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However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1\/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, and after the Omicron BA.1\/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. We found that the Omicron BA.1\/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for &gt;\u200960% of all infections in both rural and urban sites. After the Omicron BA.1\/2 wave, we found few (&lt;\u20096%) remained na\u00efve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection\/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1\/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1\/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer na\u00efve to the virus.<\/jats:p>","DOI":"10.1038\/s41467-022-35652-0","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T12:03:08Z","timestamp":1673870588000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South 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Av.G. has received grant support from Sanofi Pasteur, Pfizer related to pneumococcal vaccine, C.D.C. and the Bill & Melinda Gates Foundation. N.W. reports grants from Sanofi Pasteur and the Bill & Melinda Gates Foundation. N.A.M. has received a grant to his institution from Pfizer to conduct research in patients with pneumonia and from Roche to collect specimens to assess a novel TB assay. J.M. has received grant support from Sanofi Pasteur. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"246"}}