Abstract
Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.
Highlights
Known risk factors for severe outcomes of COVID-19 in the general population include age, sex, diabetes mellitus, and underlying cardiovascular disease [1]
Single reports suggest an increased risk of severe COVID19 in patients with NFKB2 deficiency [9] and reports including a large number of patients with common variable immunodeficiency (CVID) suggested a higher fatality rate from SARS-CoV-2 infections among a subgroup [10, 11]
Given the poor humoral immune response in patients with antibody deficiencies, one obvious therapeutic option to treat COVID-19 is convalescent plasma, as its efficacy has been demonstrated for several other viral infections such as SARS-CoV, H5N1, or H1N1 [17,18,19]
Summary
Known risk factors for severe outcomes of COVID-19 in the general population include age, sex, diabetes mellitus, and underlying cardiovascular disease [1]. While primary immunodeficiency as a whole group did not seem to add by itself to the risk of a severe COVID-19 course, some specific immunodeficiencies were associated with an increased risk [2, 3] This includes patients with deficiencies of the interferon response either genetically [4, 5] or due to their phenocopies by antibodies against interferon alpha and omega [6, 7] and patients with auto-antibodies neutralizing type I interferons due to autoimmune polyendocrine syndrome type-1 syndrome [8]. Given the poor humoral immune response in patients with antibody deficiencies, one obvious therapeutic option to treat COVID-19 is convalescent plasma, as its efficacy has been demonstrated for several other viral infections such as SARS-CoV, H5N1, or H1N1 [17,18,19]. We describe the clinical outcome of 16 patients with primary antibody deficiency from four centers after treatment with convalescent plasma
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