Are commercial antibody assays substantially underestimating SARS-CoV-2 ever infection? An analysis on a population-based sample in a high exposure setting

Nasrallah, G. K.; Dargham, S. R.; Shurrab, F.; Al-Sadeq, D. W.; Al-Jighefee, H.; Chemaitelly, H.; Al Kanaani, Z.; Al Khal, A.; Al Kuwari, E.; Coyle, P.; Jeremijenko, A.; Kaleeckal, A. H.; Latif, A. N.; Shaik, R. M.; Abdul Rahim, H. F.; Yassine, H. M.; Al Kuwari, M. G.; Qotba, H.; Al Romaihi, H. E.; Tang, P.; Bertollini, R.; Al-Thani, M. H.; Althani, A. A.; Abu-Raddad, L. J.

Background: Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 ever (past or current) infection in a population-based sample in a high exposure setting. Methods: PCR and serological testing was performed on 394 individuals. Results: SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1%-47.8%), 40.6% (95% CI 35.9%-45.5%), and 42.4% (95% CI 37.6%-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2%-95.7%, 89.3%-92.8%, and 93.8%-97.8%, respectively; Cohen kappa statistic ranged from 0.86-0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6%-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9%-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9%-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. Conclusions: All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.