In December, 2019, an outbreak of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) occurred in Wuhan, China,1 and soon spread all over the world. Rapid and accurate diagnosis of SARS-CoV-2 infection is the cornerstone of all efforts to stem its advancement. Molecular detection via RT-PCR can result in falsely negative results due to the low viral loads in a sample. Serological methods are being developed and have proven to be a useful supplementary approach in confirming SARS-CoV-2 infection.2 The US Food and Drug Administration has issued numerous Emergency Use Authorisations, including serological tests; however, the potential for cross-reactivity with antibodies present in the sera of patients with other diseases remains largely unknown. Cross-reactivity of antibodies against SARS-CoV-2 with antibodies against other coronaviruses, such as SARS-CoV, has been shown.3 In addition, cross-reactivity has been observed from autoantibodies in serum samples from patients with autoimmune disease when testing for SARS-CoV,4 which shares high sequence identity with SARS-CoV-2. As such, we wanted to determine whether autoantibodies interfere with detection of SARS-CoV-2 antibodies.
We collected 290 serum samples from patients with autoimmune disease in our serum library, consisting of 98 patients with rheumatoid arthritis, 100 patients with systemic lupus erythematosus, and 92 patients with Sjogren's syndrome. The samples were collected from Jan 1, 2016, to June 30, 2019, which predates the COVID-19 pandemic. Written informed consent was obtained from all patients. The serological test for SARS-CoV-2 IgM and IgG monoclonal antibodies was done with colloidal gold-labelled kits supplied by Innovita Biotechnology Co, Tangshan, China. The nitrocellulose filter of these colloidal gold-labelled assays are coated with two antigens of SARS-CoV-2 (N protein and S protein). The overall testing sensitivity was 89% (352/397) and specificity was 91% (116/128).
Our results showed that both IgG and IgM antibodies against SARS-CoV-2 were not detected in the serum of patients with autoimmune disease, indicating that there was no cross-reactivity between autoantibodies and SARS-CoV-2 antibodies (table ). It should be noted, however, that these sera were only analysed using one kit and other kits with different test operating characteristics might produce different results.
Table.
Clinical characteristics and auto-antibody profile of patients
| Rheumatoid arthritis (n=98) | SLE (n=100) | Sjogren's syndrome (n=92) | |
|---|---|---|---|
| Men | 17 (17%) | 10 (10%) | 8 (9%) |
| Women | 81 (83%) | 90 (90%) | 84 (91%) |
| Age, years | 52·3 (13·4) | 40·1 (15·2) | 42·6 (12·4) |
| Anti-nuclear antibody positive | 35 (36%) | 100 (100%) | 92 (100%) |
| Anti-dsDNA positive | 0 | 63 (63%) | 11 (12%) |
| Anti-Smith antibody positive | 0 | 22 (22%) | 2 (2%) |
| Anti-Sjogren's syndrome antigen positive | 3 (3%) | 48 (48%) | 58 (63%) |
| Anti-SSB positive | 0 | 8 (8%) | 26 (28%) |
| Anti-U1RNP positive | 0 | 34 (34%) | 7 (8%) |
| Anti-Rib-P positive | 0 | 14 (14%) | 4 (4%) |
| Anti-phospholipid antibodies | 0 | 23 (23%) | 3 (3·3%) |
| Rheumatoid factor | 47 (48%) | 14 (14%) | 21 (23%) |
| Anti-CCP | 51 (52%) | 3 (3%) | 1 (1%) |
Data are n (%) or mean (SD). SLE=systemic lupus erythematosus. dsDNA=double-stranded DNA. SSB= Sjogren's B. U1RNP=U1 ribonucleoprotein. Rib-P=ribosome P protein. CCP=cyclic citrullinated peptide.
In conclusion, the serological test we assessed showed no cross-reactivity with autoantibodies present in patients with autoimmune disease. Asymptomatic carriers could spread SARS-CoV-2,5 and this type of test could make large scale screening of asymptomatic SARS-CoV-2 carriers possible. We propose that serological testing of IgM and IgG antibodies, along with RT-PCR, in clinical practice should help provide an accurate COVID-19 diagnosis, including in patients with autoimmune disease.
Acknowledgments
We declare no competing interests. We appreciate all the participants and students who took part in this study. This research was not funded. Patients consent for publication was not required. Ethics approval was provided by Institutional Research Ethics Committee of Ruijin Hospital (number 2016-62), Shanghai, China. No additional data are available.
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