SARS-CoV-2 serological cross-reactivity with autoantibodies – Authors' reply
Authors: Jialin Teng, Jin Dai
Journal: The Lancet Rheumatology (2020)

We thank Kay Weng Choy for the interest in our work and we agree that the results of the chemical assays should consider endogenous compounds. However, performance analysis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assay that we used in our experiment showed that icterus and lipaemia were minimally affected, but false positive results can occur as a result of severe haemolysis.1Garnett E Jung J Tam E et al.Clinical validation and performance evaluation of the automated vitros total anti-SARS-CoV-2 antibodies assay for screening of serostatus in COVID-19.Am J Clin Pathol. 2020; (published online Aug 31 2020.)https://doi.org/10.1093/ajcp/aqaa157Crossref PubMed Scopus (13) Google Scholar However, there was no positive result in our test; therefore, there was no haemolysis in our specimens. Antibodies are known to remain stable in frozen storage over time,2Argentieri MC Pilla D Vanzati A et al.Antibodies are forever: a study using 12–26-year-old expired antibodies.Histopathology. 2013; 63: 869-876Crossref PubMed Scopus (19) Google Scholar and our specimens were stored at –80°C. Autoimmune diseases are immune disorders with overproduction of autoantibodies. Autoimmune disease with hypogammaglobulinaemia is very rare; between 1982 and 2006, detailed descriptions of patients with systemic lupus erythematosus who have hypogammaglobulinaemia only appeared in ten articles in the English literature and only 16 cases were reported.3Fernandez-Castro M Mellor-Pita S Citores MJ et al.Common variable immunodeficiency in systemic lupus erythematosus.Semin Arthritis Rheum. 2007; 36: 238-245Crossref PubMed Scopus (54) Google Scholar Some patients will develop drug-related hypogammaglobulinaemia during treatment, but our serum samples were taken from patients with new onset disease who had not received prior treatment, and no patient had hypogammaglobulinaemia. To ensure this, these patients were routinely examined (eg, for antibodies, immunoglobulins, etc) and results were recorded on our database. Although the SARS-CoV-2 test is not specific, a specificity of 91% still has a high positive predictive value, and we did not identify any false positive findings in the investigated population, which is as expected due to the absence of COVID-19 infection in patients when the samples were taken. We acknowledge and share the concerns about the negative predictive value due to the assay sensitivity of 89% but we believe the test is still a viable option for large-scale screening in an asymptomatic population. Indeed, specificity and sensitivity must be accurately identified in a low-prevalence setting.4Farnsworth CW Anderson NW SARS-CoV-2 serology: much hype, little data.Clin Chem. 2020; 66: 875-877Crossref PubMed Scopus (81) Google Scholar Nevertheless, the purpose of our analysis was not to show that this serological test for COVID-19 should be used alone to diagnose patients. We wanted to show that there is no cross-reactivity with autoantibodies from autoimmune disease, and we believe that with the further clarifications described here we can still conclude that this absence of cross-reactivity is likely to be the case. We declare no competing interests. SARS-CoV-2 serological cross-reactivity with autoantibodiesIn their report on the detection of IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with autoimmune diseases, Teng and colleagues1 found that the serological test that they assessed showed no cross-reactivity with autoantibodies present in patients with autoimmune disease. However, several potential confounding factors should be considered when assessing the study findings. Hypogammaglobulinaemia (reduced serum immunoglobulin concentrations) might result in false negative antibody test results; therefore, quantitative serum immunoglobulin measurements should be used to interpret SARS-CoV-2 serology results, along with knowledge of any patient history of immunodeficiencies. Full-Text PDF Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseasesIn 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. Full-Text PDF