The general population of RJ state had poor vaccine coverage against influenza in the winter of 2021 (55.7% of adults vaccinated) [3]. In addition, there was a mismatch between influenza virus vaccine strains in 2021 and the influenza virus which circulated in October/November 2021. Furthermore, a decline in COVID-19 cases following an epidemic Delta variant surge and higher COVID-19 immunization rates [2] led to a SARS CoV-2 void in October/December 2021. During this void, an influenza epidemic occurred out-of-season in RJ state. A decline in mitigation measures might have contributed to the exacerbation of influenza cases in the spring/summer of 2021. Although there were appropriate conditions for influenza virus to circulate in the winter of 2021, minimal to no influenza virus circulated simultaneously to the Delta SARS CoV-2 epidemic surge. Similarly, when Omicron cases appeared in January 2022 leading to a COVID-19 pandemic surge, cases of influenza virus plummeted across the state [4]. Nevertheless, the influenza epidemic migrated south and continued in the south and in other southeast areas of Brazil during January 2022, until the Omicron variant of concern surged nationally. At that point the number of influenza cases declined precipitously across the country.

Early in the COVID-19 pandemic, reports described dramatic reductions in circulating influenza and RSV strains globally [9-11], with one report even considering the extinction of specific influenza viral lineages [12]. As the pandemic progressed, other respiratory viruses were shown to circulate off-season, frequently during a period of SARS CoV-2 decline, a phenomenon likely driven by changing weather patterns, other prevailing competing viruses in the ecosystem, and possibly limited use of mitigating measures such as masks and social distancing [13]. One such example is respiratory syncytial virus, which occurred off-season in the summer of 2021 in the United States, Japan, and Australia, also coinciding with a low COVID-19 case load [14-16]. In South Africa, a similar phenomenon was observed where influenza circulated off-season [17].

In our analysis, a void in the circulating prevailing pandemic, a mismatch between the circulating influenza strain and influenza vaccination, and climate changes fostering improved weather conditions for flu viral spread may be predictive of off-season influenza virus circulation. The concept of viral interference has been demonstrated at several levels, including cellular interactions, host-mediated immune responses, and the population level [18]. Initially in the COVID-19 pandemic, interventions mitigating viral spread likely prevented circulation of other viruses. Potentially a combination of reduced mitigating measures during the brief Rio COVID-19 void period, coupled to colder weather, favoring population clustering indoors played an important role in the out-of-season Rio flu outbreak.

In the specific case of influenza, when there are available vaccines for prevention and oral antiviral treatment to abort disease progression, year-round influenza vaccines and antiviral agents would help avoid unnecessary morbidity and mortality, given that antibodies rapidly wane and are not protective for an entire year. Furthermore, while we live through cycles of COVID-19 surges during the pandemic era, we should be prepared for off-season outbreaks of other respiratory viruses which can potentially prevail unexpectedly during periods of COVID-19 remission.