Unmitigated spread in Brazil: Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from Sã o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response. Science , abh1558 and abh2644, this issue p. 821 and p. 815

The spread of SARS-CoV-2 in Brazil: Brazil has been hard-hit by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Candido et al. combined genomic and epidemiological analyses to investigate the impact of nonpharmaceutical interventions (NPIs) in the country. By setting up a network of genomic laboratories using harmonized protocols, the researchers found a 29% positive rate for SARS-CoV-2 among collected samples. More than 100 international introductions of SARS-CoV-2 into Brazil were identified, including three clades introduced from Europe that were already well established before the implementation of NPIs and travel bans. The virus spread from urban centers to the rest of the country, along with a 25% increase in the average distance traveled by air passengers before travel bans, despite an overall drop in short-haul travel. Unfortunately, the evidence confirms that current interventions remain insufficient to keep virus transmission under control in Brazil. Science , this issue p. 1255

Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-β (IFN-β) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-β response. The effect of acetate on RSV infection was abolished in Gpr43^−/− mice. Our findings reveal antiviral effects of acetate involving IFN-β in lung epithelial cells and engagement of GPR43 and IFNAR.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of “long COVID-19” syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell–derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike–NRP1 interaction. SARS-CoV-2–infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Oropouche virus is an arthropod-borne virus that has caused outbreaks of Oropouche fever in central and South America since the 1950s. This study investigates virological factors contributing to the re-emergence of Oropouche fever in Brazil between 2023 and 2024. In this observational epidemiological study, we combined multiple data sources for Oropouche virus infections in Brazil and conducted in-vitro and in-vivo characterisation. We collected serum samples obtained in Manaus City, Amazonas state, Brazil, from patients with acute febrile illnesses aged 18 years or older who tested negative for malaria and samples from people with previous Oropouche virus infection from Coari municipality, Amazonas state, Brazil. Basic clinical and demographic data were collected from the Brazilian Laboratory Environment Management System. We calculated the incidence of Oropouche fever cases with data from the Brazilian Ministry of Health and the 2022 Brazilian population census and conducted age-sex analyses. We used reverse transcription quantitative PCR to test for Oropouche virus RNA in samples and subsequently performed sequencing and phylogenetic analysis of viral isolates. We compared the phenotype of the 2023-24 epidemic isolate (AM0088) with the historical prototype strain BeAn19991 through assessment of titre, plaque number, and plaque size. We used a plaque reduction neutralisation test (PRNT₅₀) to assess the susceptibility of the novel isolate and BeAn19991 isolate to antibody neutralisation, both in serum samples from people previously infected with Oropouche virus and in blood collected from mice that were inoculated with either of the strains. 8639 (81·8%) of 10 557 laboratory-confirmed Oropouche fever cases from Jan 4, 2015, to Aug 10, 2024, occurred in 2024, which is 58·8 times the annual median of 147 cases (IQR 73-325). Oropouche virus infections were reported in all 27 federal units, with 8182 (77·5%) of 10 557 infections occurring in North Brazil. We detected Oropouche virus RNA in ten (11%) of 93 patients with acute febrile illness between Jan 1 and Feb 4, 2024, in Amazonas state. AM0088 had a significantly higher replication at 12 h and 24 h after infection in mammalian cells than the prototype strain. AM0088 had a more virulent phenotype than the prototype in mammalian cells, characterised by earlier plaque formation, between 27% and 65% increase in plaque number, and plaques between 2·4-times and 2·6-times larger. Furthermore, serum collected on May 2 and May 20, 2016, from individuals previously infected with Oropouche virus showed at least a 32-fold reduction in neutralising capacity (ie, median PRNT₅₀ titre of 640 [IQR 320-640] for BeAn19991 vs <20 [ie, below the limit of detection] for AM0088) against the reassortant strain compared with the prototype. These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to an improved understanding of the 2023-24 Oropouche virus re-emergence. Our exploratory in-vitro data suggest that the increased incidence might be related to a higher replication efficiency of a new Oropouche virus reassortant for which previous immunity shows lower neutralising capacity. São Paulo Research Foundation, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, and Brazilian National Council for Scientific and Technological Development. For the Portuguese translation of the abstract see Supplementary Materials section.