Comparative impact assessment of COVID-19 policy interventions in five South Asian countries using reported and estimated unreported death counts during 2020-2021.

There has been raging discussion and debate around the quality of COVID death data in South Asia. According to WHO, of the 5.5 million reported COVID-19 deaths from 2020-2021, 0.57 million (10%) were contributed by five low and middle income countries (LMIC) countries in the Global South: India, Pakistan, Bangladesh, Sri Lanka and Nepal. However, a number of excess death estimates show that the actual death toll from COVID-19 is significantly higher than the reported number of deaths. For example, the IHME and WHO both project around 14.9 million total deaths, of which 4.5-5.5 million were attributed to these five countries in 2020-2021. We focus our gaze on the COVID-19 performance of these five countries where 23.5% of the world population lives in 2020 and 2021, via a counterfactual lens and ask, to what extent the mortality of one LMIC would have been affected if it adopted the pandemic policies of another, similar country? We use a Bayesian semi-mechanistic model developed by Mishra et al. (2021) to compare both the reported and estimated total death tolls by permuting the time-varying reproduction number (Rt) across these countries over a similar time period. Our analysis shows that, in the first half of 2021, mortality in India in terms of reported deaths could have been reduced to 96 and 102 deaths per million compared to actual 170 reported deaths per million had it adopted the policies of Nepal and Pakistan respectively. In terms of total deaths, India could have averted 481 and 466 deaths per million had it adopted the policies of Bangladesh and Pakistan. On the other hand, India had a lower number of reported COVID-19 deaths per million (48 deaths per million) and a lower estimated total deaths per million (80 deaths per million) in the second half of 2021, and LMICs other than Pakistan would have lower reported mortality had they followed India's strategy. The gap between the reported and estimated total deaths highlights the varying level and extent of under-reporting of deaths across the subcontinent, and that model estimates are contingent on accuracy of the death data. Our analysis shows the importance of timely public health intervention and vaccines for lowering mortality and the need for better coverage infrastructure for the death registration system in LMICs.

Machine learning models of healthcare expenditures predicting mortality: A cohort study of spousal bereaved Danish individuals.

BACKGROUND: The ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using health care usage for predicting mortality remains unexplored. The aim of this study was to investigate if temporal patterns of healthcare expenditures, can improve the predictive performance for mortality, in spousal bereaved older adults, next to other widely used sociodemographic variables. METHODS: This is a population-based cohort study of 48,944 Danish citizens 65 years of age and older suffering bereavement within 2013-2016. Individuals were followed from date of spousal loss until death from all causes or 31st of December 2016, whichever came first. Healthcare expenditures were available on weekly basis for each person during the follow-up and used as predictors for mortality risk in Extreme Gradient Boosting models. The extent to which medical spending trajectories improved mortality predictions compared to models with sociodemographics, was assessed with respect to discrimination (AUC), overall prediction error (Brier score), calibration, and clinical benefit (decision curve analysis). RESULTS: The AUC of age and sex for mortality the year after spousal loss was 70.8% [95% CI 68.8, 72.8]. The addition of sociodemographic variables led to an increase of AUC ranging from 0.9% to 3.1% but did not significantly reduce the overall prediction error. The AUC of the model combining the variables above plus medical spending usage was 80.8% [79.3, 82.4] also exhibiting smaller Brier score and better calibration. Overall, patterns of healthcare expenditures improved mortality predictions the most, also exhibiting the highest clinical benefit among the rest of the models. CONCLUSION: Temporal patterns of medical spending have the potential to significantly improve our assessment on who is at high risk of dying after suffering spousal loss. The proposed methodology can assist in a more efficient risk profiling and prognosis of bereaved individuals.

Predicting mortality risk after a fall in older adults using health care spending patterns: a population-based cohort study.

OBJECTIVE: To develop a prognostic model of 1-year mortality for individuals aged 65+ presenting at the emergency department (ED) with a fall based on health care spending patterns to guide clinical decision-making. DESIGN: Population-based cohort study (n = 35,997) included with a fall in 2013 and followed 1 year. METHODS: Health care spending indicators (dynamical indicators of resilience, DIORs) 2 years before admission were evaluated as potential predictors, along with age, sex and other clinical and sociodemographic covariates. Multivariable logistic regression models were developed and internally validated (10-fold cross-validation). Performance was assessed via discrimination (area under the receiver operating characteristic curve, AUC), Brier scores, calibration and decision curve analysis. RESULTS: The AUC of age and sex for mortality was 72.5% [95% confidence interval 71.8 to 73.2]. The best model included age, sex, number of medications and health care spending DIORs. It exhibited high discrimination (AUC: 81.1 [80.5 to 81.6]), good calibration and potential clinical benefit for various threshold probabilities. Overall, health care spending patterns improved predictive accuracy the most while also exhibiting superior performance and clinical benefit. CONCLUSIONS: Patterns of health care spending have the potential to significantly improve assessments on who is at high risk of dying following admission to the ED with a fall. The proposed methodology can assist in predicting the prognosis of fallers, emphasising the added predictive value of longitudinal health-related information next to clinical and sociodemographic predictors.

Effectiveness assessment of non-pharmaceutical interventions: lessons learned from the COVID-19 pandemic.

Effectiveness of non-pharmaceutical interventions (NPIs), such as school closures and stay-at-home orders, during the COVID-19 pandemic has been assessed in many studies. Such assessments can inform public health policies and contribute to evidence-based choices of NPIs during subsequent waves or future epidemics. However, methodological issues and no standardised assessment practices have restricted the practical value of the existing evidence. Here, we present and discuss lessons learned from the COVID-19 pandemic and make recommendations for standardising and improving assessment, data collection, and modelling. These recommendations could contribute to reliable and policy-relevant assessments of the effectiveness of NPIs during future epidemics.

Sex differences in health care expenditures and mortality after spousal bereavement: A register-based Danish cohort study.

BACKGROUND: Spousal bereavement is a life event that affects older people differently. We investigated the impact of spousal bereavement on medical expenditures and mortality in the general population, emphasizing on age and sex. METHODS: Data are from a population-based, retrospective cohort study following 924,958 Danish citizens over the age of 65 years, within 2011-2016. Changes in health care expenditures in those who suffer bereavement were compared with time matched changes among those who did not. Mortality hazards were analysed with time to event analysis. RESULTS: A total of 77,722 (~8.4%) individuals experienced bereavement, 65.8% being females. Among males, bereavement was associated with increase of expenditures the year after, that was 42 Euros per week (95% CI, 36 to 48) larger than the non-bereaved group. The corresponding increase for females was 35 Euros per week (95% CI, 30 to 40). The increase of mortality hazards was highest in the first year after bereavement, higher in males than females, in young old and almost absent in the oldest old. Compared with the reference, mortality the year after spousal loss was 70% higher (HR 1.70 [95% CI 1.40 to 2.08]) for males aged 65-69 years and remained elevated for a period of six years. Mortality for females aged 65-69 years was 27% higher in the first year (HR 1.27, [1.07 to 1.52]), normalizing thereafter. CONCLUSION: Bereavement affects older people differently with younger males being most frail with limited recovery potential.

Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the US.

Importance: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. Objective: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. Design, Setting, and Participants: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. Main Outcomes and Measures: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). Results: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group. Conclusions and Relevance: The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19's role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP.

Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.