Prevention of COVID-19 Complications in High-risk Subjects Infected by SARS-CoV-2 and Eligible for Treatment Under a Cohort ATU ('Autorisation Temporaire d'Utilisation') OR or Authorisation for Early Access (AAP). A Prospectvie Cohort.

Study Overview
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Brief Summary
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This is a prospective, multicentric, non comparative study aiming to evaluate the clinical and virological evolution of high-risk patients infected with SARS-CoV-2 treated withtin the framework of a cohort ATU ('Autorisation temporaire d'utilisation') or authorisation for early access (AAP) delivered by the French drug agency (ANSM).

Official Title
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Prevention of COVID-19 Complications in High-risk Subjects Infected by SARS-CoV-2 and Eligible for Treatment Under a Cohort ATU ('Autorisation Temporaire d'Utilisation') or or Authorisation for Early Access (AAP). A Prospective Cohort.

Conditions
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Covid19, SARS-CoV Infection

Intervention / Treatment
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* Other: biobank


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with the criteria for COVID-19 treatment within the French compassionate program (ATU/AAP) Adults covered by the French social health coverage Adults who signed the informed consent form Exclusion Criteria: Exclusion criteria described in the French compassionate program (ATU/AAP) Patient participating in another biomedical research with an exclusion period ongoing at inclusion Vulnerable patient (adults legally protected: under judicial protection, guardianship, or supervision, persons deprived of their liberty) Pregnant or breastfeeding woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients treated with casirivimab/imdevimab according to the ATU protocol<br> | Other: biobank<br>* Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood) For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC) Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14) Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5<br>|
| Patients treated with bamlanivimab/etesevimab according to the ATU protocol<br> | Other: biobank<br>* Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood) For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC) Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14) Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5<br>|
| Patients treated with Xevudy according to the authorisation for early access (AAP) protocol<br> | Other: biobank<br>* Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood) For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC) Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14) Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5<br>|
| Patients treated with Paxlovid according to the authorisation for early access (AAP) protocol<br> | Other: biobank<br>* Blood samples (biobank) at Day 0, Day 7, Month 1 and possibly Month 3 (only for the first 100 participants) (serum, plasma and whole blood) For participants in the immunological ancillary study: additional blood sampling at Day 0, Day 7 and Month 1 (PBMC) Nasopharyngeal swabs: Day 0, Day 7 (Day 14 and Day 21 if RT-PCR positive respectively at Day 7 and Day 14) Specific nasopharyngeal swabs in hospitalized patients: Day 3, Day 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients hospitalized (if the patient was outpatient) or whose hospitalization was extended for complications from COVID-19 within 1 month of symtoms' onset. |  | Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients hospitalized whatever the reason |  | Month 1 and 3 | 
| Percentage of patients with an WHO score >= 5 |  | Month 1 | 
| Percentage of patients staying in an Intensive Care Unit in the month following symptoms' onset |  | Month 1 | 
| Percentage of patients who died from COVID-19 complications and any other reason |  | Month 1 | 
| Percentage of patients presenting a adverse event and percentage of treatment discontinuation caused by those adverse events |  | Month 1 | 
| Time between first symptoms and treatment and the reasons for this delay |  | Day 0 | 
| Virological response | Percentage of virological response defined by CT>=31 or negative PCR test + | Day 7 for ambulatory patients, Day 3, 5 and 7 for hospitalized patients | 
| Virological criteria linked to the emergence of resistance | Percentage of patients included developing resistance variants, genotypic and phenotypic characterization of resistance variants | from inclusion until a negative PCR test or Ct ≥31 is obtained | 
| Percentage of patients with positive anti-N and anti-S serology |  | Day 0 and Month 3 | 
| anti-S antibody level |  | Day 0 and Month 3 | 
| Flow cytometry cartography of myeloid response | Flow cytometry cartography of myeloid (functional subtypes of monocytes and dendritic cells) response | Day 0, 7 and Month 1 | 
| Flow cytometry cartography of T-lymphocyte response | Flow cytometry cartography of T-lymphocyte (conventional T-lymphocytes by identifying naïve, memory and effector Th1, Th2, Tfh and Th17 T-lymphocytes, NK and gamma-delta T-lymphocytes, regulatory T-lymphocytes; surface and intracellular markers) response | Day 0, 7 and Month 1 | 
| Flow cytometry cartography of B-lymphocyte response | Flow cytometry cartography of B-lymphocyte (transitional, naïve, memory T-lymphocyte with or without isotypic switching, plasmablasts) response | Day 0, 7 and Month 1 | 
| Dosing of a wide range of cytokines and chemokines (IFNalpha, IFNgamma, IL-6, IL-1, IL-8, IL-15, IL-18, IL1-RA, IL-7, IL-10, CXCL10, CXCL13, CCL2 and CCL3) using the Meso Scale Discovery approach |  | Day 0, 7 and Month 1 | 
| Clinical and biological predictors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants) of the onset of complications from COVID19, hospitalization, death | Identication of clinical and biological predictors of the onset of complications from COVID19, hospitalization, death by a logistic model or survival model (RMST): the response variable is the occurrence of a complication, hospitalization, death or the average survival at 1 month on these different criteria; the covariates are the parameters at inclusion, the treatment received, the virological criteria (CT, variants) which can be considered as a time-dependent covariate | from inclusion until the end of the follow-up (Month 1 or Month 3) | 
| Clinical and biological predictive factors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants)) linked to the neutralizing serological response: non-response, duration of the response | Identification of clinical and biological predictive factors (clinical parameters, treatment received, virological criteria (cycle threshold (CT), variants)) linked to the neutralizing serological response: non-response, duration of the response by a logistic model or mixed model for repeated measures | from inclusion until the end of the follow-up (Month 1 or Month 3) | 
| Clinical and biological predictors (clinical parameters, treatment received, virological criteria) of viral response (viral genotypes, emergence of resistant strains) | Identification of clinical and biological predictive factors related to the virological response (viral genotypes, emergence of resistant strains) by a logistic model: the response variable is RT-PCR negativation at D7 (or CT≥31), the covariates are the parameters at inclusion, the treatment received, the virological criteria at baseline | from inclusion until the end of the follow-up (Month 1 or Month 3) |