Rapid evaluation of COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 variants by analysis of genetic distance.

Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7-96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.

Superspreading and heterogeneity in transmission of SARS, MERS, and COVID-19: A systematic review.

BACKGROUND: Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19) have caused substantial public health burdens and global health threats. Understanding the superspreading potentials of these viruses are important for characterizing transmission patterns and informing strategic decision-making in disease control. This systematic review aimed to summarize the existing evidence on superspreading features and to compare the heterogeneity in transmission within and among various betacoronavirus epidemics of SARS, MERS and COVID-19. METHODS: PubMed, MEDLINE, and Embase databases were extensively searched for original studies on the transmission heterogeneity of SARS, MERS, and COVID-19 published in English between January 1, 2003, and February 10, 2021. After screening the articles, we extracted data pertaining to the estimated dispersion parameter (k) which has been a commonly-used measurement for superspreading potential. FINDINGS: We included a total of 60 estimates of transmission heterogeneity from 26 studies on outbreaks in 22 regions. The majority (90%) of the k estimates were small, with values less than 1, indicating an over-dispersed transmission pattern. The point estimates of k for SARS and MERS ranged from 0.12 to 0.20 and from 0.06 to 2.94, respectively. Among 45 estimates of individual-level transmission heterogeneity for COVID-19 from 17 articles, 91% were derived from Asian regions. The point estimates of k for COVID-19 ranged between 0.1 and 5.0. CONCLUSIONS: We detected a substantial over-dispersed transmission pattern in all three coronaviruses, while the k estimates varied by differences in study design and public health capacity. Our findings suggested that even with a reduced R value, the epidemic still has a high resurgence potential due to transmission heterogeneity.