Two exponential COVID-19 epidemic waves heavily hit the Brazilian state of Amazonas in early 2020 and early 2021, driven by SARS-CoV-2 variants B.1 (mainly B.1.195 and B.1.1.28) and variant of concern (VOC) Gamma (P.1), respectively [1, 2]. The high prevalence of individuals with hybrid (natural or vaccine-induced) immunity in this Brazilian state [3-5] successfully limited the previous expansion of VOCs Gamma plus (P.1.) [6] and Delta (B.1.617.2/AY.) [7] that emerged and spread during the second half of 2021 in the Amazonas. Consequently, the virus circulated at a roughly steady-state level of ~50-500 SARS-CoV-2 positive cases per day (7-day rolling average) from early May to late December 2021 [8]. In January 2022, however, the mean daily number of SARS-CoV-2 positive cases in the Amazonas rapidly increased from ~90 to ~6,500, coinciding with the global spread of the immune escape VOC Omicron (B.1.1.529/BA.*) [9].To follow up the most recent evolution of the SARS-CoV-2 in the Amazonas, we sequenced the virus genome from 1,260 patients (707 female, median age 36, IQR 26-47 and 553 male, median age 37, IQR 28-51), collected between 1st December 2021 and 17th January 2022, representing 2.9% of all laboratory-confirmed SARS-CoV-2 cases in the state in that period (n = 43,288) (Fig. 1). The Amazonas state health surveillance foundation and Central Laboratory from the State of Amazonas (LACEN-AM) sent SARS-CoV-2 positive samples from 27 out of 62 municipalities for sequencing at FIOCRUZ Amazônia, part of the local health genomics network (REGESAM) and the consortium FIOCRUZ COVID-19 Genomics Surveillance Network of the Brazilian Ministry of Health [10]. Most samples were from the capital Manaus (n = 926, 74%), followed by the Metropolitan region (n = 163, 13%) and interior municipalities from Central (n = 139, 11%), South (n = 23, 2%) and Southwest (n = 9, 1%) Amazonas regions (Fig. 2).