Sotrovimab drives SARS-CoV-2 Omicron variant evolution in immunocompromised patients

Abstract

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.

Antibody response and intra‐host viral evolution after plasma therapy in COVID‐19 patients pre‐exposed or not to B‐cell‐depleting agents

“…Thorough follow‐up allowed identifying a few cases with prolonged viral shedding who needed serial transfusion for a complete recovery. Our data are in line with a systematic review by Focosi et al, 57 reporting that CP may be associated with a lower risk of emergence of resistant variants, contrasting with the documented immune escape after treatment with monoclonal antibodies, as recently shown in immunocompromised patients who received sotrovimab as monotherapy 64–66 . This may in part be explained by the polyclonal nature of the transfused anti‐SARS‐CoV‐2 antibodies.…”

Predicting the antigenic evolution of SARS-COV-2 with deep learning

“…A reverse mutation, R493Q, for example, was found in a persistently infected, immunocompromised individual 44 . Other mutations found by our model, like E340K 45 , E484T 33 , G485R 46 , and F490L/E484G 47 , are also found in immunocompromised patients treated with monoclonal antibodies. Moreover, the unique mutations found in the emerging variants, BA.4/5, the L452R, F486V, and the reverse mutation R493Q, are also captured by our model.…”

Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

“…Mutations in the spike protein at positions 337 or 340 were shown in patients infected with the Delta ( 7 ) and the Omicron lineages ( 8 ). A recent report demonstrated across a routine genomic surveillance that these mutations occurred in 24 (0.13%) of 18,882 omicron BA.1 lineages and in one (0.02%) of 4025 omicron BA.2 lineages, affecting mostly immunocompromised patients with persistent SARS-CoV-2 excretion ( 9 ). In this work both mutations occurred in a sizeable proportion of BA.1-infected patients but did not occur among patients who experienced COVID-19-related hospitalization, and did not significantly affect the slope of Ct values.…”