ABSTRACT
ObjectivesDue to their underlying disease as well as therapeutic immunosuppression, children and adolescents with rheumatic and musculoskeletal diseases (RMD) may be at higher risk for a severe course or worse outcome of COVID-19, and SARS-CoV2 infection may trigger a flare of the RMD. To address these issues, a specific SARS-CoV-2 questionnaire was implemented in the National Pediatric Rheumatology Database (NPRD) in Germany. MethodsDemographic, clinical and treatment data from juvenile patients with RMD as well as data about SARS-CoV-2 infection like test date and method, clinical characteristics, disease course, outcome and impact on the disease activity of the RMD documented on this questionnaire were analyzed. ResultsFrom April 17th, 2020, to February 14th, 2021, data were collected from 79 patients (53% female) with RMD with median age of 14 years, diagnosed with juvenile idiopathic arthritis (57%), autoinflammatory (23%) and connective tissue disease (8%). Sixty-one patients (77%) received disease-modifying antirheumatic drugs (DMARDs), 43% biologic DMARDs, and 9% systemic glucocorticoids. Sixty patients (76%) developed symptoms of COVID-19. Disease severity was mild and outcome was good in the majority of patients. Two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure. In 84% of SARS-CoV-2-positive patients, no relevant increase in disease activity of the RMD was observed. ConclusionsIn our cohort, COVID-19 in juvenile patients with RMD under various medications was mild with good outcome in the majority of cases. SARS-CoV-2 infection does not appear to have a relevant impact on disease activity of the underlying condition.
ABSTRACT
Here we have analyzed the dynamics of the adaptive immune response triggered by SARS-CoV-2 in severely affected COVID-19 patients, as reflected by activated B cells egressing into the blood, at the single cell level. Early on, before seroconversion in response to SARS-CoV-2 spike protein, activated peripheral B cells displayed a type 1 interferon-induced gene expression signature. After seroconversion, activated B cells lost this signature, expressed IL-21- and TGF-{beta}-induced gene expression signatures, and mostly IgG1 and IgA1. In the sustained immune reaction of the COVID-19 patients, until day 59, activated peripheral B cells shifted to expression of IgA2, reflecting instruction by TGF-{beta}. Despite the continued generation of activated B cells, those cells were not found in the lungs of deceased COVID-19 patients, nor did the IgA2 bind to dominant antigens of SARS-CoV-2. In severe COVID-19, SARS-CoV-2 thus triggers a chronic immune reaction distracted from itself and instructed by TGF-{beta}.
