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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336035

ABSTRACT

ABSTRACT Background Few studies have assessed the benefits of COVID-19 vaccines in settings where most of the population had been exposed to SARS-CoV-2 infection. Methods We conducted a cost-effectiveness analysis of COVID-19 vaccine in Kenya from a societal perspective over a 1.5-year time frame. An age-structured transmission model assumed at least 80% of the population to have prior natural immunity when an immune escape variant was introduced. We examine the effect of slow (18 months) or rapid (6 months) vaccine roll-out with vaccine coverage of 30%, 50% or 70% of the adult (> 18 years) population prioritizing roll-out in over 50-year olds (80% uptake in all scenarios). Cost data were obtained from primary analyses. We assumed vaccine procurement at $7 per dose and vaccine delivery costs of $3.90-$6.11 per dose. The cost-effectiveness threshold was USD 919. Findings Slow roll-out at 30% coverage largely targets over 50-year-olds and resulted in 54% fewer deaths (8,132(7,914 to 8,373)) than no vaccination and was cost-saving (ICER=US$-1,343 (-1,345 to - 1,341) per DALY averted). Increasing coverage to 50% and 70%, further reduced deaths by 12% (810 (757 to 872) and 5% (282 (251 to 317) but was not cost-effective, using Kenya’s cost-effectiveness threshold ($ 919.11). Rapid roll-out with 30% coverage averted 63% more deaths and was more cost-saving (ICER=$-1,607 (-1,609 to -1,604) per DALY averted) compared to slow roll-out at the same coverage level, but 50% and 70% coverage scenarios were not cost-effective. Interpretation With prior exposure partially protecting much of the Kenyan population, vaccination of young adults may no longer be cost-effective. KEY QUESTIONS What is already known? The COVID-19 pandemic has led to a substantial number of cases and deaths in low-and middle-income countries. COVID-19 vaccines are considered the main strategy of curtailing the pandemic. However, many African nations are still at the early phase of vaccination. Evidence on the cost-effectiveness of COVID-19 vaccines are useful in estimating value for money and illustrate opportunity costs. However, there is a need to balance these economic outcomes against the potential impact of vaccination. What are the new findings? In Kenya, a targeted vaccination strategy that prioritizes those of an older age and is deployed at a rapid rollout speed achieves greater marginal health impacts and is better value for money. Given the existing high-level population protection to COVID-19 due to prior exposure, vaccination of younger adults is less cost-effective in Kenya. What do the new findings imply? Rapid deployment of vaccines during a pandemic averts more cases, hospitalisations, and deaths and is more cost-effective. Against a context of constrained fiscal space for health, it is likely more prudent for Kenya to target those at severe risk of disease and possibly other vulnerable populations rather than to the whole population.

2.
Lancet Reg Health Eur ; : 100381, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1783621

ABSTRACT

Background: In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe. Methods: We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation. Findings: In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. Interpretation: We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals. Funding: World Health Organization.

3.
Wellcome Open Res ; 6: 255, 2021.
Article in English | MEDLINE | ID: covidwho-1753974

ABSTRACT

Background: In countries with weak surveillance systems, confirmed coronavirus disease 2019 (COVID-19) deaths are likely to underestimate the pandemic's death toll. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data of cemeteries in Mogadishu, Somalia during 2020 to estimate the date of introduction and other epidemiologic parameters of the early spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this low-income, crisis-affected setting. Methods: We performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number ( R 0 ) and the effect of non-pharmaceutical interventions (NPIs) up to August 2020. Results: Under the assumption that excess deaths in Mogadishu March-August 2020 were attributable to SARS-CoV-2 infections, we arrived at median estimates of November-December 2019 for the date of introduction and low R 0 estimates (1.4-1.7) reflecting the slow and early rise and long plateau of excess deaths. The date of introduction, the amount of external seeding, the infection fatality rate (IFR) and the effectiveness of NPIs are correlated parameters and not separately identifiable in a narrow range from deaths data. Nevertheless, to obtain introduction dates no earlier than November 2019 a higher population-wide IFR (≥0.7%) had to be assumed than obtained by applying age-specific IFRs from high-income countries to Somalia's age structure. Conclusions: Model fitting of excess mortality data across a range of plausible values of the IFR and the amount of external seeding suggests an early SARS-CoV-2 introduction event may have occurred in Somalia in November-December 2019. Transmissibility in the first epidemic wave was estimated to be lower than in European settings. Alternatively, there was another, unidentified source of sustained excess mortality in Mogadishu from March to August 2020.

4.
Wellcome open research ; 6, 2021.
Article in English | EuropePMC | ID: covidwho-1743757

ABSTRACT

Background: In countries with weak surveillance systems, confirmed coronavirus disease 2019 (COVID-19) deaths are likely to underestimate the pandemic’s death toll. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data of cemeteries in Mogadishu, Somalia during 2020 to estimate the date of introduction and other epidemiologic parameters of the early spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this low-income, crisis-affected setting. Methods: We performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number ( R 0) and the effect of non-pharmaceutical interventions (NPIs) up to August 2020. Results: Under the assumption that excess deaths in Mogadishu March-August 2020 were attributable to SARS-CoV-2 infections, we arrived at median estimates of November-December 2019 for the date of introduction and low R 0 estimates (1.4-1.7) reflecting the slow and early rise and long plateau of excess deaths. The date of introduction, the amount of external seeding, the infection fatality rate (IFR) and the effectiveness of NPIs are correlated parameters and not separately identifiable in a narrow range from deaths data. Nevertheless, to obtain introduction dates no earlier than November 2019 a higher population-wide IFR (≥0.7%) had to be assumed than obtained by applying age-specific IFRs from high-income countries to Somalia’s age structure. Conclusions: Model fitting of excess mortality data across a range of plausible values of the IFR and the amount of external seeding suggests an early SARS-CoV-2 introduction event may have occurred in Somalia in November-December 2019. Transmissibility in the first epidemic wave was estimated to be lower than in European settings. Alternatively, there was another, unidentified source of sustained excess mortality in Mogadishu from March to August 2020.

5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328364

ABSTRACT

Background: In countries with weak surveillance systems, confirmed coronavirus disease 2019 (COVID-19) deaths are likely to underestimate the pandemic’s death toll. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data of cemeteries in Mogadishu, Somalia during 2020 to estimate the date of introduction and other epidemiologic parameters of the early spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this low-income, crisis-affected setting. Methods: : We performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number ( R 0 ) and the effect of non-pharmaceutical interventions (NPIs) up to August 2020. Results: : Under the assumption that excess deaths in Mogadishu March-August 2020 were attributable to SARS-CoV-2 infections, we arrived at median estimates of November-December 2019 for the date of introduction and low R 0 estimates (1.4-1.7) reflecting the slow and early rise and long plateau of excess deaths. The date of introduction, the amount of external seeding, the infection fatality rate (IFR) and the effectiveness of NPIs are correlated parameters and not separately identifiable in a narrow range from deaths data. Nevertheless, to obtain introduction dates no earlier than November 2019 a higher population-wide IFR (≥0.7%) had to be assumed than obtained by applying age-specific IFRs from high-income countries to Somalia’s age structure. Conclusions: : Model fitting of excess mortality data across a range of plausible values of the IFR and the amount of external seeding suggests an early SARS-CoV-2 introduction event may have occurred in Somalia in November-December 2019. Transmissibility in the first epidemic wave was estimated to be lower than in European settings. Alternatively, there was another, unidentified source of sustained excess mortality in Mogadishu from March to August 2020.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308021

ABSTRACT

Background: The outbreak of coronavirus disease 2019 (COVID-19) started in Wuhan, China in late December 2019, and subsequently became a pandemic. Hong Kong had implemented a series of control measures since January 2020, including enhanced surveillance, isolation and quarantine, border control and social distancing. Hong Kong recorded its first case on 23 January 2020, who was a visitor from Wuhan. We analysed the surveillance data of COVID-19 to understand the transmission dynamics and epidemiology in Hong Kong. Methods:  We constructed the epidemic curve of daily COVID-19 incidence from 23 January to 6 April 2020 and estimated the time-varying reproduction number ( R t ) with the R package EpiEstim, with serial interval computed from local data. We described the demographic and epidemiological characteristics of reported cases. We computed weekly incidence by age and residential district to understand the spatial and temporal transmission of the disease. Results: COVID-19 disease in Hong Kong was characterised with local cases and clusters detected after two waves of importations, first in late January (week 4 to 6) and the second one in early March (week 9 to 10). The R t increased to approximately 2 95% credible interval (CI): 0.3-3.3) and approximately 1 (95%CI: 0.2-1.7), respectively, following these importations;it decreased to below 1 afterwards from weeks 11 to 13, which coincided with the implementation, modification and intensification of different control measures. Compared to local cases, imported cases were younger (mean age: 52 years among local cases vs 35 years among imported cases), had a lower proportion of underlying disease (9% vs 5%) and severe outcome (13% vs 5%). Cases were recorded in all districts but the incidence was highest in those in the Hong Kong Island region. Conclusions: Stringent and sustained public health measures at population level could contain the COVID-19 disease at a relatively low level.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315690

ABSTRACT

Background: Countries achieving control of COVID-19 after an initial outbreak will continue to face the risk of SARS-CoV-2 resurgence. This study explores surveillance strategies for COVID-19 containment based on polymerase chain reaction tests. Methods: Using a dynamic SEIR-type model to simulate the initial dynamics of a COVID-19 introduction, we investigate COVID-19 surveillance strategies among healthcare workers, hospital patients, and community members. We estimate surveillance sensitivity as the probability of COVID-19 detection using a hypergeometric sampling process. We identify test allocation strategies that maximise the probability of COVID-19 detection across different testing capacities. We use Beijing, China as a case study. Results: Surveillance subgroups are more sensitive in detecting COVID-19 transmission when they are defined by more COVID-19-specific symptoms. In this study, fever clinics have the highest surveillance sensitivity, followed by respiratory departments. With a daily testing rate of 0.07/1000 residents, via exclusively testing at fever clinic and respiratory departments, there would have been 598 [95% eCI: 35, 2154] and 1373 [95% eCI: 47, 5230] cases in the population by the time of first case detection, respectively. Outbreak detection can occur earlier by including non-syndromic subgroups, such as younger adults in the community, as more testing capacity becomes available. Conclusions: A multi-layer approach that considers both the surveillance sensitivity and administrative constraints can help identify the optimal allocation of testing resources and thus inform COVID-19 surveillance strategies.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296765

ABSTRACT

Introduction COVID-19 related non-pharmaceutical interventions (NPIs) led to a suppression of RSV circulation in winter 2020/21 throughout Europe and an off-season resurgence in Summer 2021 in several European countries. We explore how such temporary interruption may shape future RSV epidemiology and what factors drive the associated uncertainty. Methods We developed an age-structured dynamic transmission model to simulate pre-pandemic RSV infections and hospitalisations. We sampled parameters governing RSV seasonality, immunity acquisition and duration of post-infection immunity and retained those simulations that qualitatively fit the UK’s pre-pandemic epidemiology. From Spring 2020 to Summer 2021 we assumed a 50% reduced contact frequency, returning to pre-pandemic levels from mid-May 2021. We simulated transmission forwards until 2023 and evaluated the impact of the sampled parameters on the projected trajectories of RSV hospitalisations. Results Following a lifting of contact restrictions in summer 2021 the model replicated an out-of-season resurgence of RSV. If unmitigated, paediatric RSV hospitalisation incidence in the 2021/22 season was projected to increase by 32% to 67% compared to pre-pandemic levels. The size of the increase depended most on whether infection risk was primarily determined by immunity acquired from previous exposure or general immune maturation. While infants were less affected, the increase in seasonal hospitalisation incidence exceeded 100% in 1-2 year old children and 275% in 2-5 year old children, respectively, in some simulations where immunity from previous exposure dominated. Consequently, the average age of a case increased by 1 to 5 months, most markedly if there was strong immunity acquisition from previous exposure. If immunity to infection was largely determined by age rather than previous exposure, the 2021/22 season started earlier and lasted longer but with a peak incidence lower or similar to pre-pandemic levels. For subsequent seasons, simulations suggested a quick return to pre-pandemic epidemiology, with some slight oscillating behaviour possible depending on the strength of post-exposure immunity. Conclusion COVID-19 mitigation measures stopped RSV circulation in the 2020/21 season and generated immunity debt that will likely lead to a temporary increase in RSV burden in the season following the lifting of restrictions, particularly in 1 to 5 year old children. A more accurate understanding of immunity drivers for RSV is needed to better predict the size of such an increase and plan a potential expansion of pharmaceutical and non-pharmaceutical mitigation measures.

9.
BMC Med ; 19(1): 198, 2021 08 12.
Article in English | MEDLINE | ID: covidwho-1571757

ABSTRACT

BACKGROUND: The COVID-19 pandemic has disrupted the delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to the staff delivering vaccination, the children being vaccinated, and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks. METHODS: We modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees, and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening. RESULTS: Infection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32 to 45% for vaccinators and 0.3 to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6 to 5.3% and 0.1 to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening. CONCLUSIONS: SARS-CoV-2 infection risks to vaccinators, vaccinees, and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely.


Subject(s)
COVID-19/prevention & control , Disease Outbreaks/prevention & control , Health Personnel , Immunization Programs/organization & administration , SARS-CoV-2 , Vaccination , Brazil , Burkina Faso , COVID-19/epidemiology , Child , Ethiopia , Female , Humans , Male , Pandemics , Personal Protective Equipment
10.
Proc Natl Acad Sci U S A ; 118(49)2021 12 07.
Article in English | MEDLINE | ID: covidwho-1556254

ABSTRACT

We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.8 y (95% CI 6.3 to 8.1) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Age Factors , Basic Reproduction Number , COVID-19/epidemiology , COVID-19/immunology , COVID-19/transmission , Coronavirus , Coronavirus Infections/transmission , Cross Protection , England/epidemiology , Forecasting , Humans , SARS-CoV-2 , Seasons , Wales/epidemiology
11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295186

ABSTRACT

Background: In countries with weak surveillance systems, confirmed coronavirus disease 2019 (COVID-19) deaths are likely to underestimate the pandemic’s death toll. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data of cemeteries in Mogadishu, Somalia during 2020 to estimate the date of introduction and other epidemiologic parameters of the early spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this low-income, crisis-affected setting. Methods: We performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number ( R 0 ) and the effect of non-pharmaceutical interventions (NPIs) up to August 2020. Results: Under the assumption that excess deaths in Mogadishu March-August 2020 were attributable to SARS-CoV-2 infections, we arrived at median estimates of November-December 2019 for the date of introduction and low R 0 estimates (1.4-1.7) reflecting the slow and early rise and long plateau of excess deaths. The date of introduction, the amount of external seeding, the infection fatality rate (IFR) and the effectiveness of NPIs are correlated parameters and not separately identifiable in a narrow range from deaths data. Nevertheless, to obtain introduction dates no earlier than November 2019 a higher population-wide IFR (≥0.7%) had to be assumed than obtained by applying age-specific IFRs from high-income countries to Somalia’s age structure. Conclusions: Model fitting of excess mortality data across a range of plausible values of the IFR and the amount of external seeding suggests an early SARS-CoV-2 introduction event may have occurred in Somalia in November-December 2019. Transmissibility in the first epidemic wave was estimated to be lower than in European settings. Alternatively, there was another, unidentified source of sustained excess mortality in Mogadishu from March to August 2020.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294494

ABSTRACT

Summary Background The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated effectiveness of BNT162b2 and ChAdOx1 vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods Adult index cases in the community and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment. Swabs were tested by RT-qPCR with genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Findings Between 2 February 2021 and 10 September 2021 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained of whom 113 (41%) became PCR positive. Delta lineages had 1.64 times the risk (95% Credible Interval: 1.15 – 2.44) of transmission than Alpha;contacts older than 18 years were 1.19 times (1.04 - 1.52) more likely to acquire infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 31% (−3%, 61%) and 42% (14%, 69%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 71% (12%,95%) vs 24% (−2%, 64%) respectively for BNT162b2 and 26% (−39%, 73%) vs 14% (−5%, 46%) respectively for ChAdOx1. Interpretation BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting though their protection against infection is low. Funding This study was funded by the UK Health Security Agency (formerly Public Health England) as part of the COVID-19 response.

13.
Lancet Reg Health Eur ; 12: 100267, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1540829

ABSTRACT

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection. FINDINGS: Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable. INTERPRETATION: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293018

ABSTRACT

Background: In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine could let more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals for low- and middle-income countries of Europe. Methods: We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 low- and middle-income countries in the World Health Organization European Region (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies related to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern into the model, and also conducted a benefit-risk assessment to quantify the trade-off between health benefits versus adverse events following immunisation. Findings: In 12 of the 13 countries, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20-59 years). These strategies lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.2% [range: 4.0% - 22.5%;n = 13 (countries)] more deaths. There is generally a negative association between dosing interval and COVID-19 mortality within the range we investigated. Assuming a shorter first dose waning duration of 120 days, as opposed to 360 days in the base case, led to shorter optimal dosing intervals of 8-12 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. Interpretation: We infer that longer dosing intervals of over six months, which are substantially longer than the current label recommendation for most vaccine products, could reduce COVID-19 mortality in low- and middle-income countries of WHO/Europe. Certain vaccine features, such as fast waning of first doses, significantly shorten the optimal dosing intervals.

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292887

ABSTRACT

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated effectiveness of BNT162b2 and ChAdOx1 vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Adult index cases in the community and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment. Swabs were tested by RT-qPCR with genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Findings: Between 2 February 2021 and 10 September 2021 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained of whom 113 (41%) became PCR positive. Delta lineages had 1.64 times the risk (95% Credible Interval: 1.15-2.44) of transmission than Alpha;contacts older than 18 years were 1.19 times (1.04-1.52) more likely to acquire infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 31% (-3%, 61%) and 42% (14%, 69%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 71% (12%,95%) vs 24% (-2%, 64%) respectively for BNT162b2 and 26% (-39%, 73%) vs 14% (-5%, 46%) respectively for ChAdOx1. Interpretation: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting though their protection against infection is low. Funding: This study was funded by the UK Health Security Agency (formerly Public Health England) as part of the COVID-19 response.

16.
Euro Surveill ; 26(39)2021 09.
Article in English | MEDLINE | ID: covidwho-1448678

ABSTRACT

BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Humans , Pandemics , Quarantine , United Kingdom/epidemiology
17.
Philos Trans R Soc Lond B Biol Sci ; 376(1829): 20200266, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1309686

ABSTRACT

As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.


Subject(s)
COVID-19/epidemiology , Models, Theoretical , Pandemics , SARS-CoV-2/pathogenicity , Algorithms , COVID-19/transmission , COVID-19/virology , Communicable Disease Control , England/epidemiology , Humans , United Kingdom/epidemiology
18.
Euro Surveill ; 26(20)2021 05.
Article in English | MEDLINE | ID: covidwho-1290660

ABSTRACT

We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Humans , Immunity, Herd , Vaccination
19.
Lancet Public Health ; 6(3): e175-e183, 2021 03.
Article in English | MEDLINE | ID: covidwho-1164723

ABSTRACT

BACKGROUND: In most countries, contacts of confirmed COVID-19 cases are asked to quarantine for 14 days after exposure to limit asymptomatic onward transmission. While theoretically effective, this policy places a substantial social and economic burden on both the individual and wider society, which might result in low adherence and reduced policy effectiveness. We aimed to assess the merit of testing contacts to avert onward transmission and to replace or reduce the length of quarantine for uninfected contacts. METHODS: We used an agent-based model to simulate the viral load dynamics of exposed contacts, and their potential for onward transmission in different quarantine and testing strategies. We compared the performance of quarantines of differing durations, testing with either PCR or lateral flow antigen (LFA) tests at the end of quarantine, and daily LFA testing without quarantine, against the current 14-day quarantine strategy. We also investigated the effect of contact tracing delays and adherence to both quarantine and self-isolation on the effectiveness of each strategy. FINDINGS: Assuming moderate levels of adherence to quarantine and self-isolation, self-isolation on symptom onset alone can prevent 37% (95% uncertainty interval [UI] 12-56) of onward transmission potential from secondary cases. 14 days of post-exposure quarantine reduces transmission by 59% (95% UI 28-79). Quarantine with release after a negative PCR test 7 days after exposure might avert a similar proportion (54%, 95% UI 31-81; risk ratio [RR] 0·94, 95% UI 0·62-1·24) to that of the 14-day quarantine period, as would quarantine with a negative LFA test 7 days after exposure (50%, 95% UI 28-77; RR 0·88, 0·66-1·11) or daily testing without quarantine for 5 days after tracing (50%, 95% UI 23-81; RR 0·88, 0·60-1·43) if all tests are returned negative. A stronger effect might be possible if individuals isolate more strictly after a positive test and if contacts can be notified faster. INTERPRETATION: Testing might allow for a substantial reduction in the length of, or replacement of, quarantine with a small excess in transmission risk. Decreasing test and trace delays and increasing adherence will further increase the effectiveness of these strategies. Further research is required to empirically evaluate the potential costs (increased transmission risk, false reassurance) and benefits (reduction in the burden of quarantine, increased adherence) of such strategies before adoption as policy. FUNDING: National Institute for Health Research, UK Research and Innovation, Wellcome Trust, EU Horizon 2021, and the Bill & Melinda Gates Foundation.


Subject(s)
COVID-19 Testing/methods , COVID-19/prevention & control , Contact Tracing , Quarantine , COVID-19/epidemiology , Humans , Models, Theoretical
20.
Lancet Glob Health ; 9(3): e251, 2021 03.
Article in English | MEDLINE | ID: covidwho-1149603
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