Impact of COVID-19 SARS-CoV-2 Variability in ICU Hospitalized Patients With Severe Disease (SEVARVIR)

Characterization of the Impact of SARS-CoV-2 Variability on the Course of COVID-19 in Patients With Severe Disease Hospitalized in Intensive Care Units: Prospective Observational Multicentric Study

Background:The impact of the emergence of SARS-CoV-2 variants on the severity and clinical outcomes of COVID-19 is controversial. Whether virological characteristics including the mutational patterns of the different viral proteins (e.g., Spike, NSP proteins, ORF6) could be associated with a different immune response and subsequent severity of the disease is unknown. ln the next coming months, new variants carrying the same or new mutational patterns will continue to emerge. Monitoring their dynamics over time and their impact on disease severity is required for refining national and international disease control policies.

Main objective: To unravel the relationships between specific viral mutations/mutational patterns and the clinical outcomes of COVID-19 in patients hospitalized in intensive care units (ICUs) for acute respiratory failure following severe SARS-CoV-2 infection.

Design of the study Prospective multicentre observational cohort study

Schedule for the study: Inclusion period: 24 months; Participation period: 28 days ; Total duration : 24 months + 28 days;

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV2 Infection; Mutation; COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Nasopharyngeal swab

Detailed Description

Background:The impact of the emergence of SARS-CoV-2 variants on the severity and clinical outcomes of COVID-19 is controversial. Preliminary studies estimated that the probability of death associated with variant of concern (VOC) B.1.1.7, the UK variant, is 55% higher than that associated with pre-existing variants. However, no difference has been found in another study. In Brazil, infection with VOC P1 has been suggested to be associated with an increased case fatality rate in young adults. The effect of other "variants of concern" (Beta, B.1.351; Delta, B.1.617.2, or the most recent Omicron variants) or "variants of interest" (A27, B.1.525, etc.) on the severity of the disease and the prognosis of severe forms is unknown. More generally, whether virological characteristics including the mutational patterns of the different viral proteins (e.g., Spike, NSP proteins, ORF6) could be associated with a different immune response and subsequent severity of the disease is unknown. ln the next coming months, new variants carrying the same or new mutational patterns will continue to emerge in different geographic areas, as a result of the collective immune pressure induced by natural infection and vaccination. Monitoring their dynamics over time and their impact on disease severity is required for refining national and international disease control policies.

In this project, a large prospective multicenter observational cohort promoted by the Assistance Publique-Hôpitaux de Paris (AP-HP) will be conducted, to understand the effect of SARS-CoV-2 genetic variability on the outcome of COVID-19 disease in patients with severe illness. The study will include critically ill patients hospitalized for acute respiratory failure/acute respiratory distress syndrome (ARDS) associated with COVID-19. The objective of the work will be to characterize the SARS-CoV-2 variants found in this population over time, and to identify and phenotypically characterize specific mutations/mutational patterns associated with the different clinical outcomes (primary clinical endpoint defined as mortality at day-28). The impact of the mutations on viral infectivity, sensitivity to neutralizing antibodies and ability to induced cytokine production will be assessed in vitro and ex-vivo respectively, in appropriate models available in the laboratory. Further to full-length viral genome sequencing, our in-house shotgun metagenomics method will be used to characterize the effect of SARS-CoV-2 variations on respiratory transcriptomic expression profiles and the relationship with the clinical evolutionary profiles.

Design of the study Prospective multicentre observational cohort study

Main objective: To unravel the relationships between specific viral mutations/mutational patterns and the clinical outcomes of COVID-19 in patients hospitalized in intensive care units (ICUs) for acute respiratory failure following severe SARS-CoV-2 infection.

Schedule for the study: Inclusion period: 24 months; Participation period: 28 days ; Total duration : 24 months + 28 days;

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Nicolas DE PROST, MD-PHD; Phone Number: 0033 0149878506; Email: nicolas.de-prost@aphp.fr

Study Locations

• France
  • Val De Marne
    • Créteil, Val De Marne, France, 94010
      • Recruiting
      • Assistance Publique Hôpitaux de Paris - CHU HENRI MONDOR
      • Contact: Nicolas De Prost, MD, PhD; Phone Number: +33 1 49 81 23 94; Email: nicolas.de-prost@aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients with severe SARS-CoV-2 infection and acute respiratory failure admitted in one of the participating ICUs during 2 years of inclusion period.

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Availability of nasopharyngeal swab from SOC
• SARS-CoV-2 infection as assessed by a positive RT-PCR test (CT < 32), including in SARS CoV-2 vaccinated or previously infected patients
• Patient admitted in the ICU for acute respiratory failure (SpO2 ≤ 90% and need for supplemental oxygen or any kind of ventilator support; i.e., OMS 10-category ordinal scale ≥5)
• Patient or trusted person or close or relative, And, accepting study participation

Exclusion Criteria:

• Patient with SARS-CoV-2 infection but no acute respiratory failure
• Patient deprived of liberty or under legal protection (guardianship, curators, legal protection, forced hospitalization)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day-28 vital status	vital status (living / deceased)	at Day-28 after admission in intensive care units (ICUs) for acute respiratory failure following severe SARS-CoV-2 infection

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Slim FOURATI, MD-PHD, Assistance Publique - Hôpitaux de Paris (AP-HP) Henri Mondor

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Estimated): January 16, 2026
• Study Completion (Estimated): January 16, 2026

Study Registration Dates

• First Submitted: December 10, 2021
• First Submitted That Met QC Criteria: December 10, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: APHP211494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: AP-HP is the owner of the data. The data cannot be used or disclosed to a third party without its prior permission

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No