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SARS-CoV-2 Resistant Variant Emerged In Immunocompromised Patient

A study has followed the emergence of double mutation in combination with the S2 mutation D796H and broad escape from antibody neutralization in a patient who received convalescent plasma therapy. The patient had received treatment with rituximab and was hence immunocompromised. Specific SARS-CoV-2 antibodies were measured over time. The patient received three units of convalescent plasma from three separate donors following negative results ay days 44 and 50.

Viral isolates from the patient’s room revealed strain with a lineage 20B with the D614G mutation in the spike. At days 93 and 95, the viral strains were significantly different from the early isolates, though closely related phylogenetically. Two courses of remdesivir therapy (by day 54) and two CP infusions (by day 65) failed to change the Ct values up to the first 100 days post-infection. After day 66, the viral population showed a drastic compositional shift. By day 82, the D796H mutation in S2 became almost the sole allele, along with the S1 double mutation H69/V70.

This set of mutations then dropped to a very low frequency by days 86 and 89, while spike mutations Y200H and 163 T240I became predominant. On day 93, the set of D796H along with H69/V70 was detected in less than 10% of the samples in a nose and throat sample. Simultaneously, a group of viruses with spike RBD mutation P330S and S1 NTD mutation W64G had increased to almost 100% abundance at this date. After the third course of remdesivir on day 92 and the third CP infusion on day 95, the D796H + H69/V70 strain increased. The researchers consider this to be the effect of positive selection pressure renewed by the third unit of CP.

The patient died on day 102 due to multi-organ failure. The study data suggest caution while using CP with immune suppression of both T cell and B cell arms. Antibodies have little support from cytotoxic T cells, thereby reducing chances of clearance and raising the potential for escape mutation.

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