COVID-19 Related Deaths Research Articles

P-1962. SEAL: Serology-based Assessment of Evusheld in Lung Transplant Recipients

Abstract Background The primary strategy to combat severe COVID-19 infection in Lung Transplant Recipients (LTRs) is prevention through vaccination or the use of monoclonal antibodies such as Evusheld (tixagevimab/cilgavimab), for pre-exposure prophylaxis. Data on Evusheld efficacy overall and particularly in relation to the serological status of LTRs is scarce. We evaluated treatment outcomes in LTRs within 1 year after treatment with Evusheld based on their serological status before Evusheld administration. Study Design Of the 103 Lung Transplant recipients (LTRs*) who received Evusheld, 101 patients had been tested for anti-spike antibodies against SARS-CoV-2 prior to receiving Evusheld. 61 patients tested positive (seropositive) and 40 tested negative (seronegative). All patients were followed for 12 months. Outcomes were evaluated after the first 6 months when Evusheld was active, and after the second 6 months when Evusheld either was not used or had lost its efficacy against circulating strains. Methods This is a retrospective cohort analysis of 103 LTRs treated with Evusheld between January 27 and May 25, 2022, at Corwell Health in West Michigan. LTRs were classified into seropositive (SeroPos) and seronegative (SeroNeg) groups based on the presence of anti-spike antibodies against SARS-CoV-2 before Evusheld administration and evaluated after the first 6 months, when Evusheld was active, and after the second 6 months, when Evusheld was ineffective against circulating strains (Figure 1), for outcomes listed in Figure 2. We identified patients with positive COVID-19 test, either antigen or PCR. Morbidity was assessed through the rate of ED visits, hospital, and ICU admissions within 30 days from COVID-19 diagnosis. Mortality was assessed through COVID-19-related and all-cause deaths throughout the study period. Results Of 103 LTRs, 97% were vaccinated, 19% had COVID-19 and 59% were SeroPos before receiving Evusheld. Compared with SeroNeg LTRs, SeroPos LTRs were more likely to have had prior COVID-19 infection (22.95% v 12.5%, p=0.19). Vaccination rate was similar in both groups (98.36 vs 95%, p=0.56). SeroNeg LTRs were overall more likely to contract COVID-19, with a stable infection rate of 15% across the whole study period. In SeroPos LTRs, the positivity rate doubled in the 2nd 6 months compared with the 1st 6 months (6.5% vs. 13%, p=0.24). There was no difference in the disease severity between SeroPos and SeroNeg patients at any point (Figure 3). Overall, LTRs were less likely to contract COVID-19, be admitted to the hospital/intensive care unit, or die during the first 6 months when Evusheld was effective, compared with the second 6 months, but the difference was not statistically significant. (Figure 4). Characteristics and outcomes in seropositive and seronegative groups Conclusion Overall COVID-19 infection outcomes in LTRs had tendency to be better with Evsuheld use. SeroNeg LTRs were more likely to contract COVID-19 with and without Evusheld protection but serological status may not correlate with the disease severity. Our findings suggest that prior COVID-19 infection may induce a stronger immune response than the vaccine in LTRs. Outcome in all Lung Transplant Recipients Treated with Evusheld Lung transplant recipients were more likely to contract COVID-19 (13.73% vs. 9.71%, p=0.37), visit Emergency Department (ED (4.9% vs. 4.85%, p=1), get admitted to hospital (5.88% vs. 2.91%, p=0.33) or Intensive Care Unit (ICU) (1.96% vs. 0%, p=0.25), within the second 6 months compared with the first 6 months. All-cause mortality was significantly higher in the second 6 months (8.82% vs. 0.97%, p= 0.0097) but there was no difference in COVID-19 related deaths (0.98% vs. 0%, p=0.5). Disclosures All Authors: No reported disclosures

Addressing Health-Related Social Needs During COVID-19 Through a Hospital-Based, Community Health Worker Program: A Case Study.

Background. Despite accounting for 34% of the population in Austin, Texas, Latinx individuals made up 50% of those who tested positive for coronavirus, 54% of COVID-related hospitalizations, and 51% of COVID-related deaths between March and June 2020. Of hospitalized Latinx patients, 40% had never seen a primary care provider and many had undiagnosed health conditions. A community health worker (CHW) pilot program was implemented based on these disparities. Method. This mixed-method implementation study describes a hospital-based, CHW program for Latinx patients hospitalized with COVID-19 at an academic medical center in Austin, Texas. The program included a social needs assessment, care coordination, and post-discharge follow-up. Patient data include demographics from the full sample (N = 57), social determinants of health (n = 24), and qualitative interviews (n = 6). Focus group data from health care professionals (n = 26) is also presented to describe the benefits of the CHW program. Results. Latinx patients in this study, two-thirds of who primarily spoke Spanish, reported high levels of satisfaction with the CHW program with fewer reported social needs after the CHW program. Health care providers underscored CHW expertise in addressing complex social needs, providing continuity of care within the hospital, and closing the loop through community resource navigation. Conclusion. This study demonstrated the capacity of CHWs to provide holistic care in hospital settings through trust building and increased capacity to address health-related social needs. Investment in hospital-based, CHW programs for vulnerable populations such as uninsured, Spanish-speaking patients is necessary to reduce health disparities beyond COVID-19.

The effects of deprivation, age, and regional differences in COVID-19 mortality from 2020 to 2022: a retrospective analysis of public provincial data

BackgroundCoronavirus disease (COVID-19) quickly spread around the world after its initial identification in Wuhan, China in 2019 and became a global public health crisis. COVID-19 related hospitalizations and deaths as important disease outcomes have been investigated by many studies while less attention has been given to the relationship between these two outcomes at a public health unit level. In this study, we aim to establish the relationship of counts of deaths and hospitalizations caused by COVID-19 over time across 34 public health units in Ontario, Canada, taking demographic, geographic, socio-economic, and vaccination variables into account.MethodsWe analyzed daily data of the 34 health units in Ontario between March 1, 2020 and June 30, 2022. Associations between numbers of COVID-19 related deaths and hospitalizations were explored over three subperiods according to the availability of vaccines and the dominance of the Omicron variant in Ontario. A generalized additive model (GAM) was fit in each subperiod. Heterogeneity across public health units was formulated via a random intercept in each of the models.ResultsMean daily COVID-19 deaths increased quickly as daily hospitalizations increased, particularly when daily hospitalizations were less than 20. In all the subperiods, mean daily deaths of a public health unit was significantly associated with its population size and the proportion of confirmed cases in subjects over 60 years old. The proportion of fully vaccinated (2 doses of primary series) people in the 60 + age group was a significant factor after the availability of the COVID-19 vaccines. The deprivation index, a measure of poverty, had a significantly positive effect on COVID-19 mortality after the dominance of the Omicron variant in Ontario. Quantification of these effects was provided, including effects related to public health units.ConclusionsThe differences in COVID-19 mortality across health units decreased over time, after adjustment for other covariates. In the last subperiod when most public health protections were released and the Omicron variant dominated, the least advantaged group might suffer higher COVID-19 mortality. Interventions such as paid sick days and cleaner indoor air should be made available to counter lifting of health protections.

Study protocol: Comparison of different risk prediction modelling approaches for COVID-19 related death using the OpenSAFELY platform

On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both individual and collective, good predictive models are required. For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance. This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.

COVID-19 in Relation to Chronic Antihistamine Prescription.

No hospitalizations or deaths occurred in residents with the COVID-19 infection, treated with antihistamines and azithromycin, of two external nursing homes during the first wave. We assessed whether patients receiving chronic antihistamines in our institution showed better clinical evolution. COVID-19 admissions and related deaths in the public Hospital of Terrassa (n = 1461) during the pandemic period (11 March 2020-5 May 2023) and cases (n = 32,888) during the period of full suspicion diagnosis (1 June 2020-23 March 2022) were referred to as the number of chronic treatments (nT) including or not including antihistamines (AntiHm or NOAntiHm), and their vaccination status before the first infection (VAC or NoVAC) in our assigned population (n = 140,681 at March 2020) was recorded. No deaths occurred in patients treated with up to ≤6 nT in the AntiHm group in all ages. A significant reduction in hospital admission was observed in the 2-7 nT groups either below or over 60 years old [Odds Ratio (OR) NoAntiHm/AntiHm = 1.76-1.32, respectively, in NoVAC or VAC (OR = 2.10 overall] and in the older ≥8 nT group (OR = 2.08 in NoVac]. In conclusion, patients with chronic antihistamine prescriptions, alone or with polypharmacy, showed reduced hospital admission and mortality rates, suggesting the safety of antihistamine treatment and the need to confirm its effectiveness in a prospective trial.

Health Literacy and Patient Compliance: Implications for Public Health Interventions from a COVID-19 Study

A wealth of research has documented the detrimental consequences of health illiteracy and its impact on a multitude of health-related issues. Scholars across various disciplines have consistently shown that individuals with higher educational attainment, those born in the United States, and those with greater English proficiency, are more likely to exhibit higher levels of health literacy. However, the extent to which these individuals adhere to established health guidelines remains an understudied area. Therefore, we analyzed data from one of the largest cities impacted by COVID-19 in the United States, to determine whether traditional predictors of high health literacy levels translated into higher levels of vaccination intentions and vaccination doses, to protect themselves and their communities from COVID-19 related illness and death. The results indicated that individuals with high health literacy levels do not necessarily exhibit higher levels of compliance, thus challenging conventional wisdom.

Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform

BackgroundBiological evidence suggests ursodeoxycholic acid (UDCA)—a common treatment of cholestatic liver disease—may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).MethodsWith the approval of NHS England, we conducted a population-based cohort study using primary care records between 1 March 2020 and 31 December 2022, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-varying UDCA exposure and COVID-19 related hospitalisation or death, stratified by geographical region and considering models unadjusted and fully adjusted for pre-specified confounders.ResultsWe identify 11,305 eligible individuals, 640 were hospitalised or died with COVID-19 during follow-up, 400 (63%) events among UDCA users. After confounder adjustment, UDCA is associated with a 21% relative reduction in the hazard of COVID-19 hospitalisation or death (HR 0.79, 95% CI 0.67–0.93), consistent with an absolute risk reduction of 1.35% (95% CI 1.07%–1.69%).ConclusionsWe found evidence that UDCA is associated with a lower hazard of COVID-19 related hospitalisation and death, support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.

Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial.

Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19. This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure. Among 2113 randomized patients enrolled from July 2021 through December 2021, 1966 (NMV/r, n=977; placebo, n=989) were included in the prespecified analysis population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio [HR]=1.27, p<0.0001) and resolution (16 vs 19 days; HR=1.20, p=0.0022) through Day 28 and significantly reduced the number of COVID-19‒related medical visits and the proportion of patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none required ICU admission or mechanical ventilation, and all were discharged to home/self-care. Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated patients died through Week 24 compared with 15 placebo-treated patients. In addition to reducing COVID-19‒related hospitalization or death from any cause through Day 28, NMV/r was found to also reduce duration of COVID-19 symptoms and utilization of healthcare resources versus placebo in patients at high risk of progressing to severe disease. ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202.

Is country leaders’ education relevant for policy making? The case of the Covid-19 pandemic

AbstractThis paper examines the impact of a country leader’s education on policy responses and policy outcomes during the onset of the Covid-19 pandemic. Relying on a quasi-experimental event-study approach, I find that political leaders with a graduate education responded more stringently to the first nationally registered infection than political leaders with lower educational attainment. Subsequently, political leaders with a graduate education reported fewer Covid-19 infections and Covid-19 related deaths at the onset of the pandemic. The results suggest that the education of political leaders can explain policy differences, particularly in countries with low electoral accountability. The low level of accountability allowed political leaders with a graduate education to implement stringent, evidence-based policies to contain the pandemic without fear of electoral punishment.

The effect of Covid deaths on premature mortality trends in Northern Dimension partnership countries

Abstract Background Potential Years Life Lost (PYLL) is an established method to measure, follow trends and compare disease burden within and between countries. Northern Dimension Partnership in Health and Social wellbeing (NDPHS) network was established in 2003 and includes the following countries: Estonia, Finland, Germany, Iceland, Latvia, Lithuania, Norway, Poland, Russia, and Sweden. Due to the Russian invasion to Ukraine, Russia is now excluded from the collaboration. Methods Premature mortality is defined as a death before the age of 70 years. PYLL-rates per 100,000 population are presented in six cause of deaths categories: total mortality, external causes, vascular diseases, cancers, alcohol-related deaths and suicides. Furthermore, 2021 data included deaths due to the Covid infection. Data were obtained from Eurostat and analyses are standardized to EU standard population. Results PYLL-rates declined from 2003 to 2017 in all countries and in most causes of death sub-groups. The total (all causes, all countries) PYLL-rate declined between 2003 and 2017 from 7072 to 5154 in men and from 3263 to 2532 in women. However, from 2017 to 2021 the total PYLL-rate increased to 5469 in men and 2623 in women. The increase was explained by Covid mortality. When Covid deaths were excluded, a minor decrease was observed also between 2017 and 2021. In 2021, total PYLL-rates vary largely between countries: from 2804 to 12,393 in men and from 1781 to 4460 in women. Differences between countries in Covid-related and other cause-specific PYLL-rates were also large. In all countries and causes of death sub-groups PYLL-rates were markedly higher in men compared to women. Conclusions The number of years lost due to premature preventable mortality have declined markedly in all NDPHS countries in the last two decades. Between 2017 and 2021, some increase was observed due to the Covid-related deaths. Differences between countries in premature mortality are still large. Key messages • The number of years lost due to premature preventable mortality have declined markedly in all NDPHS countries since 2003 but still, in 2021, differences between countries were large. • Covid-related deaths caused an increase in premature mortality between 2017 and 2021.

Fighting collective threats: socialist revolutions and the management of the COVID-19 pandemic

Abstract I investigate why some countries were more successful in containing the death toll than others during the COVID-19 pandemic. I focus on the role of socialism and on the existence of long-term regime-driven legacies that may have had an impact on the containment of COVID-related deaths. I claim that countries that went through successful socialist revolutions have specific features that equip them with better resources to cope with public challenges such as pandemics. Furthermore, these features remain even after the demise of the socialist regime. I find a positive effect of socialist revolutions over COVID-19 containment at the country level. I investigate three possible causal mechanisms for this relationship: authoritarianism, state capacity, and mass mobilization. Through mediation analysis, I find the socialist legacy seems to be channeled through higher levels of mobilization and also more authoritarian institutions.

The Political Economy of Disability and the Nursing Home Industry in the United States

While the mass of Covid-19 related deaths in nursing homes has begun to draw attention to the corruption of the industry, the existing literature focuses primarily on the post-productive population (the elderly), or on the unpaid and underpaid care workers, while the discussion of the young and disabled, making up over 15% of residents in U. S. nursing homes, is largely absent. What can a Marxist analysis of disability tell us about both the nature of disability oppression and of the nursing home industry in the United States? Why are 16.9% of nursing home residents young disabled people? How are nursing homes in the U. S. funded? What political conclusions can we draw from this analysis? Building on the work of the late disabled socialist activist Marta Russell, I argue that the trapping of young disabled people in nursing homes is a result of their absorption by the nursing home industry due to capitalism's “compulsory unemployment” of the disabled and the segregation of those who cannot produce surplus value (Russell, 2019). Furthermore, private nursing homes do not “extract” from the disabled, as some have argued, as surplus value can only be extracted from the living labor of nursing-home and other workers. The incorporation of the non-working, institutionalized disabled into class struggle, then, is the only path to ending capitalist exploitation of the entire working class.

Clinical characteristics, treatment, and outcomes for elderly patients in a dedicated Covid-19 ward at a primary health care facility in western Norway: a retrospective observational study

BackgroundThe coronavirus pandemic has hit the oldest and frailest individuals hard, particularly patients and residents in nursing homes. In March 2020, we established a Covid-19 ward at a nursing home in Bergen, western Norway for elderly patients with Sars-CoV-2 infection and in the need of treatment and care in a primary health care facility. The aims of this study were to describe the organization of the ward, the clinical outcomes of infection, treatment, mortality rates in the population, the level of advanced care planning, and end-of-life care for those who died.MethodsWe present patient characteristics, outcomes, vaccination status, treatment, decisions regarding treatment intensity upon clinical deterioration, and mortality for the patients in the ward. Clinical factors possibly related to a fatal outcome were analysed with chi square test (categorical variables) or t-test (continuous variables).Results257 patients were included from March 2020 to April 2022. Fifty-nine patients (23.0%) developed respiratory failure. Ten patients (3.9%) were admitted to hospital. Advance care planning was undertaken for 245 (95.3%) of the patients. 30-day mortality rate decreased from 42 to 4% during the study period. Of the 29 (11.3%) patients who died, all were well alleviated in the terminal phase, and 26 (89.7%) of them had a Clinical Frailty Scale (CFS) value ≥ 7. A high score for CFS, respiratory failure and respiratory co-infection were significantly associated with Covid-19 related death within 30 days.ConclusionsCovid-19-related mortality markedly decreased during the study period, and a high score for CFS was related to a fatal outcome. Thorough planning of treatment intensity upon deterioration, low hospitalization rates, and good relief for those who died suggest that dedicated Covid-19 wards in nursing homes can provide good treatment for the patients and relieve other nursing homes and specialist health care services.

Comparison of fatalities due to COVID-19 and other nonexternal causes during the first five pandemic waves

BackgroundOlder age is a risk factor for a fatal course of SARS-CoV‑2 infection, possibly due to comorbidities whose exact role in this context, however, is not yet well understood. In this paper, the characteristics and comorbidities of persons who had died of COVID-19 in Bavaria by July 2022 are shown and compared with the characteristics of other fatalities during the pandemic.MethodsBased on data from multiple cause of death statistics, odds ratios for dying from COVID-19 (compared to dying from other nonexternal causes of death) were calculated by using logistic regression models, stratified by age, sex, and pandemic waves.ResultsIn Bavaria, a total of 24,479 persons (6.5% of all deaths) officially died from COVID-19 between March 2020 and July 2022. In addition to increasing age and male sex, preexisting diseases and comorbidities such as obesity, degenerative diseases of the nervous system, dementia, renal insufficiency, chronic lower respiratory diseases, and diabetes mellitus were significantly associated with COVID-19–related deaths. Dementia was mainly associated with increased COVID-19 mortality during the first and second waves, while obesity was strongly associated during the fourth wave.DiscussionThe frequency of specific comorbidities in COVID-19 deaths varied over the course of the pandemic. This suggests that wave-specific results also need to be interpreted against the background of circulating virus variants, changing immunisation levels, and nonpharmaceutical interventions in place at the time.

Pathological Grief in Geriatric Age Group Affected by COVID-19 Deaths: A Community-Based Study

Background: Deaths by COVID-19 have left behind nearly 12 million recent bereaved individuals worldwide and researchers have raised concerns that the circumstances of COVID-19 related deaths will lead to a rise in prevalence of prolonged grief disorder (PGD) cases. Nevertheless, no research has looked at the PGD incidence among older Indians who have lost a loved one to COVID-19. The aim this research is to determine the prevalence of PGD and the demographics of older people who have experienced COVID-19-related bereavement. Methods: This is a cross-sectional study and house to house survey was conducted between August 2022 and August 2023. Forty geriatric adults aged above 60 years, who consented to participate were assessed for PGD. Demographic details and loss-related information were collected. Self-reported prolonged grief symptoms were measured using Pandemic Grief Scale (PGS) and Traumatic Grief Inventory Self Report (TGI-SR). Anxiety and depression were measured using Hamilton Rating Scale for Anxiety (HAM-A) and Hamilton Rating Scale for Depression (HAM-D). Multiple linear regression analysis was used to determine the associated factors of grief symptoms. Results: Our study indicates that individuals who experienced loss due to COVID-19 exhibited higher levels of grief. Most of the participants were females (65%). Prevalence of PGD was 10% by TGI-SR. HAM-A scores (14.28 +/- 1.42) were higher than HAM-D scores (12.02 +/- 1.58). Conclusion: It is essential to counsel families early and offer supportive services to prevent pathological grief associated with COVID-19 deaths.

Eight-Fold Increased COVID-19 Mortality in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations: An Observational Study.

MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD- MUC1 patients produce approximately 50% of normal mucin-1. To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. Surveys were emailed to 637 individuals, with responses from 89 ADTKD- MUC1 and 132 ADTKD- UMOD individuals. 19/83 (23%) ADTKD- MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD- UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD- MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD- UMOD , with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD- MUC1 individuals was 7.06±4.12 vs. 10.21±4.02 U/mL ( P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD- MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD- UMOD individuals (0.6%) ( P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD- MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m 2 ) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Individuals with ADTKD- MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD- UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

CDK4/6 inhibitors as adjuvant therapy in early breast cancer? Uncertain benefits, guaranteed harms

CDK4/6 inhibitors are oral agents inhibiting key molecules of the cell cycle regulation. In patients with endocrine receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, the combination of CDK4/6 inhibitors with endocrine therapy is an effective treatment in the metastatic setting. Now, two studies in the adjuvant setting – MonarchE (2 years of abemaciclib) and NATALEE (3 years of ribociclib) – report positive invasive disease-free survival. Here, we re-evaluate these seminal trials. First, an excess drop-out or loss-to-follow up occurred early in the control arms of both studies. Since both trials are open-label, there is concern that the patients who drop-out do not do so at random but based on socioeconomic factors and alternative options. Is it possible that the results merely appear favorable due to loss to follow up? Based on re-constructed Kaplan-Meier curves, we concluded the results of these studies remain fragile, being prone to informative censoring. Secondly, adverse events were notably higher in both trials, and some of them, like COVID-19 related deaths in NATALEE, raise serious concerns. Third, the potential costs associated with CDK4/6 inhibition given as adjuvant therapy are unprecedented. The NATALEE strategy, in particular, could affect up to 35 % of patients with newly diagnosed breast cancer, which is the cancer with the highest incidence worldwide. Without confirmatory data based on a placebo-controlled trial, or better identification of patients that would benefit from the addition of CDK4/6 inhibitors in the adjuvant setting, we argue against their routine use as adjuvant therapy in ER+ /HER2- early breast cancer.

Religion and Coronavirus Response in Kano State, Nigeria

Abstract In April 2020 there was an inordinate spike in COVID-19 related deaths in Kano State, northern Nigeria, due to a lack of adherence to the national public health emergency recommendations. This article aims to explain why this public health fiasco occurred. Utilizing secondary academic literature and news reports from local media, the article interrogates the manifestation of Islam in northern Nigeria and the resulting undermining of the country’s coronavirus mitigation response. The evidence from Kano State indicates that religious authorities failed to heed the suspension of congregational prayers as the relevant health agencies advised, due to a belief in the exceptionality of northern Nigeria as a theocratic substate in a secular federation. The article therefore highlights the challenges of communicating public health risk in a context where the authority of religious leaders, real or imagined, undercuts the power of state institutions.

Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization.

An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, and all twenty-nine SARS-CoV-2 genes of major virulent strains of alpha, delta and omicron demonstrates that the SARS-CoV-2 genome originally emerged (ω ~ 0.04) with a strong purifying selection (ω < 1) and reached (ω ~ 0.85) in omicron towards diversifying selection (ω > 1). A marked increase in the ω occurred in the spike gene from alpha (ω = 0.2) to omicron (ω = 1.97). The ω of the replication machinery genes including RDRP, NSP3, NSP4, NSP7, NSP8, NSP10, NSP13, NSP14, and ORF9 are markedly increased, indicating that these genes/proteins are yet to be evolutionary stabilized and are contributing to the evolution of novel virulent strains. The delta-specific maximum increase in ω in the immunomodulatory genes of NSP8, NSP10, NSP16, ORF4, ORF5, ORF6, ORF7A, and ORF8 compared to alpha or omicron indicates delta-specific vulnerabilities for severe COVID-19 related hospitalization and death. The maximum values of ω are observed for spike (S), NSP4, ORF8 and NSP15, which indicates that the gene-specific temporal estimation of ω identifies specific genes for its super-infectivity and virulency that could be targeted for drug development.

Provider perspectives on the impact of COVID-19 on treatment of substance use and opioid use disorders among American Indian and Alaska Native adults.

American Indian/Alaska Native (AI/AN) communities are more likely to suffer negative consequences related to substance misuse. The COVID-19 pandemic exacerbated the opioid poisoning crisis, in combination with ongoing treatment barriers resulting from settler-colonialism, systemic oppression and racial discrimination. AI/AN adults are at greatest risk of COVID-19 related serious illness and death. In collaboration with an Indigenous community advisory board and Tribal leadership, this study explored AI/AN treatment provider perceptions of client-relatives' (i.e., SUD treatment recipients) experiences during the pandemic from 2020 to 2022. Providers who underwent screening and were eligible to participate (N = 25) represented 6 programs and organizations serving rural and urban areas in Washington, Utah, and Minnesota. Participants engaged in audio-recorded 60-90 min semi-structured individual interviews conducted virtually via Zoom. The interview guide included 15 questions covering regulatory changes, guidance for telemedicine, policy and procedures, staff communication, and client-relatives' reactions to implemented changes, service utilization, changes in treatment modality, and perceptions of impact on their roles and practice. Interview recordings were transcribed and de-identified. Members of the research team independently reviewed transcripts before reaching consensus. Coding was completed in Dedoose, followed by analyses informed by a qualitative descriptive approach. Five main domains were identified related to client-relative experiences during the COVID-19 pandemic, as observed by providers: (1) accessibility, (2) co-occurring mental health, (3) social determinants of health, (4) substance use, coping, and harm reduction strategies, and (5) community strengths. Providers reported the distinctive experiences of AI/AN communities, highlighting the impact on client-relatives, who faced challenges such as reduced income, heightened grief and loss, and elevated rates of substance use and opioid-related poisonings. Community and culturally informed programming promoting resilience and healing are outlined. Findings underscore the impact on SUD among AI/AN communities during the COVID-19 pandemic. Identifying treatment barriers and mental health impacts on client-relatives during a global pandemic can inform ongoing and future culturally responsive SUD prevention and treatment strategies. Elevating collective voice to strengthen Indigenous informed systems of care to address the gap in culturally-and community-based services, can bolster holistic approaches and long-term service needs to promote SUD prevention efforts beyond emergency response efforts.