Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2

Time and intimacy drive transmission A minority of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmit most infections. How does this happen? Sun et al. reconstructed transmission in Hunan, China, up to April 2020. Such detailed data can be used to separate out the relative contribution of transmission control measures aimed at isolating individuals relative to population-level distancing measures. The authors found that most of the secondary transmissions could be traced back to a minority of infected individuals, and well over half of transmission occurred in the presymptomatic phase. Furthermore, the duration of exposure to an infected person combined with closeness and number of household contacts constituted the greatest risks for transmission, particularly when lockdown conditions prevailed. These findings could help in the design of infection control policies that have the potential to minimize both virus transmission and economic strain. Science, this issue p. eabe2424 Modeling results indicate that SARS-CoV-2 control requires case isolation, contact quarantine, and population-level interventions. INTRODUCTION The role of transmission heterogeneities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remains unclear, particularly those heterogeneities driven by demography, behavior, and interventions. To understand individual heterogeneities and their effect on disease control, we analyze detailed contact-tracing data from Hunan, a province in China adjacent to Hubei and one of the first regions to experience a SARS-CoV-2 outbreak in January to March 2020. The Hunan outbreak was swiftly brought under control by March 2020 through a combination of nonpharmaceutical interventions including population-level mobility restriction (i.e., lockdown), traveler screening, case isolation, contact tracing, and quarantine. In parallel, highly detailed epidemiological information on SARS-CoV-2–infected individuals and their close contacts was collected by the Hunan Provincial Center for Disease Control and Prevention. RATIONALE Contact-tracing data provide information to reconstruct transmission chains and understand outbreak dynamics. These data can in turn generate valuable intelligence on key epidemiological parameters and risk factors for transmission, which paves the way for more-targeted and cost-effective interventions. RESULTS On the basis of epidemiological information and exposure diaries on 1178 SARS-CoV-2–infected individuals and their 15,648 close contacts, we developed a series of statistical and computational models to stochastically reconstruct transmission chains, identify risk factors for transmission, and infer the infectiousness profile over the course of a typical infection. We observe overdispersion in the distribution of secondary infections, with 80% of secondary cases traced back to 15% of infections, which indicates substantial transmission heterogeneities. We find that SARS-CoV-2 transmission risk scales positively with the duration of exposure and the closeness of social interactions, with the highest per-contact risk estimated in the household. Lockdown interventions increase transmission risk in families and households, whereas the timely isolation of infected individuals reduces risk across all types of contacts. There is a gradient of increasing susceptibility with age but no significant difference in infectivity by age or clinical severity. Early isolation of SARS-CoV-2–infected individuals drastically alters transmission kinetics, leading to shorter generation and serial intervals and a higher fraction of presymptomatic transmission. After adjusting for the censoring effects of isolation, we find that the infectiousness profile of a typical SARS-CoV-2 patient peaks just before symptom onset, with 53% of transmission occurring in the presymptomatic phase in an uncontrolled setting. We then use these results to evaluate the effectiveness of individual-based strategies (case isolation and contact quarantine) both alone and in combination with population-level contact reductions. We find that a plausible parameter space for SARS-CoV-2 control is restricted to scenarios where interventions are synergistically combined, owing to the particular transmission kinetics of this virus. CONCLUSION There is considerable heterogeneity in SARS-CoV-2 transmission owing to individual differences in biology and contacts that is modulated by the effects of interventions. We estimate that about half of secondary transmission events occur in the presymptomatic phase of a primary case in uncontrolled outbreaks. Achieving epidemic control requires that isolation and contact-tracing interventions are layered with population-level approaches, such as mask wearing, increased teleworking, and restrictions on large gatherings. Our study also demonstrates the value of conducting high-quality contact-tracing investigations to advance our understanding of the transmission dynamics of an emerging pathogen. Transmission chains, contact patterns, and transmission kinetics of SARS-CoV-2 in Hunan, China, based on case and contact-tracing data from Hunan, China. (Top left) One realization of the reconstructed transmission chains, with a histogram representing overdispersion in the distribution of secondary infections. (Top right) Contact matrices of community, social, extended family, and household contacts reveal distinct age profiles. (Bottom) Earlier isolation of primary infections shortens the generation and serial intervals while increasing the relative contribution of transmission in the presymptomatic phase. A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities, which are driven by demography, behavior, and interventions. On the basis of detailed patient and contact-tracing data in Hunan, China, we find that 80% of secondary infections traced back to 15% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primary infections, which indicates substantial transmission heterogeneities. Transmission risk scales positively with the duration of exposure and the closeness of social interactions and is modulated by demographic and clinical factors. The lockdown period increases transmission risk in the family and households, whereas isolation and quarantine reduce risks across all types of contacts. The reconstructed infectiousness profile of a typical SARS-CoV-2 patient peaks just before symptom presentation. Modeling indicates that SARS-CoV-2 control requires the synergistic efforts of case isolation, contact quarantine, and population-level interventions because of the specific transmission kinetics of this virus.