Projecting the seasonality of endemic COVID-19 (preprint)

Importance Successive waves of infection by SARS-CoV-2 have left little doubt that COVID-19 will transition to an endemic disease, yet the future seasonality of COVID-19 remains one of its most consequential unknowns. Foreknowledge of spatiotemporal surges would have immediate and long-term consequences for medical and public health decision-making. Objective To estimate the impending endemic seasonality of COVID-19 in temperate population centers via a phylogenetic ancestral and descendent states approach that leverages long-term data on the incidence of circulating coronaviruses. Design We performed a comparative evolutionary analysis on literature-based monthly verified cases of HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43 infection within populations across the Northern Hemisphere. Ancestral and descendent states analyses on human-infecting coronaviruses provided projections of the impending seasonality of endemic COVID-19. Setting Quantitative projections of the endemic seasonality of COVID-19 were based on human endemic coronavirus infection incidence data from New York City (USA); Denver (USA); Tampere (Finland); Trøndelag (Norway); Gothenburg (Sweden); Stockholm (Sweden); Amsterdam (Netherlands); Beijing (China); South Korea (Nationwide); Yamagata (Japan); Hong Kong; Nakon Si Thammarat (Thailand); Guangzhou (China); and Sarlahi (Nepal). Main Outcome(s) and Measure(s) The primary projection was the monthly relative frequency of SARS-CoV-2 infections in each geographic locale. Four secondary outcomes consisted of empirical monthly relative frequencies of the endemic human-infecting coronaviruses HCoV-NL63, -229E, -HKU1, and -OC43. Results We project asynchronous surges of SARS-CoV-2 across locales in the Northern Hemisphere. In New York City, SARS-CoV-2 incidence is projected in late fall and winter months (Nov.–Jan.), In Tampere, Finland; Yamagata, Japan; and Sarlahi, Nepal incidence peaks in February. Gothenburg and Stockholm in Sweden reach peak incidence between November and February. Guangzhou, China; and South Korea. In Denver, incidence peaks in early Spring (Mar.). In Amsterdam, incidence rises in late fall (Dec.), and declines in late spring (Apr.). In Hong Kong, the projected apex of infection is in late fall (Nov.–Dec.), yet variation in incidence is muted across other seasons. Seasonal projections for Nakhon Si Thammarat, Thailand and for Beijing, China are muted compared to other locations. Conclusions and Relevance This knowledge of likely spatiotemporal surges of COVID-19 is fundamental to medical preparedness and expansions of public health interventions that anticipate the impending endemicity of this disease and mitigate COVID-19 transmission. These results provide crucial guidance for adaptive public health responses to this disease, and are vital to the long-term mitigation of COVID-19 transmission. Key Points Question Under endemic conditions, what are the projected spatiotemporal seasonal surges of COVID-19? Findings We applied a phylogenetic ancestral and descendent states approach, leveraging long-term data on the incidence of circulating coronaviruses. We found that seasonal surges are expected in or near the winter months; dependent on the specific population center, infections are forecasted to surge in the late fall, winter, or early spring. Meaning Globally, endemic COVID-19 surges should be expected to occur asynchronously, often coincident with local expected surges of other human-infecting respiratory viruses.

Impact of accelerating booster vaccination amidst Omicron surge in the United States (preprint)

COVID-19 infections driven by the Omicron variant are sweeping across the United States. Although early evidence suggests that the Omicron variant may cause less severe disease than previous variants, the explosive spread of infections threatens to drive hospitalizations and deaths to unprecedented high levels, swamping already overburdened hospitals. Booster vaccination appears to be effective at preventing severe illness and hospitalization. However, the pace of booster vaccination in the US has been slow despite the available infrastructure to administer doses at a much higher rate. We used an age-stratified, multi-variant agent-based model to project the reduction in COVID-related deaths and hospitalizations that could be achieved by accelerating the current daily pace of booster vaccination in the US. We found that doubling the rate of booster vaccination would prevent over 400,000 hospitalizations and 48,000 deaths. Tripling the booster vaccination rate would avert over 600,000 hospitalizations and save 70,000 lives during the first four months of 2022.

Lives saved and hospitalizations averted by COVID-19 vaccination in New York City (preprint)

Despite the emergence of highly transmissible variants, the number of cases in NYC has fallen from over 5,500 average daily cases in January, 2020 to less than 350 average daily cases in July, 2021. The impact of vaccination in saving lives and averting hospitalizations in NYC has not been formally investigated yet. We used an age-stratified agent-based model calibrated to COVID-19 transmission and vaccination in NYC to evaluate the impact of the vaccination campaign in suppressing the COVID-19 burden. We found that the vaccination campaign has prevented over 250,000 COVID-19 cases, 44,000 hospitalizations and 8,300 deaths from COVID-19 infection since the start of vaccination through July 1, 2021. Notably, the swift vaccine rollout suppressed another wave of COVID-19 that would have led to sustained increase in cases, hospitalizations and deaths during spring triggered by highly transmissible variants. As the Delta variant sweeps across the city, the findings of this study underscore the urgent need to accelerate vaccination and close the vaccine coverage gaps across the city.

COVID-19 deaths and hospitalizations averted by rapid vaccination rollout in the United States (preprint)

Importance Randomized clinical trials have shown that the COVID-19 vaccines currently approved in the US are highly efficacious. However, more evidence is needed to understand the population-level impact of the US vaccination rollout in the face of the changing landscape of COVID-19 pandemic in the US, including variants with higher transmissibility and immune escape. Objective To quantify the population-level impact of the US vaccination campaign in averting cases, hospitalizations and deaths from December 12, 2020 to June 28, 2021. Design Age-stratified agent-based model which included transmission dynamics of the Alpha, Gamma and Delta variants in addition to the original Wuhan-1 variant. Setting Our model was calibrated to COVID-19 outbreak and vaccine rollout in the US. Model predictions were made at the country level. Participants Simulated age-stratified population representing US demographics. Main Outcomes and Measures Cases, hospitalizations and deaths averted by vaccination against COVID-19 in the US, compared to the counterfactuals of no vaccination and vaccination administered at half the actual pace. Results The swift vaccine rollout in the US curbed a potential resurgence of cases in April 2021, which would have been otherwise fuelled by the Alpha variant. Compared to the scenario without vaccines, we estimated that the actual vaccination program averted more than 26 million cases, 1.2 million hospitalizations and saved 279,000 lives. A vaccination campaign with half the actual rollout rate would have led to an additional 460,000 hospitalizations and 121,000 deaths. Conclusions and Relevance The COVID-19 vaccination campaign in the US has had an extraordinary impact on reducing disease burden despite the emergence of highly transmissible variants. These findings highlight that the pace of vaccination was essential for mitigating COVID-19 in the US, and underscore the urgent need to close the vaccine coverage gaps in communities across the country. Key Points Question How effective was the United States (US) vaccination campaign in suppressing COVID-19 burden? Findings The vaccination campaign was highly effective in curbing the COVID-19 outbreak in the US. We estimated that the vaccine rollout saved over 275,000 lives and averted 1.2 million hospitalizations. Meaning The swift vaccine rollout in the US averted a remarkable number of cases, hospitalizations and deaths despite the emergence of highly transmissible variants.

Quantifying the potential dominance of immune-evading SARS-CoV-2 variants in the United States (preprint)

Recent evidence suggests that some new SARS-CoV-2 variants with spike mutations, such as P.1 (Gamma) and B.1.617.2 (Delta), exhibit partial immune evasion to antibodies generated by natural infection or vaccination. By considering the Gamma and Delta variants in a multi-variant transmission dynamic model, we evaluated the dominance of these variants in the United States (US) despite mounting vaccination coverage and other circulating variants. Our results suggest that while the dominance of the Gamma variant is improbable, the Delta variant would become the most prevalent variant in the US, driving a surge in infections and hospitalizations. Our study highlights the urgency for accelerated vaccination and continued adherence to non-pharmaceutical measures until viral circulation is driven low.

Evaluation of COVID-19 vaccination strategies with a delayed second dose (preprint)

COVID-19 vaccines currently approved in the United States require two doses, administered three to four weeks apart. Constraints in vaccine supply and distribution capacity, together with the rise of COVID-19 cases and hospitalizations, have sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose, or to continue with the recommended two-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these two vaccination strategies, while varying the temporal waning of vaccine efficacy against disease following the first dose, vaccine efficacy against infection, and the level of pre-existing immunity in the population. Our results show that for Moderna vaccines with 80% efficacy following the first dose, a delay of 9-12 weeks could enhance the program effectiveness and prevent additional infections, hospitalizations, and deaths, compared to a 4-week interval between the doses. However, for Pfizer-BioNTech vaccines with demonstrated efficacy of 52% after the first dose, there was no clear advantage for delaying the second dose beyond the 3-week tested schedule, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the durability of vaccine-induced protection after the first dose as well as vaccine efficacy against infection in order to determine the optimal time interval between the two doses.

Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada (preprint)

BackgroundCOVID-19 has caused severe outbreaks in Canadian long-term care facilities (LTCFs). ObjectiveTo evaluate the effect of mitigation measures in LTCFs including routine testing of staff and vaccination of staff and residents. DesignAgent-based transmission model parameterized with disease-specific estimates, temporal sensitivity of nasopharyngeal (NP) and saliva testing, preliminary results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. SettingCharacteristics of staff and residents were included in the model with age-dependent risk of hospitalization and deaths, calibrated to the cumulative incidence of COVID-19 reported in these settings. ParticipantsSynthetic staff and resident populations. InterventionsRoutine NP and saliva testing of staff; vaccination of residents and staff. MeasurementsDaily incidence and attack rates in the LTCF using large-scale model simulations; estimates of hospitalizations and deaths and their 95% credible intervals. ResultsWeekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 20.3% (95% CrI: 18.7-21.8%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 81.4% (95% CrI: 80.6-82.2%), and 82.1% (95% CrI: 81.5-82.7%), respectively. LimitationsTimelines of vaccine distribution and compliance rates with routine testing are key parameters affecting strategy outcomes. ConclusionRoutine testing of staff reduces silent transmission in LTCFs. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.

The effect of extended closure of red-light areas on COVID-19 transmission in India (preprint)

The novel coronavirus disease (COVID-19) pandemic has resulted in over 200,000 cases in India. Thus far, India has implemented lockdown measures to curb disease transmission. However, commercial sex work in red-light areas (RLAs) has potential to lead to COVID-19 resurgence after lockdown. We developed a model of COVID-19 transmission in RLAs, evaluating the impact of extended RLA closure compared with RLA reopening on cases, hospitalizations, and mortality rates within the RLAs of five major Indian cities, within the cities, and across India. Closure lowered transmission at all scales. More than 90% of cumulative cases and deaths among RLA residents of Kolkata, Pune, and Nagpur could be averted by the time the epidemic would peak under a re-opening scenario. Across India, extended closure of RLAs would benefit the population at large, delaying the peak of COVID-19 cases by 8 to 23 days, and avert 32% to 60.2% of cumulative cases and 43% to 67.6% of cumulative deaths at the peak of the epidemic. Extended closure of RLAs until better prevention and treatment strategies are developed would benefit public health in India.