Inferring the COVID-19 infection fatality rate in the community-dwelling population: a simple Bayesian evidence synthesis of seroprevalence study data and imprecise mortality data
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ABSTRACT:
SUBMITTER: Campbell H
PROVIDER: S-EPMC8632419 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Project description:Seroprevalence survey is the most practical method for accurately estimating infection attack rate (IAR) in an epidemic such as influenza. These studies typically entail selecting an arbitrary titer threshold for seropositivity (e.g. microneutralization [MN] 1∶40) and assuming the probability of seropositivity given infection (infection-seropositivity probability, ISP) is 100% or similar to that among clinical cases. We hypothesize that such conventions are not necessarily robust because different thresholds may result in different IAR estimates and serologic responses of clinical cases may not be representative. To illustrate our hypothesis, we used an age-structured transmission model to fully characterize the transmission dynamics and seroprevalence rises of 2009 influenza pandemic A/H1N1 (pdmH1N1) during its first wave in Hong Kong. We estimated that while 99% of pdmH1N1 infections became MN1∶20 seropositive, only 72%, 62%, 58% and 34% of infections among age 3-12, 13-19, 20-29, 30-59 became MN1∶40 seropositive, which was much lower than the 90%-100% observed among clinical cases. The fitted model was consistent with prevailing consensus on pdmH1N1 transmission characteristics (e.g. initial reproductive number of 1.28 and mean generation time of 2.4 days which were within the consensus range), hence our ISP estimates were consistent with the transmission dynamics and temporal buildup of population-level immunity. IAR estimates in influenza seroprevalence studies are sensitive to seropositivity thresholds and ISP adjustments which in current practice are mostly chosen based on conventions instead of systematic criteria. Our results thus highlighted the need for reexamining conventional practice to develop standards for analyzing influenza serologic data (e.g. real-time assessment of bias in ISP adjustments by evaluating the consistency of IAR across multiple thresholds and with mixture models), especially in the context of pandemics when robustness and comparability of IAR estimates are most needed for informing situational awareness and risk assessment. The same principles are broadly applicable for seroprevalence studies of other infectious disease outbreaks.
| S-EPMC3974861 | biostudies-literature
Project description:This 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 . Eligible were seroprevalence studies done in 2020 and identified by any of four existing systematic reviews; with ≥ 500 participants aged ≥ 70 years; presenting seroprevalence in elderly people; 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; 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 adjusted for test performance. Sample size-weighted IFRs were estimated for countries with multiple estimates. Thirteen seroprevalence surveys representing 11 high-income countries were included in the main analysis. Median IFR in community-dwelling elderly and elderly overall was 2.9% (range 1.8-9.7%) and 4.5% (range 2.5-16.7%) without accounting for seroreversion (2.2% 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. The IFR of COVID-19 in community-dwelling elderly is lower than previously reported.
| S-EPMC8934243 | biostudies-literature
Project description:The ongoing outbreak of COVID-19 challenges the health systems and epidemiological responses of all countries worldwide. Although preventive measures have been globally considered, the spatial heterogeneity of its effectiveness is evident, underscoring global health inequalities. Using Bayesian-based Markov chain Monte Carlo simulations, we identify the spatial association of socioeconomic factors and the risk for dying from COVID-19 in Colombia. We confirm that from March 16 to October 04, 2020, the COVID-19 case-fatality rate and the multidimensional poverty index have a heterogeneous spatial distribution. Spatial analysis reveals that the risk of dying from COVID-19 increases in regions with a higher proportion of poor people with dwelling (RR 1.74 95%CI = 1.54-9.75), educational (RR 1.69 95%CI = 1.36-5.94), childhood/youth (RR 1.35 95%CI = 1.08-4.03), and health (RR 1.16 95%CI = 1.06-2.04) deprivations. These findings evidence the vulnerability of most disadvantaged members of society to dying in a pandemic and assist the spatial planning of preventive strategies focused on vulnerable communities.
| S-EPMC8956344 | biostudies-literature
Project description:BackgroundThe first wave of SARS-CoV-2 infection in Chile occurred during the cold season reaching a peak by the end of June 2020, with 80 % of the cases concentrated in its capital, Santiago. The main objective of this study was to estimate the attack rate during this first wave of SARS-CoV-2 in a large, densely populated city with more than seven million inhabitants. Since the number of confirmed cases provides biased information due to individuals' potential self-selection, mostly related to asymptomatic patients and testing access, we measured antibodies against SARS-CoV-2 to assess infection prevalence during the first wave in the city, as well as estimate asymptomatic cases, and infection fatality ratio. To our knowledge this is one of the few population-based cross-sectional serosurvey during the first wave in a highly affected emerging country. The challenges of pandemic response in urban settings in a capital city like Santiago, with heterogeneous subpopulations and high mobility through public transportation, highlight the necessity of more accurate information regarding the first waves of new emerging diseases.MethodsFrom April 24 to June 21, 2020, 1326 individuals were sampled from a long-standing panel of household representatives of Santiago. Immunochromatographic assays were used to detect IgM and IgG antibody isotypes.ResultsSeroprevalence reached 6.79 % (95 %CI 5.58 %-8.26 %) in the first 107 days of the pandemic, without significant differences among sex and age groups; this figure indicates an attack rate 2.8 times higher than the one calculated with registered cases. It also changes the fatality rate estimates, from a 2.33 % case fatality rate reported by MOH to an estimated crude 1.00 % (CI95 % 0.97-1.03) infection fatality rate (adjusted for test performance 1.66 % [CI95 % 1.61-1.71]). Most seropositive were symptomatic (81,1 %).ConclusionsDespite the high number of cases registered, mortality rates, and the stress produced over the health system, the vast majority of the people remained susceptible to potential new epidemic waves. We contribute to the understanding of the initial spread of emerging epidemic threats. Consequently, our results provide better information to design early strategies that counterattack new health challenges in urban contexts.
| S-EPMC9277990 | biostudies-literature
Project description:BackgroundA number of estimates of the infection fatality ratio (IFR) of SARS-CoV-2 in different countries have been published. In Brazil, the fragile political situation, together with socioeconomic and ethnic diversity, could result in substantially different IFR estimates.MethodsWe infer the IFR in Brazil in 2020 by combining three datasets. We compute the prevalence via the population-based seroprevalence survey, EPICOVID19-BR. For the fatalities we obtain the absolute number using the public Painel Coronavírus dataset and the age-relative number using the public SIVEP-Gripe dataset. The time delay between the development of antibodies and subsequent fatality is estimated via the SIVEP-Gripe dataset. We obtain the IFR for each survey stage and 27 federal states. We include the effect of fading IgG antibody levels by marginalizing over the test detectability time window.ResultsWe infer a country-wide average IFR (maximum posterior and 95% CI) of 1.03% (0.88-1.22%) and age-specific IFRs of 0.032% (0.023-0.041%) [< 30 years], 0.22% (0.18-0.27%) [30-49 years], 1.2% (1.0-1.5%) [50-69 years], and 3.0% (2.4-3.9%) [≥ 70 years]. We find that the fatality ratio in the country increased significantly at the end of June 2020, likely due to the increased strain on the health system.ConclusionsOur IFR estimate is based on data and does not rely on extrapolating models. This estimate sets a baseline value with which future medications and treatment protocols may be confronted.
| S-EPMC8358085 | biostudies-literature
Project description:BackgroundIntroduction of the Omicron variant caused a steep rise in SARS-CoV-2 infections despite high vaccination coverage in the Danish population. We used blood donor serosurveillance to estimate the percentage of recently infected residents in the similarly aged background population with no known comorbidity.MethodsTo detect SARS-CoV-2 antibodies induced due to recent infection, and not vaccination, we assessed anti-nucleocapsid (anti-N) immunoglobulin G (IgG) in blood donor samples. Individual level data on SARS-CoV-2 RT-PCR results and vaccination status were available. Anti-N IgG was measured fortnightly from January 18 to April 3, 2022. Samples from November 2021 were analysed to assess seroprevalence before introduction of the Omicron variant in Denmark.FindingsA total of 43 088 donations from 35 309 Danish blood donors aged 17-72 years were screened. In November 2021, 1·2% (103/8 701) of donors had detectable anti-N IgG antibodies. Adjusting for test sensitivity (estimates ranging from 74%-81%) and November seroprevalence, we estimate that 66% (95% confidence intervals (CI): 63%-70%) of the healthy, similarly aged Danish population had been infected between November 1, 2021, and March 15, 2022. One third of infections were not captured by SARS-CoV-2 RT-PCR testing. The infection fatality rate (IFR) was 6·2 (CI: 5·1-7·5) per 100 000 infections.InterpretationScreening for anti-N IgG and linkage to national registers allowed us to detect recent infections and accurately assess assay sensitivity in vaccinated or previously infected individuals during the Omicron outbreak. The IFR was lower than during previous waves.FundingThe Danish Ministry of Health.
| S-EPMC9355516 | biostudies-literature
Project description:Characterizing cell-cell communication and tracking its variability over time is essential for understanding the coordination of biological processes mediating normal development, progression of disease, or responses to perturbations such as therapies. Existing tools lack the ability to capture time-dependent intercellular interactions, such as those influenced by therapy, and primarily rely on existing databases compiled from limited contexts. We present DIISCO, a Bayesian framework for characterizing the temporal dynamics of cellular interactions using single-cell RNA-sequencing data from multiple time points. Our method uses structured Gaussian process regression to unveil time-resolved interactions among diverse cell types according to their co-evolution and incorporates prior knowledge of receptor-ligand complexes. We show the interpretability of DIISCO in simulated data and new data collected from CAR-T cells co-cultured with lymphoma cells, demonstrating its potential to uncover dynamic cell-cell crosstalk.
2024-09-02 | GSE255888 | GEO
Project description:Reconstruction of gene regulatory networks (GRNs) from experimental data is a fundamental challenge in systems biology. A number of computational approaches have been developed to infer GRNs from mRNA expression profiles. However, expression profiles alone are proving to be insufficient for inferring GRN topologies with reasonable accuracy. Recently, it has been shown that integration of external data sources (such as gene and protein sequence information, gene ontology data, protein-protein interactions) with mRNA expression profiles may increase the reliability of the inference process. Here, I propose a new approach that incorporates transcription factor binding sites (TFBS) and physical protein interactions (PPI) among transcription factors (TFs) in a Bayesian variable selection (BVS) algorithm which can infer GRNs from mRNA expression profiles subjected to genetic perturbations. Using real experimental data, I show that the integration of TFBS and PPI data with mRNA expression profiles leads to significantly more accurate networks than those inferred from expression profiles alone. Additionally, the performance of the proposed algorithm is compared with a series of least absolute shrinkage and selection operator (LASSO) regression-based network inference methods that can also incorporate prior knowledge in the inference framework. The results of this comparison suggest that BVS can outperform LASSO regression-based method in some circumstances.
| S-EPMC4126456 | biostudies-literature
Project description:BackgroundRespiratory rate is a basic clinical measurement used for illness assessment. Errors in measuring respiratory rate are attributed to observer and equipment problems. Previous studies commonly report rate differences ranging from 2 to 6 breaths·min-1 between observers.MethodsTo study why repeated observations should vary so much, we conducted a virtual experiment, using continuous recordings of breathing from acutely ill patients. These records allowed each breathing cycle to be precisely timed. We made repeated random measures of respiratory rate using different sample durations of 30, 60 and 120 s. We express the variation in these repeated rate measurements for the different sample durations as the interquartile range of the values obtained for each subject. We predicted what values would be found if a single measure, taken from any patient, were repeated and inspected boundary values of 12, 20 or 25 breaths·min-1, used by the UK National Early Warning Score, for possible mis-scoring.ResultsWhen the sample duration was nominally 30 s, the mean interquartile range of repeated estimates was 3.4 breaths·min-1. For the 60 s samples, the mean interquartile range was 3 breaths·min-1, and for the 120 s samples it was 2.5 breaths·min-1. Thus, repeat clinical counts of respiratory rate often differ by >3 breaths·min-1. For 30 s samples, up to 40% of National Early Warning Scores could be misclassified.ConclusionsEarly warning scores will be unreliable when short sample durations are used to measure respiratory rate. Precision improves with longer sample duration, but this may be impractical unless better measurement methods are used.
| S-EPMC7520170 | biostudies-literature
Project description:Calcium imaging has been used as a promising technique to monitor the dynamic activity of neuronal populations. However, the calcium trace is temporally smeared which restricts the extraction of quantities of interest such as spike trains of individual neurons. To address this issue, spike reconstruction algorithms have been introduced. One limitation of such reconstructions is that the underlying models are not informed about the biophysics of spike and burst generations. Such existing prior knowledge might be useful for constraining the possible solutions of spikes. Here we describe, in a novel Bayesian approach, how principled knowledge about neuronal dynamics can be employed to infer biophysical variables and parameters from fluorescence traces. By using both synthetic and in vitro recorded fluorescence traces, we demonstrate that the new approach is able to reconstruct different repetitive spiking and/or bursting patterns with accurate single spike resolution. Furthermore, we show that the high inference precision of the new approach is preserved even if the fluorescence trace is rather noisy or if the fluorescence transients show slow rise kinetics lasting several hundred milliseconds, and inhomogeneous rise and decay times. In addition, we discuss the use of the new approach for inferring parameter changes, e.g. due to a pharmacological intervention, as well as for inferring complex characteristics of immature neuronal circuits.
| S-EPMC4760968 | biostudies-literature