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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.

SUBMITTER: Buckland MS

PROVIDER: S-EPMC7736571 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Buckland Matthew S MS Galloway James B JB Fhogartaigh Caoimhe Nic CN Meredith Luke L Provine Nicholas M NM Bloor Stuart S Ogbe Ane A Zelek Wioleta M WM Smielewska Anna A Yakovleva Anna A Mann Tiffeney T Bergamaschi Laura L Turner Lorinda L Mescia Frederica F Toonen Erik J M EJM Hackstein Carl-Philipp CP Akther Hossain Delowar HD Vieira Vinicius Adriano VA Ceron-Gutierrez Lourdes L Periselneris Jimstan J Kiani-Alikhan Sorena S Grigoriadou Sofia S Vaghela Devan D Lear Sara E SE Török M Estée ME Hamilton William L WL Stockton Joanne J Quick Josh J Nelson Peter P Hunter Michael M Coulter Tanya I TI Devlin Lisa L Bradley John R JR Smith Kenneth G C KGC Ouwehand Willem H WH Estcourt Lise L Harvala Heli H Roberts David J DJ Wilkinson Ian B IB Screaton Nick N Loman Nicholas N Doffinger Rainer R Lyons Paul A PA Morgan B Paul BP Goodfellow Ian G IG Klenerman Paul P Lehner Paul J PJ Matheson Nicholas J NJ Thaventhiran James E D JED

Nature communications 20201214 1

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 in ...[more]

PMID: 33318491

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Project description:BACKGROUND:Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS:We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS:A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS:Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

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

Publications

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

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