Estimating the population effectiveness of interventions against COVID-19 in France: a modelling study (preprint)

Background Non-pharmaceutical interventions (NPIs) and vaccines have been widely used to manage the COVID-19 pandemic. However, uncertainty persists regarding the effectiveness of these interventions due to data quality issues, methodological challenges, and differing contextual factors. Accurate estimation of their effects is crucial for future epidemic preparedness. Methods To address this, we developed a population-based mechanistic model that includes the impact of NPIs and vaccines on SARS-CoV-2 transmission and hospitalization rates. Our statistical approach estimated all parameters in one step, accurately propagating uncertainty. We fitted the model to comprehensive epidemiological data in France from March 2020 to October 2021. With the same model, we simulated scenarios of vaccine rollout. Results The first lockdown was the most effective, reducing transmission by 84% (95% confidence interval (CI) 83-85). Subsequent lockdowns had diminished effectiveness (reduction of 74% (69-77) and 11% (9-18), respectively). A 6pm curfew was more effective than one at 8 pm (68% (66-69) vs. 48% (45-49) reduction), while school closures reduced transmission by 15% (12-18). In a scenario without vaccines before November 2021, we predicted 159,000 or 194% (95% prediction interval (PI) 74-424) more deaths and 1,488,000 or 340% (136-689) more hospitalizations. If a vaccine had been available after 100 days, over 71,000 deaths (16,507-204,249) and 384,000 (88,579-1,020,386) hospitalizations could have been averted. Conclusion Our results highlight the substantial impact of NPIs, including lockdowns and curfews, in controlling the COVID-19 pandemic. We also demonstrate the value of the 100 days objective of the CEPI initiative for vaccine availability.

Protective effectiveness of prior SARS-CoV-2 infection and hybrid immunity against Omicron infection and severe disease: a systematic review and meta-regression (preprint)

Background We aimed to systematically review the magnitude and duration of the protective effectiveness of prior infection (PE) and hybrid immunity (HE) against Omicron infection and severe disease. Methods We searched pre-print and peer-reviewed electronic databases for controlled studies from January 1, 2020, to June 1, 2022. Risk of bias (RoB) was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I)-Tool. We used random-effects meta-regression to estimate the magnitude of protection at 1-month intervals and the average change in protection since the last vaccine dose or infection from 3 months to 6 or 12 months. We compared our estimates of PE and HE to previously published estimates of the magnitude and durability of vaccine effectiveness (VE) against Omicron. Findings Eleven studies of prior infection and 15 studies of hybrid immunity were included. For prior infection, there were 97 estimates (27 at moderate RoB and 70 at serious RoB), with the longest follow up at 15 months. PE against hospitalization or severe disease was 82.5% [71.8-89.7%] at 3 months, and 74.6% [63.1-83.5%] at 12 months. PE against reinfection was 65.2% [52.9-75.9%] at 3 months, and 24.7% [16.4-35.5%] at 12 months. For HE, there were 153 estimates (78 at moderate RoB and 75 at serious RoB), with the longest follow up at 11 months for primary series vaccination and 4 months for first booster vaccination. Against hospitalization or severe disease, HE involving either primary series vaccination or first booster vaccination was consistently >95% for the available follow up. Against reinfection, HE involving primary series vaccination was 69.0% [58.9-77.5%] at 3 months after the most recent infection or vaccination, and 41.8% [31.5-52.8%] at 12 months, while HE involving first booster vaccination was 68.6% [58.8-76.9%] at 3 months, and 46.5% [36.0-57.3%] at 6 months. Against hospitalization or severe disease at 6 months, hybrid immunity with first booster vaccination (effectiveness 95.3% [81.9-98.9%]) or with primary series alone (96.5% [90.2-98.8%]) provided significantly greater protection than prior infection alone (80.1% [70.3-87.2%]), first booster vaccination alone (76.7% [72.5-80.4%]), or primary series alone (64.6% [54.5-73.6%]). Results for protection against reinfection were similar. Interpretation Prior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. All protection estimates waned quickly against infection but remained high for hospitalisation or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection against all outcomes, reinforcing the global imperative for vaccination.

Mortality trends and lengths of stay among hospitalized COVID-19 patients in Ontario and Quebec (Canada): a population-based cohort study of the first three epidemic waves (preprint)

BackgroundEpidemic waves of COVID-19 strained hospital resources. We describe temporal trends in mortality risk and length of stay in intensive cares units (ICUs) among COVID-19 patients hospitalized through the first three epidemic waves in Canada. MethodsWe used population-based provincial hospitalization data from Ontario and Quebec to examine mortality risk and lengths of ICU stay. For each province, adjusted estimates were obtained using marginal standardization of logistic regression models, adjusting for patient-level characteristics and hospital-level determinants. ResultsUsing all hospitalizations from Ontario (N=26,541) and Quebec (N=23,857), we found that unadjusted in-hospital mortality risks peaked at 31% in the first wave and was lowest at the end of the third wave at 6-7%. This general trend remained after controlling for confounders. The odds of in-hospital mortality in the highest hospital occupancy quintile was 1.2 (95%CI: 1.0-1.4; Ontario) and 1.6 (95%CI: 1.3-1.9; Quebec) times that of the lowest quintile. Variants of concerns were associated with an increased in-hospital mortality. Length of ICU stay decreased over time from a mean of 16 days (SD=18) to 15 days (SD=15) in the third wave but were consistently higher in Ontario than Quebec by 3-6 days. ConclusionIn-hospital mortality risks and lengths of ICU stay declined over time in both provinces, despite changing patient demographics, suggesting that new therapeutics and treatment, as well as improved clinical protocols, could have contributed to this reduction. Continuous population-based monitoring of patient outcomes in an evolving epidemic is necessary for health system preparedness and response.

Evaluation of real-life use of Point-Of-Care Rapid Antigen TEsting for SARS-CoV-2 in schools for outbreak control (EPOCRATES) (preprint)

AbstractO_ST_ABSBackgroundC_ST_ABSWe evaluated the use of rapid antigen detection tests (RADT) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school settings to determine RADTs performance compared to PCR. MethodsIn this real-world, prospective observational cohort study, high-school students and staff were recruited from two high-schools in Montreal (Canada) and followed from January 25th to June 10th, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared to other high schools in the same area. ResultsOverall, 2,099 students and 286 school staff members consented to participate. The overall RADTs specificity varied from 99.8 to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR on D6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 57 (72.5%) were secondary to household transmission, 13 (25%) to intra-school transmission and one to community contacts between students in the same school. ConclusionRADT did not perform well as a screening tool in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADT on the spot may avoid subsequent significant exposures in class. Table of Contents SummaryRapid antigen tests were compared to standard PCR to diagnose SARS-CoV-2 infections in high-school students. They performed better in symptomatic individuals. Whats Known on This SubjectRapid antigen detection tests (RADT) are often used to diagnose respiratory pathogens at the point-of-care. Their performance characteristics vary, but they usually have high specificity and moderate sensitivity compared with PCR. What This Study AddsRADT sensitivity ranged from 28.6% in asymptomatic individuals to 83.3% in symptomatic individuals. Return to school after 7 days of quarantine was safe in exposed students. Secondary cases were identified in 28% of classes with an index case.

Geographical concentration of COVID-19 cases by social determinants of health in 16 large metropolitan areas in Canada - a cross-sectional study (preprint)

Background: There is a growing recognition that strategies to reduce SARS-CoV-2 transmission should be responsive to local transmission dynamics. Studies have revealed inequalities along social determinants of health, but little investigation was conducted surrounding geographic concentration within cities. We quantified social determinants of geographic concentration of COVID-19 cases across sixteen census metropolitan areas (CMA) in four Canadian provinces. Methods: We used surveillance data on confirmed COVID-19 cases at the level of dissemination area. Gini (co-Gini) coefficients were calculated by CMA based on the proportion of the population in ranks of diagnosed cases and each social determinant using census data (income, education, visible minority, recent immigration, suitable housing, and essential workers) and the corresponding share of cases. Heterogeneity was visualized using Lorenz (concentration) curves. Results: Geographic concentration was observed in all CMAs (half of the cumulative cases were concentrated among 21-35% of each city's population): with the greatest geographic heterogeneity in Ontario CMAs (Gini coefficients, 0.32-0.47), followed by British Columbia (0.23-0.36), Manitoba (0.32), and Quebec (0.28-0.37). Cases were disproportionately concentrated in areas with lower income, education attainment, and suitable housing; and higher proportion of visible minorities, recent immigrants, and essential workers. Although a consistent feature across CMAs was concentration by proportion visible minorities, the magnitude of concentration by social determinants varied across CMAs. Interpretation: The feature of geographical concentration of COVID-19 cases was consistent across CMAs, but the pattern by social determinants varied. Geographically-prioritized allocation of resources and services should be tailored to the local drivers of inequalities in transmission in response to SARS-CoV-2's resurgence.

Inferring global-scale temporal latent topics from news reports to predict public health interventions for COVID-19 (preprint)

The COVID-19 global pandemic has highlighted the importance of non-pharmacological interventions (NPI) for controlling epidemics of emerging infectious diseases. Despite the importance of NPI, their implementation has been monitored in an ad hoc and uncoordinated manner, mainly through the manual efforts of volunteers. Given the absence of systematic NPI tracking, authorities and researchers are limited in their ability to quantify the effectiveness of NPI and guide decisions regarding their use during the progression of a global pandemic. To address this issue, we propose 3-stage machine learning framework called EpiTopics to facilitate the surveillance of NPI by mining the vast amount of unlabelled news reports about these interventions. Building on topic modeling, our method characterizes online government reports and media articles related to COVID-19 as a mixture of latent topics. Our key contribution is the use of transfer-learning to address the limited number of NPI-labelled documents and topic modelling to support interpretation of the results. At stage 1, we trained a modified version of the unsupervised dynamic embedded topic model (DETM) on 1.2 million international news reports related to COVID-19. At stage 2, we used the trained DETM to infer topic mixture from a small set of 2000 NPI-labelled WHO documents as the input features for predicting NPI labels on each document. At stage 3, we supply the inferred country-level temporal topics from the DETM to the pretrained document-level NPI classifier to predict country-level NPIs. We identified 25 interpretable topics, over 4 distinct and coherent COVID-related themes. These topics contributed to significant improvements in predicting the NPIs labelled in the WHO documents and in predicting country-level NPIs. Together, our work lay the machine learning methodological foundation for future research in global-scale surveillance of public health interventions. The EpiTopics code is available at GitHub: https://github.com/li-lab-mcgill/covid-npi.

Effectiveness of quarantine and testing to prevent COVID-19 transmission from arriving travelers (preprint)

New COVID-19 transmission from arriving travelers represent a major risk. Countries have used various risk mitigation strategies, including travel bans and mandatory quarantine and testing. We developed a mathematical simulation to evaluate the effectiveness of quarantine and testing, alone and in combination, across a variety of scenarios. We found that quarantine was more effective than testing alone, even for quarantine as short as two days, and the value of adding testing to quarantine diminished for longer quarantine durations. Testing was most effective if performed near the end of quarantine, but testing upon arrival may be more effective in situations where compliance with later testing cannot be enforced. Compliance of travelers and the percent of infections that were asymptomatic greatly influenced policy effectiveness.

Importation of SARS-CoV-2 following the "semaine de relache" and Quebec's (Canada) COVID-19 burden - a mathematical modeling study (preprint)

Background: The Canadian epidemics of COVID-19 exhibit distinct early trajectories, with Quebec bearing a very high initial burden. The semaine de relache, or March break, took place two weeks earlier in Quebec as compared to the rest of Canada. This event may have played a role in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to examine the role of case importation in the early transmission dynamics of SARS-CoV-2 in Quebec. Methods: Using detailed surveillance data, we developed and calibrated a deterministic SEIR-type compartmental model of SARS-CoV-2 transmission. We explored the impact of altering the number of imported cases on hospitalizations. Specifically, we investigated scenarios without case importation after March break, and as scenarios where cases were imported with the same frequency/timing as neighboring Ontario. Results: A total of 1,544 and 1,150 returning travelers were laboratory-confirmed in Quebec and Ontario, respectively (with symptoms onset before 2020-03-25). The cumulative number of hospitalizations could have been reduced by 55% (95% credible interval [95%CrI]: 51-59%) had no cases been imported after Quebec's March break. However, had Quebec experienced Ontario's number of imported cases, cumulative hospitalizations would have only been reduced by 12% (95%CrI: 8-16%). Interpretation: Our results suggest that case importation played an important role in the early spread of COVID-19 in Quebec. Yet, heavy importation of SARS-CoV-2 in early March could be insufficient to resolve interprovincial heterogeneities in cumulative hospitalizations. The importance of other factors -public health preparedness, responses, and capacity- should be investigated.