SARS-CoV-2 spike 340 and 337 mutations in Omicron variants are selected after Sotrovimab infusion in immunocompromised patients (preprint)

After monoclonal antibody sotrovimab implementation, Rockett et al have warned on March 9th about two resistant mutations in the spike at position 337 and 340 occurring within the first week in four immunocompromised patients infected by a Delta variant and resulting in viable infection up to 25 days. As sotrovimab is currently the only effective treatment against BA.1 lineage of Omicron variant, we investigated the presence of these mutations in our 22,908 Omicron sequences performed from December 2021 to March 2022. Among 25 Omicron sequences with S:337 and S:340 substitutions, 9 were reported in six patients who had available clinical data and a follow up. All were immunicompromised, and presented a rapid selection of these mutations after sotrovimab monotherapy infusion. With these findings, we underscore that although these mutations are rare, they have been exclusively reported in immunocompromised patients treated with sotrovimab. We urge to consider monoclonal antibody as monotherapy in immunocompromised patients as a risk for escape mutants selection.

Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation, France, December 2021 - February 2022 (preprint)

In Dec 2021-Feb 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and we developed an unbiased bioinformatics method which can detect all co-infections irrespective of the SARS-CoV-2 lineages involved. Applied on 21,387 samples collected between weeks 49-2021 and 08-2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants.

Evidence of co-infection during Delta and Omicron variants of concern co-circulation, weeks 49-2021 to 02-2022, France (preprint)

We report evidence of Delta/Omicron SARS-CoV-2 co-infections during the fifth wave of COVID-19 pandemics in France for 7 immunocompetent and epidemiologically unrelated patients. These co-infections were detected by PCR assays targeting SARS-CoV-2 S-gene mutations K417N and L452R and confirmed by whole genome sequencing which allowed the proportion estimation of each subpopulation. For 2 patients, the analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection.

Investigation of Vaccine Breakthrough Infections by Vaccine strategy during the Delta Variant Wave in France (preprint)

Herein, we describe the characteristics of vaccine breakthrough infections (VBI) in fully vaccinated individuals according to five vaccine strategies during the Delta wave in France. Inclusion criterion was a positive test at least 2 weeks after a full vaccine schedule: homologous vaccination with Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273); heterologous vaccination with Astrazeneca and Pfizer-BioNTech (ChadOx1/BNT162b2); single-dose vaccines Johnson & Johnson (Ad26.COV2.S) or Astrazeneca (ChadOx1). A total of 1630 VBI from patients fully vaccinated between February and July were included in this study. SARS-CoV-2 sequencing performed for 1366 samples showed that the delta variant represented 94.1% (1286/1366). Delta-VBI were mainly symptomatic (mild symptoms) with no difference according to the vaccine strategy (p=0.362). The median RT-PCR Ct values at diagnosis were significantly different between symptomatic and asymptomatic cases only for BNT162b2 group (17.7 (15.07, 20.51) vs 19.00 (16.00, 23.00), p=0.004). Up to 50% of VBI was classified as early-VBI (infected less than one month after full immunization) for BNT162b2, mRNA-1273, ChadOx1, and J Ad26.COV2.S. People aged 14-49 yo were overrepresented in early VBI compared to non-early VBI for BNT162b2 and mRNA-1273 (73.92% vs 37.87% for BNT162b2 and 77.78% vs 46.67 % for mRNA-1273, p<0.05). Our data emphasize a high prevalence of Delta-VBI occurring only one month after full immunization in young patients that might be related to relaxation of barrier gestures.