[Communications Medicine, 9 July 2022]

Background: Rapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies.

Methods: We have conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates for 18 RA tests with emergency use authorization from The United States Food and Drug Administration and an RT-PCR test. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data.

Results: We demonstrate that the relative effectiveness of RA tests and RT-PCR testing in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting.

Conclusions: These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.

Citerank: (7) 679878Seyed MoghadasSeyed Moghadas is an infectious disease modeller whose research includes mathematical and computational modelling in epidemiology and immunology. In particular, he is interested in the theoretical and computational aspects of mathematical models describing the underlying dynamics of infectious diseases, with a particular emphasis on establishing strong links between micro (individual) and macro (population) levels.10019D3ABAB, 701037MfPH – Publications144B5ACA0, 703963Mobility859FDEF6, 704041Vaccination859FDEF6, 704045Covid-19859FDEF6, 704045Covid-19859FDEF6, 715328Nonpharmaceutical Interventions (NPIs)859FDEF6

[PNAS Nexus, 27 July 2022]

Quarantine and serial testing strategies for a disease depend principally on its incubation period and infectiousness profile. In the context of COVID-19, these primary public health tools must be modulated with successive SARS CoV-2 variants of concern that dominate transmission. Our analysis shows that (1) vaccination status of an individual makes little difference to the determination of the appropriate quarantine duration of an infected case, whereas vaccination coverage of the population can have a substantial effect on this duration, (2) successive variants can challenge disease control efforts by their earlier and increased transmission in the disease time course relative to prior variants, and (3) sufficient vaccine boosting of a population substantially aids the suppression of local transmission through frequent serial testing. For instance, with Omicron, increasing immunity through vaccination and boosters—for instance with 100% of the population is fully immunized and at least 24% having received a third dose—can reduce quarantine durations by up to 2 d, as well as substantially aid in the repression of outbreaks through serial testing. Our analysis highlights the paramount importance of maintaining high population immunity, preferably by booster uptake, and the role of quarantine and testing to control the spread of SARS CoV-2.

Background: Numerous countries have imposed strict travel restrictions during the COVID-19 pandemic, contributing to a large socioeconomic burden. The long quarantines that have been applied to contacts of cases may be excessive for travel policy.

Methods: We developed an approach to evaluate imminent countrywide COVID-19 infections after 0–14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as “sufficient.”

Findings: We present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases.

Interpretation: For nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts.

[Journal of Mathematical Biology, 25 April 2023]

We incorporate the disease state and testing state into the formulation of a COVID-19 epidemic model. For this model, the basic reproduction number is identified and its dependence on model parameters related to the testing process and isolation efficacy is discussed. The relations between the basic reproduction number, the final epidemic and peak sizes, and the model parameters are further explored numerically. We find that fast test reporting does not always benefit the control of the COVID-19 epidemic if good quarantine while awaiting test results is implemented. Moreover, the final epidemic and peak sizes do not always increase along with the basic reproduction number. Under some circumstances, lowering the basic reproduction number increases the final epidemic and peak sizes. Our findings suggest that properly implementing isolation for individuals who are waiting for their testing results would lower the basic reproduction number as well as the final epidemic and peak sizes.

[CMAJ OPEN, 6 December 2022]

Background: SARS-CoV-2 transmission has an impact on education. In this study, we assessed the performance of rapid antigen detection tests (RADTs) versus polymerase chain reaction (PCR) for the diagnosis of SARS-CoV-2 infection in school settings, and RADT use for monitoring exposed contacts.

Methods: In this real-world, prospective observational cohort study, high-school students and staff were recruited from 2 high schools in Montréal, Canada, and followed from Jan. 25 to June 10, 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 with those of other high schools in the same area.

Results: Overall, 2099 students and 286 school staff members consented to participate. The overall specificity of RADTs 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 result on days 6–7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 51 (72.5%) were secondary to household transmission, 13 (25.5%) to intraschool transmission, and 1 to community contacts between students in the same school.

Interpretation: Rapid antigen detection tests did not perform well compared with PCR in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADTs on the spot may avoid subsequent substantial exposures in class. Preprint: medRxiv — doi.org/10.1101/2021.10.13.21264960

Timely diagnosis of infection enables outbreak control through rapid isolation of index cases and subsequent contact tracing.1,2 Diagnosis of SARS-CoV-2 infection is predominantly based on polymerase chain reaction (PCR), which has a turnaround time of 24–48 hours. Rapid antigen detection tests (RADTs) are inexpensive and can be used at the point of care. They usually have high specificity and moderate sensitivity compared with PCR.3–6 Given their rapid turnaround time, RADTs allow for efficient triage and management of exposed individuals.7 The potential use of RADTs is especially relevant in schools, where outbreaks of SARS-CoV-2 infection can interrupt in-person teaching and negatively affect learning.8–11

Rapid antigen detection tests perform best in the early stages of infection, when viral load is generally high.12–15 Reported RADT sensitivity ranges from 28.9% to 98.3%, with improved sensitivity in samples with high viral loads and in symptomatic individuals.16,17 The usual limits of detection for PCR is 600–1000 viral RNA copies/mL, whereas RADTs usually have limits of detection 2–3 logs higher (105 to 106).18 Many studies have indicated the importance of high viral load dynamics with infectiousness. 19,20 For each unit increase in cycle threshold (Ct) value, the odds of recovering infectious virus decreased by 0.67, being under 10% when Ct values were greater than 35. Cycle threshold values of 17 to 32 corresponded to 105 and 101 SARS-CoV-2 RNA copies/μL, respectively.21

We aimed to determine the performance characteristics of RADTs for SARS-CoV-2 compared with PCR in high-school students and staff, and to determine whether serial testing of COVID-19 contacts would allow for safe faster return to school.

[PLoS ONE, 23 August 23, 2023]

Background: The effects of the COVID-19 pandemic have been more pronounced for socially disadvantaged populations. We sought to determine how access to SARS-CoV-2 testing and the likelihood of testing positive for COVID-19 were associated with demographic factors, socioeconomic status (SES) and social determinants of health (SDH) in three Canadian provinces.

Methods: An observational population-based cross-sectional study was conducted for the provinces of Ontario, Manitoba and New Brunswick between March 1, 2020 and April 27, 2021, using provincial health administrative data. After excluding residents of long-term care homes, those without current provincial health insurance and those who were tested for COVID-19 out of province, records from provincial healthcare administrative databases were reviewed for 16,900,661 healthcare users. Data was modelled separately for each province in accordance to a prespecified protocol and follow-up consultations among provincial statisticians and collaborators. We employed univariate and multivariate regression models to examine determinants of testing and test results.

Results: After adjustment for other variables, female sex and urban residency were positively associated with testing, while female sex was negatively associated with test positivity. In New Brunswick and Ontario, individuals living in higher income areas were more likely to be tested, whereas in Manitoba higher income was negatively associated with both testing and positivity. High ethnocultural composition was associated with lower testing rates. Both high ethnocultural composition and high situational vulnerability increased the odds of testing positive for SARS-CoV-2.

Discussion: We observed that multiple demographic, income and SDH factors were associated with SARS-CoV-2 testing and test positivity. Barriers to healthcare access identified in this study specifically relate to COVID-19 testing but may reflect broader inequities for certain at-risk groups.

[Journal of Biomedical Informatics, 28 September 2023]

Background: We often must conduct diagnostic tests on a massive volume of samples within a limited time during outbreaks of infectious diseases (e.g., COVID-19,screening) or repeat many times routinely (e.g., regular and massive screening for plant virus infections in farms). These tests aim to obtain the diagnostic result of all samples within a limited time. In such scenarios, the limitation of testing resources and human labor drives the need to pool individual samples and test them together to improve testing efficiency. When a pool is positive, further testing is required to identify the affected individuals; whereas when a pool is negative, we conclude all individuals in the pool are negative. How one splits the samples into pools is a critical factor affecting testing efficiency.

Objective: We aim to find the optimal strategy that adaptively guides users on optimally splitting the sample cohort into test-pools.

Methods: We developed an algorithm that minimizes the expected number of tests needed to obtain the diagnostic results of all samples. Our algorithm dynamically updates the critical information according to the result of the most recent test and calculates the optimal pool size for the next test. We implemented our novel adaptive sample pooling strategy into a web-based application, ADSP (https://ADSP.uvic.ca). ADSP interactively guides users on how many samples to be pooled for the current test, asks users to report the test result back and uses it to update the best strategy on how many samples to be pooled for the next test.

Results: We compared ADSP with other popular pooling methods in simulation studies, and found that ADSP requires fewer tests to diagnose a cohort and is more robust to the inaccurate initial estimate of the test cohort’s disease prevalence.

Conclusion: Our web-based application can help researchers decide how to pool their samples for grouped diagnostic tests. It improves test efficiency when grouped tests are conducted.

[Journal of Public Health Research, 12 May 2023]

Background: Public health surveillance data do not always capture all cases, due in part to test availability and health care seeking behaviour. Our study aimed to estimate under-ascertainment multipliers for each step in the reporting chain for COVID-19 in Toronto, Canada.

Design and methods: We applied stochastic modeling to estimate these proportions for the period from March 2020 (the beginning of the pandemic) through to May 23, 2020, and for three distinct windows with different laboratory testing criteria within this period.

Results: For each laboratory-confirmed symptomatic case reported to Toronto Public Health during the entire period, the estimated number of COVID-19 infections in the community was 18 (5th and 95th percentile: 12, 29). The factor most associated with under-reporting was the proportion of those who sought care that received a test.

Conclusions: Public health officials should use improved estimates to better understand the burden of COVID-19 and other similar infections.

[Infectious Disease Modelling, 14 December 2022]

Testing and isolation remain a key component of public health responses to both persistent and emerging infectious diseases. Although the value of these measures have been demonstrated in combating recent outbreaks including the COVID-19 pandemic and monkeypox, their impact depends critically on the timelines of testing and start of isolation during the course of disease. To investigate this impact, we developed a delay differential model and incorporated age-since-symptom-onset as a parameter for delay in testing. We then used the model to compare the outcomes of reverse-transcription polymerase chain reaction (RT-PCR) and rapid antigen (RA) testing methods when isolation starts either at the time of testing or at the time of test result. Parameterizing the model with estimates of SARS-CoV-2 infection and diagnostic sensitivity of the tests, we found that the reduction of disease transmission using the RA test can be comparable to that achieved by applying the RT-PCR test. Given constraints and inevitable delays associated with sample collection and laboratory assays in RT-PCR testing post symptom onset, self-administered RA tests with short turnaround times present a viable alternative for timely isolation of infectious cases.

[Canada Communicable Disease Report, April 2023]

Background: Case underreporting during the coronavirus disease 2019 (COVID-19) pandemic has been a major challenge to the planning and evaluation of public health responses. School children were often considered a less vulnerable population and underreporting rates may have been particularly high. In January 2022, the Canadian province of Newfoundland and Labrador (NL) was experiencing an Omicron variant outbreak (BA.1/BA.2 subvariants) and public health officials recommended that all returning students complete two rapid antigen tests (RATs) to be performed three days apart.

Methods: To estimate the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we asked parents and guardians to report the results of the RATs completed by K–12 students (approximately 59,000 students) using an online survey.

Results: When comparing the survey responses with the number of cases and tests reported by the NL testing system, we found that one out of every 4.3 (95% CI, 3.1–5.3) positive households were captured by provincial case count, with 5.1% positivity estimated from the RAT results and 1.2% positivity reported by the provincial testing system. Of positive test results, 62.9% (95% CI, 44.3–83.0) were reported for elementary school students, and the remaining 37.1% (95% CI, 22.7–52.9) were reported for junior high and high school students. Asymptomatic infections were 59.8% of the positive cases. Given the low survey participation rate (3.5%), our results may suffer from sample selection biases and should be interpreted with caution.

Conclusion: The underreporting ratio is consistent with ratios calculated from serology data and provides insights into infection prevalence and asymptomatic infections in school children; a currently understudied population.

[BMC Medicine, 23 November 2022]

Background: Diagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective.

Methods: To project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults.

Results: Assuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening.

Conclusions: Our findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.

At the end of 2021, with the rapid escalation of COVID19 cases due to the Omicron variant, testing centers in Canada were overwhelmed. To alleviate the pressure on the PCR testing capacity, many provinces implemented new strategies that promote self testing and adjust the eligibility for PCR tests, making the count of new cases underreported. We designed a novel compartmental model which captures the new testing guidelines, social behaviours, booster vaccines campaign and features of the newest variant Omicron. To better describe the testing eligibility, we considered the population divided into high risk and non-high-risk settings. The model is calibrated using data from January 1 to February 9, 2022, on cases and severe outcomes in Canada, the province of Ontario and City of Toronto. We conduct analyses on the impact of PCR testing capacity, self testing, different levels of reopening and vaccination coverage on cases and severe outcomes. Our results show that the total number of cases in Canada, Ontario and Toronto are 2.34 (95%CI: 1.22–3.38), 2.20 (95%CI: 1.15–3.72), and 1.97(95%CI: 1.13–3.41), times larger than reported cases, respectively. The current testing strategy is efficient if partial restrictions, such as limited capacity in public spaces, are implemented. Allowing more people to have access to PCR reduces the daily cases and severe outcomes; however, if PCR test capacity is insufficient, then it is important to promote self testing. Also, we found that reopening to a pre-pandemic level will lead to a resurgence of the infections, peaking in late March or April 2022. Vaccination and adherence to isolation protocols are important supports to the testing policies to mitigate any possible spread of the virus.

[BMC Infectious Diseases, 2 February 2024]

Background: Accurate estimation of SARS-CoV-2 re-infection is crucial to understanding the connection between infection burden and adverse outcomes. However, relying solely on PCR testing results in underreporting. We present a novel approach that includes longitudinal serologic data, and compared it against testing alone among people experiencing homelessness.

Methods: We recruited 736 individuals experiencing homelessness in Toronto, Canada, between June and September 2021. Participants completed surveys and provided saliva and blood serology samples every three months over 12 months of follow-up. Re-infections were defined as: positive PCR or rapid antigen test (RAT) results > 90 days after initial infection; new serologic evidence of infection among individuals with previous infection who sero-reverted; or increases in anti-nucleocapsid in seropositive individuals whose levels had begun to decrease.

Results: Among 381 participants at risk, we detected 37 re-infections through PCR/RAT and 98 re-infections through longitudinal serology. The comprehensive method identified 37.4 re-infection events per 100 person-years, more than four-fold more than the rate detected through PCR/RAT alone (9.0 events/100 person-years). Almost all test-confirmed re-infections (85%) were also detectable by longitudinal serology.

Conclusions: Longitudinal serology significantly enhances the detection of SARS-CoV-2 re-infections. Our findings underscore the importance and value of combining data sources for effective research and public health surveillance.

[Bioinformatics, 25 January 2024]

Motivation: Transcriptomic long-read (LR) sequencing is an increasingly cost-effective technology for probing various RNA features. Numerous tools have been developed to tackle various transcriptomic sequencing tasks (e.g. isoform and gene fusion detection). However, the lack of abundant gold-standard datasets hinders the benchmarking of such tools. Therefore, the simulation of LR sequencing is an important and practical alternative. While the existing LR simulators aim to imitate the sequencing machine noise and to target specific library protocols, they lack some important library preparation steps (e.g. PCR) and are difficult to modify to new and changing library preparation techniques (e.g. single-cell LRs).

Results: We present TKSM, a modular and scalable LR simulator, designed so that each RNA modification step is targeted explicitly by a specific module. This allows the user to assemble a simulation pipeline as a combination of TKSM modules to emulate a specific sequencing design. Additionally, the input/output of all the core modules of TKSM follows the same simple format (Molecule Description Format) allowing the user to easily extend TKSM with new modules targeting new library preparation steps.

Availability and implementation: TKSM is available as an open source software at:

https://github.com/vpc...