The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis
Issued Date
2024-05-02
Resource Type
eISSN
14602091
Scopus ID
2-s2.0-85191563165
Pubmed ID
38385479
Journal Title
The Journal of antimicrobial chemotherapy
Volume
79
Issue
5
Start Page
935
End Page
945
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Journal of antimicrobial chemotherapy Vol.79 No.5 (2024) , 935-945
Suggested Citation
Singh S., Boyd S., Schilling W.H.K., Watson J.A., Mukaka M., White N.J. The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis. The Journal of antimicrobial chemotherapy Vol.79 No.5 (2024) , 935-945. 945. doi:10.1093/jac/dkae045 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/98297
Title
The relationship between viral clearance rates and disease progression in early symptomatic COVID-19: a systematic review and meta-regression analysis
Corresponding Author(s)
Other Contributor(s)
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.