Successful treatment of COVID-19 with remdesivir in the absence of humoral immunity

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 successful 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. His unusual clinical course identifies a key role for SARS-CoV-2 antibodies in both viral clearance and progression to severe disease. In the absence of these confounders, we took an experimental medicine approach to examine the in vivoutility of remdesivir. Over two independent courses of treatment, we observed a dramatic, temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide unambiguous evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients

“…A major caveat to our findings is that our cohort is paediatric, for which both the clinical picture and outcome of SARS-CoV-2 infections are known to differ from adults. Notwithstanding, similar patterns of clinical and virological response to remdesivir have been described in adults (3,10,46,59) . Moreover, both clinical and viral sequence data from the use of repurposed drugs to treat other severe RNA viral infections has shown similarities in adults and children (12,50,55) .…”

“…While several drugs with in vitro activity against SARS-CoV-2 have been identified, only remdesivir has shown any clinical promise (10) . However, reports of its efficacy are mixed (3,7–9,11) and only one other report of it having an effect on viral replication in vivo has been described (46) . We show evidence of clinical improvement in all three patients whilst on remdesivir.…”

COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those With Humoral Immunodeficiency States: A Scoping Review

“…Opinion articles, ecologic studies, and articles unrelated to COVID-19 hIEI clinical outcomes were excluded. Seven articles were included for nal analysis including three case reports [19][20][21]. three cohort studies [22][23][24], and one literature review of case reports [25].…”

“…The majority of patients ( 42) had common variable immunode ciency (CVID) [19,[22][23][24][25]. Thirteen patients had agammaglobulinemia (10 X-linked, three autosomal recessive) [21][22][23][24][25]. Five patients had speci c immunoglobulin de ciencies (IgG, IgA, or both) [20,[22][23][24]; four patients had otherwise unspeci ed hypogammaglobulinemia [22,23]; two patients each had hyper-IgM disease [22,24] and antibody de ciency with syndromic features [23]; and one patient had activated PI3K delta syndrome (APDS) [23].…”

2021 update of the AGIHO guideline on evidence-based management of COVID-19 in patients with cancer regarding diagnostics, viral shedding, vaccination and therapy

“…8,9,11,12 In COVID-19, a recent case report on a patient with complete absence of humoral immunity showed viral clearance following remdesivir administration. 37 A large J o u r n a l P r e -p r o o f retrospective cohort study of cancer patients with COVID-19 (N=2186) treated in the US also found a potential benefit for remdesivir with regard to mortality. 38 While the WHO does no longer recommend remdesivir for treatment of COVID-19 in the general population, this guideline panel still sees a potential benefit for immunocompromised cancer patients at risk of impaired viral clearance.…”