Genetic mismatch explains sizable variation of COVID-19 vaccine efficacy in clinical trials

Timely evaluation of the protective effects of COVID-19 vaccines is challenging but urgently needed to inform the pandemic control planning. Based on vaccine efficacy/effectiveness (VE) data of 11 vaccine products and 297,055 SARS-CoV-2 sequences collected in 20 regions, we analyzed the relationship between genetic mismatch of circulating viruses against the vaccine strain and VE. Variations from technology platforms are controlled by a mixed-effects model. We found that the genetic mismatch measured on the RBD is highly predictive for vaccine protection and accounted for 72.0% (p-value < 0.01) of the VE change. The NTD and S protein also demonstrate significant but weaker per amino acid substitution association with VE (p-values < 0.01). The model is applied to predict vaccine protection of existing vaccines against new genetic variants and is validated by independent cohort studies. The estimated VE against the delta variant is 79.3% (95% prediction interval: 67.0 - 92.1) using the mRNA platform, and an independent survey reported a close match of 83.0%; against the beta variant (B.1.351) the predicted VE is 53.8% (95% prediction interval: 39.9 - 67.4) using the viral-vector vaccines, and an observational study reported a close match of 48.0%. Genetic mismatch provides an accurate prediction for vaccine protection and offers a rapid evaluation method against novel variants to facilitate vaccine deployment and public health responses.

Transmissibility of coronavirus disease 2019 (COVID-19) in Chinese cities with different transmission dynamics of imported cases

BackgroundMonitoring the time-varying reproduction number (Rt) of the disease is useful in determining whether there is sustained transmission in a population. In this study, we examined Rt of COVID-19 and compared its transmissibility between different intervention periods in Hangzhou and Shenzhen. MethodsDaily aggregated counts of confirmed imported and local cases between January 1, 2020 and March 13, 2020 were analysed. A likelihood function was constructed to estimate Rt, accounting for imported cases. ResultsAlthough Hangzhou had fewer number of cases than Shenzhen, Shenzhen had higher proportion of imported cases than Hangzhou (83% vs 29%). Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was kept below unity through time. On the contrary, Rt was greater than unity in Hangzhou from 16 January to 7 February due to the surge in local cases. Credits to the Wuhan lockdown and outbreak response measures following the local lockdown, Rt decreased steadily and dropped below unity in mid-February. ConclusionThe lockdown measures and local outbreak responses helped reduce the potential of local transmission in Hangzhou and Shenzhen. Meanwhile, cities with similar epidemic trend could have different transmission dynamics given the variation in imported cases.

Monitoring Disease Transmissibility of 2019 Novel Coronavirus Disease in Zhejiang, China

We monitored the transmissibility of 2019 novel coronavirus disease in Zhejiang accounting the transmissions from imported cases. Even though Zhejiang is one of the worst-affected provinces, an interruption of disease transmission (i.e. instantaneous reproduction numbers <1) was observed in early/mid-February after an early social-distancing response to the outbreak.