SARS-Cov-2 enters the body to cause an immune response, with IgM antibody appearing first, and then IgG antibody. After the appearance of IgG antibody, the concentration will continue to increase, and the IgM antibody will continue to decrease until it disappears. IgG antibody will exist for a long time. By monitoring the dynamic changes of IgM and IgG antibody, it is helpful to diagnose the SARS-Cov-2 infection and judge the infection status. IgM antibody is produced by the body's initial immune response, with fast production speed and short duration, as indicator of early infection; IgG antibody is produced later than IgM and has a long duration, and can be used as indicator of infection and previous infection.
Studies have shown that after SARS-Cov-2 infects the body, antibodies can be detected usually in 5 to 10 days[2]. Guo L et[3] research showed SARS-Cov-2 specific IgM antibodies were detected at 5 days (interquartile range [IQR], 3 to 6 days) after onset, while IgG antibodies appeared at 14 days (IQR, 10–18 days). Zhao J et [4] found over 90% of patients were seropositive for IgG antibodies after day 14 of illness. Our study showed that IgM antibody was persistent positive for 18 days, while IgG antibody and SARS-Cov-2 nucleic acid continue to be negative, so IgM antibody was judged to be false positive.
Currently, specific antibody (IgM, IgG) detection tests mainly include colloidal gold method (lateral flow immunoassays, LFIA), enzyme-linked immunosorbent assays (ELISAs), chemiluminescence immunoassays, etc[5]. Some studies have reported false positives of SARS-Cov-2 antibodies[6, 7]. The reasons are related to the following: different test kits used by various testing institutions, different settings of the positive cut-off value of the test kits, different testing instruments, differences in the level of operators, and patients situation and so on[8].
The colloidal gold method is a rapid diagnostic test based on the principle of using colloidal gold as a tracer for immunoassay. The operation of the colloidal gold method is simple, and the qualitative analysis of IgM and IgG antibodies can be performed without additional equipment[9], moreover the positive or negative result can be judged by visual observation without the positive cut-off value. However, SARS-Cov-2 antibody test may have false positive results due to the presence of some interfering substances in clinical samples. Interfering substances include endogenous substances and exogenous substances. Endogenous substances include: rheumatoid factor, heterophile antibodies, complement, anti-mouse Ig antibodies induced by the use of murine antibodies for treatment or diagnosis, and lysozyme, etc[6, 8, 10]. Exogenous substances include: specimen hemolysis, specimen storage time is too long, etc[8]. Yadouleton A et al.[11] used ELISAs to test COVID-19 cases(n = 8) and fever of unknown origin cases (as prepandemic controls, n = 60). They found < 25% false-positive results likely due to unspecific immune responses elicited by acute malaria. The higher proportion of SARS-CoV-2 false-positive in acute malaria patients compared with likely subacute or chronic malaria patients. In our case, we also considered that malaria caused a non-specific immune response leading to false positive for SARS-CoV-2 IgM antibody.