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Double-zero-event studies matter: a re-evaluation of physical distancing, face masks, and eye protection for preventing person-to-person transmission of COVID-19 and its policy impact

Objectives: High-quality meta-analyses on COVID-19 are in urgent demand for evidence-based decision making. However, conventional approaches exclude double-zero-event studies (DZS) from meta-analyses. We assessed whether including such studies impacts the conclusions in a recent systematic urgent review on prevention measures for preventing person-to-person transmission of COVID-19. Study designs and settings: We extracted data for meta-analyses containing DZS from a recent review that assessed the effects of physical distancing, face masks, and eye protection for preventing person-to-person transmission. A bivariate generalized linear mixed model was used to re-do the meta-analyses with DZS included. We compared the synthesized relative risks (RRs) of the three prevention measures, their 95% confidence intervals (CI), and significance tests (at the level of 0.05) including and excluding DZS. Results: The re-analyzed COVID-19 data containing DZS involved a total of 1,784 participants who were not considered in the original review. Including DZS noticeably changed the synthesized RRs and 95% CIs of several interventions. For the meta-analysis of the effect of physical distancing, the RR of COVID-19 decreased from 0.15 (95% CI, 0.03 to 0.73) to 0.07 (95% CI, 0.01 to 0.98). For several meta-analyses, the statistical significance of the synthesized RR was changed. The RR of eye protection with a physical distance of 2 m and the RR of physical distancing when using N95 respirators were no longer statistically significant after including DZS. Conclusions: DZS may contain useful information. Sensitivity analyses that include DZS in meta-analysis are recommended.