Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination.

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

Evolving viral and serological stages of Zika virus RNA-positive blood donors and estimation of incidence of infection during the 2016 Puerto Rican Zika epidemic: an observational cohort study.

BACKGROUND: Puerto Rico began screening blood donations for Zika virus RNA with nucleic acid amplification tests (NAATs) on April 3, 2016, because of an emerging Zika virus outbreak. We followed up positive donors to assess the dynamics of viral and serological markers during the early stages of Zika virus infection and update the estimate of infection incidence in the Puerto Rican population during the outbreak. METHODS: Blood donations from volunteer donors in Puerto Rico were screened for the presence of Zika virus RNA using the cobas Zika NAAT. Positive donations were further tested to confirm infection, estimate viral load, and identify Zika virus-specific IgM antibodies. Individuals with positive blood donations were invited to attend follow-up visits. Donations with confirmed infection (defined as detection of Zika virus RNA or IgM on additional testing of index or follow-up samples) were assessed for stage of infection according to Zika virus RNA detectability in simulated minipools, viral load, and Zika virus IgM status. A three-step process was used to estimate the mean duration of NAAT reactivity of Zika virus in human plasma from individuals identified pre-seroconversion with at least one follow up visit and to update the 2016 incidence estimate of Zika virus infection. FINDINGS: Between April 3 and Dec 31, 2016, 53 112 blood donations were screened for Zika virus, of which 351 tested positive, 339 had confirmed infections, and 319 could be staged. Compared with IgM-positive index donations (n=110), IgM-negative index donations (n=209) had higher mean viral loads (1·1 × 106vs 8·3 × 104 international units per mL) and were more likely to be detected in simulated minipools (93% [n=194] vs 26% [n=29]). The proportions of donations with confirmed infections that had viral RNA detected only in individual-donation NAATs (ie, not in simulated minipools) and were IgM positive increased as the epidemic evolved. The estimated mean duration of NAAT detectability in the 140 donors included in the follow-up study was 11·70 days (95% CI 10·06-14·36). Applying this detection period to the observed proportion of donations that were confirmed NAAT positive yielded a Zika virus seasonal incidence estimate of 21·1% (95% CI 18·1-24·1); 768 101 infections in a population of 3 638 773 in 2016. INTERPRETATION: Characterisation of early Zika virus infection has implications for blood safety because infectivity of blood donations and utility of screening methods likely correlate with viral load and serological stage of infection. Our findings also have implications for diagnostic testing, public health surveillance, and epidemiology, and we estimate that around 21% of the Puerto Rican population was infected during the 2016 outbreak. FUNDING: Biomedical Advanced Research and Development Authority, National Heart, Lung, and Blood Institute.

High Incidence of Chikungunya Virus and Frequency of Viremic Blood Donations during Epidemic, Puerto Rico, USA, 2014.

Chikungunya virus (CHIKV) caused large epidemics throughout the Caribbean in 2014. We conducted nucleic acid amplification testing (NAAT) for CHIKV RNA (n = 29,695) and serologic testing for IgG against CHIKV (n = 1,232) in archived blood donor samples collected during and after an epidemic in Puerto Rico in 2014. NAAT yields peaked in October with 2.1% of donations positive for CHIKV RNA. A total of 14% of NAAT-reactive donations posed a high risk for virus transmission by transfusion because of high virus RNA copy numbers (10 (4) -10 (9) RNA copies/mL) and a lack of specific IgM and IgG responses. Testing of minipools of 16 donations would not have detected 62.5% of RNA-positive donations detectable by individual donor testing, including individual donations without IgM and IgG. Serosurveys before and after the epidemic demonstrated that nearly 25% of blood donors in Puerto Rico acquired CHIKV infections and seroconverted during the epidemic.