Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

TLDR

COVID‑19 poses a major health threat, and current qPCR testing can yield false negatives, risking uncontrolled transmission. The study aims to chart the kinetics of SARS‑CoV‑2 antibodies and assess antibody testing as a diagnostic tool. Using ELISA against recombinant nucleocapsid protein, 208 plasma samples from 82 confirmed and 58 probable cases were analyzed for IgA, IgM, and IgG kinetics. IgM and IgA appeared around day 5, IgG around day 14, with positive rates of 85.4 %, 92.7 %, and 77.9 %; IgM detection outperformed qPCR after 5.5 days, and combining IgM ELISA with PCR raised overall detection to 98.6 % versus 51.9 % for qPCR alone.

Abstract

The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort.The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%).The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.