Impact and mitigation of sampling bias to determine viral spread: evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations (preprint)

Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies that enables reconstructing the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (BASTA and MASCOT). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for CTMC. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for CTMC, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.

Impact of BNT162b2 vaccination and isolation on SARS-CoV-2 transmission in Israeli households: an observational study (preprint)

Background Massive vaccination rollouts against SARS-CoV-2 infections have facilitated the easing of control measures in countries like Israel. While several studies have characterized the effectiveness of vaccines against severe forms of COVID-19 or SARS-CoV-2 infection, estimates of their impact on transmissibility remain limited. Here, we evaluated the role of vaccination and isolation on SARS-CoV-2 transmission within Israeli households. Methods From December 2020 to April 2021, confirmed cases were identified among healthcare workers of the Sheba Medical Centre and their family members. Households were recruited and followed up with repeated PCR for a minimum of ten days after case confirmation. Symptoms and vaccination information were collected at the end of follow-up. We developed a data augmentation Bayesian framework to ascertain how age, isolation and BNT162b2 vaccination with more than 7 days after the 2 nd dose impacted household transmission of SARS-CoV-2. Findings 210 households with 215 index cases were enrolled. 269 out of 687 (39%) household contacts developed a SARS-CoV-2 infection. Of those, 170 (63%) developed symptoms. Children below 12 years old were less susceptible than adults/teenagers (Relative Risk RR=0·50, 95% Credible Interval CI 0·32-0·79). Vaccination reduced the risk of infection among adults/teenagers (RR=0·19, 95% CI 0·07-0·40). Isolation reduced the risk of infection of unvaccinated adult/teenager (RR=0·11, 95% CI 0·05-0·19) and child contacts (RR=0·16, 95% CI 0·07-0·31) compared to unvaccinated adults/teenagers that did not isolate. Infectivity was significantly reduced in vaccinated cases (RR=0·22, 95% CI 0·06-0·70). Interpretation Within households, vaccination reduces both the risk of infection and of transmission if infected. When contacts were not vaccinated, isolation also led to important reductions in the risk of transmission. Vaccinated contacts might reduce their risk of infection if they isolate, although this requires confirmation with additional data. Funding Sheba Medical Center. Research in context Evidence before this study The efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions in households remains understudied. On June 28, 2021, we searched PubMed and medRxiv for articles published between December 1, 2020, and June 28, 2021, using the following combination of search terms: (“COVID-19” OR “SARS-CoV-2”) AND (“household*” OR “famil*”) AND “transmission” AND “vaccination”. Our search yielded two articles that investigated the effect of vaccination on SARS-CoV-2 transmission in households. They showed a lower risk of infection in households with vaccinees. Vaccine efficacy on the risk of infection was estimated to 80% after the 2 nd dose, and vaccine efficacy on the risk of transmission if infected was estimated to 49% 21 days after the 1 st dose. However, these estimates are derived from surveillance data with no active follow-up of the households. In addition, the impact of isolation precautions has not been assessed. Added value of this study Based on the active follow-up of households of health care workers from the Sheba Medical Center in Israel, we estimated the effect of vaccination on household transmission. To our knowledge, our study is the first to conjointly investigate the effect of vaccination, age, and isolation precautions on the risk of infection and the risk of transmission in households while accounting for tertiary infections in the household, infections within the community, the reduced infectivity of asymptomatic cases, misidentification of index cases, and household size. Our study confirmed the high efficacy of BNT-162b2 vaccination to reduce infection risk and transmission risk. It also suggests that isolation might remain beneficial to vaccinated contacts. Implications of all the available evidence Vaccination reduces susceptibility to infection and case infectivity in households. Isolation precautions also mitigate the risk of infection and should be implemented whenever a household member is infected. They might remain beneficial to vaccinated contacts.

The effect of human mobility and control measures on the COVID-19 epidemic in China (preprint)

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.