Demographic changes in COVID-19 mortality during the pandemic: analysis of trends in disparities among workers using California's mortality surveillance system.

BACKGROUND: There is limited information on the extent and patterns of disparities in COVID-19 mortality throughout the pandemic. We aimed to examine trends in disparities by demographics over variants in the pre- and post-vaccine availability period among Californian workers using a social determinants of health lens. METHODS: Using death certificates, we identified all COVID-19 deaths that occurred between January 2020 and May 2022 among workers aged 18-64 years in California (CA). We derived estimates for at-risk worker populations using the Current Population Survey. The waves of COVID-19 mortality in the pre-vaccine availability period were March 2020-June 2020 (wave 1), and July 2020-November 2020 (wave 2), and in the post-vaccine availability period: December 2020-May 2021 (wave 3), June 2021-January 2022 (wave 4), and February 2022-May 2022 (wave 5). Poisson regression models with robust standard errors were used to determine wave-specific mortality rate ratios (MRRs). We examined the change in MRR across waves by including an interaction term between each demographic characteristic and wave period in different models. The role of potential misclassification of Race/ethnicity on death certificates was examined using probabilistic quantitative bias analysis as sensitivity analysis. RESULTS: Among the 24.1 million working age CA population included in the study, there were 26,068 COVID-19 deaths in the period between January 2020 and May 2022. Compared with their respective reference groups, workers who were 50-64 years old, male, Native Hawaiian, Latino, or African American, foreign-born; individuals who had lower education; and unmarried were disproportionately affected by COVID-19 mortality. While disparities by sex, race/ethnicity and foreign-born status narrowed in later waves (post-vaccine availability), disparities by age, education level and marital status did not change substantially across waves. CONCLUSION: Demographic disparities in COVID-19 mortality narrowed in the post-vaccine availability waves. However, the existence of disparities across all waves of the pandemic, even in an era of widespread vaccine coverage, could indicate remaining gaps in prevention and differential vulnerability. Addressing the underlying social, structural, and occupational factors that contribute to these disparities is critical for achieving health equity.

Regional variation in financial hardship among US veterans during the COVID-19 pandemic.

Geographic variation in hardship, especially health-related hardship, was identified prior to and during the pandemic, but we do not know whether this variation is consistent among Veterans Health Administration (VHA)-enrolled veterans, who reported markedly high rates of financial hardship during the pandemic, despite general and veteran-specific federal policy efforts aimed at reducing hardship. In a nationwide, regionally stratified sample of VHA-enrolled veterans, we examined whether the prevalence of financial hardship during the pandemic varied by US Census region. We found veterans in the South, compared with those in other census regions, reported higher rates of severe-to-extreme financial strain, using up all or most of their savings, being unable to pay for necessities, being contacted by collections, and changing their employment due to the kind of work they could perform. Regional variation in veteran financial hardship demonstrates a need for further research about the role and interaction of federal and state financial-assistance policies in shaping risks for financial hardship as well as potential opportunities to mitigate risks among veterans and reduce variation across regions.

Identifying Veterans Who Benefit From Nirmatrelvir-Ritonavir: A Target Trial Emulation.

BACKGROUND: Nirmatrelvir-ritonavir is recommended for persons at risk for severe coronavirus disease 2019 (COVID-19) but remains underutilized. Information on which eligible groups are likely to benefit from treatment is needed. METHODS: We conducted a target trial emulation study in the Veterans Health Administration comparing nirmatrelvir-ritonavir treated versus matched untreated veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from April 2022 through March 2023. We measured incidence of any hospitalization or all-cause mortality at 30 days. Outcomes were measured for the entire cohort, as well as among subgroups defined by 30-day risk of death or hospitalization, estimated using an ensemble risk prediction model. RESULTS: Participants were 87% male with median age 66 years and 16% unvaccinated. Compared with matched untreated participants, those treated with nirmatrelvir-ritonavir (n = 24 205) had a lower 30-day risk for hospitalization (1.80% vs 2.30%; risk difference [RD], -0.50% points [95% confidence interval {CI}: -.69 to -.35]) and death (0.11% vs 0.30%; RD, -0.20 [95% CI: -.24 to -.13]). The greatest reductions in combined hospitalization or death were observed in the highest risk quartile (RD -2.85 [95% CI: -3.94 to -1.76]), immunocompromised persons (RD -1.91 [95% CI: -3.09 to -.74]), and persons aged ≥75 years (RD -1.16 [95% CI: -1.73 to -.59]). No reductions were observed in the 2 lowest risk quartiles or persons younger than 65 years. CONCLUSIONS: Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death in older veterans, those at highest predicted risk for severe outcomes, and immunocompromised groups. Benefit was not observed in younger veterans or groups at lower predicted risk for hospitalization and death.

Impact of SARS-CoV-2 Infection on Long-Term Depression Symptoms among Veterans.

BACKGROUND: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). OBJECTIVE: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. DESIGN: Survey-based non-randomized cohort study with matched comparators. PARTICIPANTS: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. MAIN MEASURES: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. KEY RESULTS: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. CONCLUSION: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.

Unmet Mental Health Needs Among California Workers Since the Start of the COVID-19 Pandemic.

OBJECTIVE: We sought to identify worker groups with high prevalence of unmet mental health needs to inform employer benefits programs and outreach to increase access to care. METHODS: We conducted a repeated cross-sectional study to understand unmet mental health needs among workers since the start of the COVID-19 pandemic using California Health Interview Survey data from 2013-2021. RESULTS: In 2021, 23.4% (CI: 22.4-24.4) reported unmet mental health needs, an absolute increase of 3.9% from 2019. Relative increases were highest among workers in the information industries (prevalence ratio [PR]: 1.89, CI: 1.4-2.5) and older workers (PR: 1.27, CI: 0.9-1.8). Increases in needing help were not met with comparable increases in seeking care. CONCLUSIONS: Unmet mental health needs increased for California workers during the pandemic. Employers should dedicate resources and implement strategies to increase access to care and promote worker well-being.

Healthcare personnel with laboratory-confirmed mpox in California during the 2022 outbreak.

The California Department of Public Health (CDPH) reviewed 109 cases of healthcare personnel (HCP) with laboratory-confirmed mpox to understand transmission risk in healthcare settings. Overall, 90% of HCP with mpox had nonoccupational exposure risk factors. One occupationally acquired case was associated with sharps injury while unroofing a patient's lesion for diagnostic testing.

Residual Complex I activity and amphidirectional Complex II operation support glutamate catabolism through mtSLP in anoxia.

Anoxia halts oxidative phosphorylation (OXPHOS) causing an accumulation of reduced compounds in the mitochondrial matrix which impedes dehydrogenases. By simultaneously measuring oxygen concentration, NADH autofluorescence, mitochondrial membrane potential and ubiquinone reduction extent in isolated mitochondria in real-time, we demonstrate that Complex I utilized endogenous quinones to oxidize NADH under acute anoxia. 13C metabolic tracing or untargeted analysis of metabolites extracted during anoxia in the presence or absence of site-specific inhibitors of the electron transfer system showed that NAD+ regenerated by Complex I is reduced by the 2-oxoglutarate dehydrogenase Complex yielding succinyl-CoA supporting mitochondrial substrate-level phosphorylation (mtSLP), releasing succinate. Complex II operated amphidirectionally during the anoxic event, providing quinones to Complex I and reducing fumarate to succinate. Our results highlight the importance of quinone provision to Complex I oxidizing NADH maintaining glutamate catabolism and mtSLP in the absence of OXPHOS.

Effectiveness of Nirmatrelvir-Ritonavir Against the Development of Post-COVID-19 Conditions Among U.S. Veterans : A Target Trial Emulation.

BACKGROUND: COVID-19 has been linked to the development of many post-COVID-19 conditions (PCCs) after acute infection. Limited information is available on the effectiveness of oral antivirals used to treat acute COVID-19 in preventing the development of PCCs. OBJECTIVE: To measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir-ritonavir in preventing PCCs. DESIGN: Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment. SETTING: Veterans Health Administration (VHA). PARTICIPANTS: Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022. INTERVENTION: Nirmatrelvir-ritonavir treatment for acute COVID-19. MEASUREMENTS: Cumulative incidence of 31 potential PCCs at 31 to 180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms. RESULTS: Eighty-six percent of the participants were male, with a median age of 66 years, and 17.5% were unvaccinated. Baseline characteristics were well balanced between participants treated with nirmatrelvir-ritonavir and matched untreated comparators. No differences were observed between participants treated with nirmatrelvir-ritonavir (n = 9593) and their matched untreated comparators in the incidence of most PCCs examined individually or grouped by organ system, except for lower combined risk for venous thromboembolism and pulmonary embolism (subhazard ratio, 0.65 [95% CI, 0.44 to 0.97]; cumulative incidence difference, -0.29 percentage points [CI, -0.52 to -0.05 percentage points]). LIMITATIONS: Ascertainment of PCCs using International Classification of Diseases, 10th Revision, codes may be inaccurate. Evaluation of many outcomes could have resulted in spurious associations with combined thromboembolic events by chance. CONCLUSION: Out of 31 potential PCCs, only combined thromboembolic events seemed to be reduced by nirmatrelvir-ritonavir. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Temporal assessment of disparities in California COVID-19 mortality by industry: a population-based retrospective cohort study.

PURPOSE: To assess changes in the COVID-19 mortality rate and disparities over variants or waves by industry. METHODS: We identified COVID-19 deaths that occurred between January 2020 and May 2022 among California workers aged 18-64 years using death certificates, and estimated Californians at risk using the Current Population Survey. The waves in deaths were wave 1: March-June 2020, wave 2: July-November 2020, wave 3/Epsilon and Alpha variants: December 2020-May 2021, wave 4/Delta variant: June 2021-January 2022, and wave 5/Omicron variant: February-May 2022. We used Poisson regression to generate wave-specific mortality rate ratios (MRR) and included an interaction term between industry and wave in different models to assess significance of the change in MRR. RESULTS: In all waves of the pandemic, healthcare, other services, manufacturing, transportation, and retail trade industries had higher mortality rates than the professional, scientific, and technical industry. The healthcare industry had the highest relative rate earlier in the pandemic, while other services, utilities, and accommodation and food services industries had substantial increases in MRR in later waves. CONCLUSIONS: Industries that consistently had disproportionate COVID-19 mortality may have benefitted from protections that consider workers' increased exposure and vulnerability to severe outcomes.

Occupational COVID-19 Exposures and Illnesses among Workers in California-Analysis of a New Occupational COVID-19 Surveillance System.

Little is known about occupational SARS-CoV-2 exposures and COVID-19 outcomes. We established a Doctor's First Reports of Occupational Injury or Illness (DFR)-based surveillance system to study cases of work-related COVID-19 exposures and disease. The surveillance data included demographics, occupation, industry, exposure, and illness, details including hospitalization and lost work. We classified workers into 'healthcare', non-healthcare 'public-facing', or 'other' worker groups, and rural-urban commuting areas (RUCAs). We describe worker exposures and outcomes overall by worker group and RUCA. We analyzed 2848 COVID-19 DFRs representing workers in 22 detailed occupation groups and 19 industry groups. Most DFRs were for workers in metropolitan RUCAs (89%) and those in healthcare (42%) and public-facing (24%) worker groups. While DFRs were from 382 unique worksites, 52% were from four hospitals and one prison. Among 1063 DFRs with a suspected exposure, 73% suspected exposure to a patient or client. Few DFRs indicated hospitalization (3.9%); however, the proportion hospitalized was higher among nonmetropolitan (7.4%) and public-facing (6.7%) workers. While 56% of DFRs indicated some lost work time, the proportion was highest among public-facing (80%) workers. Healthcare and prison workers were the majority of reported occupational COVID-19 exposures and illnesses. The risk of COVID-19 hospitalization and lost work may be highest among nonmetropolitan and public-facing workers.

Viability of HepG2 and MCF-7 cells is not correlated with mitochondrial bioenergetics.

Alterations in metabolism are a hallmark of cancer. It is unclear if oxidative phosphorylation (OXPHOS) is necessary for tumour cell survival. In this study, we investigated the effects of severe hypoxia, site-specific inhibition of respiratory chain (RC) components, and uncouplers on necrotic and apoptotic markers in 2D-cultured HepG2 and MCF-7 tumour cells. Comparable respiratory complex activities were observed in both cell lines. However, HepG2 cells exhibited significantly higher oxygen consumption rates (OCR) and respiratory capacity than MCF-7 cells. Significant non-mitochondrial OCR was observed in MCF-7 cells, which was insensitive to acute combined inhibition of complexes I and III. Pre-treatment of either cell line with RC inhibitors for 24-72 h resulted in the complete abolition of respective complex activities and OCRs. This was accompanied by a time-dependent decrease in citrate synthase activity, suggesting mitophagy. High-content automated microscopy recordings revealed that the viability of HepG2 cells was mostly unaffected by any pharmacological treatment or severe hypoxia. In contrast, the viability of MCF-7 cells was strongly affected by inhibition of complex IV (CIV) or complex V (CV), severe hypoxia, and uncoupling. However, it was only moderately affected by inhibition of complexes I, II, and III. Cell death in MCF-7 cells induced by inhibition of complexes II, III, and IV was partially abrogated by aspartate. These findings indicate that OXPHOS activity and viability are not correlated in these cell lines, suggesting that the connection between OXPHOS and cancer cell survival is dependent on the specific cell type and conditions.

Serial Interval and Incubation Period Estimates of Monkeypox Virus Infection in 12 Jurisdictions, United States, May-August 2022.

Using data from 12 US health departments, we estimated mean serial interval for monkeypox virus infection to be 8.5 (95% credible interval 7.3-9.9) days for symptom onset, based on 57 case pairs. Mean estimated incubation period was 5.6 (95% credible interval 4.3-7.8) days for symptom onset, based on 35 case pairs.

Increases in Prevalent Depressed Mood and Suicidal Ideation among Workers during the COVID-19 Pandemic-Findings from the California Health Interview Survey.

Limited data exist on COVID-19's mental health impact on non-healthcare workers. We estimated the prevalence of depressed mood and suicidal ideation experienced in the past year among California workers and assessed whether the prevalence changed during the COVID-19 pandemic. We analyzed 2013-2020 California Health Interview Survey data using survey-weighted methods to assess the change in the prevalence of depressed mood and suicidal ideation from 2019 to 2020 for working adults by demographics and occupational groups. We used trend-adjusted quasi-Poisson regressions and report rate ratios (RR), comparing the prevalence of outcomes during 2020 to the pre-pandemic period (2013-2019). We identified priority occupation groups with a higher-than-average outcome prevalence in 2020 and rate increases after adjusting for pre-pandemic trends. Our analysis included 168,768 respondents, of which 65% were workers. Production and service workers were the priority occupation groups for depressed mood (RR: 1.46, CI: 1.1-1.9; RR: 1.23, CI: 1.1-1.4) and suicidal ideation (RR: 1.86, CI: 1.0-3.6; RR: 1.47, CI: 1.1-1.9). Workers aged 45-65 years experienced over a 30% relative increase in both outcomes from 2019 to 2020. Depressed mood and suicidal ideation in the past year increased for production, service, and older workers during the pandemic. These groups should be considered for mental health interventions.

COVID-19 Outbreaks and Mortality Among Public Transportation Workers - California, January 2020-May 2022.

Work-related factors can contribute to risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, and subsequent COVID-19-attributable outcomes, including death. Comparing COVID-19 metrics across industries can help identify workers at highest risk. Elevated COVID-19 mortality rates have been reported among all transportation workers, as well as specifically in public transportation industries (1-3). The California Department of Public Health (CDPH) calculated public transportation industry-specific COVID-19 outbreak incidence during January 2020-May 2022 and analyzed all laboratory-confirmed COVID-19 deaths among working-age adults in California to calculate public transportation industry-specific mortality rates during the same period. Overall, 340 confirmed COVID-19 outbreaks, 5,641 outbreak-associated cases, and 537 COVID-19-associated deaths were identified among California public transportation industries. Outbreak incidence was 5.2 times as high (129.1 outbreaks per 1,000 establishments) in the bus and urban transit industry and 3.6 times as high in the air transportation industry (87.7) as in all California industries combined (24.7). Mortality rates were 2.1 times as high (237.4 deaths per 100,000 workers) in transportation support services and 1.8 times as high (211.5) in the bus and urban transit industry as in all industries combined (114.4). Workers in public transportation industries are at higher risk for COVID-19 workplace outbreaks and mortality than the general worker population in California and should be prioritized for COVID-19 prevention strategies, including vaccination and enhanced workplace protection measures.

Proline Oxidation Supports Mitochondrial ATP Production When Complex I Is Inhibited.

The oxidation of proline to pyrroline-5-carboxylate (P5C) leads to the transfer of electrons to ubiquinone in mitochondria that express proline dehydrogenase (ProDH). This electron transfer supports Complexes CIII and CIV, thus generating the protonmotive force. Further catabolism of P5C forms glutamate, which fuels the citric acid cycle that yields the reducing equivalents that sustain oxidative phosphorylation. However, P5C and glutamate catabolism depend on CI activity due to NAD+ requirements. NextGen-O2k (Oroboros Instruments) was used to measure proline oxidation in isolated mitochondria of various mouse tissues. Simultaneous measurements of oxygen consumption, membrane potential, NADH, and the ubiquinone redox state were correlated to ProDH activity and F1FO-ATPase directionality. Proline catabolism generated a sufficiently high membrane potential that was able to maintain the F1FO-ATPase operation in the forward mode. This was observed in CI-inhibited mouse liver and kidney mitochondria that exhibited high levels of proline oxidation and ProDH activity. This action was not observed under anoxia or when either CIII or CIV were inhibited. The duroquinone fueling of CIII and CIV partially reproduced the effects of proline. Excess glutamate, however, could not reproduce the proline effect, suggesting that processes upstream of the glutamate conversion from proline were involved. The ProDH inhibitors tetrahydro-2-furoic acid and, to a lesser extent, S-5-oxo-2-tetrahydrofurancarboxylic acid abolished all proline effects. The data show that ProDH-directed proline catabolism could generate sufficient CIII and CIV proton pumping, thus supporting ATP production by the F1FO-ATPase even under CI inhibition.

The Occupational Health Effects of Responding to a Natural Gas Pipeline Explosion Among Emergency First Responders - Lincoln County, Kentucky, 2019.

OBJECTIVE: The aim of the study was to assess occupational health effects 1 month after responding to a natural gas pipeline explosion. METHODS: First responders to a pipeline explosion in Kentucky were interviewed about pre- and post-response health symptoms, post-response health care, and physical exertion and personal protective equipment (PPE) use during the response. Logistic regression was used to examine associations between several risk factors and development of post-response symptoms. RESULTS: Among 173 first responders involved, 105 (firefighters [58%], emergency medical services [19%], law enforcement [10%], and others [12%]) were interviewed. Half (53%) reported at least 1 new or worsening symptom, including upper respiratory symptoms (39%), headache (18%), eye irritation (17%), and lower respiratory symptoms (16%). The majority (79%) of symptomatic responders did not seek post-response care. Compared with light-exertion responders, hard-exertion responders (48%) had significantly greater odds of upper respiratory symptoms (aOR: 2.99, 95% CI: 1.25-7.50). Forty-four percent of responders and 77% of non-firefighter responders reported not using any PPE. CONCLUSIONS: Upper respiratory symptoms were common among first responders of a natural gas pipeline explosion and associated with hard-exertion activity. Emergency managers should ensure responders are trained in, equipped with, and properly use PPE during these incidents and encourage responders to seek post-response health care when needed.

Performance Characteristics of the Abbott BinaxNOW SARS-CoV-2 Antigen Test in Comparison to Real-Time Reverse Transcriptase PCR and Viral Culture in Community Testing Sites during November 2020.

Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease, or exposure period and demographic variables are limited. During 3 to 17 November 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status, and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here, we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8 to 10 days postexposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 h for BinaxNOW and 26 h for rRT-PCR. Point-of-care antigen tests have a shorter turnaround time than laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program.

Outcomes of Acute Operative Repair of Complete Digital Proximal Interphalangeal Joint Collateral Ligament Ruptures: A Systematic Review.

Background: No consensus exists regarding the management of complete collateral ligament injuries of the proximal interphalangeal joint (PIPJ) of fingers. Methods: We aimed to systematically review the outcomes of Acute (< 1 month) surgical repairs of these injuries. Outcomes assessed included Stability, Pain, Range-of-Motion and Return to Function. The Modified Coleman Methodology Score (MCMS) was utilised in critical appraisal. Results: 70 patients with complete collateral ligament injuries of the PIPJ were identified in 5 studies. 49 were managed operatively and 21 non-operatively. All trials were methodologically flawed with a mean MCMS of 50.4, corresponding to a "Poor" Level of evidence. Conclusions: Whilst acute surgical repair of complete collateral ligament injuries of finger PIPJs are a described viable management option with promising results, there is insufficient high-quality evidence to inform current practice. Based on the current literature, no evidence-based conclusions can be made regarding superiority of acute surgical repair over conservative management or one method of surgical repair over another. Further high level studies are required.