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New science explains South Africa's low rates of omicron severe disease SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1 https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v1 Institute of Infectious Disease and Molecular Medicine, University of Cape Town SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations These contribute to escape from the neutralizing antibody responses, reducing vaccine protection from infection We assessed the ability of T cells to react with Omicron spike In participants who were vaccinated with Ad26.CoV2.S (J and J) (n = 20) or BNT162b2 (Pfizer) (n = 15 or in unvaccinated convalescent COVID-19 patients (n = 15) SARS-CoV-2-specific T cells play a key role in modulating COVID-19 severity and provide protective immunity Results 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups The magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants These results demonstrate that, despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross- recognises the variant. Well-preserved T cell immunity to Omicron, is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa. Further explanation The limited effect of Omicron’s mutations on the T cell response suggests that vaccination or prior infection may still provide substantial protection from severe disease. Indeed, South Africa has reported a lower risk of hospitalisation and severe disease compared to the previous Delta wave Cross-reactive T cell responses acquired through vaccination or infection may contribute to these apparent milder outcomes for Omicron. The resilience of the T cell response demonstrated here also bodes well in the event that more highly mutated variants emerge in the future.

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