Importation of Alpha and Delta variants during the SARS-CoV-2 epidemic in Switzerland: phylogenetic analysis and intervention scenarios (preprint)

The SARS-CoV-2 pandemic has led to the emergence of various variants of concern (VoCs) that are associated with increased transmissibility, immune evasion, or differences in disease severity. The emergence of VoCs fueled interest in understanding the potential impact of travel restrictions and surveillance strategies to prevent or delay the early spread of VoCs. We performed phylogenetic analyses and mathematical modeling to study the importation and spread of the VoCs Alpha and Delta in Switzerland in 2020 and 2021. Using a phylogenetic approach, we estimated 383-1,038 imports of Alpha and 455-1,347 imports of Delta into Switzerland. We then used the results from the phylogenetic analysis to parameterize a dynamic transmission that accurately described the subsequent spread of Alpha and Delta. We modeled different counterfactual intervention scenarios to quantify the potential impact of border closures and surveillance of travelers on the spread of Alpha and Delta. We found that implementing border closures after the announcement of VoCs would have been of limited impact to mitigate the spread of VoCs. In contrast, increased surveillance of travelers could prove to be an effective measure for delaying the spread of VoCs in situations where their severity remains unclear. Our study shows how phylogenetic analysis in combination with dynamic transmission models can be used to estimate the number of imported SARS-CoV-2 variants and the potential impact of different intervention scenarios to inform the public health response during the pandemic.

Emergence of an early SARS-CoV-2 epidemic in the United States (preprint)

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

Emergence and spread of a SARS-CoV-2 variant through Europe in the summer of 2020 (preprint)

A variant of SARS-CoV-2 emerged in early summer 2020, presumably in Spain, and has since spread to multiple European countries. The variant was first observed in Spain in June and has been at frequencies above 40% since July. Outside of Spain, the frequency of this variant has increased from very low values prior to 15th July to 40-70% in Switzerland, Ireland, and the United Kingdom in September. It is also prevalent in Norway, Latvia, the Netherlands, and France. Little can be said about other European countries because few recent sequences are available. Sequences in this cluster (20A.EU1) differ from ancestral sequences at 6 or more positions, including the mutation A222V in the spike protein and A220V in the nucleoprotein. We show that this variant was exported from Spain to other European countries multiple times and that much of the diversity of this cluster in Spain is observed across Europe. It is currently unclear whether this variant is spreading because of a transmission advantage of the virus or whether high incidence in Spain followed by dissemination through tourists is sufficient to explain the rapid rise in multiple countries.

Interactions between seasonal human coronaviruses and implications for the SARS-CoV-2 pandemic: A retrospective study in Stockholm, Sweden, 2009-2020 (preprint)

ObjectivesThe four seasonal coronaviruses 229E, NL63, OC43, and HKU1 are frequent causes of respiratory infections and show annual and seasonal variation. Increased understanding about these patterns could be informative about the epidemiology of SARS-CoV-2. MethodsResults from PCR diagnostics for the seasonal coronaviruses, and other respiratory viruses, were obtained for 55,190 clinical samples analysed at the Karolinska University Hospital, Stockholm, Sweden, between 14 September 2009 and 2 April 2020. ResultsSeasonal coronaviruses were detected in 2,130 samples (3.9%) and constituted 8.1% of all virus detections. OC43 was most commonly detected (28.4% of detections), followed by NL63 (24.0%), HKU1 (17.6%), and 229E (15.3%). The overall fraction of positive samples was similar between seasons, but at species level there were distinct biennial alternating peak seasons for the Alphacoronaviruses, 229E and NL63, and the Betacoronaviruses, OC43 and HKU1, respectively. The Betacoronaviruses peaked earlier in the winter season (Dec-Jan) than the Alphacoronaviruses (Feb-Mar). Coronaviruses were detected across all ages, but diagnostics were more frequently requested for paediatric patients than adults and the elderly. OC43 and 229E incidence was relatively constant across age strata, while that of NL63 and HKU1 decreased with age. ConclusionsBoth the Alphacoronaviruses and Betacoronaviruses showed alternating biennial winter incidence peaks, which suggests some type of immune mediated interaction. Symptomatic reinfections in adults and the elderly appear relatively common. Both findings may be of relevance for the epidemiology of SARS-CoV-2.

Cryptic transmission of SARS-CoV-2 in Washington State (preprint)

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology (preprint)

Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.

Preliminary Case Report on the SARS-CoV-2 Cluster in the UK, France, and Spain (preprint)

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

Impact of seasonal forcing on a potential SARS-CoV-2 pandemic (preprint)

A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.