (days) Time: 30 daysDescription: Subjective clinical improvement
Measure: Cohort 1+2: Days to self-reported recovery (e.g. limitations in daily life activities) during telephone interviews conducted at day 30 Time: 30 daysDescription: No of new COVID-19 infections in the household
Measure: Cohort 2: Number participant-reported secondary infection of housemates Time: 30 daysDescription: Hospital admission
Measure: Cohort 2: Time to hospital admission related to COVID-19 infection Time: 30 daysThis study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.
Description: The patient will becategorized into one of the following 8 categories depending on status of their hospitalization: Dead (yes/no) Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) Hospitalized and receiving Non-invasive ventilation or "high-flow oxygen device" (yes/no) Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) Hospitalized for observation (yes/no) Discharged from hospital with restriction of activity level (yes/no) Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be "yes".
Measure: Categorization of hospitalization status Time: 14 daysDescription: Delta PaO2 measured in arterial puncture
Measure: Change in patient's oxygen partial pressure Time: 4 daysDescription: Delta PaCO2 measured in arterial puncture
Measure: Change in patient's carbondioxid partial pressure Time: 4 daysDescription: pH measured in arterial puncture
Measure: Level of pH in blood Time: 4 daysThis is a phase 3, multi-center, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of colchicine in adult patients diagnosed with COVID-19 infection and have at least one high-risk criterion. Approximately 6000 subjects meeting all inclusion and no exclusion criteria will be randomized to receive either colchicine or placebo tablets for 30 days.
Description: The primary endpoint will be the composite of death or the need for hospitalization due to COVID-19 infection in the first 30 days after randomization.
Measure: Number of participants who die or require hospitalization due to COVID-19 infection Time: 30 days post randomizationDescription: The secondary endpoint is the occurrence of death in the 30 days following randomization.
Measure: Number of participants who die Time: 30 days post randomizationDescription: The secondary endpoint is the need for hospitalization due to COVID-19 infection in the 30 days following randomization.
Measure: Number of participants requiring hospitalization due to COVID-19 infection Time: 30 days post randomizationDescription: The secondary endpoint is the need for mechanical ventilation in the 30 days following randomization.
Measure: Number of participants requiring mechanical ventilation Time: 30 days post randomizationCoronavirus disease 2019 (COVID-19) is caused by the newly discovered coronavirus, SARS-CoV-2. The median time from onset of symptoms of COVID-19 to development of acute respiratory distress syndrome (ARDS) has been reported as short as 9 days. No effective prophylactic or post-exposure therapy is currently available. According to data from the Danish Health Authority (www.sst.dk/corona), as of March 21st, 2020, there were 1326 patients infected with the disease in Denmark, more than 250 are admitted to a hospital, and >50 of them have required intensive care. Nearly 350.000 cases and 15.000 deaths have been reported globally. These numbers are likely to markedly increase during the coming weeks, challenging the capacity of health systems worldwide. In patients infected with SARS-CoV-2, it has been described that disease severity and outcomes are related to the characteristics of the immune response. Interleukin (IL)-6 and other components of the inflammatory cascade contribute to host defense against infections. However, exaggerated synthesis of IL-6 can lead to an acute severe systemic inflammatory response known as 'cytokine storm'. In the pathogenesis of SARS-CoV-2 pneumonia, a study found that a cytokine storm involving a considerable release of proinflammatory cytokines occurred, including IL-6, IL-12, and tumor necrosis factor α (TNF-α). Studies on the Middle East respiratory syndrome caused by another coronavirus (MERS-CoV), indicate that cytokine genes of IL-6, IL-1β, and IL-8 can be markedly upregulated. Similarly, patients with SARS-CoV-2 pneumonia admitted to an intensive care unit had higher plasma levels of cytokines including IL-6, IL-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon-γ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), macrophage inflammatory protein 1 alpha (MIP1A), and TNF-α. These findings indicate that the magnitude and characteristics of the cytokine response is related to the severity and prognosis of patients with SARS-CoV-2 pneumonia. It has been suggested that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Remarkable beneficial effects of IL-6 blockade therapy using a IL-6 receptor inhibitor has been described in patients with severe SARS-CoV-2 pneumonia in a retrospective case series from China. Currently, there are two available drugs based on human monoclonal antibodies against IL-6 receptor, tocilizumab (RoActemra, Roche) and sarilumab (Kevzara, Sanofi). IL-6 receptor inhibitors are currently licensed for several autoimmune disorders and are considered well tolerated and safe in general. The most common side effects reported are upper respiratory tract infections, headache, hypertension, and abnormal liver function tests. The most serious side effects are serious infections, complications of diverticulitis, and hypersensitivity reactions. it is hypothesized that IL-6 might play a key role in the cytokine storm associated with serious adverse outcomes in patients infected with SARS-CoV-2 pneumonia, and that blockade of IL-6 would be suitable therapeutic target for these patients. The study will investigate the effect of different types of IL-6 inhibition versus no adjuvant treatment compared to standard of care in patients with severe SARS-CoV-2 pneumonia. Primary objective: To compare the effect of either one of three IL-6 inhibitor administrations, relative to the standard of care, on time to independence from supplementary oxygen therapy, measured in days from baseline to day 28, in patients with severe SARS-CoV-2 pneumonia.
Description: Measured from standard blood test
Measure: C-reactive protein (CRP) level Time: baselineDescription: Measured from standard blood test
Measure: C-reactive protein (CRP) level Time: peak during hospitalisation, up to 28 daysDescription: Measured from standard blood test
Measure: C-reactive protein (CRP) level Time: 14 daysDescription: Measured from standard blood test
Measure: C-reactive protein (CRP) level Time: 28 daysDescription: Measured as occurrence of any serious adverse events
Measure: Number of participants with serious adverse events Time: During treatment, up to 28 daysResearchers are creating a real time COVID-19 registry of current ICU/hospital care patterns to allow evaluations of safety and observational effectiveness of COVID-19 practices and to determine the variations in practice across hospitals.
Description: Primary outcome will be to measure ICU and hospital mortality up to 7 days of COVID-19 patients
Measure: ICU and hospital mortality of COVID-19 patients Time: 7 daysDescription: Secondary outcome will be to measure 30 days mortality from Hospital discharge
Measure: 30 days mortality Time: 30 daysThe overall objective of the study is to determine which treatments (e.g. immune modulator drugs) have the most favorable benefit-risk in adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. The specific aims of this Covid19 cohort are to collect observational data at regular intervals on an ongoing basis in order to embed a series of randomized controlled trials evaluating a various set of interventions for patients with COVID-19 pneumonia. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design.
Description: Overall Survival
Measure: Survival Time: 14 daysDescription: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale COVID 19 Time: 14 daysThe overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Sarilumab administration to patients enrolled in the CORIMUNO-19 cohort. Sarilumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Sarilumab will receive standard of care. Outcomes of Sarilumab-treated patients will be compared with outcomes of standard of care-treated patients as well as with outcomes of patients treated with other immune modulators.
Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14. Time: 14 daysDescription: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale <=5 at day 4 Time: 4 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 Time: 14 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event. Scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9
Measure: WHO progression scale at day 4 Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: respiratory acidosis at day 4 Time: 4 daysDescription: evolution of PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: time to oxygen supply independency
Measure: time to oxygen supply independency Time: 14 daysDescription: duration of hospitalization
Measure: duration of hospitalization Time: 90 daysDescription: time to negative viral excretion
Measure: time to negative viral excretion Time: 90 daysDescription: time to ICU discharge
Measure: time to ICU discharge Time: 90 daysDescription: time to hospital discharge
Measure: time to hospital discharge Time: 90 daysCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and had subsequently spread worldwide. Twenty-nine percent of COVID-19 patients may develop ARDS. Based on the potential beneficial mechanisms of HFNC and PP, whether early use of prone positioning combined with HFNC can avoid the need for intubation in COVID-19 induced moderate to severe ARDS patients needs to be further investigated.
Description: the treatment failure rate of HFNC/HFNC+PP support and clinical requirement for advanced respiratory support
Measure: Treatment failure Time: 28 daysDescription: the improvement of SpO2/FIO2 or PaO2/FiO2 from HFNC alone to HFNC+PP
Measure: Efficacy of PP Time: 28 daysCOVID-19 (also known as Coronavirus) originated in the Wuhan China and has since spread to at least 159 countries around the world. It was declared a pandemic by the World health organisation on the 11th of March 2020. The cases in the United Kingdom continue to increase exponentially with up to 5 683 people diagnosed as on the 22nd of March 2020. It is estimated that 1 in 5 people diagnosed will require hospital admission and 1 in 20 intensive care treatment. By developing and improving diagnostic testing, we can accurately diagnose infected cases to triage appropriate treatments, identify individuals for quarantine in order to prevent transmission and obtain information regarding patient's immune systems. At present, the diagnostic test is a highly specific method of genetic amplification called 'Reverse Transcription - Polymerase Chain Reaction' or RT-PCR, which allows detection of very small amounts of genetic mutations caused by the COVID-19 virus. However, this method must be completed in highly specialised facilities, which are few and far between, increasing time to diagnosis (currently 48-72 hours), increasing exposure to non-infected individuals, and overburdening the analysing facilities. The ideal solution is a point of care (POC) test that can give results immediately. This study aims to harness the point of care technology of the SAMBA II device (Diagnostics for the Real World Ltd.), which is a CE-marked device that has been used with success in the identification of Human Immunodeficiency Virus (HIV), by amplifying genetic material without the need to increase and decrease temperatures during the amplification process. In the COVIDx study, 200 patients meeting the Public Health England's (PHE) inpatient definition of having suspected COVID-19 will be approached, consented and a sample from throat and nasal swab (combined) or tracheal fluid taken and tested using the SAMBA II method. A combination of the standard PHE RT-PCR and an additional validated laboratory PCR technique will be used as a control in line with standard clinical practice. Patients will undergo an additional serum tests on existing samples as made available after routine clinical assessments to monitor antibody response. Patients will be followed for clinical outcomes at 28 days post-admission.
Description: Measuring the diagnostic accuracy of the SAMBA II POC-sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) tested against a dual composite reference standard
Measure: SAMBA COVID-19 POC PCR Test Time: 28 daysDescription: Evaluating the participant acceptability of the SAMBA swab intervention using a participant reported discomfort scale
Measure: Patient acceptability Time: 28 daysDescription: Time to positive IgM/IgG test positivity
Measure: Immune Response Positivity Time: 40 daysBased on data regarding the effect of colchicine on the inflammasome NLP3 and microtubule formation and associations thereof with the pathogenetic cycle of SARS-COV-2, the question arises whether colchicine, administered in a relatively low dose, could potentially have an effect the patients' clinical course by limiting the myocardial necrosis and pneumonia development in the context of COVID-19. If present, this effect would be attributed to its potential to inhibit inflammasome and (less probably) to the process of SARS-CoV-2 endocytosis in myocardial and endothelial respiratory cells.
Description: Time to increase in C-reactive protein to 3 times the ULN
Measure: CRP increase to 3 x upper limit of normal Time: 3 weeksDescription: Time to clinical deterioration (2 levels in the WHO R&D Blueprint scale)
Measure: Clinical deterioration in the semiquantitative ordinal scale suggested by the WHO R&D committee Time: 3 weeksDescription: Maximal concentration of high-sensitivity cardiac troponin
Measure: Maximal concentration of cardiac troponin Time: 10 daysCoronavirus 2019 (COVID-19) is a respiratory tropism virus transmitted through droplets emitted into the environment of infected persons. The symptoms can be extremely varied and the course can range from spontaneous healing without sequelae to death. Currently, the diagnosis of certainty for resuscitation patients (by definition "severe") is based on searching for a fragment of virus genetic material within the epithelial cells of the respiratory tree, up and/or down, by PCR. It is to be expected that the epidemic peak will make it difficult (if not impossible) to respect the stereotypical path that is currently in place, due to the lack of space in the specific unit. This will require optimization of care pathways and use of the specific sectors. It is therefore necessary to define the simple criteria, available from the moment patients are admitted, to predict the result of the COVID-19 PCR.
Description: Assessment of viral, bacterial, fungal and parasitic rate in confirmed and unconfirmed patients for COVID-19
Measure: Coinfections Time: during ICU stay, up to 28 daysDescription: it will be reported the evolution of respiratory dysfunction in patients infected with COVID-19 admitted to ICU during their stay and requiring mechanical ventilation (during, Pao2/FIO2 ratio,,features of artificial ventilation features of extra-bodied respiratory assistance)
Measure: Respiratory dysfunction requiring mechanical ventilation Time: during ICU stay, up to 28 daysDescription: the SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure).
Measure: Sequential Organ Failure Assessment (SOFA) Score Time: during ICU stay, up to 28 daysDescription: APS II was designed to measure the severity of disease for patients admitted to Intensive care units 24 hours after admission to the ICU, the measurement has been completed and resulted in an integer point score between 0 and 163 and a predicted mortality between 0% and 100%.
Measure: SAPS II score Time: at admissionDescription: The DIC Score was developed by the The International Society of Thrombosis and Haemostasis (ISTH.) The DIC score calculator accounts of the following four parameters.Each of the four parameters evaluated above have values that are weighted with a number of points varying from 0 to 3. By summing the points given to the choices, a final result between 0 and 8 is obtained
Measure: Disseminated Intravascular Coagulation (DIC) score Time: during ICU stay, up to 28 daysDescription: measuring the long-term impact of confirmed COVID-19 infection. assessment of quality of life according to 8 areas: physical activity (and related limitations), body pain, perception of one's own health, mental health (and related limitations), social life and vitality.
Measure: Short Form 36 Time: at 9 months +/- 3 months after ICU stayDescription: The scale allows to detect anxiety and depression using 14 items rated from 0-3. Measuring the long-term impact of confirmed COVID-19 infection
Measure: Hospital anxiety and depression scale (HADS) Time: at 9 months +/- 3 months after ICU stayDescription: 22-item self-report measure that assesses subjective distress caused by traumatic events Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88) Measuring the long-term impact of confirmed COVID-19 infection
Measure: Impact of Event Scale - revised (IES-R) Time: at 9 months +/- 3 months after ICU stayDescription: Question the stressful experience or event, followed by 20 multiple-choice questions. Measuring the long-term impact of confirmed COVID-19 infection
Measure: Post-traumatic stress disorder Checklist version DSM-5 (PSL-5) Time: at 9 months +/- 3 months after ICU stayDescription: The mMRC Dyspnea Scale stratifies severity of dyspnea in respiratory diseases Measuring the long-term impact of confirmed COVID-19 infection
Measure: Modified Medical Research Council (MMRC) Dyspnea Scale Time: at 9 months +/- 3 months after ICU stayDescription: Evolution of viral clearance in nasal and depp PCR during ICU
Measure: Viral clearance Time: through study completion, an average of 28 daysOpen label, two-group, phase III randomised controlled trial in up to 4170 healthcare workers to determine if BCG vaccination reduces the incidence and severity of COVID-19 during the 2020 pandemic.
Description: Number of participants with COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: COVID-19 disease incidence Time: Measured over the 6 months following randomisationDescription: Number of participants who were admitted to hospital or died (using self-reported questionnaire and/or medical/hospital records) in the context of a positive SARS-CoV-2 test
Measure: Severe COVID-19 disease incidence Time: Measured over the 6 months following randomisationDescription: Number of participants with COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: COVID-19 incidence by 12 months Time: Measured over the 12 months following randomisationDescription: Number of participants with severe COVID-19 disease defined as hospitalisation or death in the context of a positive SARS-Cov-2 test (PCR or serology)
Measure: Severe COVID-19 incidence by 12 months Time: Measured over the 12 months following randomisationDescription: Time to first symptom of COVID-19 in a participant who subsequently meets the case definition: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: Time to first symptom of COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of episodes of COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: Episodes of COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of participants with asymptomatic SARS-CoV-2 infection defined as Evidence of SARS-CoV-2 infection (by PCR or seroconversion) Absence of respiratory illness (using self-reported questionnaire) No evidence of exposure prior to randomisation (inclusion serology negative)
Measure: Asymptomatic SARS-CoV-2 infection Time: Measured over the 12 months following randomisationDescription: Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: Work absenteeism due to COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: Bed confinement due to COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of days with symptoms in any episode of illness that meets the case definition for COVID-19 disease: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: Symptom duration of COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: SARS-CoV-2 pneumonia Time: Measured over the 12 months following randomisationDescription: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Oxygen therapy with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Critical care admissions with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Critical care admission duration with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
Measure: Mechanical ventilation with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
Measure: Mechanical ventilation duration with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
Measure: Hospitalisation duration with COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of deaths (from death registry) associated with a positive SARS-CoV-2 test
Measure: Mortality with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of participants with febrile respiratory illness defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of episodes of febrile respiratory illness, defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Episodes of febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to febrile respiratory illness defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Work absenteeism due to febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days confined to bed (using self-reported questionnaire) due to febrile respiratory illness defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Bed confinement due to febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days with symptoms in any episode of illness that meets the case definition for febrile respiratory illness: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Symptom duration of febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)
Measure: Pneumonia Time: Measured over the 12 months following randomisationDescription: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
Measure: Oxygen therapy Time: Measured over the 12 months following randomisationDescription: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
Measure: Critical care admissions Time: Measured over the 12 months following randomisationDescription: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Measure: Mechanical ventilation Time: Measured over the 12 months following randomisationDescription: Number of deaths (from death registry)
Measure: Mortality Time: Measured over the 12 months following randomisationDescription: Number of days of hospitalisation due to febrile respiratory illness (using self-reported questionnaire and/or medical/hospital records)
Measure: Hospitalisation duration with febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
Measure: Unplanned work absenteeism Time: Measured over the 12 months following randomisationDescription: Cost of hospitalisation due to COVID-19 reported in Australian dollars (using hospital administrative linked costing records held by individual hospitals and state government routine costing data collections to provide an estimate of the cost to hospitals for each episode of COVID-19 care)
Measure: Hospitalisation cost to treat COVID-19 Time: Measured over the 12 months following randomisationDescription: Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.
Measure: Local and systemic adverse events to BCG vaccination in healthcare workers Time: Measured over the 3 months following randomisationPrimary Objectives: Phase 2: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe COVID-19 Phase 3: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: Phase 2 and Phase 3 - Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity - Evaluate changes in the National Early Warning Score 2 (NEWS2) - Evaluate the duration of predefined symptoms and signs (if applicable) - Evaluate the duration of supplemental oxygen dependency (if applicable) - Evaluate the incidence of new mechanical ventilation use during the study - Evaluate the duration of new mechanical ventilation use during the Study - Evaluate the proportion of patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - Evaluate the 28-day mortality rate - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Grade 4 neutropenia (ANC<500/mmˆ3) with concurrent severe or life-threatening bacterial, invasive fungal, or opportunistic infection - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Invasive bacterial or fungal infections of clinical significance with confirmed diagnosis based on the investigator's assessment with appropriate diagnostic workups and consultations
Description: Resolution of fever is defined as body temperature: ≤36.6 C (axilla) or ≤37.2 C (oral), or ≤37.8 C (rectal or tympanic).
Measure: Phase 2: Time to resolution of fever for at least 48 hours without antipyretics or until discharge, whichever is sooner Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 3: The percentage of patients reporting each severity rating on the 7-point ordinal scale Time: Baseline to Day 15Description: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Phase 2: The time to improvement in oxygenation Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 2: Mean change in 7-point ordinal scale from baseline to Day 15 Time: Baseline to Day 15Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 2: Clinical status using the 7-point ordinal scale at Day 15 Time: Baseline to Day 15Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 2: Time to improvement of two categories from admission using the 7-point ordinal scale Time: Baseline to Day 29Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
Measure: Phase 2 and 3 : Time to resolution of fever Time: Baseline to Day 29Description: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Phase 2 and 3 : Time to improvement in oxygenation Time: Baseline to Day 29Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Phase 2 and 3: Time to resolution of fever and improvement in oxygenation Time: Baseline to Day 29Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Phase 2 and 3:Time to change in NEWS2 from baseline Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Phase 2 and 3: Time to NEWS2 of <2 and maintained for 24 hours Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Phase 2 and 3: Mean change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS2 Time: Baseline to days 3, 5, 8, 11, 15, and 29Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24 period.
Measure: Phase 2 and 3:Days with fever Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Phase 2 and 3: Alive off supplemental oxygen at day 29 Time: Baseline to Day 29Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
Measure: Phase 2 and 3:Days of hypoxemia Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Phase 2 and 3: Days of supplemental oxygen use Time: Baseline to Day 29Description: For those not requiring these interventions at baseline.
Measure: Phase 2 and 3: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula Time: Baseline to Day 60Description: For patients are not in ICU at baseline
Measure: Phase 2 and 3: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available) Time: Baseline to Day 60Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 3: Mean change in the 7-point ordinal scale from baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge) Time: baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge)Description: The ordinal scale is an assessment of the clinical status. Scores range 1-7. Lower score is worse.
Measure: Phase 3: Clinical status using the 7-point ordinal scale at days 3, 5, 8, 11,15, and 29 Time: Days 3, 5, 8, 11,15, and 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 3: Time to improvement of two categories from admission using the 7-point ordinal scale Time: Baseline to Day 29Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.
Measure: COVID-19-free survival Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-CoV-2 detection Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.
Measure: Incidence of possible COVID-19 symptoms Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: up to 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.
Measure: Incidence of study medication-related side effects Time: up to 12 weeksThis is a clinical study for the prevention of SARS-CoV-2 infection in adults exposed to the virus. This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) who are close contacts of persons with laboratory confirmed SARS-CoV-2 or clinically suspected COVID-19. Eligible participants will be enrolled and randomized to receive the intervention or placebo at the level of the household (all eligible participants in one household will receive the same intervention).
Description: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected daily for 14 days
Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection Time: Day 1 through Day 14 after enrolmentDescription: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit
Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection Time: Day 28 after enrolmentDescription: Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults
Measure: Rate of participant-reported adverse events Time: 28 days from start of Hydroxychloroquine therapyDescription: PCR-confirmed COVID-19 diagnosis
Measure: Incidence rates of COVID-19 through study completion Time: 28 days from enrolmentThe overall objective of the study is to determine the therapeutic effect and tolerance of Tocizilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the COVIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
Description: Group 1. Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14. Group 1 Time: 14 daysDescription: Group 1. Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale <=5 at day 4. Group 1. Time: 4 daysDescription: Group 2. Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14. Group 2. Time: 14 daysDescription: Group 2 Early end point : proportion of patients with a decrease of WHO score of at least 1 point at day 4. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale at day 4. Group 2. Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: respiratory acidosis at day 4 Time: 4 daysDescription: evolution of PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: time to oxygen supply independency
Measure: time to oxygen supply independency Time: 14 daysDescription: duration of hospitalization
Measure: duration of hospitalization Time: 90 daysDescription: time to negative viral excretion
Measure: time to negative viral excretion Time: 90 daysDescription: time to ICU discharge
Measure: time to ICU discharge Time: 90 daysDescription: time to hospital discharge
Measure: time to hospital discharge Time: 90 daysThe coronavirus disease 2019 (COVID-19) outbreak is now considered as a public health emergency of international concern by the World Health Organization. In the context of the health emergency, research on the pathogen (the SARS-CoV-2 coronavirus), the disease and the therapeutic care is being organized. Research projects require the use of biological samples. This study aims at setting up a collection of biological samples intended for application projects in any discipline. The main objective of the study is to collect, process and store biological samples from patients and caregivers infected with SARS-CoV-2 (COVID-19) at the biological ressources center of the Bordeaux University Hospital.
Description: From blood samples: protein levels, whole genome sequence, transcriptomic analysis data. From upper respiratory samples: protein levels, virus transcriptomic analysis data. From stool: microbiota analysis data. From urine: protein level.
Measure: COVID-19 desease description Time: Inclusion visit (Day 1)Description: From blood samples: protein levels.
Measure: COVID-19 desease description Time: Day 30 to 90This study will assess the efficacy of hydroxychloroquine in reducing the severity of symptoms in patients with COVID-19
Description: This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.
Measure: Total Hospitalization Time: 14 daysDescription: This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.
Measure: Total Mechanical Ventilation Time: 14 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 2 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 5 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 10 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 14 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 2 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 5 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 10 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 14 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 2 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 5 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 10 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 14 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 2 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 5 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 10 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 14 daysDescription: Number of enrolled patients who have died within the specified time frame
Measure: Total mortality Time: 28 daysThis is a Phase II interventional study testing whether treatment with hydroxychloroquine, Vitamin C, Vitamin D, and Zinc can prevent symptoms of COVID-19
Description: Any symptoms of COVID-19 will be recorded in a daily diary. Symptoms (including fever measured in degrees Fahrenheit, dry cough, productive cough, difficulty speaking, wheezing, dry mouth, headache, chest tightness, difficulty with exertion, shortness of breath, sore throat, malaise, and diarrhea) will be rated as not present, mild, moderate, or severe.
Measure: Prevention of COVID-19 symptoms as recorded in a daily diary Time: 24 weeksDescription: To assess the presence or absence of side effects (graded 1-5), and whether they are tolerable (grade 1-2). AE and SAE will be recorded.
Measure: Safety as determined by presence or absence of Adverse Events and Serious Adverse Events Time: 24 weeksBackground: Aim: To demonstrate the efficacy of low-dose hydroxychloroquine as primary prevention in healthcare workers Design, participants and interventions: Prospective, randomized, parallel group, double-blinded, placebo controlled, study. including 440 participants who will be randomised to 2 treatment arms: hydroxychloroquine or placebo. Outcome variables: symptomatic or asymptomatic SARS-CoV-2 infection confirmed by PCR, viral load during SARS-CoV-2 infection, seroconversion during the study period, incidence of any acute respiratory infection, days of sick leave. Statistical considerations: No trials have been published investigating the efficacy of HCQ as primary prophylaxis of SARS-CoV-2 infection in health care workers. Thus, sample size calculations in the proposed trial are based on the investigators' best estimates for several parameters. In accordance to the effect of oseltamivir against symptomatic influenza, we assumed an approximate effectiveness of approximately 60% (HR of 0.4) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464969/) as realistic. As a prophylactic intervention with HCQ, which may have side effects and for which supply shortage can be expected, was judged justifiable only if its effectiveness is high, we based our sample size consideration on a HR of 0.3. To estimate the probability of an event in both the experimental and the control group, very little data is available. In a Dutch point-prevalence study 0-10% of health-care workers were infected depending on the healthcare institution, depending on the hospital. This point-prevalence study was performed between 6 and 9 March, when the reported number of cases in the Netherlands was 33 and 77, respectively, according to the RIVM (https://www.rivm.nl/nieuws/resultaat-steekproef-4-ziekenhuismedewerkers-heeft-coronavirus). Additionally, in an a report published in the Lancet, 20% of responding healthcare workers in Italy were found to be infected with SARS-CoV2 within less than one month (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30627-9/fulltext). Several media reports indicate that this proportion is similar across various healthcare institutions and countries (https://www.nytimes.com/2020/03/24/world/europe/coronavirus-europe-covid-19.html) and (https://www.aljazeera.com/news/2020/03/spain-tightens-restrictions-week-lockdown-begins-2003 30191539568.html). As the proposed study will be performed in a high-risk setting, we assumed an event (i.e. PCR positivity) probability of 10% in the control group and 3% in the experimental arm after the maximum study period. In summary, a sample size of 210 participants per arm is necessary to detect a HR of 0.3 with a power of 80.3% with an alpha-error of 0.05. To account for drop-outs and asymptomatic, undetected infection at inclusion or past infection with existing immunity, an additional 10 participants will randomized per treatment arm. The overall study population is therefore 440 participants. Statistical analysis will be based on two populations: A Modified Intention to Treat population excluding those who withdrew consent after randomization and those with a positive serology at baseline. And a per protocol population including all randomized subjects who completed at least 3 out of 4 follow-up visits and took at least 80% of all doses of study medication.
Arriving in December 2019, Coronavirus COVID-19 infection is causing a global pandemic with high morbidity and mortality among adults and especially seniors. The child appears little or no affected by this infection. It is estimated that the child could be asymptomatic or pauci-symptomatic carrier and thus be vector of the disease. For this reason, measures have been taken to close schools and contain populations in a large number of countries, including France. However, there are no data on the prevalence of COVID-19 in children.
Description: children admitted to pediatric emergencies for respiratory signs Children hospitalized as a result of travelling to pediatric emergency departments for respiratory signs Respiratory asymptomatic children admitted to pediatric emergencies
Measure: Prevalence of positivity of COVID-19 virus measured by rt-PCR in the following subpopulations of emergency patients Time: at the end an average 28 daysDescription: the degree of relationship with these contacts and the time spent in contact with them within 24 hours before emergency
Measure: Contact frequency Time: At inclusionThis is a multi-center, randomized, controlled, phase II clinical efficacy study evaluating a novel Nitric Oxide Releasing Solution (NORS) treatment for the prevention and treatment of COVID-19 in healthcare workers at risk of infection. Participants will be enrolled into one of two components of this study. Based on initial swabs/symptoms, volunteers who are COVID-19 negative will be enrolled in the Prevention study and randomized to receive standard institutional precautions or standard institutional precautions + NORS. Those who are COVID-19 positive will be enrolled in the open-label Treatment Sub-Study.
Description: Measure the proportion of subjects with either swab positive COVID-19 or presentation of clinical symptoms as measured by fatigue with either fever >37.2 (oral)and/or a persistent cough.
Measure: Prevention Study: Measure the effect of NORS on the prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19 Time: 14 daysDescription: Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Measure: Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19 Time: 21 daysDescription: Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Measure: Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19 Time: 21 daysDescription: Measure the tolerability of the NORS treatments as determined by number of adverse events, pain, discomfort or discontinuations of treatment.
Measure: Prevention Study: Measure the tolerability of NORS treatments Time: 21 daysDescription: Measure the median number of days to negative conversion of SARS-CoV-2 RT-PCR from a nasopharyngeal swabs.
Measure: Treatment Sub Study: Measure the virucidal effect of NORS Treatments Time: 21 daysDescription: Determine the time to clinical recovery in participants with COVID-19 by measuring the median number of days from enrollment to discharge (if admitted), or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air).
Measure: Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery Time: 21 daysDescription: Measure the reduction clinical symptoms in participants with COVID- 19 by the magnitude of the change in Modified Jackson Cold Score Diary Score (5-unit change is a substantial clinical benefit).
Measure: Treatment Sub Study: Determine the reduction in clinical symptoms Time: 21 daysDescription: Measure the proportion of participants that have a positive sero-conversion for SARS-CoV-2
Measure: Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2 Time: 21 daysOur aim is to conduct one trial of personalized immunotherapy in patients with SARS-CoV-2 (COVID-19) associated with organ dysfunction and with laboratory findings of macrophage activation syndrome or immune dysregulation. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be allocated to immunotherapy treatment according to their needs.
Description: At least 25% decrease between baseline sequential organ failure assessment SOFA score and measured sequential organ failure assessment SOFA score at Study Day 8
Measure: Change of baseline total sequential organ failure assessment (SOFA) score Time: Visit study day 8Description: Resolution of all criteria of lower respiratory tract involvemed that led to study inclusion (except findings from imaging studies) at Study Day 8
Measure: Improvement of lung involvement measurements Time: Visit study day 8Description: At least 50% increase of pO2/FiO2 ratio between baseline and study visit Day 8
Measure: Increase of pO2/FiO2 ratio Time: Visit Study Day 8Description: Change of total sequential organ failure assessment (SOFA) score between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Comparison of change of baseline total sequential organ failure assessment (SOFA) score in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Change of lung involvement measurements between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of change of lung involvement measurements in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Comparison of increase in pO2/FiO2 ratio towards historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of pO2/FiO2 ratio in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Change of Sequential organ failure assessment (SOFA) score on day 28 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of sequential organ failure assessment (SOFA) score Time: Day 28Description: Mortality on day 28
Measure: Rate of Mortality Time: Day 28Description: Mortality on day 90
Measure: Rate of Mortality Time: Day 90Description: Cytokine stimulation from peripheral blood mononuclear cells will be compared between days 0 and 4
Measure: Cytokine stimulation Time: Screening, Day 4Description: Gene expression of peripheral blood mononuclear cells will be compared between days 0 and 4
Measure: Gene expression Time: Screening, Day 4Description: Change of serum/plasma proteins between days 0 and 4
Measure: Serum/plasma proteins Time: Screening, Day 4Description: Classification of immune function of screened patients who are not enrolled in study drug since they are not characterized with MAS or immune dysregulation
Measure: Classification of the immune function Time: ScreeningSince December 2019, a new agent, the SARS-Cov-2 coronavirus has been rapidly spreading from China to other countries causing an international outbreak of respiratory illnesses named COVID-19. In France, the first cases have been reported at the end of January with more than 60000 cases reported since then. A significant proportion (20-30%) of hospitalized COVID-19 patients will be admitted to intensive care unit. However, few data are available for this special population in France. We conduct a large observational cohort of ICU suspected or proven COVID-19 patients that will enable to describe the initial management of COVID 19 patients admitted to ICU and to identify factors correlated to clinical outcome.
Description: Mortality at day 28
Measure: Mortality at day 28 Time: day 28Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No
Measure: severe complications Time: up to day 28Description: Delay in imaging in hours
Measure: Imaging Time: day 1Description: delay in microbiological diagnosis in hours
Measure: Delay in Microbiological diagnosis Time: day 1Description: Antiviral therapy Yes / no
Measure: Antiviral therapy Time: up to day 28Description: Antibiotic therapy Yes / No
Measure: Antibiotic therapy Time: day 28Description: Covid-19 treatments Yes / No
Measure: Covid-19 treatments Time: up to day 28Description: number
Measure: Patients receiving renal replacement therapy Time: up to day 28Description: number
Measure: Patients receiving mechanical ventilation Time: up to day 28Description: Patient alive at day 28 : yes / No
Measure: Vital status Time: day 28Coronavirus disease 2019 (COVID-19) is an infectious disease responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is highly contagious requiring restrictive and stressful measures for patients, family members and ICU healthcare providers. To avoid contagion, patient isolation has become the rule. For patients, these measures add stress to the ICU environment and deprive them of unrestricted family visits. Family members are not only left with fear but also many unanswered questions. In end-of-life situations, many family members are unable to say good-bye and unable to provide support to their loved-one throughout the process. The impact of exclusion or limited inclusion certainly needs to be explored. Moreover, ICU caregivers are having to face new challenges and to work in a unknown situation, juggling with both professional issues such as increased workload, working longer hours and safety issues, and personal issues such as child care and transport as well as family transmission of the virus. The main objective of this study is to demonstrate that the COVID-19 pandemic, as compared to seasonal flu and community acquired pneumonia, significantly increases post-traumatic stress disorder (PTSD) in family members of critically ill patients. PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge. The IES-R is a 22-item self-report measure that assesses subjective distress caused by traumatic events. It will be compared across the three groups (COVID-19, FLU and CAP).
Description: Proportion of Family members with IES-R> 22 PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge of corresponding patient. It si a scale ranging from 0 to 88. Weiss, DS.; Marmar, CR. The impact of event scale - revised. In: Wilson, JP.; Keane, TM., editors.Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. p. 399-411
Measure: PTSD Family members sup 22 Time: 90 daysDescription: Among Family members PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD Family members Time: 90 daysDescription: Among Patients PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD Patients Time: 90 daysDescription: Among healthcare providers PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Among Family members Symptoms of anxiety and depression using the HADS scale
Measure: HADS Family members Time: 90 daysDescription: Among Patients Symptoms of anxiety and depression using the HADS scale
Measure: HADS Patients Time: 90 daysDescription: Among Patients Mental and physical health-related quality of life as assessed by the SF36
Measure: SF36 Patients Time: 90 daysDescription: Among Family members Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire Family members Time: 90 daysDescription: Among Patients Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire Patients Time: 90 daysDescription: Among healthcare providers Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Among healthSymptoms of burnout on MBI scale as assessed by the Maslash Burnout Inventorycare providers
Measure: MBI healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Job Strain as assessed by the Karasec instrument
Measure: Karasec instrument healthcare providers Time: 2 months after official end of the Covid-19 peakThe overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the COVIMUNO-19 cohort. Anakinra will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14 Time: 14 daysDescription: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5.
Measure: WHO progression scale ≤ 5 Time: 4 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) or withdrawal of NIV or high flow (for > 48h), at day 14 Time: 14 daysDescription: Proportion of patients with a decrease of WHO score of at least 1 point at day 4
Measure: Decrease of at least one point in WHO progression scale score Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10.
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival.
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours.
Measure: Respiratory acidosis Time: 4 daysDescription: Evolution of PaO2/FiO2 ratio.
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: Time to oxygen supply independency.
Measure: Time to oxygen supply independency Time: 14 daysDescription: Duration of hospitalization.
Measure: Duration of hospitalization Time: 90 daysDescription: Time to negative viral excretion.
Measure: Time to negative viral excretion Time: 90 daysDescription: Time to ICU discharge.
Measure: Time to ICU discharge Time: 90 daysDescription: Time to hospital discharge.
Measure: Time to hospital discharge Time: 90 daysThere is no predictive tool for patients admitted to the emergency department with a suspicion of Covid-19 that will worsen secondarily and require a heavy lifting. In a context of saturation of the healthcare system by the pandemic at Covid-19,it is essential to identify specific, accessible prognostic markers via minimally invasive sampling with low risk of infection for personnel caregiver, for optimal allocation of resuscitation resources. This study proposes to evaluate the biological markers of routine care known to be associated with resuscitation admission in relation to hospitalization on conventional service for the prediction of worsening of patients admitted to the emergencies for Covid-19.
Description: Secondary aggravation is defined as : a re-hospitalization or aggravation in hospitalization : development or increase in oxygen dependency, hemodynamic failure, and/or respiratory, death
Measure: Rate of secondary aggravation Time: At 30 days of admission to the emergency departmentDescription: the number of leukocytes, lymphocytes, neutrophil polynuclear cells, CRP, fibrinogen, and the D-dimers.
Measure: Change of standart biological parameters Time: Between baseline and at 30 days of admission to the emergency departmentBlood samples from participants who have recovered from COVID-19 infection will be obtained and studied. The goal of the research is to identify antibodies that have been generated by the patient to fight the COVID-19 infection. By identifying the most effective antibodies, scientists can make specific antibodies to use to prevent future coronavirus outbreaks or to treat patients with severe disease.
Description: The blood specimen will be proceeded into peripheral blood mononuclear cells and plasma to be stored for testing. In brief, CD27+ memory B cells that can bind to a SARS-CoV-2 S protein bait will be sorted by flow cytometry and RNA will be extracted to obtain heavy and light chain sequences. Antibody sequences will be annotated using bioinformatics approaches, and candidate sequences will be cloned. Purified antibodies will be characterized and neutralization breadth and potency against SARS-CoV-2 and other related coronaviruses will be assessed using neutralization assays.
Measure: Number of antibodies against coronaviruses isolated and identified from patient samples Time: Up to 12 months after collection visitThe purpose of this study is to examine the impact of ascorbic acid (vitamin c) and zinc gluconate in reducing duration of symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19). Patients above the age of 18 who present to the Cleveland Clinic outpatient testing and receive a positive test for COVID-19 will be invited to participate.
Description: Outpatients who test positive for the Coronavirus 2019; number of days required in which they reach a 50 percent reduction in the cumulative 0-12 score symptom category of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102; Cough on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a 0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue. Each patient will have a composite score ranging from 0-12/day
Measure: Symptom Reduction Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102.6
Measure: Symptom Resolution: Fever Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of cough based on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe
Measure: Symptom Resolution: Cough Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of shortness of breath based on a 0-3 scale: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities
Measure: Symptom Resolution: Shortness of Breath Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of fatigue based on a 0-3 scale: 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.
Measure: Symptom Resolution: Fatigue Time: 28 daysDescription: Total symptom composite score at day 5 of study supplementation: Symptom categories of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102; Cough on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a 0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.
Measure: Day 5 Symptoms Time: 5 daysDescription: Differences in hospitalization events between the study arms
Measure: Hospitalizations Time: 28 daysDescription: Differences in severity of symptoms between study arms
Measure: Severity of Symptoms Time: 28 daysDescription: Differences in number of patients who were prescribed adjunctive medications for their diagnosis between study arms
Measure: Adjunctive Medications Time: 28 daysDescription: Differences in number of patients in study arms who experienced side effects from the supplements.
Measure: Supplementation Side Effects Time: 28 daysCCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled, multi-stage trial, which aims to assess the safety and efficacy of novel treatment option of moderate-severe COVID-19. Participants will be randomized 1:1:1:1:1:1 to parallel treatment arms: Convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.
Description: Composite outcome
Measure: All-cause mortality or need of invasive mechanical ventilation Time: 28 daysDescription: Number of participants with adverse events with possible relation to study drug
Measure: Frequency of adverse events Time: 90 daysDescription: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
Measure: Frequency of severe adverse events Time: 90 daysDescription: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities
Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status Time: 90 daysDescription: Number of days without mechanical ventilation
Measure: Ventilator-free days Time: 28 daysDescription: Number of days without organ-failure
Measure: Organ failure-free days Time: 28 daysDescription: Number of days in ICU
Measure: Duration of ICU stay Time: 90 daysDescription: Number of deaths by any cause
Measure: Mortality rate Time: 7, 14, 21, 28 and 90 daysDescription: Days from the date of hospital admission for COVID-19 to the date of discharge
Measure: Length of hospital stay Time: 90 daysDescription: Days requiring supplement oxygen
Measure: Duration of supplemental oxygen Time: 90 daysSummary of the study Study population: A representative sample of the Viennese population stratified by age and gender (data from the Vienna Health Study LEAD) Potential output and analysis: - Extent of age-specific infection and antibody formation - Cumulative incidence of infection - Rate of asymptomatic infection - Relationship with socioeconomics, lifestyle and risk factors (comorbidities) Study design: Prospective, longitudinal, stratified by age and gender Duration of study: Initial testing as soon as possible and repeat based on monitoring of the pandemic curve (probably after 2-3 months) Information to be obtained from participants: - serum samples for information on SARS-CoV2 infection and antibody formation - data on clinical symptoms
Description: Antibody Titres IgG and IgM
Measure: Prevalence of SARS-CoV-2 antibody titres Time: 5 weeksDescription: Re-Calculation including incidence of the general population
Measure: Prevalence of SARS-CoV-2 antibody titres after 3 Months Time: 4 MonthsThe goal of the research is to assess candidate COVID-19 rapid (5-15 min) antibody tests in order to judge their clinical accuracy compared to Centers for Disease Control (CDC)-recommended molecular genetic testing and clinical diagnosis. Second, it is our goal to determine if self-testing assisted by a mobile device camera acquisition software and telemedicine clinical/technical support (virtual point-of-care) improves the ease of use and interpretation of the tests, thus making self-testing comparable in accuracy and safety to testing in a clinical setting. The overall purpose of the study is to dramatically increase the capacity of COVID-19 testing by establishing the safety, ease-of-use and validity of finger-stick capillary blood self-testing assisted by mobile device imaging and telemedicine remote support.
Description: Accuracy refers to the amount of agreement between the results of the antibody-based rapid test and the results of a PCR-based reference test
Measure: Clinical accuracy of the antibody-based rapid tests compared to PCR-based test result Time: 1 yearDescription: Accuracy refers to the amount of agreement between the results of the antibody-based rapid test and a clinical diagnosis of COVID-19
Measure: Clinical accuracy of the rapid tests based on Clinical diagnosis Time: 1 yearDescription: Clinical accuracy of the subject's visual interpretation of the test result vs image analysis from clinician
Measure: Self-test interpretation of result vs expert clinical image interpretation of result Time: 1 yearDescription: Subjects will complete a survey to rate the testing procedure for ease of use and convenience. The survey will ask subjects to rate the ease of use on a scale from 1 (easiest procedure to complete and understand) to 10 (most complicated and confusing procedure)
Measure: Ease of self-testing procedure Time: 1 yearThe objective of the study is to evaluate the efficacy of helmet NIV in reducing the duration of invasive mechanical ventilation in order to minimize ventilator needs during the COVID-19 pandemic.
Description: duration of mechanical ventilation via endotracheal tube
Measure: ventilator days Time: up to 4 weeksDescription: number of days admitted to the ICU
Measure: Intensive care unit (ICU) length of stay Time: up to 6 weeksDescription: number of patients requiring endotracheal intubation after extubation
Measure: need for re-intubation Time: up to 6 weeksDescription: number of days spent in hospital during enrollment hospitalization
Measure: hospital length of stay Time: up to 6 weeksDescription: death from any cause during hospitalization time of enrollment
Measure: hospital mortality Time: up to 6 weeksDescription: death from any cause 90 day, 1year
Measure: long term mortality Time: up to 1 yearDescription: including ventilator associated pneumonia, GI hemorrhage, DVT/PE, sacral decubitus ulcer, delirium, ICU acquired weakness
Measure: ICU related complications Time: up to 6 weeksDescription: measure the location (home, rehabilitation center, nursing home)
Measure: discharge location Time: up to 90 daysDescription: days alive and institution free
Measure: health care utilization Time: up to 6 weeksDescription: ultrasound measurement at end expiration: enrollment, pre extubation, post extubation
Measure: diaphragm ultrasound thickness Time: up to 6 weeksDescription: ultrasound measurement at end expiration and inspiration to calculate thickening fraction
Measure: diaphragm thickening fraction Time: up to 6 weeksThe aim of the COVI-PRONE Trial is to determine if early awake prone positioning in COVID-19 patients with hypoxemic respiratory failure; irrespective of the mode of oxygen delivery; reduces the need for invasive mechanical ventilation.
Description: Medical procedure in which a tube is placed into the windpipe (trachea) through the mouth.
Measure: Endotracheal intubation Time: within 30 days of randomizationDescription: Death
Measure: Mortality Time: 30 daysDescription: Number of days not receiving mechanical ventilation
Measure: Invasive mechanical ventilation free days Time: 30 DaysDescription: Number of days not receiving non-invasive mechanical ventilation
Measure: Non-invasive ventilation free days Time: 30 daysDescription: Number of days admitted to ICU
Measure: ICU length of stay Time: 30 DaysDescription: Number of days admitted to the hospital
Measure: Hospital length of stay Time: 30 daysDescription: defined as the difference in SpO2: FiO2 ratio. The difference in SpO2: FiO2 ratio.
Measure: Change in oxygenation Time: 30 daysDescription: Includes any of the following: accidental removal of intravenous access, vomiting, falls from bed, pressure injuries, or cardiac arrest.
Measure: Complications from proning, Time: 30 daysPatients with COVID-19 usually present in the ED and receive their initial medical check-up here. We will try to gather information of comorbidities and other conditions at the time of presentation of COVID-19 patients to the ED. The course of the disease prior to admission as well as the momentary health status at presentation to the ED are of interest because they influence risk stratification and decision-making of treating physicians. The ratio of patients with mild or moderate to severe symptoms will help to calculate the need for hospital beds including beds on Intensive Care Units (ICU) and Intermediate Care Units (IMC), as well as the need for other hospital resources.
Description: Identification of risk factors present at the earliest stage of hospital care (i.e. in the ED) that warrant hospital admission.
Measure: Identification of risk factors present at the earliest stage of hospital care (i.e. in the ED) that warrant hospital admission. Time: 6 monthsDescription: Determination of the course of the disease (days since onset of symptoms, nature of symptoms, e.g. fever, chills, headache) and the state at which patients present to the ED
Measure: Determination of the course of the disease (days since onset of symptoms, nature of symptoms, e.g. fever, chills, headache) and the state at which patients present to the ED Time: 6 monthsDescription: Identification of the ratio of patients with mild or moderate to severe disease
Measure: Identification of the ratio of patients with mild or moderate to severe disease Time: 6 monthsProspective, observational, clinical investigation of PMX cartridge use in COVID 19 patients with septic shock
The proposed hypothesis is that high doses of hydroxychloroquine (HCQ) for at least 2 weeks can be effective antiviral medication both as a treatment in ambulatory patients and prophylaxis/treatment in health care workers because it impairs lysosomal function and reorganizes lipid raft (cholesterol and sphingolipid rich microdomains in the plasma membrane) content in cells, which are both critical determinants of Emerging Viral Disease (EVD) infection. This hypothesis is based on a growing literature linking chloroquine to antiviral activity. It is estimated that enough information exists to launch a clinical trial of hydroxychloroquine for COVID-19.
Description: Rate of hospitalization
Measure: Sub Study 1: Patients Time: 21 daysDescription: Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months
Measure: Sub Study 2: Health Care Workers Time: 2 monthsDescription: any house hold member who has reported symptoms or test positive for COVID 19 during their 14 day active participation
Measure: Sub Study 1: Patients: Rate of secondary infection of co-inhabitants Time: 14 days after enrollment of the householdDescription: Assessment of any medical events that occur during the 14 day active period that is felt to be related to receipt of HCQ
Measure: Sub Study 1: Patients: Adverse Events Time: 14 day active periodDescription: If a test comes back negative, participant would be notified as such and told to destroy their pills as they are withdrawn
Measure: Sub Study 1: Patients: Negative for COVID-19 Time: up to 5 days after enrollingDescription: Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period
Measure: Sub Study 2:Health Care Workers:Number of shifts missed Time: up to ~60 days after enrollmentDescription: Assessment of any medical events that occur during the ~60 day active period that is felt to be related to receipt of HCQ
Measure: Sub Study 2:Health Care Workers:Rate of adverse events Time: up to ~60 days after enrollmentDescription: if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period
Measure: Sub Study 2:Health Care Workers:Rate of hospitalization Time: up to ~60 days after enrollmentCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.
Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry
Measure: Fibrosis Time: 12 monthsDescription: Decreased functional capacity on ergospirometers
Measure: Ergospirometers Time: 12 monthesTo test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.
Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs
Measure: Percentage of virus free subjects Time: 7 days after initiation of trialDescription: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .
Measure: Disease severity Time: 6 daysDescription: Number of subjects in each arm who are hospitalized for Covid 19 infection
Measure: Incidence of hospitalization Time: 14 daysDescription: Number of subjects in each arm who die secondary to Covid-19 infection
Measure: Incidence of Death Time: 70 Days (10 weeks)Description: Number of subjects in each arm who have confirmed Covid-19 infection
Measure: Incidence of confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Number of subjects in each arm who discontinue or withdraw medication use for any reason
Measure: Incidence of all-cause study medication discontinuation or withdrawal Time: 14 daysDescription: Blood tests to determine level of immunity in each subject
Measure: Immunity to Covid-19 Time: 70 days (10 weeks)Acute kidney injury (AKI) is reported to occur in 0.5-9% of severe acute respiratory distress coronavirus 2-positive patients and AKI has been identified as an independent risk factor for in-hospital mortality. The present study aims to investigate the incidence of renal outcome of in-hospital patients diagnosed with COVID-19.
Description: As determined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Measure: Incidence of AKI Time: Within 7 days after admissionDescription: Serial biomarker assessment
Measure: Renal function changes during hospital stay Time: from hospital admission til discharge up to 3 monthsDescription: As determined by KDIGO criteria
Measure: Incidence of chronic kidney disease Time: 3 months post-hospital admissionThe purpose of this study is to evaluate the safety, dose-requirements, and exploratory efficacy of twice-daily subcutaneous enoxaparin as venous thromboembolism prophylaxis in children (birth to 18 years) hospitalized with signs and/or symptoms of SARS-CoV-2 infection (i.e., COVID-19).
Description: To investigate the safety of in-hospital thromboprophylaxis with twice-daily low-dose enoxaparin thromboprophylaxis as measured by cumulative incidence of ISTH-defined clinically-relevant bleeding events during hospitalization. Clinically relevant bleeding episodes may include any of the following: 1) fatal bleeding; 2) clinically overt bleeding associated with a decline in hemoglobin of ≥2g/dL in a 24h period; 3) retroperitoneal, pulmonary, or central nervous system bleeding; 4) bleeding requiring surgical intervention in an operating suite; 5) bleeding for which a blood product is administered (blood product administration not directly attributable to the patient's underlying condition); 6) bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating suite.
Measure: Safety of in-hospital thromboprophylaxis Time: Day 30Description: The median twice-daily enoxaparin dose, as measured in mg/kg, required to achieve a 4 hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL in children hospitalized with COVID-19, and to compare dose-requirements by age group (birth to <1 year old, 1-<6 years old, 6-<13 years old, and 13-<18 years old).
Measure: Median twice-daily enoxaparin dose Time: 4 hours post initial doseDescription: To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by the proportion of serial D-dimer levels obtained at standardized time points that are <2 times the upper limit of normal (<2x ULN) values for age.
Measure: Efficacy of in-hospital thromboprophylaxis as measured by the proportion of serial D-dimer levels Time: Enrollment, Day 1, Day 2, and Day 3, 7, and 14 if still hospitalizedDescription: To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by confirmed HA-VTE.
Measure: Efficacy of in-hospital thromboprophylaxis as measured by confirmed HA-VTE Time: Day 30Description: To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by median duration of in-hospital increased respiratory support (new requirement for high-flow nasal cannula, non-invasive ventilation, and/or mechanical ventilation, relative to any at-home baseline requirement).
Measure: Efficacy of in-hospital thromboprophylaxis as measured by median duration of increased respiratory support Time: Day 30The objective of this protocol is to estimate the proportion of patients hospitalized in intensive care unit for a SARS-Cov-2 viral lung infection and contaminating their environment at 1 meter. The contamination will be assessed by quantifying the viral RNA by RT-PCR on a 600-liter air sample aspirated by a Coriolis® system. This sample will be taken within 48 hours after the confirmation of SARS-Cov-2 infection, documented by RT-PCR. In fact, the hospital hygiene measures practiced in intensive care unit in patients with viral respiratory infection are identical to those practiced in other services. These measures are possibly insufficient as evidenced by recent data related to the COVID-19 epidemic.
Description: The primary objective of the study will be evaluated by the proportion of patients contaminating the air 1 meter from their face. The contamination will be assessed by quantifying the viral RNA by RT-PCR on a 600-liter air sample aspirated by a Coriolis® system. This sample will be taken within 48 hours after the confirmation of SARS-Cov-2 infection, documented by RT-PCR.
Measure: Estimate the proportion of patients hospitalized in intensive care for a SARS-Cov-2 viral lung infection and contaminating their environment at 1 meter. Time: within 48 hours of the confirmation of SARS-Cov-2 infection documented by RT-PCRInflammation and abnormalities in laboratory coagulation tests are inseparably tied. For example, coagulation abnormalities are nearly universal in septic patients. Coagulation disorders have also been reported in many patients with severe courses of Coronavirus disease 2019 (Covid-19). But it is difficult to assess these changes. Global coagulation tests have been shown to incorrectly assess in vivo coagulation in patients admitted to intensive care units. But other tests are available. Thrombin generation assay (TGA) is a laboratory test which allows the assessment of an individual's potential to generate thrombin. But also in conventional TGA the protein C system is hardly activated because of the absence of endothelial cells (containing natural thrombomodulin) in the plasma sample. Therefore the investigators add recombinant human thrombomodulin to a conventional TGA. Thereby the investigators hope to be able to depict in vivo coagulation more closely than global coagulation tests do.
Description: nM;
Measure: ETP (AUC) without rhThrombomodulin (rhTM) Time: 6 monthsDescription: nM;
Measure: ETP (AUC) with rhThrombomodulin (rhTM) Time: 6 monthsDescription: Ratio of endogenous thrombin potential (ETP) with rhTM to ETP without rhTM
Measure: ETP-ratio Time: 6 monthsDescription: Comparison of ETP-ratios from ICU patients and ETP-ratios from citrated plasma samples from healthy donors
Measure: ETP-Normalisation Time: 6 monthsThis trial will estimate the efficacy and tolerance of several experimental treatments to prevent hospitalization or death in outpatients aged 65 years or above with Symptomatic SARS-CoV-2 Infection (COVID-19).
Description: Proportion of participants with an occurrence of death
Measure: Death Time: From inclusion (day0) to day 14Description: Proportion of deaths, overall and by cause, in each group
Measure: Death and causes of death Time: From inclusion (day0) to day 28Description: Evolution of Haematological markers in each group : Complete Blood Count, prothrombin level, INR
Measure: Haematological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Biochemical markers in each group : ferritin, serum creatinine, urea, sodium, potassium, chlorine, calcium, magnesium, albumin, bicarbonates / tCO2, LDH, CPK, ASAT, ALAT, uricemia
Measure: Biochemical markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Inflammatory markers in each group : PCT, CRP
Measure: Inflammatory markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of immunological markers in each group : B ans T Cells phenotypic profiles
Measure: Immunological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse events Time: from inclusion (day 0) to day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse reactions Time: from inclusion (day 0) to day 14Description: Plasma concentration of the study drugs at D7
Measure: Plasma concentration Time: day 7Description: Acceptability of the treatment by participant will be assessed with an interview
Measure: Acceptability of the treatment Time: from inclusion (day 0) to day 10The present Diagnostic Accuracy study aims at experimentally validating the use of a rapid salivary test to detect SARS-CoV-2 infection in both symptomatic and asymptomatic individuals as a preliminary approach to a mass screening program. The study is based on a consecutive recruitment of both patients showing symptoms probably associated with COVID-19 (i.e., cough, dyspnea, fever) and asymptomatic patients with a low risk phenotype. The expected number of recruited individuals is 100. The experimental test is a prototype of salivary test based on the Lateral Flow Immunoassay technique and is able to detect the presence of SARS-CoV-2 in saliva, especially the Spike protein (S). The comparison is represented by the nasopharyngeal swab, the gold standard of COVID-19 diagnosis. Patients will undergo both salivary immunoassay and nasopharyngeal swab, thus the outcome assessors are blinded, since the results of the rRT-PCR analysis require at least 6 hours before being available. The main outcomes are sensibility and specificity of the rapid salivary test, when compared with the gold standard (nasopharyngeal swab).
Description: TP/TP+FN (TP= True Positive; FN = False Negative)
Measure: Sensibility Time: Salivary test will be interpreted after 10 minutes; the nasopharyngeal swab after 6 hours; sensitivity recorded through study completion, an average of 2 months.Description: TN/TN+FP (TN= True Negative; FP= False Positive)
Measure: Specificity Time: Salivary test will be interpreted after 10 minutes; the nasopharyngeal swab after 6 hours; specificity recorded through study completion, an average of 2 months.In the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure. Also due to the potential co-existing immunodysfunction in the context of SARS-CoV-2 infection patients will also receive trimethoprim/sulfamethoxazole as part of chemoprophylaxis.
Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.
Measure: The ratio of patients who will not develop serious respiratory failure (SRF) Time: Visit study day 14Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database Time: Visit study day 14Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of SOFA score in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7
Measure: Change of cytokine production between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7
Measure: Change of plasma inflammatory mediators levels between days 1 and 7 Time: Visit study day 1, visit study day 7This study seeks to determine whether the virus which causes COVID-19, SARS-CoV-2, is shed in the stools of patients who are infected.
Description: Relative abundance of bacterial classes within taxonomic phyla and, more broadly, within their domain will be analyzed by sequencing the gut microbiome. These data will then be categorized among specific gastrointestinal disease types.
Measure: Correlation of Microbiome to Disease via Relative Abundance Found in Microbiome Sequencing Time: One yearDescription: To validate the methods used to sequence samples
Measure: Validation of Sequencing Methods Time: One yearThe investigators hypothesize that those with respiratory failure due to COVID-19 will have different burdens of mental and physical disability than those with respiratory failure who do not have COVID-19. Detecting these potential differences will lay an important foundation for treating long term sequelae of respiratory failure in these two cohorts.
Description: SF-36 score
Measure: Quality of Life score Time: up to 12 months after dischargeDescription: Montreal Cognitive Assessment (MoCA) score
Measure: cognitive dysfunction Time: up to 12 months after dischargeDescription: (FSS-ICU)
Measure: Functional Status Score Time: up to 12 months after dischargeDescription: MRC neuromuscular Assessment
Measure: Physical Disability Time: up to 12 months after dischargeDescription: Impact Event Score
Measure: Psychological Sequelae Time: up to 12 months after dischargeDescription: hospital anxiety and depression scale
Measure: hospital anxiety and depression Time: up to 12 months after dischargeDescription: including ventilator associated pneumonia, GI hemorrhage, Deep Vein Thrombosis (DVT) /Pulmonary Embolus (PE), sacral decubitus ulcer, delirium, ICU acquired weakness
Measure: ICU related complications Time: hospitalization up to 6 weeksDescription: measure the location (home, rehabilitation center, nursing home
Measure: hospital discharge location Time: hospital discharge up to 6 weeksDescription: number of days admitted to the ICU
Measure: lCU length of stay Time: hospitalization up to 6 weeksDescription: number of days admitted to the hospital
Measure: hospital length of stay Time: hospitalization up to 6 weeksACCESS enables individuals to contribute to critical research, via an iOS and Android smartphone mobile application. ACCESS combines patient reported outcomes, data from wearable devices and real-world data (such as claims, EHRs, etc), with an opt-in to participate in current and future studies for diagnostics, treatments and vaccines. The data that people share can be quickly and anonymously matched to research studies, providing researchers with a foundational framework for dynamic research at scale and participants a way to be personally matched and prescreened for future research.
Description: To use multifaceted participant data consisting of participant reported outcomes, environmental surface and presence or absence of COVID-19 based on testing results, prescription medications (including off-label use), claims, lab, and medical record data to develop population-based models of disease risk, short and long-term outcomes, and efficacy of interventions and prevention measures.
Measure: Development of population-based models of disease risk Time: Up to 10 yearsDescription: To leverage geolocation and lab results to provide population-level real-time data regarding disease burden at the community, state and national levels.
Measure: Relation between disease burden and geolocation Time: Up to 10 yearsDescription: To specifically identify medications and regimens that address disease symptoms
Measure: Effect of medications on symptoms of COVID19 Time: Up to 10 yearsDescription: To specifically identify medications and regimens that treat and reduce disease severity.
Measure: Effect of medications on disease severity of COVID19 Time: Up to 10 yearsDescription: To identify regional variations in disease incidence and outcomes.
Measure: Rate of COVID19 infection and disease outcomes Time: Up to 10 yearsDescription: To understand long-term outcomes such as risk of pulmonary and cardiovascular disease complications.
Measure: Effect of COVID19 on health outcomes Time: Up to 10 yearsDescription: To conduct long-term follow up of individuals who tested positive for COVID-19 compared to demographically matched individuals that did not.
Measure: Long-term follow up and recontact Time: Up to 10 yearsThis a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.
Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay
Measure: Incidence of symptomatic COVID-19 infection in healthcare workers Time: 12 weeksDescription: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection
Measure: Absenteeism from work due to COVID-19 Time: 12 weeksDescription: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)
Measure: Severity of COVID-19 infection Time: 12 weeksCoronavirus (COVID-19) is a pandemic-like disease caused by a new coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) isolated in China in 2019. Clinical manifestations vary widely from one individual to another, from asymptomatic carrier to a febrile cough that can rapidly lead to acute respiratory distress syndrome. Since the beginning of the COVID-19 epidemic, screening by chest X-ray (RT) and polymerase chain reaction (PCR) SARS-CoV-2 conducted by the Cornwall Hospital Union laboratory has shown that among symptomatic patients and hospital staff suspected of being COVID-19, only 7.8% were attributable to COVID-19. Two nosocomial clusters were also identified, in the emergency department (10 carers) and in the cardiology department (6 carers and one patient). However, direct diagnosis by RT-PCR has sensitivity limits and can lead to false negative results when the subject is indeed suffering from COVID-19. This lack of sensitivity is inherent to the technique on the one hand, but also to the quality of the sample and the kinetics of the infection. Indeed, the virological window during which the virus is present in the respiratory mucous membranes sampled seems relatively narrow, hence a progressive negativation of the respiratory samples as the disease progresses. Moreover, clinical symptoms vary from one individual to another, and it is now recognized that some infected persons are asymptomatic but carry the virus. Thus, the use of a second diagnostic technique is a necessity, and serology could be a relevant diagnostic support. In the literature, several publications report the performance of COVID-19 serology in clusters of cases or cohorts of subjects. The serological techniques employed are variable (target epitopes in particular) and frequently homemade. Serology is mainly studied in comparison or association with RT-PCR in order to highlight the increased performance of COVID-19 diagnosis when the two techniques are combined. Correlation with chest CT imaging data is also encountered. Numerous serological tests are therefore being tested to determine retrospectively whether the individual has been exposed to the virus by looking for specific antibodies to the virus. The supreme health authority has drawn up specifications dated 16 April 2020, defining the methods for evaluating the performance of serological tests detecting antibodies directed against SARSCoV-2 in order to provide a framework for these practices. Several clinical studies are also underway, in particular to assess the kinetics of the appearance of the antibodies, whether these specific antibodies would be protective and whether their appearance would coincide with a cessation of contagiousness. Thus, the main objective of this study is to evaluate the diagnostic performance of the COVID-19 immunoglobulin (IgG) Dia-Pro serological test, in view of its deployment at the Cornish Hospital Union Laboratory. Subsequently, given the low prevalence of COVID-19 in Brittany and the risk of a second epidemic wave when the confinement is lifted, the evaluation of the seroprevalence of the staff of the Cornish Hospital Union is necessary in order to assess the attack rate of COVID-19 within the establishment and particularly within departments where nosocomial clusters have been reported; and to prevent the impact of deconfinement. Indeed, knowledge of the proportion of immunized personnel and its distribution according to services will make it possible to establish internal recommendations and to effectively manage personal protective equipment inventories, in conjunction with the deconfinement strategy that will be implemented by the government. The goal is to protect hospital staff from overexposure to the virus;
Description: The performance of the COVID-19 IgG Dia-Pro serological test is evaluated in terms of sensitivity/specificity.
Measure: Serological test evaluation Time: 1 dayDescription: Population seroprevalence among hospital staff (caregivers and non-caregivers) in Quimper Hospital is assessed
Measure: Population seroprevalence Time: 1 monthSuspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Hospitalized Patients With Coronavirus Infection.
Description: The primary outcome of the study will be days alive and outside the hospital (DAOH) at 30 days. This endpoint will be calculated for each included patient and the calculation will be from the date of randomization to the 30-day post-randomization. The DAOH endpoint represents the follow-up time (30 days) subtracted from the hospitalization days and/or the days between death and the end of follow-up.
Measure: Median days alive and out of the hospital Time: 30 daysDescription: Cardiovascular outcomes such as evolution with acute myocardial infarction, stroke, myocarditis, pericarditis, arrhythmias requiring treatment, thromboembolic phenomena, increase in troponin and D-dimer, respiratory failure, hemodynamic decompensation, sepsis, renal failure and death.All events will be reported according to CTCAE 4.0
Measure: Number of participants with adverse cardiovascular outcomes and new worsening heart failure Time: 30 daysDescription: Evaluation of test results troponin, NT-ProBNP, BNP, and D-dimer will also be assessed as secondary outcome.
Measure: Cardiovascular biomarkers related to COVID-19 Time: up to 30 daysThis study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in hospitalized patients with moderate COVID-19 disease.
Description: Number and severity of adverse events
Measure: Phase 1: Frequency and Severity of Adverse Events (AE) Time: Up to 12 monthsDescription: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR
Measure: Time to Clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Rate of Clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Time from the date of randomization to the first date of clinical improvement of cough.
Measure: Time to Clinical Improvement of cough Time: Up to 28 daysDescription: Time from the date of randomization to the first date of clinical improvement of fever
Measure: Time to Clinical Improvement of fever Time: Up to 28 daysDescription: Time from the date of randomization to the first date of clinical improvement of radiological evaluation of disease related chest x-ray
Measure: Time to Clinical Improvement in radiological evaluation of disease related chest x-ray Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of fever
Measure: Rate of Clinical Improvement of fever Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of cough
Measure: Rate of Clinical Improvement of cough Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of radiological evaluation of disease related chest x-ray
Measure: Rate of Clinical Improvement of radiological evaluation of disease related chest x-ray Time: Up to 28 daysDescription: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).
Measure: Time to Pulmonary Clearance Time: Up to 28 daysDescription: Proportion of subjects who achieve pulmonary clearance
Measure: Rate of Pulmonary Clearance Time: Up to 28 daysDescription: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score Time: Up to 28 daysDescription: Number and severity of adverse events
Measure: Phase 2: Frequency and Severity of Adverse Events (AE) Time: up to 12 monthsDescription: Time to medical discharge as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by time to medical discharge Time: up to 12 monthsDescription: Hospital utilization will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by hospital utilization Time: up to 12 monthsDescription: Mortality rate will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by measuring mortality rate Time: up to 12 monthsProspective registry for multimodal assessment of neuromuscular pathology associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, enrolling consecutive patients with corona virus disease 2019 (Covid-19), who are admitted to the intensive care unit of the department of anesthesiology and intensive care medicine, or the department of neurology at Tübingen University Hospital.
Description: Elevation of creatine kinase during hyperacute phase of corona virus disease 2019 (Covid-19)
Measure: Rate of elevated creatine kinase in hyperacute phase Time: 1 weekDescription: Elevation of creatine kinase during hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Rate of elevated creatine kinase Time: 24 monthsDescription: Two-peak elevation of creatine kinase during acute phase of corona virus disease 2019 (Covid-19)
Measure: Rate of two-peak elevation of creatine kinase during acute phase Time: 30 daysDescription: Presence of myositis-specific antibodies on admission, at two weeks, and at end of follow-up
Measure: Rate of myositis-specific antibodies Time: 24 monthsDescription: Presence of antimyocardial antibodies on admission, at two weeks, and at end of follow-up
Measure: Rate of antimyocardial antibodies Time: 24 monthsDescription: Level of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19) assessed by the area under the curve (AUC)
Measure: Area under the curve (AUC) of elevated creatine kinase Time: 24 monthsDescription: Maximal value of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of elevated creatine kinase Time: 24 monthsDescription: Maximal value of troponin in the acute phase of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of troponin Time: 30 daysDescription: Maximal value of urine myoglobin in the acute of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of urine myoglobin Time: 30 daysDescription: Muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Rate of muscle hyperechogenicity Time: 24 monthsDescription: Peak-muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Peak-muscle hyperechogenicity Time: 24 monthsPurpose: To determine the number of asymptomatic individuals who have antibodies to SARS-CoV-2, the virus which causes COVID-19
Description: Presence or absence of IgG antibodies to SARS-CoV2
Measure: Percentage of Asymptomatic patients with an IgG response from SARS-CoV-2 infection. Time: at enrollmentDescription: swab for presence of SARS-CoV-2 virus
Measure: Percentage of Asymptomatic patients with viral presence of SARS-CoV-2 infection. Time: at enrollmentThis concerns a single-center prospective interventional cohort study. Laboratory-confirmed COVID-19 patients will be asked to donate blood at at least two different timepoints. This will allow us to investigate T and B cell evolutions during the course of infection and recovery. The expected duration of the study is four months or the total duration of the SARS-CoV-2 circulation in Belgium (whichever is shortest).
Prophylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.
Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)
Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections Time: 12 weeks after initiation of therapyDescription: defined as combined endpoint of hospitalization rate or death
Measure: Number of severe COVID-19 cases Time: 12 weeks after initiation of therapyDescription: grading as outlined by the world health organization (WHO)
Measure: Severity of COVID-19 cases Time: 12 weeks after initiation of therapyDescription: significant clinical and laboratory abnormalities according to CTCAE criteria
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: 12 weeks after initiation of therapyDescription: other than COVID-19
Measure: Number of viral and bacterial infections Time: 12 weeks after initiation of therapyDescription: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test
Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test Time: 12 weeks after initiation of therapyTo compare various treatments provided to positive COVID-19 patients at locations across the OSF Ministry. Provide the opportunity to compare the effectiveness of various treatments and treatment timelines provided to specific cohorts of patients that have the potential to impact future treatment plans for COVID-19 patients and/or future research hypotheses.
Patient are being asked to provide respiratory and blood samples for a clinical research study because the patients have a virus called the novel coronavirus, or SARS-CoV-2, that causes the disease known as Covid-19. Investigators do not know a lot about this virus, including all the ways it travels from person to person. Investigators also do not know if a person will get sick or not from the virus after being in close contact with someone who has the virus. Because of this, investigators are performing research on the virus found in respiratory secretions to get more information on how investigators can best detect and treat this new virus in the future. Primary Objective - To determine the clinical characteristics and outcomes of Covid-19 in children. - To characterize the clinical risk factors of Covid-19 in children.. Secondary Objectives - To characterize the immunological risk factors and serologic response to SARS-CoV-2 infection in children.- To evaluate the duration of viral shedding in children. - To evaluate the duration of SARS-CoV-2 viral shedding in children. Exploratory Objective
Description: Clinical characteristics, including demographics, underlying diagnosis, and signs/symptoms, and outcomes, such as hospitalization, oxygen requirements, and mortality, will be summarized with counts and percentages.
Measure: Characteristics and outcomes of acute respiratory infections due to COVID-19 in children. Time: Baseline-Day 60Description: Pearson or Spearman's correlation of clinical risk factors such as age, underlying diagnosis, immunosuppression with outcomes as detailed in primary objective 1 will be evaluated.
Measure: Clinical risk factors of acute respiratory infection due to COVID-19 in children. Time: Baseline-day 60Description: Immunological (e.g., Absolute lymphocyte/monocyte counts, Immunoglobulin level) and serological (antibodies against the virus) response measures will be summarized with mean, standard deviation, median and range.
Measure: Immunologic response to acute respiratory infection due to COVID-19 in children. Time: Baseline-day 60Description: The duration of viral shedding, defined as the time between the first positive test date and the first negative test date, will be summarized for all participants with mean, standard deviation, median and range.
Measure: Duration of viral shedding and evolution in children longitudinally. Time: Baseline-Day 60The objectives of PROVIDE are to: 1. Determine if prophylactic once weekly hydroxychloroquine reduces the incidence of conversion from SARS-2-CoVnasopharyngeal swab negative to positive 2. To determine if weekly prophylactic hydroxychloroquine reduced the severity of COVID-19 symptoms 3. To determine the safety of taking weekly prophylactic hydroxychloroquine
Description: The number of HCW that tested positive for SARS-CoV-2
Measure: Positive for SARS-CoV-2 Time: 8 weeksDescription: The number of HCW that required hospital admission secondary to SARS-CoV-2
Measure: Hospital admissions Time: at any time after first dose to hospital discharge, truncated at 60 daysDescription: The number of HCW that required intensive care unit admission
Measure: Intensive care unit admissions Time: at any time after first dose to hospital discharge, truncated at 60 daysDescription: The number of HCW that required intubation and mechanical ventilation
Measure: Intubation and mechanical ventilation Time: at any time after first dose, truncated at 60 daysDescription: number of days admitted to the ICU
Measure: ICU length of stay Time: from randomization to hospital discharge, truncated at 60 daysDescription: number of days admitted to the hospital
Measure: Hospital length of stay Time: from randomization to hospital discharge, truncated at 60 daysDescription: Death
Measure: Mortality Time: from randomization to 60 daysDescription: Gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting), Hypoglycemia, Abdominal LFTs, Angioedema, Opthalmic (corneal changes, decreased visual acuity, macular degeneration, retinal changes), Bronchospasm
Measure: Incidence of adverse events Time: from randomization to 60 days