SARS CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study (preprint)

Background: SARS-CoV-2 variant of concern (VOC) α spread worldwide, including in France, at the beginning of 2021. This variant was suggested to be associated with a higher risk of mortality than other variants. Little information is available in the subset of patients with severe disease admitted in the intensive care unit (ICU). We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 in order to unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. Methods: : Prospective multicentre observational cohort study. Patients aged ≥18 years admitted in 11 ICUs from Great Paris area hospitals between October 1, 2020, and May 30, 2021 (before the introduction of VOC δ (B.617.2) in France) for acute respiratory failure (SpO2≤90% and need for supplemental oxygen or ventilator support) were included. SARS-CoV-2 infection, determined by RT-PCR testing. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). Results: : 413 patients were included, 183 (44.3%) had been infected with pre-existing variants, 197 (47.7%) with variant α (B.1.1.7), and 33 (8.0%) with other variants. Patients infected with pre-existing variants were significantly older (64.9±11.9 vs 60.5±11.8 years; p=0.0005); they had significantly more frequent COPD (11.5% (n=21/183) vs 4.1% (n=8/197); p=0.009), and higher SOFA score (4 [3-8] vs 3 [2-4]; 0.0002). Day-28 mortality was not different between patients infected with pre-existing, α (B.1.1.7) or other variants (31.1% (n=57/183) vs 26.2% (n=51/197) vs 30.3% (n=10/33), respectively; p=0.550). There was no association between day-28 mortality with a specific variant or the presence of specific mutations in SARS CoV-2 genome, including 17 mutations selected in the spike protein and all 1017 non-synonymous mutations detected throughout the entire viral genome. Conclusions: : At ICU admission, patients infected with pre-existing variants had a different clinical presentation from those infected with variant α (B.1.1.7) and other variants later in the course of the pandemic, but mortality did not differ between these groups. There was no association between a specific variant or SARS CoV-2 genome mutational pattern and day-28 mortality.

Prevention of Sars-Cov-2 Transmission During a Large, Live, Indoor Gathering: The Noninferiority Randomised-Controlled Spring Trial (preprint)

Background: Mass indoor gatherings were banned in early 2020 to prevent SARS-CoV-2 spread. We aimed to assess, under controlled conditions, whether systematic antigen-screening within 3 days, medical mask-wearing and optimized ventilation could prevent SARS-CoV-2 spread during a large, indoor gathering without physical distancing.Methods: The non-inferiority, prospective, open-label, randomized (2:1)-controlled SPRING trial was conducted on May 29, 2021 in Paris, France. Participants, 18–45 years old, had no comorbidities, COVID-19 symptoms and recent case contact, and a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated to the experimental arm (attendees) or to the control arm (non-attendees). The primary outcome measure was the number of SARS-CoV-2–positive RT-PCR on self-collected saliva 7 days (D7) post-gathering. An artificial intelligence tool analyzing anonymised, continuous video-capture data evaluated participants’ mask-wearing compliance. This trial is registered with ClinicalTrials.gov, NCT04872075.Findings: Among 6678 randomized participants (median age 28 years; 59% women), 88% of each group complied with follow-up requirements. The D7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0.20%; 95% Confidence Interval [CI], 0.09 to 0.40) and 3 of the 1,947 non-attendees (0.15%; 0.03 to 0.45) (absolute difference, 95%CI, –0.26% to +0.28%), findings that met the non-inferiority criterion (margin <0.35%) for the primary endpoint. Global facemask-wearing compliance (i.e., covering nose and mouth) was estimated at 91.4% (95%CI, 87.7 to 95.4).Interpretation: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2–transmission risk, provided a comprehensive preventive intervention was implemented.Trial Registration: This study was registered on ClinicalTrials.gov (NCT04872075).Funding: French Ministry of HealthDeclaration of Interest: All authors declare no competing interestsEthical Approval: The trial protocol was approved by the Scientific Ethics Committee of the Sud-Ouest and Outremer Regions of France and the French Data-Protection Agency

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR cycle amplification values (preprint)

The SARS-CoV-2 pandemic has led to an unprecedented daily use of molecular RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of amplification cycles (Ct), is debated because of strong potential biases. We analyze a national database of tests performed on more than 2 million individuals between January and November 2020. Although we find Ct values to vary depending on the testing laboratory or the assay used, we detect strong significant trends with patient age, number of days after symptoms onset, or the state of the epidemic (the temporal reproduction number) at the time of the test. These results suggest that Ct values can be used to improve short-term predictions for epidemic surveillance.