Serological testing reveals the hidden COVID-19 burden among healthcare workers experiencing a SARS-CoV-2 nosocomial outbreak

Abstract

We describe the results of testing healthcare workers from a tertiary care hospital in Japan, which had experienced a COVID-19 outbreak during the first peak of the pandemic, for SARS-CoV-2 specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing unveiled that a surprising 42.2% (27/64) of overlooked COVID-19 diagnoses had occurred when case detection had relied solely on SARS-CoV-2 nucleic acid amplification testing. This undetected portion of the COVID-19 iceberg beneath the surface may potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures, i.e. non-invasive ventilation, having had conveyed the highest transmission risks and served as the origin of outbreak. Our observations are supportive of a multi-tiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum.

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

“…Study groups also differed in age, yet multivariable analysis revealed no confounding impact of said age differences between study cohorts on avidity results, a finding supported by a previous study from our group that showed no difference in avidity maturation across age (33). We consider higher avidity in vaccinated individuals likely to reflect a possible benefit of repeated exposure to the antigen (28,34,35); a perception also in line with our finding that vaccination was shown to be a predictor of avidity maturation toward the new variant, independent of antibody titer.…”

Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response

“…We previously carried out a SARS-CoV-2 seroprevalence survey targeting healthcare workers (HCWs) from a tertiary care hospital in Japan. This revealed a nosocomial cluster infection accumulating to a 15.5% overall seroprevalence among the personnel (5,6). Through longitudinal follow-up and further serological description of the cohort of HCWs (7), we took advantage of the opportunity to investigate a uniformly conditioned population endowed with the combined response of infection-and vaccine-induced immunity: those infected through a nosocomial cluster infection, and later administered the BNT162b2 vaccine through the nation's mass vaccination campaign following similar intervals after the infection.…”

“…The participants in this study were HCWs at the St. Marianna University, Yokohama Seibu Hospital, Kanagawa, Japan, where we previously conducted an anti-SARS-CoV-2 seroprevalence survey in June 2020 (5). In the previous study, 64 COVID-19-affected HCWs and 350 non-infected individuals were identified following an outbreak having occurred in the hospital during April-May 2020.…”

“…To the contrary, increasing age has been associated with stronger antibody responses in convalescent plasma donors (12,13). This can be explained by the fact that older individuals are more prone to symptomatic, and possibly more severe, SARS-CoV-2 infection, which in turn is often accompanied by a potentiated circulating IgG response (5). Our study, analyzing the combined effect of infection-and vaccine-induced antibody responses in the 'prior infection' group, has also demonstrated an accentuation of difference in the antibody titer with increasing age.…”