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Background: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients., Methods: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks., Findings: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent., Interpretation: While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Access to paid family and medical leave (PFML), including leave to care for a seriously ill loved one or recover from one's own serious illness, conveys health and economic benefits for workers and their families. However, without a national PFML policy, access to paid leave remains limited and unequal. Previous work documenting inequitable access by socioeconomic status and race/ethnicity primarily focuses on parental leave, measures theoretical access to paid leave rather than actual leave uptake, and lacks an accounting for why workers of color and women may have less access to PFML. We extend this literature by looking at leave-taking for medical needs or caregiving among a high-risk population during the COVID-19 pandemic., Methods: We draw on data from 2595 service-sector workers surveyed by the Shift Project in 2020 and 2021 to estimate inequities in leave uptake among workers who experienced qualifying events. We then estimate the relative importance of worker demographic characteristics, qualifying event types (medical vs. caregiving leave), proxies for access to state and employer PFML policies, job characteristics, and ultimately within-firm differences to these gaps., Results: Overall, one-fifth of workers reported sufficient leave. Women are significantly more likely than men to report insufficient or no leave. Hispanic and Black workers are more likely to take insufficient or no leave, respectively, but these differences were attenuated when controlling for covariates., Conclusions: The dearth of PFML laws leaves women and workers of color without access to leave that is paid and of sufficient duration when facing a qualifying event., (© 2023 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

BACKGROUNDDespite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia.METHODSWe performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.RESULTSCarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.CONCLUSIONSUnsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.

Purpose: To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19)., Methods: We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation)., Results: 1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, - 0.1 [95% CI - 0.15 to - 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%-11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%-4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%-22.5]). Severity scores 3 and 4 did not differ consistently from score 2., Conclusions: COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

The emergence of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inspired rapid research efforts targeting the host range, pathogenesis and transmission mechanisms, and the development of antiviral strategies. Genetically modified mice, rhesus macaques, ferrets, and Syrian golden hamsters have been frequently used in studies of pathogenesis and efficacy of antiviral compounds and vaccines. However, alternatives to in vivo experiments, such as immortalized cell lines, primary respiratory epithelial cells cultured at an air-liquid interface, stem/progenitor cell-derived organoids, or tissue explants, have also been used for isolation of SARS-CoV-2, investigation of cytopathic effects, and pathogen-host interactions. Moreover, initial proof-of-concept studies for testing therapeutic agents can be performed with these tools, showing that animal-sparing cell culture methods could significantly reduce the need for animal models in the future, following the 3R principles of replace, reduce, and refine. So far, only few studies using animal-derived primary cells or tissues have been conducted in SARS-CoV-2 research, although natural infection has been shown to occur in several animal species. Therefore, the need for in-depth investigations on possible interspecies transmission routes and differences in susceptibility to SARS-CoV-2 is urgent. This review gives an overview of studies employing alternative culture systems like primary cell cultures, tissue explants, or organoids for investigations of the pathophysiology and reverse zoonotic potential of SARS-CoV-2 in animals. In addition, future possibilities of SARS-CoV-2 research in animals, including previously neglected methods like the use of precision-cut lung slices, will be outlined.

The COVID-19 pandemic has focused public and policy attention on the acute lack of paid sick leave for service-sector workers in the United States. The lack of paid sick leave is potentially a threat not only to workers' well-being but also to public health. However, the literature on the effects of paid sick leave in the US is surprisingly limited, in large part because instances of paid sick leave expansion are relatively uncommon. We exploit the fact that large firms in the US were not required to expand paid sick leave during the COVID-19 pandemic but that one casual dining restaurant in particular, Olive Garden, faced intense public pressure to do so. We drew on data collected from 2017 through fall 2020 from 10,306 food service-sector workers in the US by the Shift Project, which include employer identifiers. Using a difference-in-differences design, we found strong evidence of an increase in paid sick leave coverage among Olive Garden workers, as well as evidence that this expansion reduced the incidence of working while sick among front-line food service workers.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.

Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome 1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia 2 . Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.

Introduction: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil., Methods: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include all-cause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes., Ethics and Dissemination: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals.

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR). Study participants were also separated into COVID-19 pre-exposure (hybrid immunity) positive (n = 407) versus negative (n = 2223) groups. (3) Results: COVID-19 pre-exposure improved most vaccination-related positive immunity rates in KTR and DP at 2 months but not in MP, where rates reached almost 100% independent of hybrid immunity. In the COVID-19-negative study, patients' immunity faded between two and nine months, evaluated via the percentage of patients with an RBD antibody decrease >50%, and was markedly group- (MP-17.8%, DP-52.2%, and KTR-38.6%) and vaccine type-dependent. In contrast, in all patient groups with COVID-19, pre-exposure RBD antibody decreases of >50% were similarly rare (MP-4.3%, DP-7.2%, and KTR-0%) but still vaccine type-dependent, with numerically reduced numbers in mRNA-1273- versus BNT162b2mRNA-treated patients. Multivariable regression analysis of RBD antibody changes between two and nine months by interval scale categorization confirmed COVID-19 pre-exposure as a factor in inhibiting strong RBD Ab fading. COVID-19 pre-exposure in MP and DP also numerically reduced T-cell immunity fading. In DP, symptomatic (versus asymptomatic) COVID-19 pre-exposure was identified as a factor in reducing strong RBD Ab fading after vaccination. (4) Conclusions: After mRNA vaccination, immunity positivity rates in DP and KTR but not MP, as well as immunity preservation in MP/DP/KTR, are markedly improved via prior COVID-19 infection. In DP, prior symptomatic compared to asymptomatic COVID-19 disease was particularly effective in blocking immunity fading after mRNA vaccination. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has exacted a historic toll on Americans' health and longevity. It has also shaped socioeconomic inequalities along the lines of gender, race, ethnicity, nativity, and class in America. The effects of COVID-19 are evident in the stratified experiences of Americans in work, unemployment, and unpaid labor; in stark inequalities in wealth and income; in the historic expansions and retrenchments in social welfare spending; and in the increase in violence and changes in the criminal justice system. While there has been an outpouring of research on the social and economic consequences of COVID-19, far less work draws together research across these varied, but interrelated, domains. In this introduction, we provide a broad narrative of how the COVID-19 pandemic unfolded in America and reshaped, in some instances fleetingly and in others more permanently, the landscape of socioeconomic inequality in America. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic dramatically reshaped the labor market, especially for service sector workers. Frontline service sector workers, already coping with precarious working conditions, faced proximate risks of COVID-19 transmission on the job and navigated new workplace safety measures, including masking, social distancing, and staying home while sick, all in a polarized political environment. We examine polarization in the effects of COVID-19 workplace safety measures on workers' feelings of safety and well-being. Specifically, we examine how support for former President Trump moderates the relationship between COVID-19 safety practices (masking, social distancing, staying home while sick) and workers' feelings of safety and well-being. To do so, we draw on novel data collected by The Shift Project from 2,039 service sector workers at 89 large firms during the COVID-19 pandemic. We find that workplace safety measures are positively associated with workers' self-assessments of feeling safe and with mental health, but only for Biden voters. [ABSTRACT FROM AUTHOR]

Introduction: The long-term effects caused by COVID-19 are unknown. The present study aims to assess factors associated with health-related quality of life and long-term outcomes among survivors of hospitalization for COVID-19 in Brazil. Methods: This is a multicenter prospective cohort study nested in five randomized clinical trials designed to assess the effects of specific COVID-19 treatments in over 50 centers in Brazil. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed-up for a period of 1 year by means of structured telephone interviews. The primary outcome is the 1-year utility score of health-related quality of life assessed by the EuroQol-5D3L. Secondary outcomes include allcause mortality, major cardiovascular events, rehospitalizations, return to work or study, physical functional status assessed by the Lawton-Brody Instrumental Activities of Daily Living, dyspnea assessed by the modified Medical Research Council dyspnea scale, need for long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-Revised, and self-rated health assessed by the EuroQol-5D3L Visual Analog Scale. Generalized estimated equations will be performed to test the association between five sets of variables (1- demographic characteristics, 2- premorbid state of health, 3- characteristics of acute illness, 4- specific COVID-19 treatments received, and 5- time-updated postdischarge variables) and outcomes. Ethics and dissemination: The study protocol was approved by the Research Ethics Committee of all participant institutions. The results will be disseminated through conferences and peer-reviewed journals. [ABSTRACT FROM AUTHOR]

Testing for COVID-19 remains limited in the United States and across the world. Poor allocation of limited testing resources leads to misutilization of health system resources, which complementary rapid testing tools could ameliorate. To predict SARS-CoV-2 PCR positivity based on complete blood count components and patient sex. A retrospective case-control design for collection of data and a logistic regression prediction model was used. Participants were emergency department patients > 18 years old who had concurrent complete blood counts and SARS-CoV-2 PCR testing. 33 confirmed SARS-CoV-2 PCR positive and 357 negative patients at Stanford Health Care were used for model training. Validation cohorts consisted of emergency department patients > 18 years old who had concurrent complete blood counts and SARS-CoV-2 PCR testing in Northern California (41 PCR positive, 495 PCR negative), Seattle, Washington (40 PCR positive, 306 PCR negative), Chicago, Illinois (245 PCR positive, 1015 PCR negative), and South Korea (9 PCR positive, 236 PCR negative). A decision support tool that utilizes components of complete blood count and patient sex for prediction of SARS-CoV-2 PCR positivity demonstrated a C-statistic of 78 %, an optimized sensitivity of 93 %, and generalizability to other emergency department populations. By restricting PCR testing to predicted positive patients in a hypothetical scenario of 1000 patients requiring testing but testing resources limited to 60 % of patients, this tool would allow a 33 % increase in properly allocated resources. A prediction tool based on complete blood count results can better allocate SARS-CoV-2 testing and other health care resources such as personal protective equipment during a pandemic surge. [ABSTRACT FROM AUTHOR]