National Case Fatality Rates Research Articles

Prevalence and Levels of Anti-SARS-CoV-2 Antibodies in the Eswatini Population and Subsequent Severity of the Fourth COVID-19 Epidemic Wave

Background: Seroepidemiology studies are useful for quantifying the magnitude of past infections and estimating the extent of population-based immunity to inform risk mitigation strategies for the future. We report on the only national population-based survey of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immunoglobulin G (IgG) seroprevalence in Eswatini. Methods: The survey was undertaken from 31 August to 30 September 2021, following three earlier waves of coronavirus disease (COVID-19), and preceded the onset of the fourth wave, which was dominated by the Omicron variant of concern. We also report on epidemiological trends of recorded COVID-19 cases and hospitalizations before and after the fourth COVID-19 wave through to March 2022. We evaluated the immunoglobulin G (IgG) seropositivity based on either anti-nucleocapsid (N) or anti-spike (S) antigens. Results: Of 4564 individuals, 58.5% were female, 36.0% were aged 18–50 years, and 863 (18.9%) of adults who were older than 18 years had received at least a single dose of COVID-19 vaccine. Overall, 2769 (60.7%) were seropositive with heterogeneity across sub-regions (53.7%; 95% CI:49.2–58.1 to 68.6%; 95% CI:64.5–72.4), with the highest rates occurring in sub-regions of the Manzini region. Seropositivity was higher in vaccinated individuals (84.5%; 95% CI: 81.9–86.7) compared to unvaccinated individuals (55.1%; 95% CI:53.5–56.7). Amongst unvaccinated individuals, seropositivity was highest in 18–50-year-olds (59.5%;95% CI: 56.9–62.1). Seropositivity was associated with female gender, previous positive SARS-CoV-2 NAAT status and being vaccinated, non-smoking, and being formally employed. We estimated as of 15 September 2021 that there had been 639,475 SARS-CoV-2 infections (95% CI; 620,824–658,003) in Eswatini, which was 25.5-fold greater than the 25,048 COVID-19 cases that had been recorded by then. The national case fatality rate (CFR) based on recorded cases was 4.8%, being 25-fold greater than the infection fatality rate (0.19; 95% CI: 0.18–0.19) based on recorded deaths and extrapolating the force of infection from seroprevalence. Nationally and across all four regions, we report the decoupling of COVID-19 cases from hospitalisations and deaths, observed as early as during the third wave, which was dominated by the Delta variant compared with earlier waves. Conclusions: We identified that 60.7% of people in Eswatini had been infected by SARS-CoV-2 at least once and before the onset of the Omicron wave in mid-November 2021. Despite a modest uptake of COVID-19 vaccines, the evolution of population immunity from infection has likely contributed to the decoupling of infection and severe COVID-19 in Eswatini.

Author's Responses to Peer Reviews of “The Influence of SARS-CoV-2 Variants on National Case-Fatality Rates: Correlation and Validation Study”

Author's Responses to Peer Reviews of “The Influence of SARS-CoV-2 Variants on National Case-Fatality Rates: Correlation and Validation Study”

Food Anaphylaxis in the United Kingdom: Analysis of National Data, 1998–2018

To analyze trends in hospital admissions for food anaphylaxis in the United Kingdom from 1998 to 2018, including case-fatality rates.All patients admitted to hospitals for anaphylaxis in the United Kingdom (England, Scotland, Wales, and Northern Ireland) were studied. Children were identified as age ≤15 years.International Classification of Diseases, 10th Revision, codes were analyzed for all allergy-related admissions with both food-related and non–food-related causes, by using the Hospital Episodes Statistics database via the National Health Services. Fatal food-induced anaphylaxis data has been recorded through the UK’s Fatal Anaphylaxis Registry. Admission data were compared along time trends among different age groups, sex, and inciting triggers. Trends in the national case-fatality rate and epinephrine autoinjector (EAI) prescriptions were also analyzed.Across all age groups, allergy-related hospital admissions increased during the study period from 10 to 28 admissions per 100 000 population per year, at a rate ratio of 1.043 (1.042 to 1.043; P < .001). A total of 255 913 admissions occurred during the 10-year interval, of which 39.8% were due to anaphylaxis. The rate of anaphylaxis-associated admissions increased by 179%, with a rate ratio of 1.047 (1.046 to 1.048; P < .001) and was similar across all age groups. Girls had a higher rate of admission for nonfood anaphylaxis admissions. Boys (age: <15) had a higher rate of admission with food triggers, but this predominance dissipated into adulthood. A total of 30.1% of admissions for anaphylaxis were identified with a food trigger, with an annual rate ratio of 1.057 (1.055 to 1.059; P < .001). The greatest increase was observed in children, from 2.1 to 9.2 admissions per 100 000 or an increase of 339%. Individuals aged 15 to 59 years had an increase of 214%, whereas those aged >60 years had an increase of 78% over the same time interval. Despite a national recommendation in 2016 encouraging admission for children with suspected anaphylaxis, the admission rate for children did not significantly increase. The annual fatality rates from food-induced anaphylaxis were 0.009 and 0.008 per 100c000 population in 1998 and 2018, respectively, but the case-fatality rate had decreased from 0.70% to 0.19% in the same period. The highest rate of fatalities occurred in teenagers. Children <5 years of age were more likely to be admitted for anaphylaxis but had lower rates of death. A total of 46% of fatalities were associated with peanuts or tree nuts. Additionally, the fatality rate associated with cow’s milk increased since 1992, with 26% of deaths in children and 5% in adults caused by cow’s milk exposure. The rates of death from peanuts and tree nuts decreased during this interval. Prescriptions for EAI devices increased by 336% overall or by an 11% increase on a year-by-year basis.From 1998–2018, the number of hospital admissions for anaphylaxis and prescriptions for EAIs in the United Kingdom significantly increased, and the case-fatality rate for anaphylaxis decreased. Peanuts and tree nuts accounted for the greatest portion of fatal reactions, but among children <5 years of age, cow’s milk was the most common trigger.The strengths of this study include the use of 20 years of data and a national database that examined >255 000 admissions. This study also revealed the increasing role of cow’s milk anaphylaxis in food allergy fatalities. This study relied on International Classification of Diseases, 10th Revision, codes. It is possible that the data regarding admissions and fatalities are an underestimate because anaphylaxis and its triggers are often not coded accurately.

National case fatality rates of the COVID-19 pandemic

ObjectivesThe case fatality rate (CFR) of coronavirus disease 2019 (COVID-19) varies significantly between countries. We aimed to describe the associations between health indicators and the national CFRs of COVID-19. MethodsWe identified for each country health indicators potentially associated with the national CFRs of COVID-19. We extracted data for 18 variables from international administrative data sources for 34 member countries of the Organization for Economic Cooperation and Development (OECD). We excluded the collinear variables and examined the 16 variables in multivariable analysis. A dynamic web-based model was developed to analyse and display the associations for the CFRs of COVID-19. We followed the Guideline for Accurate and Transparent Health Estimates Reporting (GATHER). ResultsIn multivariable analysis, the variables significantly associated with the increased CFRs were percentage of obesity in ages >18 years (β = 3.26; 95%CI = 1.20, 5.33; p 0.003), tuberculosis incidence (β = 3.15; 95%CI = 1.09, 5.22; p 0.004), duration (days) since first death due to COVID-19 (β = 2.89; 95%CI = 0.83, 4.96; p 0.008), and median age (β = 2.83; 95%CI = 0.76, 4.89; p 0.009). The COVID-19 test rate (β = –3.54; 95%CI = –5.60, –1.47; p 0.002), hospital bed density (β = –2.47; 95%CI = –4.54, –0.41; p 0.021), and rural population ratio (β = –2.19; 95%CI = –4.25, –0.13; p 0.039) decreased the CFR. ConclusionsThe pandemic hits population-dense cities. Available hospital beds should be increased. Test capacity should be increased to enable more effective diagnostic tests. Older patients and patients with obesity and their caregivers should be warned about a potentially increased risk.

Understanding COVID-19: A hypothesis regarding digit ratio (2D:4D), ACE I/D polymorphism, oxygen metabolism and national case fatality rates

ObjectiveMale digit ratio (2D:4D) correlates positively with the national case fatality rate (CFR) for COVID-19. The severity of COVID-19 may be influenced by a counterbalance between the angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2). SARS-CoV2 cleaves with ACE2 and enters cells leaving an unopposed effect of ACE in the lungs. Both 2D:4D and the ACE I/D polymorphism are covariates of oxygen metabolism. COVID-19 leads to lung damage and a reduction in oxygen saturation of the blood. Here, we examine the interrelationships between 2D:4D, ACE polymorphism, and COVID-19 CFR. MethodsNational frequencies/rates were obtained for 2D:4D from the BBC Internet study (n = 41), published values of ACE I/II (n = 39), and COVID-19 CFR from three World Health Organization situation reports (n = 41). Results2D:4D was negatively associated with national ACE I/II frequencies. However, there was a positive relationship between male 2D:4D and CFR (right and left 2D:4D, two, and three situation reports respectively). The relationships between ACE I/II and CFR were non-significant. Relationships between male 2D:4D and CFR's were independent of female 2D:4D and ACE I/II. ConclusionsThe ACE I/D polymorphism may influence 2D:4D such that ACE II individuals have lower 2D:4D than ACE DD individuals. Low 2D:4D and ACE II individuals show efficient oxygen metabolism. Therefore, low 2D:4D and ACE II together may protect against COVID-19 severity. The sex-dependent positive correlation between male 2D:4D and CFR is independent of ACE I/II, suggesting that the sex-dependent variation in the ACE2 gene may also influence the 2D:4D phenotype.

Oxygen and Mortality in COVID-19 Pneumonia: A Comparative Analysis of Supplemental Oxygen Policies and Health Outcomes Across 26 Countries

Background: During the COVID-19 pandemic some countries have reduced access to supplemental oxygen by means of rationing or implementing conservative oxygen strategies, whereas other nations have maintained and even improved access to supplemental oxygen. Given hypoxia is the main cause of morbidity and mortality in COVID-19, we sought to analyse any potential effects on mortality of these divergent oxygen strategies. Methods: We examined the different oxygen policies across 29 nations in order to identify whether access to supplemental oxygen had any bearing on mortality in COVID-19. Specifically, we extracted the national recommendations for when to commence oxygen in patients with COVID-19, and through linear regression analysis compared these target oxygen values against national case fatality rates. Findings: Of the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden and the UK guidelines advised commencing oxygen when oxygen saturations (SpO2) fell to 91% or less. Target SpO2 ranged from 92% to 95% in the other 16 nations. Linear regression analysis demonstrated a strong inverse correlation between target SpO2 and national case fatality rates ( rs = -0.622, p Interpretation: Our study highlights the marked disparity in oxygen provision for COVID-19 patients between the nations analysed, and indicates such disparity may represent a modifiable factor associated with mortality. Together with the growing body of evidence, our results suggest that limited access to supplemental oxygen, whether through rationing, conservative oxygen strategies or resource limitations, is likely to increase the mortality associated with COVID-19 pneumonia. Funding: There was no external funding for this study.Declaration of Interests: The authors declare no conflicts of interests.

Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates

BackgroundThe reported national case fatality rates (CFRs) for coronavirus disease 2019 (COVID-19) shows a sex bias with males > females. The relative lengths of the index (2D) and ring (4D) fingers (digit ratio; 2D:4D) is a sexually dimorphic (males < females) proxy of fetal sex steroids (low 2D:4D indicates high prenatal testosterone/low prenatal estrogen). AimTo examine sex-specific relationships of 2D:4D per nation with national values of COVID-19 CFRs. Study design: COVID-19 CFRs and the percent of male deaths were related to mean national (self-reported) 2D:4D by sex and hand from a large online survey (the BBC Internet Study). Subjects103,482 men and 83,366 women. Outcome measuresRelationships of mean national 2D:4D with CFRs from 41 countries and with national male death rates from 16 countries. ResultsMale right and left hand 2D:4D showed positive relationships with CFR. These relationships remained significant after removing the influence of female 2D:4D. A positive association of male right and left 2D:4D was detected with the percentage of male deaths. ConclusionsAt the national level, high mean 2D:4D (indicating low prenatal testosterone/high prenatal estrogen) is associated with high CFRs and percent male mortality. At the individual level, high 2D:4D may be a risk factor for severity of COVID-19 in males. We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).

317 Acute Respiratory Illness among a Prospective Cohort of Pediatric Patients Using Emergency Medical Services in India: Demographic, Environmental, and Out-of-Hospital Clinical Predictors of Mortality in a High-Risk Population

In India, acute respiratory illnesses (ARIs), including pneumonia, are the leading cause of early childhood death. Emergency medical services (EMS) in India have been shown to be a critical component in the public health infrastructure; however, literature on the prehospital care of pediatric patients in low- and middle-income countries (LMICs) is severely limited. This study describes the demographic, environmental, and clinical characteristics associated with 30-day mortality among pediatric patients transported via EMS in India with an acute respiratory complaint. We conducted a prospective observational study of patients <18 years using EMS for “shortness of breath” or a primary chief complaint of “fever” with a secondary complaint of “difficulty breathing” or “cough” across 7 Indian states from June 20 to September 2, 2016. The primary outcome was 2, 7, and 30-day mortality. Baseline descriptive characteristics are provided as numbers and percents. Multivariate modeling, owing to predictors of increased mortality at 7 and 30 days, was constructed. A total of 1443 pediatric patients <18 years of age were enrolled during the study period: 981 (68.5%) were collected from the field, and 452 (31.5%) were interfacility transports (IFTs). Response rates were 87.0%, 85.8%, and 83.4% (N=1222) at 2, 7, and 30 days, respectively. The median age of all patients was 2 years (IQR: 0.17-10); 93.9% (N=1347) of patients lived on family incomes below the poverty level; and 54.1% (N=706) were male. The majority of calls were to rural or tribal areas (N=1122; 78.2%), with an average length of transport from initial call to health facility of 72 mins (IQR: 47-105). Overall cumulative mortality at 2, 7, and 30-days was 5.2%, 7.1%, and 7.7%, respectively, with a total of 94 deaths by 30-days. Stratified by age, the largest burden of mortality fell to neonates (0-28 days) with a mortality of 17.0% at 30-days, while under-5 mortality (U5M) was 9.8% during the same follow-up period. IFT patients carried an almost 3-fold risk of death as compared to field transports (14% versus 5%, p value<0.0001). In multivariate modeling evidence of an oxygen saturation <95% in the prehospital setting (OR: 3.18 CI: 1.77-5.71), respiratory distress (OR: 3.72 CI: 2.17-6.36) and familial use of an open cook stove (OR: 2.61 CI: 1.59-4.29), were the strongest predictors of mortality at 30 days among all patients. This is the first known study to detail the out-of-hospital clinical predictors of death among pediatric patients with shortness of breath in a LMIC. EMS rapidly connects critically ill children to needed care in India. Despite this, U5M remains high. While national case fatality rates (CFRs) for India are not widely published, U5M from ARIs remains higher than various previously published hospital-based studies (CFR range: 3.8%-8.1%) and significantly more than published CFRs for developed countries (range: 0.4%-4.8%). The risk of death remains particularly acute for those patients transported as IFTs and among those with respiratory distress, or hypoxia. Early recognition of critically ill children, targeted out-of-hospital interventions, and diversion to higher level of care may help to mitigate the burden of mortality in this population.

Constant Lethality of Gunshot Injuries From Firearm Assault: United States, 2003–2012

To investigate the validity of the apparent downward trend in the national case-fatality rate for gunshot wounds from assault. We reanalyzed the estimated annual number of nonfatal firearm injuries the National Electronic Injury Surveillance System reported from 2003 to 2012. We adjusted the estimates for discontinuities created by the substitution of 1 hospital for another in the sample and for a downward trend in the percentage of gunshot injuries classified as "unknown circumstance." Firearm homicide data are from the Centers for Disease Control and Prevention, Web-based Injury Statistics Query and Reporting System. The unadjusted National Electronic Injury Surveillance System estimate increased by 49%, yielding a decline in the case-fatality rate from 25% to 18%. Our adjustments eliminated these trends; the case-fatality rate was 22% in both 2003 and 2012. With reasonable adjustments, the trend in nonfatal injuries from interpersonal firearms assault tracks the flat trend in firearms homicides, suggesting that there was no increase in firearms violence during this period. The case-fatality rate did not change, and trauma care improvements did not influence the firearms homicide trend.

Evaluation of severe malaria case management in Mazowe District, Zimbabwe, 2014.

IntroductionMalaria is a preventable and curable disease. Mazowe district had been experiencing a lower malaria transmission rate in comparison to other districts in the Mashonaland Central province but it experienced a huge outbreak in the 2013-2014 rainy seasons with a case fatality rate (CFR) of 0.21%. This CFR was the highest in the province and it was twice as much as the national CFR (0.12%) for the same period. We evaluated severe malaria case management in Mazowe district to determine if practice is as per standard treatment guidelines.MethodsA descriptive cross sectional study was conducted in Mazowe district using the Logical Framework approach. District Health Executives (DHE) members, nurses and severe malaria case notes were purposively and conveniently selected into the study. Key informant Interviews and review of case notes were carried out. All data were analysed using Epi Info 3.5.1.to calculate means and frequencies. Permission to conduct the study was obtained from the Mashonaland Central Provincial Medical Directorate (PMD) Institutional Ethical Review Board (IRB).ResultsThe median age in years of the cases was 16 (Q1=7.3; Q3=30.8) and up to 58.1% of the cases were female. Inputs including staff, medicines and medical and laboratory equipment for severe case management were inadequate in the district. Only 60% of severe cases were diagnosed using blood slides and up to 95.6% of cases presented with one or more of the clinical signs of severe malaria. All severe cases were treated using correct anti-malarial and analgesic doses. Patient monitoring was not done as per prerequisite intervals and up to 5% of cases died. The health workers had above average knowledge on severe malaria.ConclusionSevere malaria case management inputs were inadequate in the district. For many cases, the district did not follow complicated malaria treatment guidelines for diagnosis, treatment and monitoring. Untrained staff needs training in Severe Malaria Case Management and monitoring of commodity stocks needs to be strengthened.

Measles Outbreak among Unvaccinated Children in Bajura

Measles outbreak occurs when there are three or more laboratory confirmed measles cases in a village in a period of one month. Integrated surveillance system has helped to identify the measles outbreak, to characterize its epidemiology and to timely respond it. This is a descriptive study of measles outbreak that occurred in Bajura district in February to March 2010. The epidemiological characteristics of the outbreak are described. The outbreak was investigated from 4-8 March 2010 with necessary epidemiological information and biological specimen collection. One month follow up was done to determine the clinical outcome of the measles cases. A total of 36 people had measles; 97% of them were under 15 years of age and 89% had not been immunized with measles vaccine. Attack rate and vaccine efficacy was 23% and 50% amongst children less than 15 years of age and case fatality rate (CFR) was 3%. Biological samples were collected from 11 patients; all of which tested IgM positive for measles and genotype D8 was isolated. CFR of this outbreak is higher than the national CFR. Vaccine efficacy of 50% points towards the need for investigation of vaccine logistics and cold chain system. Moreover, this laboratory test confirmed an outbreak showing that the measles virus could be imported from an endemic region and rapidly spread through a susceptible population who were previously not immunized.

Reye syndrome: treatment by exchange transfusion with special reference to the 1974 epidemic in Cincinnati, Ohio.

The treatment of 66 children with Reye syndrome proved by hepatic biopsy or autopsy is described. Prior to the utilization of exchange transfusion early in the course of the disease, our case fatality rate was 100% of nine patients. With early diagnosis and early exchange transfusion, the case fatality rate was reduced to 27% of 44 patients. During the 1974 epidemic of Reye syndrome, 26 children were treated. In 18 children the diagnosis was established by hepatic biopsy; 16 received one or more exchange transfusions. There were no deaths among these 26 patients. In the 1974 epidemic, the national case fatality rate was estimated to be 40%. Exchange transfusion appears to have been an important factor in the reduction of the case fatality rate among our patients.