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.

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.

Transmission routes of SARS-CoV-2 among healthcare workers of a French university hospital in Paris, France: a case-control study (preprint)

In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with COVID-19 patients or with colleagues were associated with infection with SARS-CoV-2, while working in a COVID-dedicated unit, using public transportation and having children kept in childcare facilities were not.

Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris (preprint)

Background: From the start of the pandemic, health-care workers (HCW) have paid a heavy toll to the coronavirus disease-19 (COVID-19) outbreak. Objectives: To describe the dynamics and determinants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in HCW. Design: Prospective observational study conducted from February 24th until April 10th, 2020. Setting: Comparison of a 1,500-bed adult and a 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. Participants: All symptomatic HCW screened for SARS-CoV-2 on a nasopharyngeal swab. Measurements: HCW screened positive were prospectively questioned on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. Results: Among 1344 symptomatic HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death were reported. Most HCW (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p=0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0.046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. Limitations: Lack of COVID-19 negative controls and recall bias. Conclusion: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.