Lack of cross-reactivity between rheumatoid factor IgM and anti-S1 receptor binding domain of SARS-CoV-2 IgM: a case-control study

Objective. Since the onset of the COVID-19 outbreak, concern has been raised about reliability of SARS-CoV-2 serological tests in people with serum positivity for rheumatoid factor (RF), due to its ability to interfere during tests carried out with immunoassay tech-niques, leading to false positive results. The aim of this study was to analyse, on sera from RF seropositive rheumatoid arthritis (RA) patients, the interference between RF IgM and anti-S1 RBD IgM. Methods. The study was conducted on consecutive patients affected by RF seropositive RA and, as control group, COVID-19 patients with SARS-CoV-2 pneumonia hospitalised at Sapienza University of Rome from April 2020 and April 2021. Serum samples from COVID-19 patients during their hospi-talisation were collected, while RA sub-jects' samples were harvested prior to the onset of the COVID-19 pandemic. All samples were tested for RF IgM us-ing nephelometry and ELIA, and for anti-S1 RBD IgM by ELISA.Results. Forty RF seropositive RA and 42 COVID-19 patients were enrolled. In all RA patients, both nephelometric assay and ELIA showed RF IgM posi-tivity, while only one patient of the con-trol group tested positive for RF IgM by nephelometric assay and ELIA. IgM directed to S1 RBD were not de-tected in sera of RA patients, while all COVID-19 patients presented anti-S1 RBD IgM (median anti-S1 RBD IgM COVID-19 vs. RA: 368.5 IU/mL, IQR 654 IU/mL vs. 18.45 IU/mL, IQR 20 IU/ mL; p<0.0001).Conclusion. This study confirmed the lack of cross-reactivity between RF and anti-S1 RBD IgM, offering to clinicians a valuable tool for a better manage-ment of RA patients undergoing SARS-CoV-2 serological tests.