SARS-CoV-2 viral load dynamics in immunocompromised critically ill patients on remdesivir treatment
Keywords:
Remdesivir, COVID-19, immunosuppression, viral load, SARS-CoV-2Abstract
The relationship between SARS-CoV-2 quantitative viral load and risk of disease progression, morbidity such as long-COVID or mortality in immunosuppressed, remains largely undefined in COVID-19 patients. Critically ill immunosuppressed patients potentially benefit from remdesivir treatment because of the prolonged course of their infection. Four critically ill immunocompromised patients and the impact of remdesivir on viral dynamics in lower respiratory samples were studied. Bronchoalveolar lavage (BAL) samples were assessed to measure SARS-CoV-2 quantitative viral load using real-time PCR. Corresponding plasma levels of remdesivir and its metabolite GS-441524 were determined. Mean virus load of 39.74 x 107 geq/ml (±33.25 x 107 geq/ml) on day 1 dropped significantly (p<0.008) to 3.54 x 106 geq/ml (±6.93 x 106 geq/ml) on day 3 and to 1.4 x 105 geq/ml (±2.35 x 105 geq/ml) on day 5 of remdesivir treatment. Mean virus load dropped below <1% between day 1 and 5 of remdesivir treatment. Parent prodrug remdesivir and also GS441524 metabolite levels of antiviral activity in our patients were far in excess of EC 50. Our data present that remdesivir treatment potentially reduces the SARS-CoV-2 viral load in immunosuppressed critically ill patients. However, the implication of viral load reduction on morbidity and mortality needs further investigation.
References
Dölken L, Stich A, Spinner CD. Remdesivir for early COVID-19 treatment of high-risk individuals prior to or at early disease onset-lessons learned. Viruses 2021;13:963.
Tsukagoshi H, Shinoda D, Saito M, Okayama K, Sada M, Kimura H, et al. Relationships between viral load and the clinical course of COVID-19. Viruses 2021;13:304.
Fajnzylber J, Regan J, Coxen K, Corry H, Wong C, Rosenthal A, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun 2020;11:5493.
Sörgel F, Malin JJ, Hagmann H, Kinzig M, Bilal M, Eichenauer DA, et al. Pharmacokinetics of remdesivir in a COVID-19 patient with end-stage renal disease on intermittent haemodialysis. J Antimicrob Chemother 2021;76:825-7.
Frediansyah A, Nainu F, Dhama K, Mudatsir M, Harapan H. Remdesivir and its antiviral activity against COVID-19: A systematic review. Clin Epidemiol Glob Health 2021;9:123-7.
Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature 2020;585:273-6.
Goldberg E, Ben Zvi H, Sheena L, Sofer S, Krause I, Sklan EH, et al. A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel. Clin Microbiol Infect 2021;27:917.
Chokkalingam A, Li H, Asubonteng J, Mozaffari E, Wang JR, Bush C, et al. Comparative effectiveness of remdesivir treatment in patients hospitalized with COVID-19. World Microbe Forum ASM 2021. Poster 2970. Available from: https://www.askgileadmedical.com/downloads/pdfs/conference-materials/covid-19/asm%202021/Chokkalingam%20AP.pdf
Buckland MS, Galloway JB, Fhogartaigh CN, Meredith L, ProvineNM, Bloor S, et al. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. Nat Commun 2020;11:6385.
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