Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants (preprint)

The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics - such as varying levels of immunity - can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics - such as vaccination status, exposure history and age - we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.

Impact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia (preprint)

Estimation of the impact of vaccination and non-pharmaceutical interventions (NPIs) on COVID-19 incidence is complicated by several factors, including the successive emergence of SARS-CoV-2 variants of concern and changing population immunity resulting from vaccination and previous infection. We developed an age-structured multi-strain COVID-19 transmission model framework that could estimate the impact of vaccination and NPIs while accounting for these factors. We applied this framework to French Polynesia, which unlike many countries experienced multiple large COVID-19 waves from multiple variants over the course of the pandemic, interspersed with periods of elimination. We estimated that the vaccination programme averted 54.3% (95% CI 54.0-54.6%) of the 6840 hospitalisations and 60.2% (95% CI 59.9-60.5%) of the 1280 hospital deaths that would have occurred in a baseline scenario without any vaccination up to May 2022. Vaccination also averted an estimated 28.4% (95% CI 28.2-28.7%) of 193,000 symptomatic cases in the baseline scenario. We estimated the booster campaign contributed 3.4%, 2.9% and 3.3% to overall reductions in cases, hospitalisations and hospital deaths respectively. Our results suggested that removing, or altering the timings of, the lockdowns during the first two waves had non-linear effects on overall incidence owing to the resulting effect on accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.

Seroprevalence of SARS-CoV-2 Antibodies in French Polynesia and Perspective for Vaccine Strategies (preprint)

In French Polynesia, Wuhan, Delta and Omicron SARS-CoV-2 variants-of-concern (VOCs) caused epidemics with variable severities. We assessed the prevalence and titers of anti-SARS-CoV-2 antibodies related to natural infection and/or vaccination, from a representative sample (N=673) of the adult population of Tahiti recruited during November-December 2021 (after the Delta outbreak and just before the Omicron epidemic). Of the 673 participants tested, 644 (95.7%) had detectable antibodies against SARS-CoV-2-S and/or -N proteins resulting from natural infection and/or vaccination, and 388 (57.7%) were positive only for the detection of anti-N antibodies indicating natural infection. SARS-CoV-2 seroprevalence extrapolated to the adult population of Tahiti was estimated at 95.9%. Concentrations of anti-SARS-CoV-2-S antibodies significantly increased with age, number of self-reported SARS-CoV-2 infections (0 or ≥1), and number of COVID-19 vaccine doses (0, 1, 2, or 3) received by the participants. Elderly people, who are at higher risk of severe outcomes, had received more vaccine doses than younger individuals both in our sample and in the general population. The high level of antibody responses related to past infections and vaccination, especially booster doses, has likely contributed to reducing the severity of the Omicron outbreak in French Polynesia.

Unexposed populations and potential COVID-19 burden in European countries as of 21st November 2021 (preprint)

We estimate the potential remaining COVID-19 burden in 19 European countries by estimating the proportion of each country’s population that has acquired immunity to severe disease through infection or vaccination. Our results suggest that many European countries could still face a substantial burden of hospitalisations and deaths, particularly those with lower vaccination coverage, less historical transmission, and/or older populations. Continued non-pharmaceutical interventions and efforts to achieve high vaccination coverage are required in these countries to limit severe COVID-19 outcomes.

Comparison of COVID-19 vaccine prioritization strategies (preprint)

Background: For countries that have only recently started COVID-19 vaccinations, there remains a key public health question of who should be prioritized for early vaccination. Most vaccine prioritization analyses have only considered variation in risk of infection and death by age. We provide a more granular analysis with stratification by demographics, risk factors, and location. Methods: We used a simulation model to compare the impact of different prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout. We calibrated the model to demographic and location data on 28,175 COVID-19 deaths in California up to December 30, 2020, and incorporated variation in risk by occupation and comorbidity status using published estimates. We estimated the proportion of clinical cases, deaths and DALYs averted relative to a scenario of no vaccination for strategies prioritizing vaccination by a single risk factor (special population status (e.g. incarcerated individual), age, essential worker status, comorbidity status) or multiple risk factors (e.g. age and location). Results: We found that age-based targeting averted the most deaths (65% for 5 million individuals vaccinated) and DALYs (40%) of strategies targeting by a single risk factor and targeting essential workers averted the least deaths (33%) and DALYs (25%) over the first 6 months of vaccine rollout. However, targeting by two or more risk factors simultaneously averted up to 40% more DALYs. Conclusions: Our findings highlight the potential value of multiple-risk-factor targeting of COVID-19 vaccination. Where vaccine supply is limited and logistical challenges in vaccine delivery persist, age-based targeting offers a means of ensuring that vaccines reach those most at risk of poor health outcomes. If operational challenges can be overcome, more granular vaccination strategies that overlap age with other risk factors can be adopted.

Routine Asymptomatic Testing Strategies for Airline Travel During the COVID-19 Pandemic: A Simulation Analysis (preprint)

Background: Airline travel has been significantly reduced during the COVID-19 pandemic due to concern for individual risk of SARS-CoV-2 infection and population-level transmission risk from importation. Routine viral testing strategies for COVID-19 may facilitate safe airline travel through reduction of individual and/or population-level risk, although the effectiveness and optimal design of these “test-and-travel” strategies remain unclear.Methods: We developed a microsimulation of SARS-CoV-2 transmission in a cohort of airline travelers to evaluate the effectiveness of various testing strategies to reduce individual risk of infection and population-level risk of transmission. We evaluated five testing strategies in asymptomatic passengers: i) anterior nasal polymerase chain reaction (PCR) within 3 days of departure; ii) PCR within 3 days of departure and PCR 5 days after arrival; iii) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection); iv) rapid antigen test on the day of travel and PCR 5 days after arrival; and v) PCR within 3 days of arrival alone. The travel period was defined as three days prior to the day of travel and two weeks following the day of travel, and we assumed passengers followed guidance on mask wearing during this period. The primary study outcome was cumulative number of infectious days in the cohort over the travel period (population-level transmission risk); the secondary outcome was the proportion of infectious persons detected on the day of travel (individual-level risk of infection). Sensitivity analyses were conducted.Findings: Assuming a community SARS-CoV-2 incidence of 50 daily infections, we estimated that in a cohort of 100,000 airline travelers followed over the travel period, there would be a total of 2,796 (95% UI: 2,031, 4,336) infectious days with 229 (95% UI: 170, 336) actively infectious passengers on the day of travel. The pre-travel PCR test (within 3 days prior to departure) reduced the number of infectious days by 35% (95% UI: 27, 42) and identified 88% (95% UI: 76, 94) of the actively infectious travelers on the day of flight; the addition of PCR 5 days after arrival reduced the number of infectious days by 79% (95% UI: 71, 84). The rapid antigen test on the day of travel reduced the number of infectious days by 32% (95% UI: 25, 39) and identified 87% (95% UI: 81, 92) of the actively infectious travelers; the addition of PCR 5 days after arrival reduced the number of infectious days by 70% (95% UI: 65, 75). The post-travel PCR test alone (within 3 days of landing) reduced the number of infectious days by 42% (95% UI: 31, 51). The ratio of true positives to false positives varied with the incidence of infection. The overall study conclusions were robust in sensitivity analysis.Interpretation: Routine asymptomatic testing for COVID-19 prior to travel can be an effective strategy to reduce individual risk of COVID-19 infection during travel, although post-travel testing with abbreviated quarantine is likely needed to reduce population-level transmission due to importation of infection when traveling from a high to low incidence setting.Funding: NCL is supported by the University of California, San Francisco (Department of Medicine). MVK is supported in part by the National Institute on Drug Abuse of the National Institutes of Health (K99DA051534).Conflict of Interest: NCL has received grants and personal fees from the World Health Organization and the California Department of Public Health unrelated to the current study. GWR has received funding from the San Francisco Department of Public Health and the California Department of Public Health for COVID-19-related work unrelated to the current study.