The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Positive fluid balance within the first 72 hours in the intensive care unit is associated with higher mortality in adult patients

Objective: To identify the association between cumulative fluid balance in the first 72 hours of ICU stay and outcomes. Methodology: retrospective observational cohort with data analysis of adult patients hospitalized in an ICU of a tertiary teaching hospital. Results: a total of 86 patients who remained in the ICU for more than 72 hours were evaluated. The fluid balance in the first 72 hours was higher in the subgroup of patients who died in the ICU (5210.3 ± 2787.7 vs. 3017.4 ± 2847.2 mL, p = 0.004). The fluid balance in the first 72 hours was an independent factor directly associated with death in the ICU (OR: 1,000; p = 0.009). The area under the ROC curve was 0.7119 (95% CI: 0.58-0.84, p = 0.005). The optimal cutoff point for the fluid balance in the first 72 hours as a predictor of death in the ICU was + 3.900mL and the relative risk of death among those who presented a fluid balance higher than this value was 1.702 (95% CI: 1, 15-2.53, p = 0.009). Conclusion: an association was identified between the cumulative value in the fluid balance in the first 72 hours of ICU stay and the highest risk of death, which is an independent factor of the patient's severity at admission.

Consequences of COVID-19 vaccine allocation inequity in Chicago

During Chicago's initial COVID-19 vaccine rollout, the city disproportionately allocated vaccines to zip codes with high incomes and predominantly White populations. However, the impact of this inequitable distribution on COVID-19 outcomes is unknown. This observational study determined the association between zip-code level vaccination rate and COVID-19 mortality in residents of 52 Chicago zip codes. After controlling for age distribution and recovery from infection, a 10% higher vaccination rate by March 28, 2021, was associated with a 39% lower relative risk of death during the peak of the spring wave of COVID-19. Using a difference-in-difference analysis, Chicago could have prevented an estimated 72% of deaths in the least vaccinated quartile of the city (vaccination rates of 17.8 - 26.9%) if it had had the same vaccination rate as the most vaccinated quartile (39.9 - 49.3%). Inequitable vaccine allocation in Chicago likely exacerbated existing racial disparities in COVID-19 mortality.

Risk of Death from Hypertension among Chernobyl Accident Liquidators – Nuclear Industry Workers

The aim of the study was to assess the radiation risk of death from hypertension in liquidators of the Chernobyl nuclear power plant accident consequences — workers of the nuclear industry — using doses from various types of irradiation. Materials and methods of the study. The study was conducted using data from the Industry Register of Persons exposed to radiation as a result of the Chernobyl accident — workers of the nuclear power industry. Information on 12659 liquidators (all male) was included in the analysis. 1327 of them got occupational radiation doses. Crude relative risks of death from hypertension were estimated for five dose groups using internal controls. Based on the stratified data file, a Poisson regression procedure was performed using the AMFIT module of Epicure program and the excess relative risk of death from hypertension was calculated and the nature of the dose-dependent excess relative mortality was investigated. Results of the study and their analysis. Direct estimates of radiogenic risk of death from hypertension were obtained. No increase in mortality from hypertensive disease per unit dose was found for both the doses received during the liquidation of the Chernobyl accident consequences and for the total doses. The results of the study can be used in the development of radiation safety regulations for persons working with sources of ionizing radiation.

Primary kidney disease modifies the effect of comorbidities on kidney replacement therapy patients’ survival

Background Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients’ survival. Methods An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000–2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses. Results In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups. Conclusions Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease.

Adherence to Attendance at Outpatient Clinic and Longterm Survival of Patients after Stroke in Outpatient Setting: the Data of REGION-M Registry

Aim. Assess the two-year survival rate of patients who have undergone acute cerebral circulation disorder, depending on their commitment to visiting the district polyclinic before and after discharge from the hospital.Material and methods. The outpatient part of the REGION-M register included 684 patients attached to the Moscow City Polyclinic №64, discharged from the Moscow City Clinical Hospital n.a. F.I. Inozemtsev of from 01.01.2012 to 04.30.2017 with a confirmed diagnosis of acute cerebral circulation disorder (cerebral stroke / transient ischemic attack).Results. Of the entire cohort, 83.2% of patients and 84.2% after hospital discharge attended the clinic during the year before the development of reference acute cerebral circulation disorder. Patients who attended the clinic before and after the reference stroke were older, more likely to have diabetes, comorbid disease and disability. For 22 months of follow-up, mortality was 28.8% (197 out of 684 people). Among those who applied and did not apply to the clinic before the reference acute cerebral circulation disorder, the difference in mortality tended to be reliable (27.4% versus 35.7%, p <0.1), while mortality was almost twice as low among patients who applied to the clinic at least 1 time after discharge (25.7%) than among patients who did not apply after discharge - 45.4%, p<0.0001. When adjusting for sex and age (the relative risk of death for them was 1.009, 95% confidence interval 1.005-1.01 2, p<0.0001 ), the statistical validity of reducing the risk of death was maintained when patients were committed to visiting the clinic after discharge - the relative risk of death 0.366 (95% confidence interval 0.269-0.500, p<0.0001 ).Conclusion. Lower mortality among those who visited the district polyclinic after undergoing stroke confirms the important role of medical observation in the posthospital period. At the same time, there is a reserve in improving the long-term prognosis of the lives of patients who have suffered a cerebral stroke or transient ischemic attack, due to greater coverage of patients with medical supervision in the clinic.

Mortality after electroconvulsive therapy

Background There are limited studies examining mortality associated with electroconvulsive therapy (ECT), and many studies do not include a control group or method to identify all patient deaths. Aims We aimed to evaluate the risk of death associated with ECT treatments over 30 days and 1 year. Method We conducted a study analysing electronic medical record data from the Department of Veterans Affairs healthcare system between 2000 and 2017. We compared mortality among patients who received ECT with a matched group of patients created through propensity score matching. Results Our sample included 123 479 individual ECT treatments provided to 8720 patients (including 5157 initial index courses of ECT). Mortality associated with individual ECT treatments was 3.08 per 10 000 treatments over the first 7 days after treatment. When comparing patients who received ECT with a matched group of mental health patients, those receiving ECT had a relative odds of all-cause mortality in the year after their index course of 0.87 (95% CI 0.79–1.11; P = 0.10), and a relative risk of death from causes other than suicide of 0.79 (95% CI 0.66–0.95; P < 0.01). The similar relative odds of all-cause mortality in the first 30 days after ECT was 1.06 (95% CI 0.65–1.73) for all-cause mortality, and 1.02 (95% CI 0.58–1.8) for all-cause mortality excluding suicide deaths. Conclusions There was no evidence of elevated or excess mortality after ECT. There was some indication that mortality may be reduced in patients receiving ECT compared with similar patients who do not receive ECT.

White Blood Cell and Platelet Dynamics Define Human Inflammatory Recovery

Inflammation is the physiologic reaction to cellular and tissue damage caused by pathologic processes including trauma, infection, and ischemia. Effective inflammatory responses integrate molecular and cellular functions to prevent further tissue damage, initiate repair, and restore homeostasis, while futile or dysfunctional responses allow escalating injury, delay recovery, and may hasten death. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not established. Patient responses appear to vary dramatically with no clearly defined signs of good prognosis, leaving physicians reliant on qualitative interpretations of laboratory trends. We studied the human acute inflammatory response to trauma, ischemia, and infection by tracking the longitudinal dynamics of cellular and serum markers in hospitalized patients. Unexpectedly, we identified a conserved pattern of recovery defined by co-regulation of WBC and platelet (PLT) populations. Across all inflammatory conditions studied, recovering patients followed a consistent WBC-PLT trajectory shape that is well-approximated by exponential WBC decay and delayed linear PLT growth. This recovery trajectory shape may represent a fundamental archetype of human physiologic response at the cellular population scale, and provides a generic approach for identifying high-risk patients: 32x relative risk of adverse outcomes for cardiac surgery patients, 9x relative risk of death for COVID-19, and 5x relative risk of death for myocardial infarction.