Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

Background The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. Methods To evaluate seroconversion of NAAT-negative pneumonia patients, IgM and IgG targeting the spike protein of SARS-CoV-2 were semi-quantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. Results Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27d). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51d). Conclusion Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multi-tiered diagnostic algorithm for COVID-19. This article is protected by copyright. All rights reserved.