Performance of SARS COV-2 IgG Anti-N as an Independent Marker of Exposure to SARS COV-2 in an Unvaccinated West African Population
Adam Abdullahi, James Opoku Frimpong, Mark T. K. Cheng, Sani H. Aliyu, Colette Smith, Alash’le Abimiku, Richard Odame Phillips, Michael Owusu, Ravindra K. Gupta
Abstract
Determination of previous SARS-COV-2 infection is hampered by the absence of a standardized test. The marker used to assess previous exposure is IgG antibody to the nucleocapsid (IgG anti-N), although it is known to wane quickly from peripheral blood. The accuracies of seven antibody tests (virus neutralization test, IgG anti-N, IgG anti-spike [anti-S], IgG anti-receptor binding domain [anti-RBD], IgG anti-N + anti-RBD, IgG anti-N + anti-S, and IgG anti-S + anti-RBD), either singly or in combination, were evaluated on 502 cryopreserved serum samples collected before the COVID-19 vaccination rollout in Kumasi, Ghana. The accuracy of each index test was measured using a composite reference standard based on a combination of neutralization test and IgG anti-N antibody tests. According to the composite reference, 262 participants were previously exposed; the most sensitive test was the virus neutralization test, with 95.4% sensitivity (95% CI: 93.6-97.3), followed by 79.0% for IgG anti-N + anti-S (95% CI: 76.3-83.3). The most specific tests were virus neutralization and IgG anti-N, both with 100% specificity. Viral neutralization and IgG anti-N + anti-S were the overall most accurate tests, with specificity/sensitivity of 100/95.2% and 79.0/92.1%, respectively. Our findings indicate that IgG anti-N alone is an inadequate marker of prior exposure to SARS COV-2 in this population. Virus neutralization assay appears to be the most accurate assay in discerning prior infection. A combination of IgG anti-N and IgG anti-S is also accurate and suited for assessment of SARS COV-2 exposure in low-resource settings.