Genomic sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely instituted during the coronavirus disease 2019 (COVID-19) pandemic to track the emergence and spread of new lineages. While this powerful tool can influence public health decisions and therapeutic development, not all regions of the world have had equal access to sequencing capacity, affecting surveillance. One such underrepresented region is the Caribbean islands, including the Dominican Republic (DR). To determine retrospectively what lineages were circulating in the DR in the first year of the pandemic, when there were strict travel restrictions imposed, we sequenced SARS-CoV-2 from nasal swab and saliva samples collected between July 2020 and February 2021. We investigated whether COVID-19 outbreaks were seeded by single or multiple introductions and established epidemiological linkages to other countries. Using 98 newly sequenced samples, we identified 16 SARS-CoV-2 lineages in the DR, indicating many independent introductions from diverse geographic areas. Further, we show that analyzing both globally prevalent and globally rare lineages within the DR highlights different aspects of international disease transmission.IMPORTANCEThis study uses genome sequencing of severe acute respiratory syndrome coronavirus 2 samples collected in an undersampled region of the world-the Caribbean, specifically the Dominican Republic-to make novel inferences about the dynamics of disease spread during a period of the coronavirus disease 2019 pandemic when many diverse lineages were co-circulating globally.
-
Genomic analysis reveals dynamics of SARS-CoV-2 during the initial phases of the COVID-19 outbreak in the Dominican Republic
-
Genomic analysis of the early COVID-19 pandemic in Haiti reveals Caribbean-specific variant dynamics
Pathogen sequencing during the COVID-19 pandemic has generated more whole genome sequencing data than for any other epidemic, allowing epidemiologists to monitor the transmission and evolution of SARS-CoV-2. However, large parts of the world are heavily underrepresented in sequencing efforts, including the Caribbean islands. We performed genome sequencing of SARS-CoV-2 from upper respiratory tract samples collected in Haiti during the spring of 2020. We used phylogenetic analysis to assess the pandemic dynamics in the Caribbean region and observed that the epidemic in Haiti was seeded by multiple introductions, primarily from the United States. We identified the emergence of a SARS-CoV-2 lineage (B.1.478) from Haiti that spread into North America, as well as evidence of the undocumented spread of SARS-CoV-2 within the Caribbean. We demonstrate that the genomic analysis of a relatively modest number of samples from a severely under-sampled region can provide new insight on a previously unobserved spread of a specific lineage, demonstrating the importance of geographically widespread genomic epidemiology.
-
Origins and Evolution of Seasonal Human Coronaviruses
Four seasonal human coronaviruses (sHCoVs) are endemic globally (229E, NL63, OC43, and HKU1), accounting for 5-30% of human respiratory infections. However, the epidemiology and evolution of these CoVs remain understudied due to their association with mild symptomatology. Using a multigene and complete genome analysis approach, we find the evolutionary histories of sHCoVs to be highly complex, owing to frequent recombination of CoVs including within and between sHCoVs, and uncertain, due to the under sampling of non-human viruses. The recombination rate was highest for 229E and OC43 whereas substitutions per recombination event were highest in NL63 and HKU1. Depending on the gene studied, OC43 may have ungulate, canine, or rabbit CoV ancestors. 229E may have origins in a bat, camel, or an unsampled intermediate host. HKU1 had the earliest common ancestor (1809-1899) but fell into two distinct clades (genotypes A and B), possibly representing two independent transmission events from murine-origin CoVs that appear to be a single introduction due to large gaps in the sampling of CoVs in animals. In fact, genotype B was genetically more diverse than all the other sHCoVs. Finally, we found shared amino acid substitutions in multiple proteins along the non-human to sHCoV host-jump branches. The complex evolution of CoVs and their frequent host switches could benefit from continued surveillance of CoVs across non-human hosts.
-
Tracking the UK SARS-CoV-2 outbreak
-
Coordinating SARS-CoV-2 genomic surveillance in the United States
The United States has rapidly responded to the emergence of new severe acute respiratory syndrome coronavirus 2 variants of concern by scaling up genomic surveillance. Tens of thousands of viral genomes are now sequenced in American labs each week to track the spread of variants originating in the United States (Annavajhala et al. 2021; Deng et al. 2021) or imported from other countries (Washington et al. 2021) to keep diagnostics, therapeutics, and vaccines up to date (Walensky, Walke, and Fauci 2021). An influx of Federal funding provides an unprecedented opportunity to build a new US genomic surveillance system from the ground up, informed by in-country expertise (National Academies of Sciences 2020; Black et al. 2020) as well as existing models of successful genomic surveillance systems established in other countries (COVID-19 Genomics UK (COG-UK) 2020; Seemann et al. 2020; Msomi, Mlisana, and Tulio 2020). Fully leveraging genetic data require a centrally coordinated national sampling strategy and consortiums for sharing valuable metadata, which are needed to study how new variants evade host immunity, cause severe disease, or transmit differently in human populations. However, US public and private labs have a history of autonomy and strong protections for patient privacy, presenting ongoing barriers to central coordination and data sharing.
-
The emergence of SARS-CoV-2 in Europe and North America
Accurate understanding of the global spread of emerging viruses is critical for public health responses and for anticipating and preventing future outbreaks. Here we elucidate when, where, and how the earliest sustained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission networks became established in Europe and North America. Our results suggest that rapid early interventions successfully prevented early introductions of the virus from taking hold in Germany and the United States. Other, later introductions of the virus from China to both Italy and Washington state, United States, founded the earliest sustained European and North America transmission networks. Our analyses demonstrate the effectiveness of public health measures in preventing onward transmission and show that intensive testing and contact tracing could have prevented SARS-CoV-2 outbreaks from becoming established in these regions.
-
Accommodating individual travel history and unsampled diversity in Bayesian phylogeographic inference of SARS-CoV-2
Spatiotemporal bias in genome sampling can severely confound discrete trait phylogeographic inference. This has impeded our ability to accurately track the spread of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, despite the availability of unprecedented numbers of SARS-CoV-2 genomes. Here, we present an approach to integrate individual travel history data in Bayesian phylogeographic inference and apply it to the early spread of SARS-CoV-2. We demonstrate that including travel history data yields i) more realistic hypotheses of virus spread and ii) higher posterior predictive accuracy compared to including only sampling location. We further explore methods to ameliorate the impact of sampling bias by augmenting the phylogeographic analysis with lineages from undersampled locations. Our reconstructions reinforce specific transmission hypotheses suggested by the inclusion of travel history data, but also suggest alternative routes of virus migration that are plausible within the epidemiological context but are not apparent with current sampling efforts.