Individuals with autoimmune diseases, such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), that require long-term immunosuppression are regarded as particularly vulnerable in the current COVID-19 pandemic [1].… Click to show full abstract
Individuals with autoimmune diseases, such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), that require long-term immunosuppression are regarded as particularly vulnerable in the current COVID-19 pandemic [1]. However, few details about the effect of individual immunotherapies have been reported, which could instruct us about the immunological control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specific antibodies are detectable within 2–19 days [2] and have been extensively analyzed for diagnostic purposes [3] and vaccine development [4]. It is unclear whether a durable antibody response is required for recovery of COVID-19 or whether it might even contribute to the pathogenesis by perpetuating hyperinflammation as has been shown for the closely related middle-east-respiratory-syndrome (MERS) coronavirus [5]. Here, we report on two individuals with underlying neuroimmunological diseases who were under stable rituximab therapy—a B cell-depleting monoclonal antibody [6, 7]—when confirmed COVID-19 developed. Infection with SARS-CoV-2 was verified in both cases by PCR. Patient 1 was a 44-year-old woman with a history of breast carcinoma, which was treated by breast-conserving surgery in 2010 and a relapsing–remitting MS (diagnosed 1999; EDSS 2.0) that has been treated with rituximab since 2013 (last infusion in January 2020). She was admitted with malaise, muscle ache, cough, fever and mild dyspnea, which first developed during a ski-trip in a high-risk area on March 14th, 2020 and she was tested positive ten days later. On the day of admission, she showed elevated inflammatory biomarkers (CRP 34 mg/L, interleukin-6 371.9 ng/L, ferritin 292.7 μg/L), cardiac biomarkers (proBNP 253 ng/L) and D-dimers (0.61 mg/L) but normal procalcitonin (< 0.02 μg/L) and negative blood cultures. Radiologic findings of bilateral infiltrations indicated atypical pneumonia. On the second day of admission SARS-CoV-2 RNA was only detectable in pharyngeal swabs in low concentrations close to detection limit (Ct 37.4). Immunologically, she had normal lymphocyte counts (1.12 billion/mL) but absent B cells (not detectable, Supplementary Table 1). Serologically, we could not detect antibodies against SARS-CoV-2 IgG. The patient was clinically and serologically stable and was discharged after four days of inpatient symptomatic treatment against fever into home quarantine. Four weeks later, she electively visited our outpatient clinic and her PCR from Marcel S. Woo, David Steins, Julian Schulze zur Wiesch and Manuel A. Friese have contributed equally to the manuscript.
               
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