Treatment of chronic or relapsing COVID-19 in immunodeficiency

BACKGROUND: Patients with some types of immunodeficiency can suffer chronic or relapsing infection with SARS-CoV-2. This leads to morbidity and mortality, infection control challenges and the risk of evolution of novel viral variants. Optimal treatment for chronic COVID-19 is unknown. OBJECTIVE: To characterise a cohort of patients with chronic or relapsing COVID-19 disease and to record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features and treatment response of immune deficient patients with chronic (at least 21 days) or relapsing (at least two episodes) of COVID-19. RESULTS: We identified 31 cases with a median age of 49 years. Underlying immune deficiency was characterised by antibody deficiency with absent or profoundly reduced peripheral B cells; prior anti-CD20 therapy and X-linked agammaglobulinemia were most common. Clinical features of COVID-19 were similar to the general population, but the median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to five episodes of illness. Remdesivir monotherapy (including when given for prolonged courses up to 20 days) was associated with sustained viral clearance in 7/23 (30.4%) clinical episodes whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 monoclonal antibodies resulted in viral clearance in 13/14 (92.8%) episodes. Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.