Treatment of chronic or relapsing COVID-19 in immunodeficiency

J Allergy Clin Immunol. 2022 Feb;149(2):557-561.e1. doi: 10.1016/j.jaci.2021.10.031. Epub 2021 Nov 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • COVID-19 / immunology
  • COVID-19 / pathology
  • COVID-19 / therapy*
  • COVID-19 / virology
  • COVID-19 Serotherapy
  • Chronic Disease
  • Female
  • Humans
  • Immunization, Passive
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Immunologic Deficiency Syndromes / therapy*
  • Immunologic Deficiency Syndromes / virology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage
  • Recurrence
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / pathogenicity
  • Treatment Failure

Substances

  • Antibodies, Monoclonal
  • Antiviral Agents
  • Recombinant Fusion Proteins
  • anti-CD20Fab-LDM protein
  • remdesivir
  • Adenosine Monophosphate
  • Alanine