ABSTRACT
The infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection is important to estimate accurately, since 94% of the global population is younger than 70 years and 86% is younger than 60 years. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.035% (interquartile range (IQR) 0.013 - 0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036 - 0.125%,) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.003% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.129% at 50-59 years, and 0.501% at 60-69 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants. Highlights*Across 31 systematically identified national seroprevalence studies in the pre-vaccination era, the median infection fatality rate of COVID-19 was estimated to be 0.035% for people aged 0-59 years people and 0.095% for those aged 0-69 years. *The median IFR was 0.0003% at 0-19 years, 0.003% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.129% at 50-59 years, and 0.501% at 60-69 years. *At a global level, pre-vaccination IFR may have been as low as 0.03% and 0.07% for 0-59 and 0-69 year old people, respectively. *These IFR estimates in non-elderly populations are lower than previous calculations had suggested.
ABSTRACT
BackgroundCOVID-19 exhibits a steep age gradient of infection fatality rate. There has been debate about whether extra protection of elderly and other vulnerable individuals (precision shielding) is feasible, and, if so, to what extent. MethodsWe used systematically retrieved data from national seroprevalence studies conducted in the pre-vaccination era. Studies were identified through SeroTracker and PubMed searches (last update May 17, 2022). Studies were eligible if they targeted representative general populations without high risk of bias. Seroprevalence estimates were noted for children, non-elderly adults, and elderly adults, using cut-offs of 20, and 60 years (or as close to these ages, if they were not available). ResultsThirty-eight national seroprevalence studies from 36 different countries were included in the analysis. 26/38 also included pediatric populations. 25/38 studies were from high-income countries. The median ratio of seroprevalence in the elderly versus non-elderly adults (or non-elderly in general, if pediatric and adult population data were not offered separately) was 0.90-0.95 in different analyses with large variability across studies. In 5 studies (all of them in high-income countries), there was significant protection of the elderly with ratio <0.40. The median was 0.83 in high-income countries and 1.02 in other countries. The median ratio of seroprevalence in children versus adults was 0.89 and only one study showed a significant ratio of <0.40. ConclusionPrecision shielding of elderly community-dwelling populations before the availability of vaccines was feasible in some high-income countries, but most countries failed to achieve any substantial focused protection of this age group. summary38 COVID-19 nationally representative seroprevalence studies conducted before vaccination campaigns were systematically identified. Median seroprevalence ratio in elderly versus non-elderly adults was 0.90-0.95, indicating no generally achieved precision shielding of elderly. In 5 studies, substantial protection (ratio <0.40) was observed.
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BackgroundMost countries initially deployed COVID-19 vaccines preferentially in elderly populations. Population-level vaccine effectiveness may be heralded by an increase in the proportion of deaths among non-elderly populations that were less covered by vaccination programs. MethodsWe collected data from 40 countries on age-stratified COVID-19 deaths during the vaccination period (1/14/2021-5/31/2021) and two control periods (entire pre-vaccination period and excluding the first wave). We meta-analyzed the proportion of deaths in different age groups in vaccination versus control periods in countries with low vaccination rates; (2) countries with age-independent vaccination policies; and (3) countries with standard age-dependent vaccination policies. FindingsCountries that prioritized vaccination among older people saw an increasing share of deaths among 0-69 year old people in the vaccination versus the two control periods (summary prevalence ratio 1{middle dot}32 [95 CI% 1{middle dot}24-1{middle dot}41] and 1{middle dot}35 [95 CI% 1{middle dot}26-1{middle dot}44)]. No such change was seen on average in countries with age-independent vaccination policies (1{middle dot}05 [95 CI% 0{middle dot}78-1{middle dot}41 and 0{middle dot}97 [95 CI% 0{middle dot}95-1{middle dot}00], respectively) and limited vaccination (0{middle dot}93 [95 CI% 0{middle dot}85-1{middle dot}01] and 0{middle dot}95 [95 CI% 0{middle dot}87-1{middle dot}03], respectively). Prevalence ratios were associated with the difference of vaccination rates in elderly versus non-elderly people. No significant changes occurred in the share of deaths in age 0-49 among all 0-69 deaths in the vaccination versus pre-vaccination periods. InterpretationThe substantial shift in the age distribution of COVID-19 deaths in countries that rapidly implemented vaccination predominantly among elderly may herald the population level-effectiveness of COVID-19 vaccination and a favorable evolution of the pandemic towards endemicity with fewer elderly deaths. FundingThis study received no specific funding.
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ObjectiveThis mixed design synthesis aimed to estimate the infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) in community-dwelling elderly populations and other age groups from seroprevalence studies. Protocol: https://osf.io/47cgb. Methods and analysesEligible were seroprevalence studies done in 2020 and identified by any of four existing systematic reviews; with [≥]1000 participants aged [≥]70 years that presented seroprevalence in elderly people; that aimed to generate samples reflecting the general population; and whose location had available data on cumulative COVID-19 deaths in elderly (primary cutoff [≥]70 years; [≥]65 or [≥]60 also eligible). We extracted the most fully adjusted (if unavailable, unadjusted) seroprevalence estimates. We also extracted age- and residence-stratified cumulative COVID-19 deaths (until 1 week after the seroprevalence sampling midpoint) from official reports, and population statistics, to calculate IFRs corrected for unmeasured antibody types. Sample size-weighted IFRs were estimated for countries with multiple estimates. Secondary analyses examined data on younger age strata from the same studies. ResultsTwenty-five seroprevalence surveys representing 14 countries were included. Across all countries, the median IFR in community-dwelling elderly and elderly overall was 2.9% (range 0.2%-6.9%) and 4.9% (range 0.2%-16.8%) without accounting for seroreversion (2.4% and 4.0%, respectively, accounting for 5% monthly seroreversion). Multiple sensitivity analyses yielded similar results. IFR was higher with larger proportions of people >85 years. Younger age strata had low IFR values (median 0.0013%, 0.0088%, 0.021%, 0.042%, 0.14%, and 0.65%, at 0-19, 20-29, 30-39, 40-49, 50-59, and 60-69 years even without accounting for seroreversion). ConclusionsThe IFR of COVID-19 in community-dwelling elderly people is lower than previously reported. Very low IFRs were confirmed in the youngest populations.
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IntroductionAssessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. This study systematically reviewed the strength of evidence in the published COVID-19 policy impact evaluation literature. MethodsWe included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on November 26, 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation, assessing what impact evaluation method was used, graphical display of outcomes data, functional form for the outcomes, timing between policy and impact, concurrent changes to the outcomes, and an overall rating. ResultsAfter 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. The majority (n=23/36) of studies in our sample examined the impact of stay-at-home requirements. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-section), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 1/27 studies passed all of the above checks, and 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes. DiscussionThe reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigor to be actionable by policy-makers. This was largely driven by the circumstances under which policies were passed making it difficult to attribute changes in COVID-19 outcomes to particular policies. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.
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OBJECTIVETo examine whether the age distribution of COVID-19 deaths and the share of deaths in nursing homes changed in the second versus the first pandemic wave. ELIGIBLE DATAWe considered all countries that had at least 4000 COVID-19 deaths occurring as of January 14, 2020, at least 200 COVID-19 deaths occurring in each of the two epidemic wave periods; and which had sufficiently detailed information available on the age distribution of these deaths. We also considered countries with data available on COVID-19 deaths of nursing home residents for the two waves. MAIN OUTCOME MEASURESChange in the second wave versus the first wave in the proportion of COVID-19 deaths occurring in people <50 years ("young deaths") among all COVID-19 deaths and among COVID-19 deaths in people <70 years old; and change in the proportion of COVID-19 deaths in nursing home residents among all COVID-19 deaths. RESULTSData on age distribution were available for 14 eligible countries. Individuals <50 years old had small absolute difference in their share of the total COVID-19 deaths in the two waves across 13 high-income countries (absolute differences 0.0-0.4%). Their proportion was higher in Ukraine, but it decreased markedly in the second wave. The odds of young deaths was lower in the second versus the first wave (summary odds ratio 0.80, 95% CI 0.70-0.92) with large between-country heterogeneity. The odds of young deaths among deaths <70 years did not differ significantly across the two waves (summary odds ratio 0.95, 95% CI 0.85-1.07). Eligible data on nursing home COVID-19 deaths were available for 11 countries. The share of COVID-19 deaths that were accounted by nursing home residents decreased in the second wave significantly and substantially in 8 countries (odds ratio estimates: 0.22 to 0.66), remained the same in Denmark and Norway and markedly increased in Australia. CONCLUSIONSIn the examined countries, age distribution of COVID-19 deaths has been fairly similar in the second versus the first wave, but the contribution of COVID-19 deaths in nursing home residents to total fatalities has decreased in most countries in the second wave.
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Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
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OBJECTIVETo provide estimates of the relative risk of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATACountries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 11 European countries (Belgium, France, Germany, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, UK), Canada, and 12 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey and New York) We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURESProportion of COVID-19 deaths in people <65 years old; relative risk of COVID-19 death in people <65 versus [≥]65 years old; absolute risk of COVID-19 death in people <65 and in those [≥]80 years old in the general population as of May 1, 2020; absolute COVID-19 death risk expressed as equivalent of death risk from driving a motor vehicle. RESULTSIndividuals with age <65 account for 4.8-9.3% of all COVID-19 deaths in 10 European countries and Canada, 13.0% in the UK, and 7.8-23.9% in the US locations. People <65 years old had 36- to 84-fold lower risk of COVID-19 death than those [≥]65 years old in 10 European countries and Canada and 14- to 56-fold lower risk in UK and US locations. The absolute risk of COVID-19 death as of May 1, 2020 for people <65 years old ranged from 6 (Canada) to 249 per million (New York City). The absolute risk of COVID-19 death for people [≥]80 years old ranged from 0.3 (Florida) to 10.6 per thousand (New York). The COVID-19 death risk in people <65 years old during the period of fatalities from the epidemic was equivalent to the death risk from driving between 13 and 101 miles per day for 11 countries and 6 states, and was higher (equivalent to the death risk from driving 143-668 miles per day) for 6 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7-2.6% of all COVID-19 deaths (data available from France, Italy, Netherlands, Sweden, Georgia, and New York City). CONCLUSIONSPeople <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.