Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England.

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe.

Following the detection of the new coronavirus1 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics of coronavirus disease 2019 (COVID-19). In response, many European countries have implemented non-pharmaceutical interventions, such as the closure of schools and national lockdowns. Here we study the effect of major interventions across 11 European countries for the period from the start of the COVID-19 epidemics in February 2020 until 4 May 2020, when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks previously, allowing for the time lag between infection and death. We use partial pooling of information between countries, with both individual and shared effects on the time-varying reproduction number (Rt). Pooling allows for more information to be used, helps to overcome idiosyncrasies in the data and enables more-timely estimates. Our model relies on fixed estimates of some epidemiological parameters (such as the infection fatality rate), does not include importation or subnational variation and assumes that changes in Rt are an immediate response to interventions rather than gradual changes in behaviour. Amidst the ongoing pandemic, we rely on death data that are incomplete, show systematic biases in reporting and are subject to future consolidation. We estimate that-for all of the countries we consider here-current interventions have been sufficient to drive Rt below 1 (probability Rt < 1.0 is greater than 99%) and achieve control of the epidemic. We estimate that across all 11 countries combined, between 12 and 15 million individuals were infected with SARS-CoV-2 up to 4 May 2020, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions-and lockdowns in particular-have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.

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.

Unifying incidence and prevalence under a time-varying general branching process.

Renewal equations are a popular approach used in modelling the number of new infections, i.e., incidence, in an outbreak. We develop a stochastic model of an outbreak based on a time-varying variant of the Crump-Mode-Jagers branching process. This model accommodates a time-varying reproduction number and a time-varying distribution for the generation interval. We then derive renewal-like integral equations for incidence, cumulative incidence and prevalence under this model. We show that the equations for incidence and prevalence are consistent with the so-called back-calculation relationship. We analyse two particular cases of these integral equations, one that arises from a Bellman-Harris process and one that arises from an inhomogeneous Poisson process model of transmission. We also show that the incidence integral equations that arise from both of these specific models agree with the renewal equation used ubiquitously in infectious disease modelling. We present a numerical discretisation scheme to solve these equations, and use this scheme to estimate rates of transmission from serological prevalence of SARS-CoV-2 in the UK and historical incidence data on Influenza, Measles, SARS and Smallpox.

Using Hawkes Processes to model imported and local malaria cases in near-elimination settings.

Developing new methods for modelling infectious diseases outbreaks is important for monitoring transmission and developing policy. In this paper we propose using semi-mechanistic Hawkes Processes for modelling malaria transmission in near-elimination settings. Hawkes Processes are well founded mathematical methods that enable us to combine the benefits of both statistical and mechanistic models to recreate and forecast disease transmission beyond just malaria outbreak scenarios. These methods have been successfully used in numerous applications such as social media and earthquake modelling, but are not yet widespread in epidemiology. By using domain-specific knowledge, we can both recreate transmission curves for malaria in China and Eswatini and disentangle the proportion of cases which are imported from those that are community based.

Tracking progress towards malaria elimination in China: Individual-level estimates of transmission and its spatiotemporal variation using a diffusion network approach.

In order to monitor progress towards malaria elimination, it is crucial to be able to measure changes in spatio-temporal transmission. However, common metrics of malaria transmission such as parasite prevalence are under powered in elimination contexts. China has achieved major reductions in malaria incidence and is on track to eliminate, having reporting zero locally-acquired malaria cases in 2017 and 2018. Understanding the spatio-temporal pattern underlying this decline, especially the relationship between locally-acquired and imported cases, can inform efforts to maintain elimination and prevent re-emergence. This is particularly pertinent in Yunnan province, where the potential for local transmission is highest. Using a geo-located individual-level dataset of cases recorded in Yunnan province between 2011 and 2016, we introduce a novel Bayesian framework to model a latent diffusion process and estimate the joint likelihood of transmission between cases and the number of cases with unobserved sources of infection. This is used to estimate the case reproduction number, Rc. We use these estimates within spatio-temporal geostatistical models to map how transmission varied over time and space, estimate the timeline to elimination and the risk of resurgence. We estimate the mean Rc between 2011 and 2016 to be 0.171 (95% CI = 0.165, 0.178) for P. vivax cases and 0.089 (95% CI = 0.076, 0.103) for P. falciparum cases. From 2014 onwards, no cases were estimated to have a Rc value above one. An unobserved source of infection was estimated to be moderately likely (p>0.5) for 19/ 611 cases and high (p>0.8) for 2 cases, suggesting very high levels of case ascertainment. Our estimates suggest that, maintaining current intervention efforts, Yunnan is unlikely to experience sustained local transmission up to 2020. However, even with a mean of 0.005 projected up to 2020, locally-acquired cases are possible due to high levels of importation.

A comparison of five epidemiological models for transmission of SARS-CoV-2 in India.

BACKGROUND: Many popular disease transmission models have helped nations respond to the COVID-19 pandemic by informing decisions about pandemic planning, resource allocation, implementation of social distancing measures, lockdowns, and other non-pharmaceutical interventions. We study how five epidemiological models forecast and assess the course of the pandemic in India: a baseline curve-fitting model, an extended SIR (eSIR) model, two extended SEIR (SAPHIRE and SEIR-fansy) models, and a semi-mechanistic Bayesian hierarchical model (ICM). METHODS: Using COVID-19 case-recovery-death count data reported in India from March 15 to October 15 to train the models, we generate predictions from each of the five models from October 16 to December 31. To compare prediction accuracy with respect to reported cumulative and active case counts and reported cumulative death counts, we compute the symmetric mean absolute prediction error (SMAPE) for each of the five models. For reported cumulative cases and deaths, we compute Pearson's and Lin's correlation coefficients to investigate how well the projected and observed reported counts agree. We also present underreporting factors when available, and comment on uncertainty of projections from each model. RESULTS: For active case counts, SMAPE values are 35.14% (SEIR-fansy) and 37.96% (eSIR). For cumulative case counts, SMAPE values are 6.89% (baseline), 6.59% (eSIR), 2.25% (SAPHIRE) and 2.29% (SEIR-fansy). For cumulative death counts, the SMAPE values are 4.74% (SEIR-fansy), 8.94% (eSIR) and 0.77% (ICM). Three models (SAPHIRE, SEIR-fansy and ICM) return total (sum of reported and unreported) cumulative case counts as well. We compute underreporting factors as of October 31 and note that for cumulative cases, the SEIR-fansy model yields an underreporting factor of 7.25 and ICM model yields 4.54 for the same quantity. For total (sum of reported and unreported) cumulative deaths the SEIR-fansy model reports an underreporting factor of 2.97. On October 31, we observe 8.18 million cumulative reported cases, while the projections (in millions) from the baseline model are 8.71 (95% credible interval: 8.63-8.80), while eSIR yields 8.35 (7.19-9.60), SAPHIRE returns 8.17 (7.90-8.52) and SEIR-fansy projects 8.51 (8.18-8.85) million cases. Cumulative case projections from the eSIR model have the highest uncertainty in terms of width of 95% credible intervals, followed by those from SAPHIRE, the baseline model and finally SEIR-fansy. CONCLUSIONS: In this comparative paper, we describe five different models used to study the transmission dynamics of the SARS-Cov-2 virus in India. While simulation studies are the only gold standard way to compare the accuracy of the models, here we were uniquely poised to compare the projected case-counts against observed data on a test period. The largest variability across models is observed in predicting the "total" number of infections including reported and unreported cases (on which we have no validation data). The degree of under-reporting has been a major concern in India and is characterized in this report. Overall, the SEIR-fansy model appeared to be a good choice with publicly available R-package and desired flexibility plus accuracy.

Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource.

BACKGROUND: Before the advent of an effective vaccine, nonpharmaceutical interventions, such as mask-wearing, social distancing, and lockdowns, have been the primary measures to combat the COVID-19 pandemic. Such measures are highly effective when there is high population-wide adherence, which requires information on current risks posed by the pandemic alongside a clear exposition of the rules and guidelines in place. OBJECTIVE: Here we analyzed online news media coverage of COVID-19. We quantified the total volume of COVID-19 articles, their sentiment polarization, and leading subtopics to act as a reference to inform future communication strategies. METHODS: We collected 26 million news articles from the front pages of 172 major online news sources in 11 countries (available online at SciRide). Using topic detection, we identified COVID-19-related content to quantify the proportion of total coverage the pandemic received in 2020. The sentiment analysis tool Vader was employed to stratify the emotional polarity of COVID-19 reporting. Further topic detection and sentiment analysis was performed on COVID-19 coverage to reveal the leading themes in pandemic reporting and their respective emotional polarizations. RESULTS: We found that COVID-19 coverage accounted for approximately 25.3% of all front-page online news articles between January and October 2020. Sentiment analysis of English-language sources revealed that overall COVID-19 coverage was not exclusively negatively polarized, suggesting wide heterogeneous reporting of the pandemic. Within this heterogenous coverage, 16% of COVID-19 news articles (or 4% of all English-language articles) can be classified as highly negatively polarized, citing issues such as death, fear, or crisis. CONCLUSIONS: The goal of COVID-19 public health communication is to increase understanding of distancing rules and to maximize the impact of governmental policy. The extent to which the quantity and quality of information from different communication channels (eg, social media, government pages, and news) influence public understanding of public health measures remains to be established. Here we conclude that a quarter of all reporting in 2020 covered COVID-19, which is indicative of information overload. In this capacity, our data and analysis form a quantitative basis for informing health communication strategies along traditional news media channels to minimize the risks of COVID-19 while vaccination is rolled out.

Correction: Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource.

[This corrects the article DOI: 10.2196/28253.].

A unified machine learning approach to time series forecasting applied to demand at emergency departments.

BACKGROUND: There were 25.6 million attendances at Emergency Departments (EDs) in England in 2019 corresponding to an increase of 12 million attendances over the past ten years. The steadily rising demand at EDs creates a constant challenge to provide adequate quality of care while maintaining standards and productivity. Managing hospital demand effectively requires an adequate knowledge of the future rate of admission. We develop a novel predictive framework to understand the temporal dynamics of hospital demand. METHODS: We compare and combine state-of-the-art forecasting methods to predict hospital demand 1, 3 or 7 days into the future. In particular, our analysis compares machine learning algorithms to more traditional linear models as measured in a mean absolute error (MAE) and we consider two different hyperparameter tuning methods, enabling a faster deployment of our models without compromising performance. We believe our framework can readily be used to forecast a wide range of policy relevant indicators. RESULTS: We find that linear models often outperform machine learning methods and that the quality of our predictions for any of the forecasting horizons of 1, 3 or 7 days are comparable as measured in MAE. Our approach is able to predict attendances at these emergency departments one day in advance up to a mean absolute error of ±14 and ±10 patients corresponding to a mean absolute percentage error of 6.8% and 8.6% respectively. CONCLUSIONS: Simple linear methods like generalized linear models are often better or at least as good as ensemble learning methods like the gradient boosting or random forest algorithm. However, though sophisticated machine learning methods are not necessarily better than linear models, they improve the diversity of model predictions so that stacked predictions can be more robust than any single model including the best performing one.

Response to COVID-19 in South Korea and implications for lifting stringent interventions.

BACKGROUND: After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the USA. This has led to substantial interest in their "test, trace, isolate" strategy. However, it is important to understand the epidemiological peculiarities of South Korea's outbreak and characterise their response before attempting to emulate these measures elsewhere. METHODS: We systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. RESULTS: We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI, 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June, Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent "lockdown" measures, strong social distancing measures were implemented in high-incidence areas and studies measured a considerable national decrease in movement in late February. Testing the capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly; however, we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. CONCLUSIONS: Whilst early adoption of testing and contact tracing is likely to be important for South Korea's successful outbreak control, other factors including regional implementation of strong social distancing measures likely also contributed. The high volume of testing and the low number of deaths suggest that South Korea experienced a small epidemic relative to other countries. Caution is needed in attempting to replicate the South Korean response in populations with larger more geographically widespread epidemics where finding, testing, and isolating cases that are linked to clusters may be more difficult.

Differential responses of SARS-CoV-2 variants to environmental drivers during their selective sweeps.

Previous work has shown that environmental variables affect SARS-CoV-2 transmission, but it is unclear whether different strains show similar environmental responses. Here we leverage genetic data on the transmission of three (Alpha, Delta and Omicron BA.1) variants of SARS-CoV-2 throughout England, to unpick the roles that climate and public-health interventions play in the circulation of this virus. We find evidence for enhanced transmission of the virus in colder conditions in the first variant selective sweep (of Alpha, in winter), but limited evidence of an impact of climate in either the second (of Delta, in the summer, when vaccines were prevalent) or third sweep (of Omicron, in the winter, during a successful booster-vaccination campaign). We argue that the results for Alpha are to be expected if the impact of climate is non-linear: we find evidence of an asymptotic impact of temperature on the alpha variant transmission rate. That is, at lower temperatures, the influence of temperature on transmission is much higher than at warmer temperatures. As with the initial spread of SARS-CoV-2, however, the overwhelming majority of variation in disease transmission is explained by the intrinsic biology of the virus and public-health mitigation measures. Specifically, when vaccination rates are high, a major driver of the spread of a new variant is it's ability to evade immunity, and any climate effects are secondary (as evidenced for Delta and Omicron). Climate alone cannot describe the transmission dynamics of emerging SARS-CoV-2 variants.

The interaction of disease transmission, mortality, and economic output over the first 2 years of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused over 7.02 million deaths as of January 2024 and profoundly affected most countries' Gross Domestic Product (GDP). Here, we study the interaction of SARS-CoV-2 transmission, mortality, and economic output between January 2020 and December 2022 across 25 European countries. METHODS: We use a Bayesian mixed effects model with auto-regressive terms to estimate the temporal relationships between disease transmission, excess deaths, changes in economic output, transit mobility and non-pharmaceutical interventions (NPIs) across countries. RESULTS: Disease transmission intensity (logRt) decreases GDP and increases excess deaths, where the latter association is longer-lasting. Changes in GDP as well as prior week transmission intensity are both negatively associated with each other (-0.241, 95% CrI: -0.295 - -0.189). We find evidence of risk-averse behaviour, as changes in transit and prior week transmission intensity are negatively associated (-0.055, 95% CrI: -0.074 to -0.036). Our results highlight a complex cost-benefit trade-off from individual NPIs. For example, banning international travel is associated with both increases in GDP (0.014, 0.002-0.025) and decreases in excess deaths (-0.014, 95% CrI: -0.028 - -0.001). Country-specific random effects, such as the poverty rate, are positively associated with excess deaths while the UN government effectiveness index is negatively associated with excess deaths. INTERPRETATION: The interplay between transmission intensity, excess deaths, population mobility and economic output is highly complex, and none of these factors can be considered in isolation. Our results reinforce the intuitive idea that significant economic activity arises from diverse person-to-person interactions. Our analysis quantifies and highlights that the impact of disease on a given country is complex and multifaceted. Long-term economic impairments are not fully captured by our model, as well as long-term disease effects (Long COVID).

N-acetyltransferase and cytochrome P450 2E1 gene polymorphisms and susceptibility to antituberculosis drug hepatotoxicity in an Indian population.

Background. Antituberculosis drug hepatotoxicity (ATDH) is common in India. Isoniazid, a constituent of most anti- tuberculosis drug regimens, is metabolized by N-acetyltransferase (NAT2) and cytochrome P450 2E1 (CYP2E1) enzymes. We therefore studied the association of some single-nucleotide polymorphisms (SNPs) in these enzyme genes with ATDH. Methods. Allelic and genotypic frequencies at three SNP loci in the NAT2 gene (rs1799929, rs1799930 and rs1799931) and one locus (rs2031920) in the CYP2E1 gene were studied using restriction fragment length polymorphism in 33 patients who developed ATDH following an isoniazid- containing antituberculosis drug regimen and 173 healthy blood donors. After confirming adherence of the control data to the Hardy-Weinberg equilibrium model, genotype and allele frequencies in the two groups were compared. Results. For SNP rs1799930 in the NAT2 gene, 7 (21%), 21 (64%) and 5 (15%) patients, and 93 (54%), 62 (36%) and 18 (10%) controls had GG, GA and AA genotypes, respectively (p=0.003; odds ratio [OR] for GA v. GG=4.50 [95% CI 1.80-11.22] and for AA v. GG=3.69 [1.05-12.93]). Allele frequency for G nucleotides for this SNP was 0.53 among patients and 0.72 among controls (OR 2.24 [1.31-3.84], p=0.007). The allele and genotype frequencies of the other NAT2 SNPs and the CYP2E1 SNP showed no significant difference between cases and controls. All the 33 patients and 151 (87%) of 173 controls had mutant allele at one or more of the three NAT2 SNP loci (p=0.03). The presence of two or more mutant alleles, a marker of slow acetylator status, was more frequent in patients (23/33 [70%]) than in controls (73/173 [42%]; OR 3.23 [95% CI 1.45-7.19], p=0.004). Conclusion. In India, the risk of ATDH is increased in persons with 'A' allele at SNP rs1799930 in the NAT2 gene, but is not associated with rs2031920 polymorphism in the CYP2E1 gene.

Application of referenced thermodynamic integration to Bayesian model selection.

Evaluating normalising constants is important across a range of topics in statistical learning, notably Bayesian model selection. However, in many realistic problems this involves the integration of analytically intractable, high-dimensional distributions, and therefore requires the use of stochastic methods such as thermodynamic integration (TI). In this paper we apply a simple but under-appreciated variation of the TI method, here referred to as referenced TI, which computes a single model's normalising constant in an efficient way by using a judiciously chosen reference density. The advantages of the approach and theoretical considerations are set out, along with pedagogical 1 and 2D examples. The approach is shown to be useful in practice when applied to a real problem -to perform model selection for a semi-mechanistic hierarchical Bayesian model of COVID-19 transmission in South Korea involving the integration of a 200D density.

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.