COVID-19 Related Deaths Research Articles

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.

Comparative efficacy of Bruton tyrosine kinase inhibitors in the treatment of relapsed/refractory chronic lymphocytic leukemia: A network meta-analysis (NMA).

7048 Background: Next-generation Bruton’s tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory (R/R) CLL; defined based on the presence of genetic mutations and a high unmet need. Given the lack of head-to-head trials comparing these treatments in R/R CLL, a NMA was performed to estimate the relative efficacy of BTKis used to treat high-risk patients. Methods: Randomized controlled trials ALPINE (zanubrutinib vs. ibrutinib), ELEVATE-RR (acalabrutinib vs. ibrutinib), and ASCEND (acalabrutinib vs. bendamustine + rituximab/idelalisib + rituximab [BR/IR]) were included in the NMA. High-risk populations were defined based on the pre-specified subgroups within each trial, including patients with del17p and/or TP53 mutations in ALPINE (zanubrutinib: 75/327 and ibrutinib: 75/325), ASCEND (acalabrutinib: 44/155 and BR/IR: 42/155), and del17p/del11q in ELEVATE-RR (acalabrutinib: 268/268 and ibrutinib: 265/265). Bayesian NMAs were used to estimate hazard ratios (HRs) or odds ratios (ORs) with 95% credible intervals (CrIs), and probability better (PB) for zanubrutinib versus all other treatments. Outcomes analysed included investigator-assessed progression-free survival (PFS), overall survival (OS), overall response (ORR), and complete response (CR). Given the timing of the included trials in relation to the COVID-19 pandemic, ALPINE data were analyzed with and without adjustment for COVID-19 related deaths. Results: The NMA found a statistically significant improvement in PFS for zanubrutinib over acalabrutinib in high-risk patients and a trend towards improvement in OS, ORR, and CR (Table). Zanubrutinib led to statistically significant improvements in PFS versus ibrutinib (HR [95% CrI]: 0.49 [0.30, 0.78], PB: 99.9%) and BR/IR (0.12 [0.05, 0.26], PB: 100.0%). For OS, zanubrutinib showed a trend towards improvement versus ibrutinib (0.59 [0.31, 1.12] PB: 94.8%) and BR/IR (0.64 [0.24, 1.74] PB: 80.7%). Conclusions: This NMA found zanubrutinib to be the most efficacious BTKi for patients with high-risk R/R CLL, offering significantly delayed disease progression, and favourable survival and response vs. alternative BTKi treatments. [Table: see text]

#2547 Humoral response to COVID vaccine and infection is intact during sibeprenlimab treatment of IgAN: data from the ENVISION trial

Abstract Background and Aims In the Phase 2 placebo-controlled ENVISION trial, the APRIL (A Proliferation Inducing Ligand) inhibitor sibeprenlimab significantly decreased proteinuria and stabilized estimated glomerular filtration rate decline in patients with immunoglobulin A nephropathy (IgAN) [1]. A substudy was conducted to evaluate the humoral response to SARS-CoV-2 mRNA vaccination and infection. Here, we report the unblinded analysis of COVID outcomes in the overall and substudy populations of ENVISION. Method Patients enrolled in ENVISION (NCT04287985) received 12 monthly intravenous infusions of sibeprenlimab (2, 4, or 8 mg/kg) or placebo and were followed for 16 months after the first dose of study drug. Recognized COVID infection (reported as an adverse event [AE]) and vaccination data were recorded for all patients. For patients in the substudy, serum antibody responses to SARS-CoV-2 spike and nucleocapsid proteins were measured monthly using a validated Meso Scale Discovery V-PLEX SARS-CoV-2 Panel 24 multiplex assay. Vaccine responses among those who received a primary two-dose mRNA COVID vaccine series, with no recent or concurrent COVID infection, were evaluated. Peak post-vaccine serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin G (IgG) titers were reported in World Health Organization binding antibody units (BAU)/mL. Slopes of RBD IgG decline curves were used to generate estimates of time above a protective threshold of 300 BAU/mL. Welch's two-sample t-test was applied to log-transformed peak RBD titers for significance testing. COVID infection–induced antibody responses and severity of COVID symptoms were also assessed. In substudy patients, retrospective serologic diagnosis of COVID infection was established when simultaneous elevation of nucleocapsid and spike antibody titers, unexplained by vaccine history, was observed. Results Among 155 patients who received sibeprenlimab (n = 117) or placebo (n = 38), 56 (36.1%) had COVID infection reported as an AE during the study (Table 1). Overall, proportionally fewer sibeprenlimab recipients (33.3%) had a reported COVID AE compared with placebo recipients (44.7%). Two patients (one each in the sibeprenlimab and placebo groups) were hospitalized with serious COVID AEs in accordance with local management protocols; none were admitted to intensive care or mechanically ventilated and there were no COVID-related deaths. The majority of COVID AEs were of mild severity, regardless of treatment/dosing arm. In the serology substudy (n = 74), symptomatic COVID (reported as an AE) occurred in 47.3% of all patients. With the addition of serologic diagnoses (in the absence of AEs), the overall rate of COVID infection increased to 68.9%. Asymptomatic COVID was identified in 1 of 15 (6.7%) placebo recipients versus 15 of 36 (41.7%) sibeprenlimab recipients, raising the possibility that patients treated with sibeprenlimab may have had attenuated symptom presentation compared with patients who received placebo. COVID seroconversion rates were 100% and peak RBD IgG antibody titers following primary mRNA vaccination exceeded the protective threshold of 300 BAU/mL in all patients (Fig. 1a), with higher geometric mean peak titers in placebo (4670 BAU/mL) compared with sibeprenlimab (1700 BAU/mL) recipients (p = 0.005). The rate of decline of peak RBD IgG titers after mRNA vaccination (in patients with ≥1 dose without confounding subsequent vaccination or infection) was similar between groups (Fig. 1b), with modeled time above the 300 BAU/mL threshold of 192 and 174 days in the sibeprenlimab and placebo groups, respectively. Conclusion COVID-specific antibody responses to vaccination or infection were preserved in patients with IgAN treated with sibeprenlimab. The possibility that COVID symptom presentation may have been modulated by sibeprenlimab warrants further investigation.

Distribution of COVID-19 related deaths in municipalities from Sonora, Mexico, 2020

Introduction: The COVID-19 pandemic has challenged societies, not only because of its magnitude and impact, but also because it has deepened health inequalities and inequities. Socially disadvantaged groups show a higher frequency of adverse health events due to COVID-19, particularly in Latin America. With that in mind, we describe the distribution of deaths in COVID-19 patients stratified by sociodemographic characteristics and medical comorbidities, and explore perceptions related to disease-care, in selected rural and urban localities from Sonora, Mexico. Methods: We conducted a cross-sectional study on 160 deaths attributed to COVID-19, from the period April 1st and July 31st 2020, using death certificates as a data source. Furthermore, to explore the variables of interest, a verbal autopsy was applied to a relative caregiver for the patient’s health. Data collected was analyzed by descriptive statistics and qualitative technique. Results: We did not find significant differences in sociodemographic conditions among the COVID-19 deaths. Interestingly, 85.6% of the deceased had a chronic medical condition and 74.4% of all deaths took place in an urban locality. Caregivers frequently consigned deficiencies from medical services over the disease-care process of COVID-19 deaths.

Direct impact of COVID-19 vaccination in Chile: averted cases, hospitalizations, ICU admissions, and deaths

BackgroundChile rapidly implemented an extensive COVID-19 vaccination campaign, deploying a diversity of vaccines with a strategy that prioritized the elderly and individuals with comorbidities. This study aims to assess the direct impact of vaccination on the number of COVID-19 related cases, hospital admissions, ICU admissions and deaths averted during the first year and a half of the campaign.MethodsVia Chile’s transparency law, we obtained access to weekly event counts categorized by vaccination status and age. Integrating this data with publicly available census and vaccination coverage information, we conducted a comparative analysis of weekly incidence rates between vaccinated and unvaccinated groups from December 20, 2020 to July 2, 2022 to estimate the direct impact of vaccination in terms of the number of cases, hospitalizations, ICU admissions and deaths averted, using an approach that avoids the need to explicitly specify the effectiveness of each vaccine deployed.ResultsWe estimated that, from December 20, 2020 to July 2, 2022 the vaccination campaign directly prevented 1,030,648 (95% Confidence Interval: 1,016,975-1,044,321) cases, 268,784 (95% CI: 264,524-273,045) hospitalizations, 85,830 (95% CI: 83,466-88,194) ICU admissions and 75,968 (95% CI: 73,909-78,028) deaths related to COVID-19 among individuals aged 16 years and older. This corresponds to a reduction of 26% of cases, 66% of hospital admissions, 70% of ICU admissions and 67% of deaths compared to a scenario without vaccination. Individuals 55 years old or older represented 67% of hospitalizations, 73% of ICU admissions and 89% of deaths related to COVID-19 prevented.ConclusionsThis study highlights the role of Chile's vaccination campaign in reducing COVID-19 disease burden, with the most substantial reductions observed in severe outcomes.

Association between SARS-CoV-2 gene specific Ct values and COVID-19 associated in-hospital mortality.

Since there are currently no specific SARS-CoV-2 prognostic viral biomarkers for predicting disease severity, there has been interest in using SARS-CoV-2 polymerase chain reaction (PCR) cycle-threshold (Ct) values to predict disease progression. This study assessed the association between in-hospital mortality of hospitalized COVID-19 cases and Ct-values of gene targets specific to SARS-CoV-2. Clinical data of hospitalized COVID-19 cases from Gauteng Province from April 2020-July 2022 were obtained from a national surveillance system and linked to laboratory data. The study period was divided into pandemic waves: Asp614Gly/wave1 (7 June-22 Aug 2020); beta/wave2 (15 Nov 2020-6 Feb 2021); delta/wave3 (9 May-18 Sept 2021) and omicron/wave4 (21 Nov 2021-22 Jan 2022). Ct-value data of genes specific to SARS-CoV-2 according to testing platforms (Roche-ORF gene; GeneXpert-N2 gene; Abbott-RdRp gene) were categorized as low (Ct < 20), mid (Ct20-30) or high (Ct > 30). There were 1205 recorded cases: 836(69.4%; wave1), 122(10.1%;wave2) 21(1.7%; wave3) and 11(0.9%;in wave4). The cases' mean age(±SD) was 49 years(±18), and 662(54.9%) were female. There were 296(24.6%) deaths recorded: 241(81.4%;wave1), 27 (9.1%;wave2), 6 (2%;wave3), and 2 (0.7%;wave4) (p < 0.001). Sample distribution by testing platforms was: Roche 1,033 (85.7%), GeneXpert 169 (14%) and Abbott 3 (0.3%). The median (IQR) Ct-values according to testing platform were: Roche 26 (22-30), GeneXpert 38 (36-40) and Abbott 21 (16-24). After adjusting for sex, age and presence of a comorbidity, the odds of COVID-19 associated death were high amongst patients with Ct values 20-30[adjusted Odds Ratio (aOR) 2.25; 95% CI: 1.60-3.18] and highest amongst cases with Ct-values <20 (aOR 3.18; 95% CI: 1.92-5.27), compared to cases with Ct-values >30. Although odds of COVID19-related death were high amongst cases with Ct-values <30, Ct values were not comparable across different testing platforms, thus precluding the comparison of SARS-CoV-2 Ct-value results.

The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan.

This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023-August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer-BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer-BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios.