Abstract

ABSTRACTWe describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might 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., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum.IMPORTANCE 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. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.

Highlights

  • We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion

  • Antibody seroconversion reveals the true burden of the nosocomial outbreak, which is underestimated by symptom-driven nucleic acid amplification testing (NAAT) screening

  • Thirty-seven (20% of those tested by NAAT and 8.9% of the entire health care workers (HCWs) cohort) tested positive for SARS-CoV-2

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Summary

Introduction

We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Infections free of symptoms (i.e., presymptomatic or asymptomatic infections) and left untested were hypothesized to constitute a major burden and to contribute to transmission [2] In support of this hypothesis, reports from later active screening studies revealed a significant majority of SARS-CoV-2 infections to manifest atypical nonrespiratory presentations or even at times to remain asymptomatic [3]. Such minimally symptomatic individuals, never to be suspected of having COVID-19, lack the opportunity to undergo SARS-CoV-2 nucleic acid amplification testing (NAAT) and, together with those with false-negative NAAT results, continue to carry the risk of becoming a source of transmission. NAAT alone is prone to overlooking the hidden burden, and multitiered testing with the use of various diagnostic modalities should aid in exhaustive case detection along the whole spectrum

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