Serological assay for anti-SARS-CoV-2 antibodies improves sensitivity of diagnosis of COVID-19 patients

Abstract

The emergence of SARS-CoV-2, responsible for coronavirus disease-2019 (COVID-19), has become a major global health problem. The molecular testing is the accepted assay in SARS-CoV-2 detection. However, there are several reasons for low sensitivity by RNA detection, causing challenges in SARS-CoV-2 diagnosis. In this study, we aimed to investigate serological patterns of SARS-CoV-2 specific IgM, and IgG in 111 hospitalized, and 34 recovered COVID-19 patients and 311 prepandemic normal serum specimens by ELISA. The validity of the ELISA kits was evaluated using samples from normal and recovered cases. This showed that 98.1%, and 98.4% of prepandemic normal samples were negative for anti-SARS-CoV-2 IgM, and IgG, respectively. Assessment of 34 COVID-19 confirmed recovered patients showed a test sensitivity of 76.5%, and 94.1% for IgM, and IgG, respectively. In COVID-19 hospitalized patients, 42.3%, and 51.4% were positive for IgM and IgG, respectively. Viral RNA was not detectable in 43.3% of the hospitalized patients. Interestingly, combined molecular and serological testing improved the sensitivity of COVID-19 diagnosis to 79.6%. Using PCR with combined IgM/IgG results augmented the patient diagnosis sensitivity to 65.3% and 87.2% in ≤ 7 days, and > 7 days intervals, respectively. Overall, serological tests in combination with PCR can improve the sensitivity of COVID-19 diagnosis.

Keywords: Antibody; COVID-19; Diagnosis; ELISA; PCR; SARS-CoV-2; Serology.

Fig. 1

Levels of SARS-CoV-2 specific IgM, and IgG antibodies in different intervals after symptoms onset in hospitalized COVID-19 patients. The scatter dot plots indicate cut-off values of IgM and IgG specific to SARS-CoV-2 of each sample. The sampling time was subdivided into two periods encompassing ≤ 7 days, and > 7 days (8–18 days) after the onset of symptoms, then, the seropositivity rate for each of IgM, and IgG antibodies was analyzed in defined intervals. The horizontal line defines cut-off value to separate IgM and IgG positive and negative samples

Fig. 2

Comparison of SARS-CoV-2 specific IgM, and IgG antibodies in hospitalized and recovered COVID-19 patients. Cut off values were calculated as sample ODs divided by cut-off index as instructed by the manufacturer. Means of cut-off value in each group for IgM and IgG specific to SARS-CoV-2 have been shown in the graph