Treatment of chronic or relapsing COVID-19 in immunodeficiency

Abstract

Background: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown.

Objective: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response.

Methods: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19.

Results: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). 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.

Keywords: COVID-19; SARS-CoV-2; immunodeficiency; remdesivir; therapeutic monoclonal.

Fig 1

A, Eventual virologic outcome according to maximal treatment received in 31 antibody-deficient patients with chronic or relapsing COVID-19. B, Outcome per episode of clinical illness (n = 62 episodes) among the patient group. CP, Convalescent plasma; neg, negative; pos, positive.

Fig E1

Proportion of clinical episodes in which patients experienced clinical improvement, reduction in fever, reduction in serum C-reactive protein concentration, reduction in oxygen requirement, and discharge from the hospital according to treatment received: combination therapy (remdesivir plus convalescent plasma or REGN-COV2 monoclonals [n = 14]), remdesivir monotherapy (n = 23), or no treatment (n = 22). N/A, not applicable; NK, not known.