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

Since the 1970s, introduction of serological assays targeting virus-specific antibodies and antigens has been effective in identifying blood donations infected with the classic transfusion-transmitted infectious (TTI) agents (HBV, HIV, HTLV-I/II, HCV). Subsequently, progressive implementation of nucleic acid-amplification technology (NAT) screening for HIV, HCV, and HBV has reduced the residual risk of infectious window period donations, such that per unit risks are <1 in 1,000,000 in the US, other high-income countries, and in high incidence regions performing NAT. NAT screening has emerged as the preferred option for detection of newer TTI agents including West Nile virus, Zika virus, and Babesia microti. While there is continual need to monitor current risks due to established TTI, ongoing challenges in blood safety relate primarily to surveillance for emerging agents coupled with development of rapid response mechanisms when such agents are identified. Recent progress in development and implementation of pathogen reduction technologies (PRT) provide the opportunity for proactive rather than reactive response to blood safety threats. Risk-based decision-making tools and cost-effectiveness models have proved useful to quantify infectious risks and place new interventions in context. However, as evidenced by the 2015-2017 Zika virus pandemic, a level of tolerable risk has yet to be defined in such a way that conflicting factors (e.g. theoretical recipient risk, blood availability, cost, and commercial interests) can be reconciled. A unified approach to TTIs is needed, whereby novel tests and PRT replace rather than add to existing interventions, thereby ameliorating cost and logistical burden to blood centers and hospitals.

The dynamics of the early stages of West Nile virus (WNV) infection can be assessed by follow-up studies of viremic blood donors. A total of 245 donors with WNV viremia were followed up weekly for 4 weeks and then monthly for up to 6 additional months or until seroconversion. Plasma samples were tested for WNV RNA by transcription-mediated amplification (TMA) and for WNV-specific IgM and IgG antibodies. RNA persistence was investigated by 6 replicate TMA tests; samples that were viremic for >40 days were tested for WNV-neutralizing activity. Follow up of 35 additional viremic donors for up to 404 days was conducted to evaluate persistence of WNV-specific antibody. The median time from RNA detection to IgM seroconversion was 3.9 days; to IgG seroconversion, 7.7 days; to RNA negativity by single-replicate TMA, 13.2 days; and to RNA negativity by 6-replicate TMA, 6.1 additional days after results of single-replicate TMA are negative. For 4 donors in whom RNA persisted for >40 days after the index donation, all samples obtained after this threshold were also positive for WNV IgG and neutralizing activity. The mean times to IgM and IgA negativity were 156 and 220 days, respectively. IgM and IgG develop rapidly after viremia and before RNA levels become undetectable, which occurred a mean of 13.2 days after the index donation among donors in this study. WNV RNA detection by replicate TMA rarely persists for >40 days after the index donation and is accompanied by WNV-specific neutralizing antibody, consistent with an absence of WNV transmission via transfusion of seropositive blood components.

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.

Antibody detection of prior SARS-CoV-2 infection depends on severity, assay, and timing with implications for serosurveillance.