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.

COVID-19 vaccines: a geographic, social and policy view of vaccination efforts in Ontario, Canada

In recent months, more studies are emerging regarding how various nations and regions fared during the initial two years of the COVID-19 pandemic. Canada is cited as an example of a country that had performed reasonably well versus other countries with comparable infrastructures and health care systems (Razek et al., 2022). The reason is largely attributed to a combination of several public health measures coupled with widespread vaccination uptake, as a result of a country-wide vaccination campaign. This paper is based on a keynote talk given at the Autumn 2021 CJRES Annual Conference, by Dr. Isaac I. Bogoch. Dr Bogoch is an Associate Professor in the Department of Medicine at the University of Toronto, and an Infectious Diseases Consultant in the Division of Infectious Diseases at the Toronto General Hospital. Dr. Bogoch was a member of Ontario's Vaccine Distribution Taskforce, which helped guide vaccine policy during the initial rollout of COVID-19 vaccines between December 2020 through August 2021. Dr. Bogoch explains the unique vaccine policy in the Province of Ontario and in particular the social innovation around prioritising the most vulnerable and disadvantaged neighbourhoods first, thus leading to an important intra-regional social policy view of vaccine efforts on the path beyond the 'emergency phase' of the COVID-19 pandemic. What is clearly obvious from his presentation is the heightened role of urban geography tools and techniques and intra-regional policy in vaccine equity efforts. Policy lessons learned in Ontario may help us sort out future urban, social, economic, epidemiologic and public health challenges and their sometimes-complex intersections in regions, economy and society. The following is an edited transcript from Dr. Bogoch's talk.

COVID-19 in Canada-The Fourth Through Seventh Waves.

This Viewpoint discusses Canada's experience and response to COVID-19 pandemic­related events during the fourth through seventh waves.

SARS-CoV-2 rapid antigen screening of asymptomatic employees: a pilot project.

SETTING: Rapid antigen screening can be effective in identifying infectious individuals in occupational settings to reduce transmission and outbreaks. We report results from a pilot project at the Greater Toronto Airports Authority (GTAA) and describe the operationalization. Toronto Pearson is a large international airport encompassing over 400 employers and, pre-pandemic, with approximately 50,000 employees. INTERVENTION: An employee screening program was piloted between March 8 and May 28, 2021, to implement rapid antigen testing for asymptomatic employees. Recruitment targeted enrolment of 400 employees and yielded participation of 717 from 58 companies. Employees were recommended to book three times per week for nasal swabs on site, and were tested on the Abbot PanbioTM rapid antigen test. No action was taken from a negative result, and if positive, the employee was told to isolate at home and obtain a confirmatory polymerase chain reaction test. OUTCOMES: A total of 5117 tests were performed on 717 individuals over 12 weeks; 5091 tests were negative (99.5%), and 22 individuals tested positive (3.1% positivity rate). One hundred twenty-four (17%) completed the post-participation survey. All respondents reported that testing did not change their behaviour at work with respect to public health recommendations, and only 1 (1%) reported behaviour change outside of work (socializing with family) as a result of the program. IMPLICATIONS: This pilot program identified 22 (3.1%) potentially infectious employees. Onsite testing was feasible and highly accepted by this group of employees who completed the survey. Education resulted in reasonable uptake and no substantial change in behaviour, although the survey response rate may limit generalizability. Home-based testing may facilitate larger recruitment.

RéSUMé: LIEU: Le dépistage antigénique rapide peut être efficace pour repérer les personnes infectieuses en milieu de travail afin de réduire la transmission et les éclosions. Nous rendons compte des résultats d'un projet pilote mené par l'Autorité aéroportuaire du Grand Toronto (GTAA) et nous en décrivons l'opérationnalisation. L'aéroport Toronto Pearson est un vaste aéroport international qui compte plus de 400 employeurs et, avant la pandémie, environ 50 000 employés. INTERVENTION: Un programme de dépistage au travail a fait l'objet d'un projet pilote entre le 8 mars et le 28 mai 2021 pour mettre en œuvre le dépistage antigénique rapide chez les employés asymptomatiques. Le recrutement visait l'inscription de 400 employés et a donné lieu à une participation de 717 personnes dans 58 entreprises. Il était recommandé aux employés de s'inscrire à un prélèvement nasal sur place trois fois par semaine; le test antigénique rapide d'Abbot PanbioTM était utilisé pour les prélèvements. Un résultat négatif ne donnait lieu à aucune mesure, mais si le résultat était positif, l'employé recevait l'instruction de s'isoler à la maison et d'obtenir un test de réaction de polymérisation en chaîne pour confirmer. RéSULTATS: En tout, 5 117 tests ont été effectués sur 717 personnes sur une période de 12 semaines; 5 091 tests (99,5 %) ont été négatifs, et 22 ont été positifs (taux de positivité de 3,1 %). Cent vingt-quatre personnes (17 %) ont répondu au sondage après la participation. Tous les répondants ont déclaré que le dépistage n'avait pas changé leur comportement au travail en ce qui a trait aux recommandations sanitaires, et une seule personne (1 %) a déclaré avoir changé ses comportements en dehors du travail (sa socialisation en famille) en raison du programme. CONSéQUENCES: Ce programme pilote a repéré 22 employés potentiellement infectieux (3,1 %). Le dépistage sur place était faisable et a été bien accepté par le groupe d'employés ayant répondu au sondage. La sensibilisation a donné lieu à une participation raisonnable sans modification sensible des comportements, mais le faible taux de réponse au sondage pourrait limiter la généralisabilité des résultats. Le dépistage à domicile pourrait favoriser un meilleur recrutement.

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).

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada.

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.

Development of a repeated-measures predictive model and clinical risk score for mortality in ventilated COVID-19 patients.

PURPOSE: The COVID-19 pandemic has caused intensive care units (ICUs) to reach capacities requiring triage. A tool to predict mortality risk in ventilated patients with COVID-19 could inform decision-making and resource allocation, and allow population-level comparisons across institutions. METHODS: This retrospective cohort study included all mechanically ventilated adults with COVID-19 admitted to three tertiary care ICUs in Toronto, Ontario, between 1 March 2020 and 15 December 2020. Generalized estimating equations were used to identify variables predictive of mortality. The primary outcome was the probability of death at three-day intervals from the time of ICU admission (day 0), with risk re-calculation every three days to day 15; the final risk calculation estimated the probability of death at day 15 and beyond. A numerical algorithm was developed from the final model coefficients. RESULTS: One hundred twenty-seven patients were eligible for inclusion. Median ICU length of stay was 26.9 (interquartile range, 15.4-52.0) days. Overall mortality was 42%. From day 0 to 15, the variables age, temperature, lactate level, ventilation tidal volume, and vasopressor use significantly predicted mortality. Our final clinical risk score had an area under the receiver-operating characteristics curve of 0.9 (95% confidence interval [CI], 0.8 to 0.9). For every ten-point increase in risk score, the relative increase in the odds of death was approximately 4, with an odds ratio of 4.1 (95% CI, 2.9 to 5.9). CONCLUSION: Our dynamic prediction tool for mortality in ventilated patients with COVID-19 has excellent diagnostic properties. Notwithstanding, external validation is required before widespread implementation.

RéSUMé: OBJECTIF: En raison de la pandémie de COVID-19, les unités de soins intensifs (USI) ont atteint des taux d'occupation nécessitant un triage. Un outil pour prédire le risque de mortalité chez les patients sous ventilation atteints de COVID-19 pourrait éclairer la prise de décision et l'attribution des ressources tout en permettant des comparaisons populationnelles entre les établissements. MéTHODE: Cette étude de cohorte rétrospective a inclus tous les adultes atteints de COVID-19 sous ventilation mécanique admis dans trois USI de centres de soins tertiaires à Toronto, en Ontario, entre le 1er mars 2020 et le 15 décembre 2020. Des équations d'estimation généralisées ont été utilisées pour identifier les variables prédictives de mortalité. Le critère d'évaluation principal était la probabilité de décès à des intervalles de trois jours à partir du moment de l'admission à l'USI (jour 0), avec un nouveau calcul du risque tous les trois jours jusqu'au jour 15; le calcul final du risque a estimé la probabilité de décès au jour 15 et au-delà. Un algorithme numérique a été mis au point à partir des coefficients du modèle final. RéSULTATS: Cent vingt-sept patients étaient éligibles à l'inclusion. La durée médiane de séjour à l'USI était de 26,9 jours (écart interquartile, 15,4 à 52,0). La mortalité globale était de 42 %. Du jour 0 au jour 15, les variables que sont l'âge, la température, les taux de lactate, le volume courant de ventilation et l'utilisation de vasopresseurs ont constitué des prédicteurs significatifs de mortalité. Notre score de risque clinique final avait une aire sous la courbe ROC de 0,9 (intervalle de confiance [IC] à 95 %, 0,8 à 0,9). Pour chaque augmentation de dix points du score de risque, l'augmentation relative des risques de décès était d'environ 4, avec un rapport de cotes de 4,1 (IC 95 %, 2,9 à 5,9). CONCLUSION: Notre outil de prédiction dynamique de la mortalité pour les patients ventilés atteints de COVID-19 possède d'excellentes propriétés diagnostiques. Néanmoins, une validation externe est nécessaire avant sa mise en œuvre généralisée.

Geographic Clustering of Travel-acquired Infections in Ontario, Canada, 2008-2020

Background As rates of international travel increase, more individuals are at risk of travel-acquired infections (TAIs). We aimed to review all microbiologically confirmed cases of malaria, dengue, chikungunya, and enteric fever (Salmonella enterica serovar Typhi/Paratyphi) in Ontario, Canada between 2008-2020 to identify high-resolution geographical clusters that could be targeted for pre-travel prevention. Methods Retrospective cohort study of over 174,000 unique tests for the four above TAIs from Public Health Ontario Laboratories. Test-level data were processed to calculate annual case counts and crude population-standardized incidence ratios (SIRs) at the forward sortation area (FSA) level. Moran’s I statistic was used to test for global spatial autocorrelation. Smoothed SIRs and 95% posterior credible intervals (CIs) were estimated using a spatial Bayesian hierarchical model, which accounts for statistical instability and uncertainty in small-area incidence. Posterior CIs were used to identify high- and low-risk areas, which were described using sociodemographic data from the 2016 Census. Finally, a second model was used to estimate the association between drivetime to the nearest travel clinic and risk of TAI within high-risk areas. Results There were 5962 cases of the four TAIs across Ontario over the study period. Smoothed FSA-level SIRs are shown in Figure 1a, with an inset for the Greater Toronto Area (GTA) in 1b. There was spatial clustering of TAIs (Moran’s I=0.61, p< 2.2e-16). Identified high- and low-risk areas are shown in panels c and d. Compared to low-risk areas, high-risk areas were significantly more likely to have higher proportions of immigrants (p< 0.0001), lower household after-tax income (p=0.04), more university education (p< 0.0001), and were less knowledgeable of English/French (p< 0.0001). In the high-risk GTA, each minute increase in drivetime to the closest travel clinic was associated with a 4% reduction in TAI risk (95% CI 2 - 6%). Bayesian hierarchical model (BHM) smoothed standardized incidence ratios (SIRs) for travel-acquired infections (TAIs) and estimated risk levels (a and c) with insets for the Greater Toronto Area (b and d). High-risk areas are defined as those with smoothed SIR 95% CIs greater than 2, and low-risk areas with smoothed SIR 95% CIs less than 0.25. Conclusion Urban neighbourhoods in the GTA had elevated risks of becoming ill with TAIs. However, geographic proximity to a travel clinic was not associated with an area-level risk reduction in TAI, suggesting other barriers to seeking and adhering to pre-travel advice. Disclosures Isaac Bogoch, MD, MSc, BlueDot (Consultant)National Hockey League Players' Association (Consultant) Andrea Boggild, MSc MD DTMH FRCPC, Nothing to disclose Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK (Speaker's Bureau)Pfizer (Advisor or Review Panel member)Pfizer (Grant/Research Support)

Complications of Critical COVID-19: Diagnostic and Therapeutic Considerations for the Mechanically Ventilated Patient.

Patients admitted to the ICU with critical COVID-19 often require prolonged periods of mechanical ventilation. Difficulty weaning, lack of progress, and clinical deterioration are commonly encountered. These conditions should prompt a thorough evaluation for persistent or untreated manifestations of COVID-19, as well as complications from COVID-19 and its various treatments. Inflammation may persist and lead to fibroproliferative changes in the lungs. Infectious complications may arise including bacterial superinfection in the earlier stages of disease. Use of immunosuppressants may lead to the dissemination of latent infections, and to opportunistic infections. Venous thromboembolic disease is common, as are certain neurologic manifestations of COVID-19 including delirium and stroke. High levels of ventilatory support may lead to ventilator-induced injury to the lungs and diaphragm. We present diagnostic and therapeutic considerations for the mechanically ventilated patient with COVID-19 who shows persistent or worsening signs of critical illness, and we offer an approach to treating this complex but common scenario.

COVID-19 vaccination intention during early vaccine rollout in Canada: a nationwide online survey.

BACKGROUND: Understanding vaccination intention during early vaccination rollout in Canada can help the government's efforts in vaccination education and outreach. METHOD: Panel members age 18 and over from the nationally representative Angus Reid Forum were invited to complete an online survey about their experience with COVID-19, including their intention to get vaccinated. Respondents were asked "When a vaccine against the coronavirus becomes available to you, will you get vaccinated or not?" Having no intention to vaccinate was defined as choosing "No - I will not get a coronavirus vaccination" as a response. Odds ratios and predicted probabilities are reported for no vaccine intentionality in demographic groups. FINDINGS: 14,621 panel members completed the survey. Having no intention to vaccinate against COVID-19 is relatively low overall (9%) with substantial variation among demographic groups. Being a resident of Alberta (predicted probability = 15%; OR 0.58 [95%CI 0.14-2.24]), aged 40-59 (predicted probability = 12%; OR 0.87 [0.78-0.97]), identifying as a visible minority (predicted probability = 15%; OR 0.56 [0.37-0.84]), having some college level education or lower (predicted probability = 14%) and living in households of at least five members (predicted probability = 13%; OR 0.82 [0.76-0.88]) are related to lower vaccination intention. INTERPRETATION: The study identifies population groups with greater and lesser intention to vaccinate in Canada. As the Canadian COVID-19 vaccination effort continues, policymakers may use this information to focus outreach, education, and other efforts on the latter groups, which also have had higher risks for contracting and dying from COVID-19. FUNDING: Pfizer Global Medical, Unity Health Foundation, Canadian COVID-19 Immunity Task Force.

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.