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

Singh et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkae045, PROSPERO CRD42023413208
Feb 2024  
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Systematic review and meta-analysis of 44 RCTs of antiviral treatments for early symptomatic COVID-19, including 52,384 participants, assessing the relationship between the SARS-CoV-2 viral clearance rate and the risk of hospitalization or death. After excluding one outlier trial, half of the variation (R2=50.4%) in clinical benefit was explained by differences in the viral clearance rate. Higher viral clearance rate was significantly associated with greater clinical benefit (lower risk of hospitalization/death).
Singh et al., 22 Feb 2024, Randomized Controlled Trial, placebo-controlled, Thailand, peer-reviewed, 6 authors, study period March 2020 - October 2022, trial PROSPERO CRD42023413208. Contact:
This PaperMiscellaneousAll
The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis
Shivani Singh, Simon Boyd, William H K Schilling, James A Watson, Mavuto Mukaka, Nicholas J White
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% (R 2 ) 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 (R 2 = 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.
Transparency declarations The authors have none to report. Supplementary data Supplementary methods and Tables S1 to S8 are available as Supplementary data at JAC Online.
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