The emergence and progression of highly divergent SARS-CoV-2 variants have posed increased risks to global public health, triggering the significant impacts on countermeasures since 2020. However, in addition to vaccination, the effectiveness of non-pharmaceutical interventions, such as social distancing, masking, or hand washing, on different variants of concern (VOC) remains largely unknown. This study provides a mechanistic approach by implementing a control measure model and a risk assessment framework to quantify the impacts of control measure combinations on the transmissions of five VOC (Alpha, Beta, Delta, Gamma, and Omicron), along with a different perspective of risk assessment application. We applied uncontrollable ratios as an indicator by adopting basic reproduction number (R 0) data collected from a regional-scale survey. A risk assessment strategy was established by constructing VOC-specific dose-response profiles to implicate practical uses in risk characterization when exposure data are available. We found that social distancing alone was ineffective without vaccination in almost all countries and VOC when the median R 0 was greater than two. Our results indicated that Omicron could not be contained, even when all control measure combinations were applied, due to its low threshold of infectivity (~3×10-4 plague-forming unit (PFU) mL-1). To facilitate better decision-making in future interventions, we provide a comprehensive evaluation of how combined control measures impact on different countries and various VOC. Our findings indicate the potential application of threshold estimates of infectivity in the context of risk communication and policymaking for controlling future emerging SARS-CoV-2 variant infections.
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