Concise guide to coronavirus disease 2019 (COVID-19) diagnostics

Several months after its emergence, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still prepotently disrupting health, societies and economies worldwide. The current approach for diagnosing SARS-CoV-2 remains based on identification of viral RNA by means of molecular biology techniques in upper or lower respiratory tracts specimens. Nevertheless, the development of immune response against the virus may also provide valuable diagnostic information. The paradigmatic kinetics of anti-SARS-CoV-2 antibodies in patients with COVID-19 would allow to conclude that serological testing shall not replace viral RNA detection in diagnosing acute SARS-CoV-2 infection, but may instead remain an essential tool for identifying patients who have been infected and have developed an immune response, as well as for monitoring the progress of herd immunity. For this purpose, the choice of the antigens used for constructing the immunoassays appears critical, as these shall use epitopes towards which neutralizing antibodies could be generated. Other important aspects in serological testing encompass the absence of cross-reactivity with other coronaviruses, the ability to distinguish the antibody class (i.e. IgG, IgA and/or IgM), quantitative assessment, wide range of linearity and low imprecision at diagnostic thresholds. A finalaspect, almost essential for both clinical and public health purposes, is the evidence of analytical and clinical validation before each method enters clinical practice.