The mutational steps of SARS-CoV-2 to become like Omicron within seven months: the story of immune escape in an immunocompromised patient

Abstract

We studied a unique case of prolonged viral shedding in an immunocompromised patient that generated a series of SARS-CoV-2 immune escape mutations over a period of seven months. During the persisting SARS-CoV-2 infection seventeen non-synonymous mutations were observed, thirteen (13/17; 76.5%) of which occurred in the genomic region coding for spike. Fifteen (15/17; 88.2%) of these mutations have already been described in the context of variants of concern and include the prominent immune escape mutations S:E484K, S:D950N, S:P681H, S:N501Y, S:del(9), N:S235F and S:H655Y. Fifty percent of all mutations acquired by the investigated strain (11/22) are found in similar form in the Omicron variant of concern. The study shows the chronology of the evolution of intra-host mutations, which can be seen as the straight mutational response of the virus to specific antibodies and should therefore be given special attention in the rating of immune escape mutations of SARS-CoV-2.

A first-in-human clinical study of an intranasal spray of a cocktail containing two synergetic antibodies neutralizes Omicron BA.4/5

“…Synergetic neutralizing mechanism was found to largely rely on a unique complimentary addition of an RBM-targeted NAb (58G6) to a non-RBM NAb 55A8 to completely occlude ACE2 accessibility, with potential mutual inhibitions for the occurrence of escape mutations often seen with long-term application (41)(42)(43). This might greatly support the current lack of single NAb in face of Omicron and its sub variants that dramatically escape the majority of existing SARS-CoV-2 NAbs, and put the cocktail at the center stage for the development of clinically effective prophylactic regiments against the Omicron pandemic ( 44).…”