Evidence of a Sjogrens disease-like phenotype following COVID-19

ObjectivesSjogrens Disease (SjD) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth resulting from the secretory dysfunction of the exocrine glands. SARS-CoV-2 may trigger the development or progression of autoimmune diseases, as evidenced by increased autoantibodies in patients and the presentation of cardinal symptoms of SjD. The objective of the study was to determine whether SARS-CoV-2 induces the signature clinical symptoms of SjD. MethodsThe ACE2-transgenic mice were infected with SARS-CoV-2. SJD profiling was conducted. COVID-19 patients sera were examined for autoantibodies. Clinical evaluations of convalescent COVID-19 subjects, including minor salivary gland (MSG) biopsies, were collected. Lastly, monoclonal antibodies generated from single B cells of patients were interrogated for ACE2/spike inhibition and nuclear antigens. ResultsMice infected with the virus showed a decreased saliva flow rate, elevated antinuclear antibodies (ANAs) with anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. Sera of COVID-19 patients showed an increase in ANA, anti-SSA/Ro52, and anti-SSB/La. The male patients showed elevated levels of anti-SSA/Ro52 compared to female patients, and female patients had more diverse ANA patterns. Minor salivary gland biopsies of convalescent COVID-19 subjects showed focal lymphocytic infiltrates in four of six subjects, and 2 of 6 subjects had focus scores >2. Lastly, we found monoclonal antibodies produced in recovered patients can both block ACE2/spike interaction and recognize nuclear antigens. ConclusionOverall, our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD salivary glands were histologically indistinguishable from convalescent COVID-19 subjects. The results potentially implicate that SARS-CoV-2 could be an environmental trigger for SjD. Key MessagesWhat is already known about this subject? O_LISAR-CoV-2 has a tropism for the salivary glands. However, whether the virus can induce clinical phenotypes of Sjogrens disease is unknown. C_LI What does this study add? O_LIMice infected with SAR-CoV-2 showed loss of secretory function, elevated autoantibodies, and lymphocyte infiltration in glands. C_LIO_LICOVID-19 patients showed an increase in autoantibodies. Monoclonal antibodies produced in recovered patients can block ACE2/spike interaction and recognize nuclear antigens. C_LIO_LIMinor salivary gland biopsies of some convalescent subjects showed focal lymphocytic infiltrates with focus scores. C_LI How might this impact on clinical practice or future developments? O_LIOur data provide strong evidence for the role of SARS-CoV-2 in inducing Sjogrens disease-like phenotypes. C_LIO_LIOur work has implications for how patients will be diagnosed and treated effectively. C_LI