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

Virus genomes reveal the establishment of Zika virus in Brazil and the Americas, and provide an appropriate timeframe for baseline (pre-Zika) microcephaly in different regions. Three papers in this issue present a wealth of new Zika virus (ZIKV) genome sequences and further insights into the genetic epidemiology of ZIKV. Nathan Grubaugh et al. provide 39 new ZIKV genome sequences from infected patients and Aedes aegypti mosquitoes in Florida. Phylogenetic analysis suggests that the virus has been introduced on multiple separate occasions, probably linked to travel from the Caribbean. They find a low probability of long-term persistence of ZIKV transmission chains within Florida, suggesting that the potential for future ZIKV outbreaks there will depend on transmission dynamics in the Americas. Nuno Faria et al. and Hayden Metsky et al. reconstruct the spread of ZIKV in Brazil and the Americas. Faria et al. provide 54 new ZIKV genomes, several sequenced in real time in a mobile genomics laboratory. They trace the spatial origins and spread of ZIKV in Brazil and the Americas and date the timing of the international spread of ZIKV from Brazil. They find that northeast Brazil had a crucial role in the establishment of the epidemic and the spread of the virus within Brazil and the Americas. Metsky et al. generate 110 ZIKV genomes from clinical and mosquito samples from ten regions. They also see rapid expansion of the epidemic within Brazil and multiple introductions to other geographic areas. In agreement with Faria et al., they find that ZIKV circulated unobserved for many months before transmission was detected. Metsky et al. additionally describe ZIKV evolution and discuss how the accumulation of mutations might affect the performance of diagnostic tests in the future. Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil1. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 20162) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 20162). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease3. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

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

Attack rate in Manaus: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence peaked in Manaus, Brazil, in May 2020 with a devastating toll on the city's inhabitants, leaving its health services shattered and cemeteries overwhelmed. Buss et al. collected data from blood donors from Manaus and São Paulo, noted when transmission began to fall, and estimated the final attack rates in October 2020 (see the Perspective by Sridhar and Gurdasani). Heterogeneities in immune protection, population structure, poverty, modes of public transport, and uneven adoption of nonpharmaceutical interventions mean that despite a high attack rate, herd immunity may not have been achieved. This unfortunate city has become a sentinel for how natural population immunity could influence future transmission. Events in Manaus reveal what tragedy and harm to society can unfold if this virus is left to run its course. Science , this issue p. 288 ; see also p. 230

Arbovirus risk in Brazil: Despite the existence of an effective vaccine for yellow fever, there are still almost 80,000 fatalities from this infection each year. Since 2016, there has been a resurgence of cases in Africa and South America—and this at a time when the vaccine is in short supply. The worry is that yellow fever will spread from the forests to the cities, because its vector, Aedes spp. mosquitoes, are globally ubiquitous. Faria et al. integrate genomic, epidemiological, and case distribution data from Brazil to estimate patterns of geographic spread, the risks of virus exposure, and the contributions of rural versus urban transmission (see the Perspective by Barrett). Currently, the yellow fever epidemic in Brazil seems to be driven by infections acquired while visiting forested areas and indicates spillover from susceptible wild primates. Science , this issue p. 894 ; see also p. 847