The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 7513617 Publication Model: Print Cited Medium: Internet ISSN: 1460-2091 (Electronic) Linking ISSN: 03057453 NLM ISO Abbreviation: J Antimicrob Chemother Subsets: MEDLINE
    • Publication Information:
      Publication: 1997- : London : Oxford University Press
      Original Publication: London, New York, Academic Press.
    • Subject Terms:
      COVID-19*/virology ; Antiviral Agents*/therapeutic use ; SARS-CoV-2*/drug effects ; Disease Progression* ; COVID-19 Drug Treatment*; Humans ; Randomized Controlled Trials as Topic ; Viral Load/drug effects ; Treatment Outcome ; Hospitalization
    • Abstract:
      Background: Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear.
      Methods: A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14 days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR). The VCRR is the ratio of viral clearance rates between the intervention and control arms. The relationship between the clinical and virological treatment effects was assessed by mixed-effects meta-regression.
      Results: From 57 potentially eligible RCTs, VCRRs were derived for 44 (52 384 participants); 32 had ≥1 clinical endpoint in each arm. Overall, 9.7% (R2) of the variation in clinical benefit was explained by variation in VCRRs with an estimated linear coefficient of -0.92 (95% CI: -1.99 to 0.13; P = 0.08). However, this estimate was highly sensitive to the inclusion of the recent very large PANORAMIC trial. Omitting this outlier, half the variation in clinical benefit (R2 = 50.4%) was explained by variation in VCRRs [slope -1.47 (95% CI -2.43 to -0.51); P = 0.003], i.e. higher VCRRs were associated with an increased clinical benefit.
      Conclusion: Methods of determining viral clearance in COVID-19 studies and the relationship to clinical outcomes vary greatly. As prohibitively large sample sizes are now required to show clinical treatment benefit in antiviral therapeutic assessments, viral clearance is a reasonable surrogate endpoint.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
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    • Grant Information:
      United Kingdom WT_ Wellcome Trust; 223195/Z/21/Z United Kingdom WT_ Wellcome Trust; 223195/Z/21/Z) United Kingdom WT_ Wellcome Trust
    • Accession Number:
      0 (Antiviral Agents)
    • Publication Date:
      Date Created: 20240222 Date Completed: 20240501 Latest Revision: 20240724
    • Publication Date:
      20240725
    • Accession Number:
      PMC11062948
    • Accession Number:
      10.1093/jac/dkae045
    • Accession Number:
      38385479