Dispersal Patterns and Influence of Air Travel During the Global Expansion of SARS-CoV-2 Variants of Concern

The Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated globally during 2020-21, fueling waves of infections. They were displaced by Delta during a third wave worldwide in 2021, in turn displaced by Omicron in late 2021. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of VOCs worldwide. We find that source-sink dynamics varied substantially by VOC, and identify countries that acted as global and regional hubs of dissemination. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal, estimating that India contributed <15% of Delta exports and South Africa <1-2% of Omicron dispersal. We estimate that >80 countries had received introductions of Omicron within 100 days of emergence, associated with accelerating passenger air travel and higher transmissibility. Our study highlights the rapid dispersal of highly transmissible variants with implications for genomic surveillance along the hierarchical airline network. Graphical Data analysis clarifies that dispersal of SARS-CoV-2 variants from their sites of initial detection was related to the amount of global air travel at the time of the variant's emergence, and that travel volume through "hub” sites distinct from the site of emergence was a key driver of variant spread.

Governing partnerships with technology companies as part of the COVID-19 response in Canada: A qualitative case study.

Cross-sector partnerships are vital for maintaining resilient health systems; however, few studies have sought to empirically assess the barriers and enablers of effective and responsible partnerships during public health emergencies. Through a qualitative, multiple case study, we analyzed 210 documents and conducted 26 interviews with stakeholders in three real-world partnerships between Canadian health organizations and private technology startups during the COVID-19 pandemic. The three partnerships involved: 1) deploying a virtual care platform to care for COVID-19 patients at one hospital, 2) deploying a secure messaging platform for physicians at another hospital, and 3) using data science to support a public health organization. Our results demonstrate that a public health emergency created time and resource pressures throughout a partnership. Given these constraints, early and sustained alignment on the core problem was critical for success. Moreover, governance processes designed for normal operations, such as procurement, were triaged and streamlined. Social learning, or the process of learning from observing others, offset some time and resource pressures. Social learning took many forms ranging from informal conversations between individuals at peer organisations (e.g., hospital chief information officers) to standing meetings at the local university's city-wide COVID-19 response table. We also found that startups' flexibility and understanding of the local context enabled them to play a highly valuable role in emergency response. However, pandemic fueled "hypergrowth" created risks for startups, such as introducing opportunities for deviation away from their core value proposition. Finally, we found each partnership navigated intense workloads, burnout, and personnel turnover through the pandemic. Strong partnerships required healthy, motivated teams. Visibility into and engagement in partnership governance, belief in partnership impact, and strong emotional intelligence in managers promoted team well-being. Taken together, these findings can help to bridge the theory-to-practice gap and guide effective cross-sector partnerships during public health emergencies.

Shifts in global mobility dictate the synchrony of SARS-CoV-2 epidemic waves.

BACKGROUND: Human mobility changed in unprecedented ways during the SARS-CoV-2 pandemic. In March and April 2020, when lockdowns and large travel restrictions began in most countries, global air-travel almost entirely halted (92% decrease in commercial global air travel in the months between February and April 2020). Initial recovery in global air travel started around July 2020 and subsequently nearly tripled between May and July 2021. Here, we aim to establish a preliminary link between global mobility patterns and the synchrony of SARS-CoV-2 epidemic waves across the world. METHODS: We compare epidemic peaks and human global mobility in two time periods: November 2020 to February 2021 (when just over 70 million passengers travelled), and November 2021 to February 2022 (when more than 200 million passengers travelled). We calculate the time interval during which continental epidemic peaks occurred for both of these time periods, and we calculate the pairwise correlations of epidemic waves between all pairs of countries for the same time periods. RESULTS: We find that as air travel increases at the end of 2021, epidemic peaks around the world are more synchronous with one another, both globally and regionally. Continental epidemic peaks occur globally within a 20 day interval at the end of 2021 compared to 73 days at the end of 2020, and epidemic waves globally are more correlated with one another at the end of 2021. CONCLUSIONS: This suggests that the rebound in human mobility dictates the synchrony of global and regional epidemic waves. In line with theoretical work, we show that in a more connected world, epidemic dynamics are more synchronized.

Inferring the true number of SARS-CoV-2 infections in Japan.

INTRODUCTION: In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities. METHODS: We used reported COVID-19 deaths and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies and were adjusted to reflect the effects of pharmaceutical interventions, mass vaccination, and evolving variants. To account for the uncertainty in IFR, we sampled values from relevant distributions. RESULTS: We estimated that as of December 31, 2021, 3.07 million (CrI: 2.05-4.24 million) people had been infected in Japan, which is 1.77 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan. CONCLUSIONS: We have estimated that a substantial number of COVID-19 infections in Japan were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.

Assessing spread risk of COVID-19 within and beyond China in early 2020

A novel coronavirus emerged in Wuhan in late 2019 and has caused the COVID-19 pandemic announced by the World Health Organization on March 12, 2020. This study was originally conducted in January 2020 to estimate the potential risk and geographic range of COVID-19 spread within and beyond China at the early stage of the pandemic. A series of connectivity and risk analyses based on domestic and international travel networks were conducted using historical aggregated mobile phone data and air passenger itinerary data. We found that the cordon sanitaire of Wuhan was likely to have occurred during the latter stages of peak population numbers leaving the city, with travellers departing into neighbouring cities and other megacities in China. We estimated that 59,912 air passengers, of which 834 (95% uncertainty interval: 478–1349) had COVID-19 infection, travelled from Wuhan to 382 cities outside of mainland China during the two weeks prior to the city’s lockdown. Most of these destinations were located in Asia, but major hubs in Europe, the US and Australia were also prominent, with a strong correlation seen between the predicted risks of importation and the number of imported cases found. Given the limited understanding of emerging infectious diseases in the very early stages of outbreaks, our approaches and findings in assessing travel patterns and risk of transmission can help guide public health preparedness and intervention design for new COVID-19 waves caused by variants of concern and future pandemics to effectively limit transmission beyond its initial extent.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).

Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions.

Regional connectivity and land travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding in the early pandemic to more regional seeding for the travel restrictions period. We show that land travel, particularly freight transport, drove introduction risk during the travel restrictions period. High regional connectivity and land travel also drove Jordan's export risk. Our findings emphasize regional connectedness and land travel as drivers of transmission in the Middle East.

Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 with grinch.

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers.

Pneumonia of unknown aetiology in Wuhan, China: potential for international spread via commercial air travel.

There is currently an outbreak of pneumonia of unknown aetiology in Wuhan, China. Although there are still several unanswered questions about this infection, we evaluate the potential for international dissemination of this disease via commercial air travel should the outbreak continue.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate 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 had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early 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 the festival dramatically accelerated transmission. 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 epidemics.

Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK.

The United Kingdom's COVID-19 epidemic during early 2020 was one of world's largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country's first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whereas lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.

Estimating internationally imported cases during the early COVID-19 pandemic.

Early in the COVID-19 pandemic, predictions of international outbreaks were largely based on imported cases from Wuhan, China, potentially missing imports from other cities. We provide a method, combining daily COVID-19 prevalence and flight passenger volume, to estimate importations from 18 Chinese cities to 43 international destinations, including 26 in Africa. Global case importations from China in early January came primarily from Wuhan, but the inferred source shifted to other cities in mid-February, especially for importations to African destinations. We estimate that 10.4 (6.2 - 27.1) COVID-19 cases were imported to these African destinations, which exhibited marked variation in their magnitude and main sources of importation. We estimate that 90% of imported cases arrived between 17 January and 7 February, prior to the first case detections. Our results highlight the dynamic role of source locations, which can help focus surveillance and response efforts.

Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States.

The novel coronavirus SARS-CoV-2 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 United States, 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 effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.