SARS-CoV-2 evolves increased infection elicited cell death and fusion in an immunosuppressed individual
Lustig, G.; Ganga, Y.; Rodel, H.; Tegally, H.; Jackson, L.; Cele, S.; Khan, K.; Jule, Z.; Reedoy, K.; Karim, F.; Bernstein, M.; Moosa, M.-Y.; Archary, D.; de Oliveira, T.; Lessells, R.; Abdool Karim, S.; Sigal, A.
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The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS-CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction of cell fusion and cell death in SARS-CoV-2 evolved from ancestral virus during long-term infection. Both cell fusion and death were reduced in Omicron BA.1 infection relative to ancestral virus. Evolved virus was isolated at different times during a 6-month infection in an immunosuppressed individual with advanced HIV disease. The virus isolated 16 days post-reported symptom onset induced fusogenicity and cell death at levels similar to BA.1. However, fusogenicity was increased in virus isolated at 6 months post-symptoms to levels intermediate between BA.1 and ancestral SARS-CoV-2. Similarly, infected cell death showed a graded increase from earlier to later isolates. These results may indicate that, at least by the cellular measures used here, evolution in long-term infection does not necessarily attenuate the virus.
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