To investigate endogenous interference factors of the detection results of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM/IgG. Enzyme-linked immunosorbent assay (ELISA) was used to detect SARS-CoV-2 IgM/IgG in sera of 200 patients without COVID-19 infection, including rheumatoid factor (RF) positive group, antinuclear antibody (ANA) positive group, pregnant women group and normal senior group, with 50 in each group and 100 normal controls. The level of SARS-CoV-2 IgG in pregnant women was significantly higher than that in normal control group (P = 0.000), but there was no significant difference between other groups. The levels of SARS-CoV-2 IgM in pregnant women group, normal senior group, ANA positive group and RF positive group were significantly higher than that in normal control group (P<0.05), with significant higher false positive rates in these groups (P = 0.036, P = 0.004, P = 0.000, vs normal control group). Serum RF caused SARS-CoV-2 IgM false-positive in concentration dependent manner, especially when its concentration was higher than 110.25 IU/L, and urea dissociation test can turn the false positive to negative. ANA, normal seniors, pregnant women and RF can lead to false-positive reactivity of SARS-CoV-2 IgM and/or IgG detected using ELISA. These factors should be considered when SARS-CoV-2 IgM or IgG detection is positive, false positive samples caused by RF positive can be used for urea dissociation test.

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