A systematic review and meta-analysis of published research data on COVID-19 infection fatality rates

An important unknown during the coronavirus disease-2019 (COVID-19) pandemic has been the infection fatality rate (IFR). This differs from the case fatality rate (CFR) as an estimate of the number of deaths and as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy makers and the lay public as an estimate of the overall mortality from COVID-19. Methods: Pubmed, Medline, SSRN, and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020 and re-searched on 14/05/2020, 21/05/2020 and 16/06/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 by using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. Results: After exclusions, there were 24 estimates of IFR included in the final meta-analysis, from a wide range of countries, published between February and June 2020. The meta-analysis demonstrated a point estimate of IFR of 0.68% (0.53%–0.82%) with high heterogeneity (p < 0.001). Conclusion: Based on a systematic review and meta-analysis of published evidence on COVID-19 until July 2020, the IFR of the disease across populations is 0.68% (0.53%–0.82%). However, due to very high heterogeneity in the meta-analysis, it is difficult to know if this represents a completely unbiased point estimate. It is likely that, due to age and perhaps underlying comorbidities in the population, different places will experience different IFRs due to the disease. Given issues with mortality recording, it is also likely that this represents an underestimate of the true IFR figure. More research looking at age-stratified IFR is urgently needed to inform policymaking on this front

SARS-CoV-2 sero-surveillance in Greece: evolution over time and epidemiological attributes during the pre-vaccination pandemic era

BACKGROUND: Nation-wide SARS-CoV-2 seroprevalence surveys provide valuable insights into the course of the pandemic, including information often not captured by routine surveillance of reported cases. METHODS: A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between March and December 2020. It was designed as a cross-sectional survey repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. RESULTS: Of 55,947 serum samples collected, 705 (1.26%) were found positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (9.09%) observed in December 2020. Highest seropositivity levels were observed in the "0-29" and "30-49" year age groups. Seroprevalence increased with age in the "0-29" age group. Highly populated metropolitan areas were characterized with elevated seroprevalence levels (11.92% in Attica, 12.76% in Thessaloniki) compared to the rest of the country (5.90%). The infection fatality rate (IFR) was estimated at 0.451% (95% CI: 0.382-0.549%) using aggregate data until December 2020, and the ratio of actual to reported cases was 9.59 (7.88-11.33). CONCLUSIONS: The evolution of seroprevalence estimates aligned with the course of the pandemic and varied widely by region and age group. Young and middle-aged adults appeared to be drivers of the pandemic during a severe epidemic wave under strict policy measures

A hierarchical Bayesian model for estimating age-specific COVID-19 infection fatality rates in developing countries

The COVID-19 infection fatality rate (IFR) is the proportion of individuals infected with SARS-CoV-2 who subsequently die. As COVID-19 disproportionately affects older individuals, age-specific IFR estimates are imperative to facilitate comparisons of the impact of COVID-19 between locations and prioritize distribution of scare resources. However, there lacks a coherent method to synthesize available data to create estimates of IFR and seroprevalence that vary continuously with age and adequately reflect uncertainties inherent in the underlying data. In this paper we introduce a novel Bayesian hierarchical model to estimate IFR as a continuous function of age that acknowledges heterogeneity in population age structure across locations and accounts for uncertainty in the estimates due to seroprevalence sampling variability and the imperfect serology test assays. Our approach simultaneously models test assay characteristic, serology, and death data, where the serology and death data are often available only for binned age groups. Information is shared across locations through hierarchical modeling to improve estimation of the parameters with limited data. Modeling data from 26 developing country locations during the first year of the COVID-19 pandemic, we found seroprevalence did not change dramatically with age, and the IFR at age 60 was above the high-income country benchmark for most locations

Assessing the determinants of COVID-19 burden to address disease-control policy decisions

Mathematical modeling has been crucial to address fundamental issues related to COVID-19 disease-control policy decisions. This thesis deals with the robust quantification of the disease burden associated with COVID-19 across different socio-demographic settings. The presented work includes the statistical analysis of novel epidemiological records to provide solid estimates describing the clinical course of SARS-CoV-2 infections and the simulation of data-driven models to forecast the potential impact of COVID-19 in rural and urban areas of Ethiopia. Obtained estimates show that being older than 60 years of age is associated with about 40% likelihood of developing symptoms after SARS-CoV-2 infection and 1% risk of requiring intensive care. The analysis of potential SARS-CoV-2 transmission in Ethiopia suggests that the low prevalence and mortality observed during 2020 can be explained by combined effect of younger demography and a reduced transmission generated by school closures implemented in response to the pandemic. Provided estimates highlight that in this country, after the launch of vaccination in 2021, the highest fraction of severe cases is expected to arise from the interaction between children (who are the main responsible for the spread of the disease) with the elderly (representing the most vulnerable population segment). Remarkably, prioritizing the vaccination of the elderly emerged as the best strategy to reduce the number of critical patients, irrespectively to the limited number of doses made available to low-income settings

Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission

Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission

Nationally representative results on SARS-CoV-2 seroprevalence and testing in Germany at the end of 2020

Pre-vaccine SARS-CoV-2 seroprevalence data from Germany are scarce outside hotspots, and socioeconomic disparities remained largely unexplored. The nationwide representative RKI-SOEP study (15,122 participants, 18–99 years, 54% women) investigated seroprevalence and testing in a supplementary wave of the Socio-Economic-Panel conducted predominantly in October–November 2020. Self-collected oral-nasal swabs were PCR-positive in 0.4% and Euroimmun anti-SARS-CoV-2-S1-IgG ELISA from dry-capillary-blood antibody-positive in 1.3% (95% CI 0.9–1.7%, population-weighted, corrected for sensitivity = 0.811, specificity = 0.997). Seroprevalence was 1.7% (95% CI 1.2–2.3%) when additionally correcting for antibody decay. Overall infection prevalence including self-reports was 2.1%. We estimate 45% (95% CI 21–60%) undetected cases and lower detection in socioeconomically deprived districts. Prior SARS-CoV-2 testing was reported by 18% from the lower educational group vs. 25% and 26% from the medium and high educational group (p < 0.001, global test over three categories). Symptom-triggered test frequency was similar across educational groups. Routine testing was more common in low-educated adults, whereas travel-related testing and testing after contact with infected persons was more common in highly educated groups. This countrywide very low pre-vaccine seroprevalence in Germany at the end of 2020 can serve to evaluate the containment strategy. Our findings on social disparities indicate improvement potential in pandemic planning for people in socially disadvantaged circumstances

Estimates and determinants of SARS-CoV-2 seroprevalence and infection fatality ratio using latent class analysis: the population-based Tirschenreuth study in the hardest-hit German county in spring 2020

SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60–69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers

Time Trend in SARS-CoV-2 Seropositivity, Surveillance Detection- and Infection Fatality Ratio until Spring 2021 in the Tirschenreuth County—Results from a Population-Based Longitudinal Study in Germany

Herein, we provide results from a prospective population-based longitudinal follow-up (FU) SARS-CoV-2 serosurveillance study in Tirschenreuth, the county which was hit hardest in Germany in spring 2020 and early 2021. Of 4203 individuals aged 14 years or older enrolled at baseline (BL, June 2020), 3546 participated at FU1 (November 2020) and 3391 at FU2 (April 2021). Key metrics comprising standardized seroprevalence, surveillance detection ratio (SDR), infection fatality ratio (IFR) and success of the vaccination campaign were derived using the Roche N- and S-Elecsys anti-SARS-CoV-2 test together with a self-administered questionnaire. N-seropositivity at BL was 9.2% (1st wave). While we observed a low new seropositivity between BL and FU1 (0.9%), the combined 2nd and 3rd wave accounted for 6.1% new N-seropositives between FU1 and FU2 (ever seropositives at FU2: 15.4%). The SDR decreased from 5.4 (BL) to 1.1 (FU2) highlighting the success of massively increased testing in the population. The IFR based on a combination of serology and registration data resulted in 3.3% between November 2020 and April 2021 compared to 2.3% until June 2020. Although IFRs were consistently higher at FU2 compared to BL across age-groups, highest among individuals aged 70+ (18.3% versus 10.7%, respectively), observed differences were within statistical uncertainty bounds. While municipalities with senior care homes showed a higher IFR at BL (3.0% with senior care home vs. 0.7% w/o), this effect diminished at FU2 (3.4% vs. 2.9%). In April 2021 (FU2), vaccination rate in the elderly was high (>77.4%, age-group 80+)

Seroprevalence of anti-SARS-CoV-2 IgG antibodies, risk factors for infection and associated symptoms in Geneva, Switzerland: a population-based study.

Aims: To assess SARS-CoV-2 seroprevalence over the first epidemic wave in the canton of Geneva, Switzerland, as well as risk factors for infection and symptoms associated with IgG seropositivity. Methods: Between April and June 2020, former participants of a representative survey of the 20-74-year-old population of canton Geneva were invited to participate in the study, along with household members aged over 5 years. Blood samples were tested for anti-SARS-CoV-2 immunoglobulin G. Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. Results: We included 8344 participants, with an overall adjusted seroprevalence of 7.8% (95% credible interval 6.8-8.9). Seroprevalence was highest among 18-49 year-olds (9.5%), and lowest in 5-9-year-old children (4.3%) and individuals >65 years (4.7-5.4%). Odds of seropositivity were significantly reduced for female retirees and unemployed men compared to employed individuals, and smokers compared to non-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. The symptom most strongly associated with seropositivity was anosmia/dysgeusia. Conclusions: Anti-SARS-CoV-2 population seroprevalence remained low after the first wave in Geneva. Socioeconomic factors were not associated with seropositivity in this sample. The elderly, young children and smokers were less frequently seropositive, although it is not clear how biology and behaviours shape these differences