Covid-19: monoclonal antibodies and immunocompromised people

Use with caution. Monoclonal antibodies (which recognize one dot of the virus) such as GlaxoSmithKline’s sotrovimab and Eli Lilly’s bamlanivimab are part of the arsenal available to fight Covid-19. Mainly for patients who have not been vaccinated or who have not developed a sufficient immune response to fight the virus, in particular for immunocompromised patients. Very effective against previous variants, these monoclonal antibodies have lost effectiveness against Omicron and its sub-variants due to their significant ability to evade the immune response. Thus, only sotrovimab is effective against BA.1 (the first strain of Omicron). Therefore, it is only natural that this monoclonal antibody is used to treat immunocompromised patients infected with the coronavirus. Problem: This treatment appears to be able to generate resistant variants in these patients.

Resistance mutations selected after this treatment in immunocompromised patients

“We have been interested in immunocompromised patients since the beginning of the pandemic, because immunocompromised people can be reservoirs for SARS-CoV-2, because they have a hard time clearing it, and therefore it can develop in their bodies,” Lawrence explains to us. Josse, Research Fellow at the Infectious Agents Institute of the Lyon Hospices, a laboratory associated with the National Reference Center for Respiratory Infection Viruses. The virus replicates at a faster rate in these patients and stays there longer, which increases the risk of mutations in the virus and thus evolution. In this context, only viruses that can escape the antibody used will replicate, creating selection for that resistance.”

Indeed, Lawrence Josse and colleagues have demonstrated that treatment with sotrovimab creates a selection pressure that may promote certain resistance mutations to this antibody. In particular, mutations at positions 340 and 337 of the Spike protein are known to significantly reduce the effectiveness of this antibody.

After analyzing almost 23,000 Omicron sequences collected in France between December 2021 and March 2022, the researchers found these mutations in 25 sequences in 18 patients. Clinical information was only available for 8 of these patients, all of whom were immunocompromised and treated with sotrovimab. According to their analysis, published online in a (not yet peer-reviewed) preprint on April 16, 2022, these mutations appeared one to two weeks after treatment. Due to this persistence, the treatment failed to eliminate the coronavirus, which was still detectable up to 43 days after infection. With the exception of one patient who was subsequently treated with convalescent plasma.

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