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.

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.

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).

Study Overview

• Status: Completed
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Other: biobank

• Study Type: Observational
• Enrollment (Actual): 756

Contacts and Locations

Study Locations

• France
  • Agen, France
    • CH Agen-Nérac
  • Angers, France
    • CHU d'Angers
  • Ars-Laquenexy, France
    • CHR Metz-Thionville
  • Bobigny, France
    • Hopital Avicenne
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Clermont-Ferrand, France
    • Chu Gabriel Montpied
  • Corbeil-Essonnes, France, 91106
    • Centre Hospitalier Sud Francilien - Hématologie
  • Corbeil-Essonnes, France, 91106
    • Centre Hospitalier Sud Francilien - Néphrologie
  • Dijon, France
    • CHU de Dijon
  • Fort-de-France, France, 97261
    • CHU de Martinique
  • Le Kremlin-Bicêtre, France, 94275
    • Hôpital Bicêtre - Médecine interne
  • Le Kremlin-Bicêtre, France, 94275
    • Hôpital Bicêtre - SMIT
  • Limoges, France
    • CHU de Limoges
  • Lyon, France
    • Hospices Civils de Lyon (HCL)
  • Montpellier, France
    • CHU de Montpellier
  • Nancy, France, 54511
    • CHRU de Nancy
  • Nantes, France
    • CHU de Nantes
  • Nîmes, France
    • CHU de Nîmes
  • Paris, France
    • Hopital Pitie-Salpetriere
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Paris, France, 75020
    • Hopital Tenon
  • Paris, France
    • Hôpital Saint-Louis
  • Paris, France, 75018
    • Hopital Bichat Claude-Bernard
  • Paris, France, 75010
    • Hôpital Lariboisière - SMIT
  • Paris, France
    • Hôpital Bichat Claude-Bernard - SAU
  • Paris, France
    • Hôpital Lariboisière - SAU SMUR
  • Paris, France
    • Hôpital Saint Antoine - SAU
  • Paris, France
    • Hôpital Universitaire Necker Enfants Malades
  • Paris, France
    • Hôpitaux Cochin - Port Royal
  • Poissy, France
    • CHI Poissy St Germain en Laye
  • Poitiers, France
    • CHU de Poitiers
  • Rennes, France
    • CHU de Rennes
  • Tarbes, France
    • CH de Tarbes
  • Toulouse, France
    • CHU de Toulouse
  • Toulouse, France
    • CHU de Toulouse - IUCT - Oncopole
  • Tourcoing, France
    • CH de Tourcoing
  • Tours, France
    • CHRU de Tours - Hôpital Bretonneau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients infected with SARS-CoV-2 referred by their doctor (general practitioner, specialist, SOS doctor, etc.) to a prescribing center authorized to prescribe and deliver treatments benefiting from an ATU/AAP.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with casirivimab/imdevimab according to the ATU protocol	Other: biobank; 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
Patients treated with bamlanivimab/etesevimab according to the ATU protocol	Other: biobank; 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
Patients treated with Xevudy according to the authorisation for early access (AAP) protocol	Other: biobank; 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
Patients treated with Paxlovid according to the authorisation for early access (AAP) protocol	Other: biobank; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Youri Yordanov, Dr, Saint Antoine Hospital

Publications and helpful links

General Publications

• Bruel T, Vrignaud LL, Porrot F, Staropoli I, Planas D, Guivel-Benhassine F, Puech J, Prot M, Munier S, Henry-Bolland W, Soulie C, Zafilaza K, Lusivika-Nzinga C, Meledge ML, Dorival C, Molino D, Pere H, Yordanov Y, Simon-Loriere E, Veyer D, Carrat F, Schwartz O, Marcelin AG, Martin-Blondel G; ANRS 0003S CoCoPrev Study Group. Antiviral activities of sotrovimab against BQ.1.1 and XBB.1.5 in sera of treated patients. medRxiv [Preprint]. 2023 May 30:2023.05.25.23290512. doi: 10.1101/2023.05.25.23290512.
• Bruel T, Vrignaud LL, Porrot F, Staropoli I, Planas D, Guivel-Benhassine F, Puech J, Prot M, Munier S, Bolland WH, Soulie C, Zafilaza K, Lusivika-Nzinga C, Meledge ML, Dorival C, Molino D, Pere H, Yordanov Y, Simon-Loriere E, Veyer D, Carrat F, Schwartz O, Marcelin AG, Martin-Blondel G; ANRS 0003S CoCoPrev Study Group. Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients. Med. 2023 Oct 13;4(10):664-667. doi: 10.1016/j.medj.2023.07.007.
• Martin-Blondel G, Marcelin AG, Soulie C, Kaisaridi S, Lusivika-Nzinga C, Zafilaza K, Dorival C, Nailler L, Boston A, Ronchetti AM, Melenotte C, Cabie A, Choquet C, Trinh-Duc A, Lacombe K, Gaube G, Coustilleres F, Pourcher V, Martellosio JP, Peiffer-Smadja N, Chauveau M, Housset P, Piroth L, Devaux M, Pialoux G, Martin A, Dubee V, Frey J, Le Bot A, Cazanave C, Petua P, Liblau R, Carrat F, Yordanov Y. Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir. Clin Microbiol Infect. 2023 Apr;29(4):543.e5-543.e9. doi: 10.1016/j.cmi.2022.12.016. Epub 2022 Dec 28.
• Martin-Blondel G, Marcelin AG, Soulie C, Kaisaridi S, Lusivika-Nzinga C, Dorival C, Nailler L, Boston A, Melenotte C, Gaube G, Choquet C, Liblau R, Carrat F, Yordanov Y; COCOPREV Study Group. Outcome of very high-risk patients treated by Sotrovimab for mild-to-moderate COVID-19 Omicron, a prospective cohort study (the ANRS 0003S COCOPREV study). J Infect. 2022 Jun;84(6):e101-e104. doi: 10.1016/j.jinf.2022.04.010. Epub 2022 Apr 7. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Actual): June 18, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Severe Acute Respiratory Syndrome
• Other Study ID Numbers: ANRS0003S COCOPREV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No