Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review

Highlights • Positive serological test results have marked heterogeneity of sensitivity. • Diagnosis of coronavirus disease 2019 with either IgM+ or IgG+ has favourable diagnostic accuracy. • The sensitivity of antibody testing might be improved by testing 2 weeks after symptom onset. • IgA might be a surrogate providing better diagnostic accuracy compared with IgG or IgM.
Background The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. Methods A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG−); (2) IgG-positive but IgM-negative (IgG+IgM−); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/−); (5) IgG-positive without IgM information (IgG+IgM+/−); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). Results Sixty-eight studies were included. Pooled sensitivities for IgM+IgG−, IgG+IgM−, IgM+IgG+, IgM+IgG+/−, IgG+IgM+/−, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. Discussion These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.