Comparative epidemic expansion of SARS-CoV-2 variants Delta and Omicron in Amazonas, a Brazilian setting with high levels of hybrid immunity

The SARS-CoV-2 variants of concern (VOCs) Delta and Omicron spread globally during mid and late 2021, respectively, with variable impact according to the immune population landscape. In this study, we compare the dissemination dynamics of these VOCs in the Amazonas state, one of Brazil’s most heavily affected regions. We sequenced the virus genome from 4,128 patients collected in Amazonas between July 1st, 2021 and January 31st, 2022 and investigated the lineage replacement dynamics using a phylodynamic approach. The VOCs Delta and Omicron displayed similar patterns of phylogeographic spread but significantly different epidemic dynamics. The Delta and Omicron epidemics were fueled by multiple introduction events, followed by the successful establishment of a few local transmission lineages of considerable size that mainly arose in the Capital, Manaus. The VOC Omicron spread and became dominant much faster than the VOC Delta. We estimate that under the same epidemiological conditions, the average Re of Omicron was ∼3.3 times higher than that of Delta and the average Re of the Delta was ∼1.3 times higher than that of Gamma. Furthermore, the gradual replacement of Gamma by Delta occurred without an upsurge of COVID-19 cases, while the rise of Omicron fueled a sharp increase in SARS-CoV-2 infection. The Omicron wave displayed a shorter duration and a clear decoupling between the number of SARS-CoV-2 cases and deaths compared with previous (B.1.* and Gamma) waves in the Amazonas state. These findings suggest that the high level of hybrid immunity (infection plus vaccination) acquired by the Amazonian population by mid-2021 was able to limit the spread of the VOC Delta and was also probably crucial to curb the number of severe cases, although not the number of VOC Omicron new infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Financial Support was provided by FAPEAM (PCTI EmergeSaude/AM call 005/2020; Rede Genomica de Vigilancia em Saude REGESAM); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (grant 403276/2020 9); Inova Fiocruz/Fundacao Oswaldo Cruz (GrantVPPCB 007 FIO 18 2 30 - Geracao de conhecimento); Centers for Disease Control and Prevention (CDC Grant Award 002174); Departamento de Ciencia e Tecnologia (DECIT) of the Brazilian MoH; PAHO, Brazilian office and AIDS Healthcare Foundation (AHF Global Public Health institute). F.G.N., G.L.W., G.B., and M.M.S. are supported by the CNPq through their productivity research fellowships (306146/2017 7, 303902/2019 1, 304883/2020 4 and 313403/2018 0, respectively). G.B. is also funded by FAPERJ (Grant number E 26/202.896/2018). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Committee of Amazonas State University (no. 25430719.6.0000.5016) waived ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All the SARS-CoV-2 genomes generated and analyzed in this study are available at the EpiCoV database in GISAID () and could be assesed at the following EPI_SET ID: .