Clinical pearls and pitfalls of SARS-CoV-2 serology

All laboratory tests – thus including SARS-CoV-2 serology – must be thoughtfully used considering their costs, as well as their advantages and limitations, in order to ensure that precious human and economic resources are not wasted and that the clinical decision making will be not be biased by inappropriate usage or interpretation of diagnostic tests. SARS-CoV-2 serology cannot be used as a standalone test for diagnosing acute infections in symptomatic individuals, nor for purposes of contact tracing, whilst it can only complement other technologies for detecting viral RNA or viral antigens when these tests are repeatedly negative in highly suspected cases. Nonetheless, additional and perhaps more clinically relevant options have emerged for SARS-CoV-2 serology, i.e., complementing direct SARS-CoV-2 RNA and/or antigen testing, risk assessment of infection and clinical progression, serology-guided COVID-19 vaccination, convalescent plasma assessment and serosurveillance. Granted that – when appropriately used – SARS-CoV-2 serology provides important biological and clinical information (as summarized in Table 1), its clinical use is plagued by a number of drawbacks and pitfalls, which must be acknowledged to prevent misleading clinical interpretations, as discussed in this article.