Zika virus genomes from Brazil The Zika virus outbreak is a major cause for concern in Brazil, where it has been linked with increased reports of otherwise rare birth defects and neuropathology. In a phylogenetic analysis, Faria et al. infer a single introduction of Zika to the Americas and estimated the introduction date to be about May to December 2013—some 12 months earlier than the virus was reported. This timing correlates with major events in the Brazilian cultural calendar associated with increased traveler numbers from areas where Zika virus has been circulating. A correlation was also observed between incidences of microcephaly and week 17 of pregnancy. Science , this issue p. 345

Background Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015. Objectives To determine the etiology of three fatal adult cases. Study design Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination. Results The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13 days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV.

Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection.

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

transmission in Brazil was linked to a large outbreak of microcephaly but less is known about longer term anthropometric and neurological outcomes. We studied a cohort of infants born between October 31, 2015, and January 9, 2016, in a state maternity hospital, followed up for 101 ± 28 days by home visits. Microcephaly (< 2 standard deviations, Intergrowth standard) occurred in 62 of 412 (15%) births. Congenital Zika syndrome (CZS) was diagnosed in 29 patients. Among CZS patients, we observed a significant gain in anthropometric measures ( < 0.001) but no significant gain in percentile for these measures. The main neurological outcome was epilepsy, occurring in 48% of infants at a rate of 15.6 cases per 100 patient-months, frequently requiring multiple anti-seizure medications. The cumulative fatality rate was 7.4% (95% confidence interval: 2.1-23.4%). Health-care professionals should be alerted on the high risk of epilepsy and death associated with CZS in early infancy and the need to actively screen for seizures and initiate timely treatment.

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Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P &lt; 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

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