Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin.

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aORs) for mortality were 1.58 (95% CI: 1.46, 1.70) and 1.04 (95% CI: 0.96, 1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and amongst those with current cancer (aOR = 0.69, 95% CI = 0.53 to 0.90). CONCLUSIONS: Current cancer, especially amongst younger patients, posed a substantially increased risk for death and ICU admission among COVID-19 patients; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic.

The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems.

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. RESULTS AND SIGNIFICANCE: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. CONCLUSIONS: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Quality and Safety in Hospital Pediatrics During COVID-19: A National Qualitative Study.

OBJECTIVE: To describe challenges in inpatient pediatric quality and safety during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a previous qualitative study, our team sought to broadly describe changes in pediatric inpatient care during the pandemic. For both that study and this ancillary analysis, we purposefully sampled participants from community and children's hospitals in the 6 US states with the highest COVID-19 hospitalization rates from March to May 2020. We recruited 2 to 3 participants from each hospital (administrators, front-line physicians, nurses, caregivers) for semistructured interviews. We used constant comparative methods to identify themes regarding quality and safety challenges during the pandemic. RESULTS: We interviewed 30 participants from 12 hospitals. Participants described several impacts to clinical workflows, including decreased direct clinician-patient interactions and challenges to communication, partly addressed through innovative use of telehealth technology. Participants reported changes in the discharge and transfer process (eg, discharges, difficulties accessing specialized facilities). Participants also described impacts to hospital operations, including changes in quality monitoring and operations (eg, decreased staff, data collection), increased health risks for clinicians and staff (eg, COVID-19 exposure, testing delays), and staff and supply shortages. Participants voiced concerns that negative quality and safety impacts could include increased risk of preventable safety events and hospital readmissions, and decreased patient engagement, education, and satisfaction. CONCLUSIONS: We identified several impacts to clinical workflows and hospital operations during the pandemic that may have affected inpatient pediatric care quality and safety. Our findings highlight potentially important areas of focus for planning pandemic recovery, preparing for future pandemics, and conducting future research on inpatient pediatric quality and safety.

Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

Changes in pediatric hospital care during the COVID-19 pandemic: a national qualitative study.

BACKGROUND: The COVID-19 pandemic has necessitated rapid changes in healthcare delivery in the United States, including changes in the care of hospitalized children. The objectives of this study were to identify major changes in healthcare delivery for hospitalized children during the COVID-19 pandemic, identify lessons learned from these changes, and compare and contrast the experiences of children's and community hospitals. METHODS: We purposefully sampled participants from both community and children's hospitals serving pediatric patients in the six U.S. states with the highest COVID-19 hospitalization rates at the onset of the pandemic. We recruited 2-3 participants from each hospital (mix of administrators, front-line physicians, nurses, and parents/caregivers) for semi-structured interviews. We analyzed interview data using constant comparative methods to identify major themes. RESULTS: We interviewed 30 participants from 12 hospitals. Participants described how leaders rapidly developed new hospital policies (e.g., directing use of personal protective equipment) and how this was facilitated by reviewing internal and external data frequently and engaging all relevant stakeholders. Hospital leaders optimized communication through regular, transparent, multi-modal, and bi-directional communication. Clinicians increased use of videoconference and telehealth to facilitate physical distancing, but these technologies may have disadvantaged non-English speakers. Due to declining volumes of hospitalized children and surges of adult patients, clinicians newly provided care for hospitalized adults. This was facilitated by developing care teams supported by adult hospitalists, multidisciplinary support via videoconference, and educational resources. Participants described how the pandemic negatively impacted clinicians' mental health, and they stressed the importance of mental health resources and wellness activities/spaces. CONCLUSIONS: We identified several major changes in inpatient pediatric care delivery during the COVID-19 pandemic, including the adoption of new hospital policies, video communication, staffing models, education strategies, and staff mental health supports. We outline important lessons learned, including strategies for successfully developing new policies, effectively communicating with staff, and supporting clinicians' expanding scope of practice. Potentially important focus areas in pandemic recovery include assessing and supporting clinicians' mental health and well-being, re-evaluating trainees' skills/competencies, and adapting educational strategies as needed. These findings can help guide hospital leaders in supporting pandemic recovery and addressing future crises.

Deployed: One Pediatric Department's Experience of Adult Care During COVID-19.

OBJECTIVES: The number of hospitalized coronavirus disease 2019 patients in March 2020 to April 2020 in our New York City hospital required increased physician staffing, including deployment of pediatricians to adult care. To improve the deployment process, we sought to understand the mindset, preparations for, and experience during deployment of pediatric faculty in our institution. METHODS: Faculty members of the Department of Pediatrics completed pre- and postsurveys evaluating perspectives, fears, and preparations relevant to deployment. Demographic characteristics of the faculty members were collected. Survey questions included Likert scale, multiple choice, and free-text responses. Descriptive statistics, Fisher's exact test, and χ2 test were used to compare groups. Free-text responses were categorized by topic. Survey responses were shared with leadership in real time and adjustments to the deployment process made. RESULTS: The predeployment survey was sent to 202 pediatric faculty members, with a 29% (n = 59) completion rate. Of the 36 deployed faculty, 29 (81%) completed all items of the postsurvey. The majority (74%, n = 42) expressed discomfort with care of adults and fear and/or nervousness about deployment (61%, n = 35). Most faculty (88%, n = 52) prepared for deployment and cited local guidelines and published literature as helpful preparation materials (55%, n = 16). Dissemination of details about schedules and role clarification before deployment were areas for improvement. CONCLUSIONS: Pediatric faculty facing deployment to adult care have concerns about the process of deployment as well as the work itself. Specific information distributed in advance, along with consistent and frequent communication, may help mitigate these fears.

Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C).

Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.

Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C).

Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.