We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection.

Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable.

Background Cross-neutralizing capacity of antibodies against SARS-CoV-2 variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. Methods Sera from SARS-CoV-2 convalescents at 2-, 6-, or 10-months post-recovery, and BNT162b2 vaccine recipients at 3- or 25-weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. Results Compared with early-convalescence, avidity indices of late-convalescent sera were significantly higher (median 37.7 (interquartile range 28.4–45.1) vs. 64.9 (57.5–71.5), p < 0.0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman’s r = 0.49 vs. 0.67 (wild-type); 0.18–0.52 vs. 0.48–0.83 (variants)). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (p < 0.001 (Alpha); p < 0.01 (Delta and Omicron)). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week-25. Conclusions Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the two building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

spinout. Quantum Molecular Diagnostics targets infectious diseases to develop and provide innovative diagnostics and is engaged in the codevelopment of the serological assay along with Mokobio Biotechnology R&D, USA. The other authors declare that there are no conflict of interests.

The prompt rollout of the coronavirus disease (COVID-19) messenger RNA (mRNA) vaccine facilitated population immunity, which shall become more dominant than natural infection-induced immunity. At the beginning of the vaccine era, the initial epitope profile in naive individuals will be the first step to build an optimal host defense system towards vaccine-based population immunity. In this study, the high-resolution linear epitope profiles between Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The vaccine-induced antibodies targeting RBD had broader distribution across the RBD than that induced by the natural infection. The relatively lower neutralizing antibody titers observed in vaccine-induced sera could attribute to less efficient epitope selection and maturation of the vaccine-induced humoral immunity compared to the infection-induced. Furthermore, additional mutation panel assays showed that the vaccine-induced rich epitope variety targeting the RBD may aid antibodies to escape rapid viral evolution, which could grant an advantage to the vaccine immunity.