Each bar is an individual healthy control or patient. nucleoprotein TMC353121 of SARS-CoV-2, and we compared them with respective titers in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). == Findings == Despite immune dysfunction and immunosuppressive treatment, JIA, JDM, and JSLE patients maintained comparable or stronger humoral responses than healthier peers, which was dominated by immunoglobulin G (IgG) antibodies to HCoV-OC43 spike, and harbored IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM, and JSLE patients, which argues TMC353121 against increased exposure. == Conclusions == Consequently, autoimmune rheumatic diseases and their treatment were associated with a favorable ratio of spike to nucleoprotein antibodies. == Funding == This work was supported by a Centre of Excellence Centre for Adolescent Rheumatology Versus Arthritis grant, 21593, UKRI funding reference MR/R013926/1, the Great Ormond Street Childrens Charity, Cure JM Foundation, Myositis UK, Lupus UK, and the NIHR Biomedical Research Centres at GOSH and UCLH. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust. Keywords:seasonal coronavirus, rheumatic diseases, SARS-CoV-2, antibody response, spike protein, nucleoprotein, immunosuppression == Graphical abstract == == Context and significance == Children and adolescents with rheumatic diseases are considered to be at risk of COVID-19. However, data on the ability of such patients to fight SARS-CoV-2 are lacking, as infections are rare due to shielding or undetected due to a lack of severe symptoms and limited mass testing. Instead, Deakin et al. studied how well such patients defended themselves against a common-cold coronavirus, TMC353121 HCoV-OC43, a relative of SARS-CoV-2 that frequently infects this age group. By studying children and adolescents with arthritis, dermatomyositis, or lupus before the COVID-19 pandemic, they found that these prevalent inflammatory rheumatic diseases did not impede the antibody response to a common-cold coronavirus, raising the possibility that the response to SARS-CoV-2 may also be unaffected. Deakin et al. examined the antibody response to the common-cold coronavirus HCoV-OC43 and cross-reactive response to SARS-CoV-2 in pre-COVID-19 pandemic sera from JIA, JDM, and JSLE patients. They found that these prevalent inflammatory rheumatic diseases or their immunosuppressive treatment did not adversely affect the response to a common-cold coronavirus. == Rabbit Polyclonal to PPP2R3C Introduction == Four types of human coronaviruses (HCoVs) are endemic in the human population, causing frequent infection with relatively mild disease.1,2,3,4The multiple introductions of zoonotic coronaviruses in the last couple of decades have highlighted their considerable pathogenic potential.5This is exemplified by the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that currently continues to spread globally.6 The outcome of SARS-CoV-2 infection is highly variable both in presentation and prevalence. Several subtypes of coronavirus disease 19 (COVID-19) are now recognized, ranging from a mild flu-like, severe gastrointestinal or respiratory disease to multiorgan failure.6,7Severe complications of COVID-19 are comparatively rare and depend on age, sex, ethnicity, access to healthcare, socioeconomic status, and underlying health conditions.6,7A sizable proportion of SARS-CoV-2 infections may also be asymptomatic, particularly in younger individuals. 8Children appear relatively protected from severe COVID-19.9This observation mirrors findings from previous epidemics caused by SARS-CoV TMC353121 and Middle East respiratory syndrome coronavirus (MERS-CoV), again sparing children, although transmission of earlier zoonotic coronaviruses was much less widespread or documented.10In contrast, children experience more frequent infections than adults with one or more of the four seasonal HCoVs3,11and are more likely to harbor pre-existing antibodies and memory B cells that cross-react with SARS-CoV-2.12,13 Although they appear protected from severe COVID-19, unexplained inflammation following SARS-CoV-2 infection is being increasingly recognized in a very small fraction of children.