Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains (preprint)

Since the start of the SARS-CoV-2 pandemic, the search for antiviral therapies has been at the forefront of medical research. To date, the 3CLpro inhibitor nirmatrelvir (Paxlovid(R)) has shown the best results in clinical trials and the greatest robustness against variants. A second SARS-CoV-2 protease inhibitor, ensitrelvir (Xocova(R)), has been developed. Ensitrelvir, currently in Phase 3, was approved in Japan under the emergency regulatory approval procedure in November 2022, and is available since March 31, 2023. One of the limitations for the use of antiviral monotherapies is the emergence of resistance mutations. Here, we experimentally generated mutants resistant to nirmatrelvir and ensitrelvir in vitro following repeating passages of SARS-CoV-2 in the presence of both antivirals. For both molecules, we demonstrated a loss of sensitivity for resistance mutants in vitro. Using a Syrian golden hamster infection model, we showed that the ensitrelvir M49L mutation confers a high level of in vivo resistance. Finally, we identified a recent increase in the prevalence of M49L-carrying sequences, which appears to be associated with multiple repeated emergence events in Japan and may be related to the use of Xocova(R) in the country since November 2022. These results highlight the strategic importance of genetic monitoring of circulating SARS-CoV-2 strains to ensure that treatments administered retain their full effectiveness. HighlightsO_LISARS-CoV-2 resistant strains to clinical stage protease inhibitors have been generated after 16 passages in vitro C_LIO_LIThe ensitrelvir resistance mutation M49L induces a strong resistance to ensitrelvir in vitro in three different isolates C_LIO_LIM49L mutation alone renders ensitrelvir treatment ineffective in vivo C_LIO_LIThe prevalence of naturally occurring M49L-mutants has increased over recent months C_LI

Did A Fruit and Vegetable Incentive Program Support low-income Households in North Carolina during the COVID-19 Pandemic? A Mixed Methods Assessment of the Healthy Helping Program and Other Pandemic-Related Food Assistance

In 2020, the Healthy Helping Fruit and Vegetable Program provided SNAP-eligible beneficiaries with $40/month, for up to 3 months, to purchase fruits and vegetablesata chainsupermarket inNorthCarolina.A survey to describeparticipants' experiences with the program and interviews to explore whether these experiences were shaped byparticipating inotherpandemic-related food access programs were conducted.In conjunction with other food access programs,programs that allow participants freedom to choose what they purchase mayalleviate household hardships and provide greater access tonutrient-dense foods during the COVID-19 pandemic and beyond..Copyright © 2022 Taylor & Francis Group, LLC.

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial.

BACKGROUND: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. METHODS: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to <60 mL/min per 1·73 m2 and ≥60 mL/min per 1·73 m2) and urine protein excretion at screening (≤1·75 g/day and >1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. FINDINGS: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. INTERPRETATION: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. FUNDING: Travere Therapeutics.

Observed Mask Use in Kindergarten Through Grade 12 Schools in Georgia-Fall, 2021.

BACKGROUND: Universal masking, with additional layered prevention strategies, was an essential tool for limiting the transmission of SARS-CoV-2 and ensuring a safe return to in-person learning for kindergarten through 12th grade (K-12) students and staff. Few studies have examined mask adherence in this setting and none have described types of masks worn or locations of mask adherence. This project sought to assess mask adherence, types worn, and location of mask adherence in K-12 settings. METHODS: This study used direct in-person observations to measure the proportion of persons wearing masks correctly; type of masks worn; and location of mask adherence in 19 K-12 schools in Georgia. RESULTS: A total of 16,222 observations were conducted. Among those observed, 85.2% wore masks, with 80.3% wearing the mask correctly. Persons in high school were less likely to wear masks correctly. Correct mask use was most often observed among persons wearing N95-type masks. The prevalence of persons wearing masks correctly in transitional spaces was 5% higher than in congregate spaces. CONCLUSION: In K-12 schools with a universal masking policy, correct mask adherence was high among individuals. Examining adherence to recommended prevention measures can provide K-12 schools feedback to inform targeted messaging and policies during future disease outbreaks.

Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism.

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics-and an understanding of pathobiology and epizootiology of rabies in testament to One Health-before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable-occasional treatment-of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral-essentially 'one and done'. Exploiting mammalian social behaviors, future 'spreadable vaccines' might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

Reduction in Hospital Transfers at a US COVID-19 Alternate Care Site: Maintaining Surge Capacity Support in Imperial County, California.

OBJECTIVE: The transfer rate for patients from an Alternate Care Site (ACS) back to a hospital may serve as a metric of appropriate patient selection and the ability of an ACS to treat moderate to severely ill patients accepted from overwhelmed health-care systems. During the coronavirus infectious disease 2019 (COVID-19) pandemic, hospitals worldwide experienced acute surges of patients presenting with acute respiratory failure. METHODS: An ACS in Imperial County, California was re-established in November 2020 to help decompress 2 local hospitals experiencing surges of COVID-19 cases. The patients treated often had multiple comorbid illnesses and required a median supplemental oxygen of 3 L/min (LPM) on admission. Numerous interventions were initiated during a 2-wk period to improve clinical care delivery. RESULTS: The objectives of this retrospective observational study are to evaluate the impact of these clinical and staff interventions at an ACS on the transfer rate and to provide issues to consider for future ACS sites managing COVID-19 patients. CONCLUSIONS: The data suggest that continuous, real-time process-improvement interventions helped reduce the transfer rate back to hospitals from 36.7% to 14.5% and that an ACS is a viable option for managing symptomatic COVID-19 positive patients requiring hospital-level care when hospitals are overburdened.

The Luciferase Immunoprecipitation System (LIPS) Targeting the Spike Protein of SARS-CoV-2 Is More Accurate than Nucleoprotein-Based LIPS and ELISAs for Mink Serology

Since anthropo-zoonotic outbreaks of SARS-CoV-2 have been reported in mink farms, it is important to monitor the seroprevalence within this population. To investigate the accuracy of nucleo (N) or spike (S) protein-based assays to detect anti-SARS-CoV-2 antibodies in animal serum, we compared four assays, two commercial N-based enzyme-linked immunosorbent assays (ELISA) validated for animal sera and two luciferase immunoprecipitation systems (LIPS-N and LIPS-S), to the reference standard plaque reduction neutralisation test (PRNT). Samples included in this study were derived from a naturally infected mink population. For the first time in this study, serum samples of mink were collected over a 307-day period, at different time points, thus providing an overview of performances of four different rapid serological tests over time. The assays were compared by performing a correlation analysis using R2, Spearman's rank-order correlation coefficient, and Fleiss' and Cohen's kappa for analysis of agreement to PRNT, and an UpSet chart was created to visualize the number of shared positive samples between assays. Cohen's kappa test on categorical data showed an excellent agreement between PRNT and LIPS-S, while agreements between PRNT and N-based methods decreased from fair for LIPS-N to poor agreements for the ELISA kits. In addition, LIPS-S revealed the highest number of true-positive SARS-CoV-2 samples compared to N-based methods. Despite an excellent agreement between LIPS-S and PRNT, a weak correlation was detectable between PRNT titres and relative light units. This study shows that the LIPS-S assay can be used for serological surveillance within a naturally exposed mink population, while N-based serological assays are less accurate providing a higher number of false-negative results, especially at a later stage of infection, thus indicating that N antibodies are less persistent in naturally exposed mink. Our findings provide crucial information for veterinarians and competent authorities involved in surveillance and outbreak investigation in wild and farmed minks. [ FROM AUTHOR] Copyright of Transboundary & Emerging Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in hospitalized hemodialysis patients: An epidemiologic and genomic investigation.

We performed an epidemiological investigation and genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to define the source and scope of an outbreak in a cluster of hospitalized patients. Lack of appropriate respiratory hygiene led to SARS-CoV-2 transmission to patients and healthcare workers during a single hemodialysis session, highlighting the importance of infection prevention precautions.

Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection.

Background and objective: COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Methods: Expression of IFN activation signaling pathway molecules, including cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNß were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Results: Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. Conclusions: STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

Antithrombin Activity Is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness.

INTRODUCTION: Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients. METHODS: This was a single-center, prospective observational study enrolling SARS-CoV-2-positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-factor Xa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and categorical variables were compared using χ2 tests. Multivariable logistic regression was used to determine the association between AT activity and mortality. RESULTS: In 36 patients, 3 thromboembolic events occurred, and 18 (50%) patients died. Patients who died had higher fibrinogen, D-dimer, and C-reactive protein (CRP) levels and lower AT activity. Reduced AT activity was independently associated with mortality and correlated with both markers of hypercoagulability (D-dimer) and inflammation (CRP). CONCLUSION: Low AT activity is associated with mortality and persistent hypercoagulable and proinflammatory states in severe COVID-19 patients. The anti-thromboinflammatory properties of AT make it an appealing therapeutic target for future studies.

Health Care Transitions for Adolescents.

The transition from pediatric to adult models of care poses many challenges to adolescent and young adult (AYA) patients. Several academic societies have established clinical reports to help providers prepare patients for this transition, facilitate the transfer of care between providers, and integrate patients into adult models of care. Furthermore, several novel care delivery models have been developed to expand health care transition (HCT) services. Despite this, a minority of patients receive transition services meeting the goals of these clinical reports and few data exist on their effectiveness. Given this, ongoing research and clinical innovation in the field are imperative. This article aims to summarize the current landscape of HCT for AYAs, outline the contemporary imperative for its integration into preventive health care given the unique challenges of the COVID-19 pandemic, and expand the current literature by providing a summary of novel emerging strategies being used to meet the health care transition (HCT) needs of adolescent and young adult (AYA) patients.

Symptoms of Depression, Anxiety, and Post-Traumatic Stress Disorder, and Suicidal Ideation Among School Nurses in Prekindergarten through Grade 12 Schools - United States, March 2022.

School nurses are integral to creating safe environments in U.S. schools. Many experienced increased work burden and stress during the COVID-19 pandemic. CDC collaborated with the National Association of School Nurses and the National Association of State School Nurse Consultants to distribute a 121-item online, anonymous survey to school nurses nationwide during March 7-30, 2022. Among the 7,971 respondents, symptoms of depression, anxiety and PTSD, and suicidal ideation were measured, and prevalence ratios were used to identify associations with demographics, workplace characteristics, and support. Results found high levels of work-related stressors and indicated that employment characteristics, COVID-19-related job duties, and other workplace stressors and supports affected school nurse mental health. The survey findings underscore the mental health challenges many school nurses experienced during the 2021/2022 school year. The findings can inform supportive policies and practices to reduce workplace stressors and increase workplace supports for school nurses.

Pregnancy-related COVID worry, depressive symptom severity, and mediation through sleep disturbance in a low-income, primarily Latinx population in California's Central valley.

PURPOSE: This study (1) assessed the psychometric properties of a pregnancy-related COVID worry scale, (2) explored variations in pregnancy-related COVID worry over the course of the pandemic, and (3) examined associations between pregnancy-related COVID worry and depressive symptom severity, and evaluated sleep disturbance as a mediator. METHODS: Data were drawn from an ongoing randomized trial comparing the effectiveness of two enhanced forms of prenatal care. The current analysis includes baseline pre-randomization data collected from participants who enrolled November 2020-November 2021 (n = 201). Participants were pregnant individuals with low income and primarily Latinx. RESULTS: Our 7-item scale was valid and reliable for assessing pregnancy-related COVID worry. Pregnancy-related COVID worry did not vary significantly by any participant characteristic or pandemic stage. Pregnancy-related COVID worry was significantly associated with depressive symptom severity in multivariate analysis (p = .002). For each unit increase on the 10-point pregnancy-related COVID worry scale, the odds of mild-to-severe depression increased by 16% (odds ratio = 1.16, 95% confidence interval 1.02-1.32, p = .02), holding all other variables constant. Sleep disturbance mediated the pregnancy-related COVID worry-depressive symptom relationship (48% of the total effect mediated). CONCLUSIONS: Worry about how COVID may impact their baby, birth, and postpartum experiences was associated with higher depressive symptom severity, partly through its effect on sleep. These findings suggest that interventions related to improving sleep quality among perinatal populations may reduce depressive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04154423, "Engaging Mothers & Babies; Reimagining Antenatal Care for Everyone (EMBRACE) Study".

Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection

Background and objective COVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy. Methods Expression of IFN activation signaling pathway molecules, including cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNβ were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review. Results Except BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells;IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs);and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells. Conclusions STING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

Perceived Access to Contraception via Telemedicine Among Young Adults: Inequities by Food and Housing Insecurity.

BACKGROUND: Telemedicine expanded rapidly during the COVID-19 pandemic, including for contraceptive services. Data are needed to understand whether young people can access telemedicine for contraception, especially in underserved populations. OBJECTIVE: To compare young people's perceived access to telemedicine visits for contraception during the COVID-19 pandemic by food and housing insecurity. DESIGN: Supplementary study to a cluster randomized controlled trial in 25 community colleges in California and Texas. Online surveys were administered May 2020 to April 2021. Mixed-effects logistic regression models with random effects for site were used to examine differences in access to contraception through telemedicine by food and housing insecurity status, controlling for key sociodemographic characteristics, including race/ethnicity, non-English primary language, health insurance status, and state of residence, and contraceptive method used. PARTICIPANTS: 1,414 individuals assigned female at birth aged 18-28. MAIN MEASURES: Survey measures were used to capture how difficult it would be for a participant to have a telemedicine visit (phone or video) for contraception. KEY RESULTS: Twenty-nine percent of participants were food insecure, and 15% were housing insecure. Nearly a quarter (24%) stated that it would be difficult to have a phone or video visit for contraception. After accounting for sociodemographic factors and type of method used, food insecure (adjusted odds ratio [aOR], 2.17; 95% confidence interval [CI], 1.62-2.91) and housing insecure (aOR, 1.62; 95% CI, 1.13-2.33) participants were significantly more likely to report that it would be difficult to use telemedicine for contraception during the pandemic. CONCLUSIONS: Underserved patients are those who could benefit most from the expansion of telemedicine services, yet our findings show that young people experiencing basic needs insecurity perceive the greatest difficulty accessing these services for essential reproductive care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03519685.

Workplace Violence and the Mental Health of Public Health Workers During COVID-19.

INTRODUCTION: During the COVID-19 pandemic, public health workers were at an increased risk for violence and harassment due to their public health work and experienced adverse mental health conditions. This article quantifies the prevalence of job-related threats, harassment, and discrimination against public health workers and measures the association of these incidents with mental health symptoms during the COVID-19 pandemic. METHODS: A nonprobability convenience sample of state, local, and tribal public health workers completed a self-administered, online survey in April 2021. The survey link was emailed to members of national public health associations and included questions on workplace violence, demographics, workplace factors, and mental health symptoms. Mental health symptoms were measured using standardized, validated tools to assess depression, anxiety, post-traumatic stress disorder, and suicidal ideation. Multivariable Poisson models calculated adjusted prevalence ratios of mental health symptoms, with workplace violence as the primary risk factor. Analyses were conducted in 2021-2022. RESULTS: Experiencing any type or combination of workplace violence was significantly associated with an increased likelihood of reporting depression symptoms (prevalence ratio=1.21, 95% CI=1.15, 1.27), anxiety (prevalence ratio=1.21, 95% CI=1.15, 1.27), post-traumatic stress disorder (prevalence ratio=1.31, 95% CI=1.25, 1.37), and suicidal ideation (prevalence ratio=1.26, 95% CI=1.14, 1.38), after adjusting for confounders. A dose‒response relationship was found between the number of workplace violence events experienced by a public health worker and the likelihood of reporting mental health symptoms. CONCLUSIONS: Violence targeted at the public health workforce is detrimental to workers and their communities. Ongoing training, workplace support, and increased communication after a workplace violence incident may be helpful. Efforts to strengthen public health capacities and support the public health workforce are also needed.

Community Mitigation of COVID-19 and Portrayal of Testing on TikTok: Descriptive Study.

BACKGROUND: COVID-19 testing remains an essential element of a comprehensive strategy for community mitigation. Social media is a popular source of information about health, including COVID-19 and testing information. One of the most popular communication channels used by adolescents and young adults who search for health information is TikTok-an emerging social media platform. OBJECTIVE: The purpose of this study was to describe TikTok videos related to COVID-19 testing. METHODS: The hashtag #covidtesting was searched, and the first 100 videos were included in the study sample. At the time the sample was drawn, these 100 videos garnered more than 50% of the views for all videos cataloged under the hashtag #covidtesting. The content characteristics that were coded included mentions, displays, or suggestions of anxiety, COVID-19 symptoms, quarantine, types of tests, results of test, and disgust/unpleasantness. Additional data that were coded included the number and percentage of views, likes, and comments and the use of music, dance, and humor. RESULTS: The 100 videos garnered more than 103 million views; 111,000 comments; and over 12.8 million likes. Even though only 44 videos mentioned or suggested disgust/unpleasantness and 44 mentioned or suggested anxiety, those that portrayed tests as disgusting/unpleasant garnered over 70% of the total cumulative number of views (73,479,400/103,071,900, 71.29%) and likes (9,354,691/12,872,505, 72.67%), and those that mentioned or suggested anxiety attracted about 60% of the total cumulative number of views (61,423,500/103,071,900, 59.59%) and more than 8 million likes (8,339,598/12,872,505, 64.79%). Independent one-tailed t tests (α=.05) revealed that videos that mentioned or suggested that COVID-19 testing was disgusting/unpleasant were associated with receiving a higher number of views and likes. CONCLUSIONS: Our finding of an association between TikTok videos that mentioned or suggested that COVID-19 tests were disgusting/unpleasant and these videos' propensity to garner views and likes is of concern. There is a need for public health agencies to recognize and address connotations of COVID-19 testing on social media.

Drug-drug interaction between dexamethasone and direct-acting oral anticoagulants: a nested case-control study in the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The goal of this work is to evaluate if there is an increase in the risk of thromboembolic events (TEEs) due to concomitant exposure to dexamethasone and apixaban or rivaroxaban. Direct oral anticoagulants (DOACs), as well as corticosteroid dexamethasone, are commonly used to treat individuals hospitalised with COVID-19. Dexamethasone induces cytochrome P450-3A4 enzyme that also metabolises DOACs apixaban and rivaroxaban. This raises a concern about possible interaction between dexamethasone and DOACs that may reduce the efficacy of the DOACs and result in an increased risk of TEE. DESIGN: We used nested case-control study design. SETTING: This study was conducted in the National COVID Cohort Collaborative (N3C), the largest electronic health records repository for COVID-19 in the USA. PARTICIPANTS: Study participants were adults over 18 years who were exposed to a DOAC for 10 or more consecutive days. Exposure to dexamethasone was at least 5 or more consecutive days. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary exposure variable was concomitant exposure to dexamethasone for 5 or more days after exposure to either rivaroxaban or apixaban for 5 or more consecutive days. We used McNemar's Χ2 test and adjusted logistic regression to evaluate association between concomitant use of dexamethasone with either apixaban or rivaroxaban. RESULTS: McNemar's Χ2 test did not find a discernible association of TEE in patients concomitantly exposed to dexamethasone and a DOAC (χ2=0.5, df=1, p=0.48). In addition, a conditional logistic regression model did not find an increase in the risk of TEE (adjusted OR 1.15, 95% CI 0.32 to 4.18). CONCLUSION: This nested case-control study did not find evidence of an association between concomitant exposure to dexamethasone and a DOAC with an increase in risk of TEE. Due to small sample size, an association cannot be completely ruled out.

Falling through the cracks: the invisible hospital cleaning workforce.

PURPOSE: This paper explores the role of hospital cleaners and their contribution to healthcare safety. Few studies have examined the activities and input of hospital cleaners, rendering them largely invisible in healthcare research. Yet, as coronavirus disease 2019 (COVID-19) has demonstrated, this sizeable workforce carries out tasks critical to healthcare facilities and wider health system functioning. DESIGN/METHODOLOGY/APPROACH: Drawing on the work of Habermas, the authors examine the literature surrounding cleaners and quality and safety in healthcare. The authors theorise cleaners' work as both instrumental and communicative and examine the perceptions of healthcare professionals and managers, as well as cleaners themselves, of healthcare professionals and managers' role and contribution to quality and safety. FINDINGS: Cleaners are generally perceived by the literature as performing repetitive - albeit important - tasks in isolation from patients. Cleaners are not considered part of the "healthcare team" and are excluded from decision-making and interprofessional communication. Yet, cleaners can contribute to patient care; ubiquity and proximity of cleaners to patients offer insights and untapped potential for involvement in hospital safety. ORIGINALITY/VALUE: This paper brings an overdue focus to this labour force by examining the nature and potential of their work. This paper offers a new application of Habermas' work to this domain, rendering visible how the framing of cleaners' role works to exclude this important workforce from participation in the patient safety agenda.

Temporal Associations of Plasma Levels of the Secreted Phospholipase A2 Family and Mortality in Severe COVID-19 (preprint)

Previous research suggests that group IIA secreted phospholipase A2 (sPLA2-IIA) plays a role in and predicts severe COVID-19 disease. The current study reanalyzed a longitudinal proteomic data set to determine the temporal (days 0, 3 and 7) relationship between the levels of several members of a family of sPLA2 isoforms and the severity of COVID-19 in 214 ICU patients. The levels of six secreted PLA2 isoforms, sPLA2-IIA, sPLA2-V, sPLA2-X, sPLA2-IB, sPLA2-IIC, and sPLA2-XVI, increased over the first 7 ICU days in those who succumbed to the disease. sPLA2-IIA outperformed top ranked cytokines and chemokines as predictors of patient outcome. A decision tree corroborated these results with day 0 to day 3 kinetic changes of sPLA2-IIA that separated the death and severe categories from the mild category and increases from day 3 to day 7 significantly enriched the lethal category. In contrast, there was a time-dependent decrease in sPLA2-IID and sPLA2-XIIB in patients with severe or lethal disease, and these two isoforms were at higher levels in mild patients. Taken together, proteomic analysis revealed temporal sPLA2 patterns that reflect the critical roles of sPLA2 isoforms in severe COVID-19 disease.