Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

Abstract

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

“…With such limited substrate for selection to act upon, the short window of time between treatment and transmission could limit the spread of a variant selected within a host. Even during prolonged infections in immunocompromised hosts, there is only limited evidence of resistance to various COVID-19 therapeutics [33][34][35].…”

Targeting SARS-CoV-2 M3CLpro by HCV NS3/4a Inhibitors: In Silico Modeling and In Vitro Screening

“… 12 , 13 The value of this drug for the treatment of SARS-CoV-2 infection remains unclear with recent study suggesting the efficacy of remdesivir in selective patients. 14 Remdesivir treatment for COVID-19 patients with a rare autoimmune disorder had dramatic improvement of the symptoms with eradication of the virus. In addition, it remains to be determined if serious side effects will emerge as this new drug becomes more widely distributed.…”

Resolution of Persistent COVID-19 After Convalescent Plasma in a Patient with B Cell Aplasia

“…The efficacy of convalescent plasma in the treatment of COVID-19 in patients has been reported in small case series of individuals with both congenital and acquired B cell aplasia [ 7 – 9 ]. Of note, two reports demonstrate that viral persistence can occur despite the generation of CD4 and CD8 T cell responses to viral antigens and that magnitude of ex vivo antiviral T cell responses is augmented following the administration of convalescent plasma [ 10 , 11 ]. These data point to a non-redundant role for humoral immunity in immunological control of SARS-CoV-2, potentially via mechanisms such as antibody-dependent cellular cytotoxicity or opsonization, and suggest convalescent plasma is a rational therapeutic choice for individuals with humoral immune deficiencies, particularly when current immunoglobulin replacement products lack SARS-CoV-2-specific antibodies [ 12 ].…”