Pre-hospital Aspirin Use and Patient Outcomes in COVID-19: Results from the International Viral Infection and Respiratory Illness Universal Study (VIRUS).

INTRODUCTION: The goal of this investigation is to assess the association between prehospital use of aspirin (ASA) and patient-centered outcomes in a large global cohort of hospitalized COVID-19 patients. METHODS: This study utilizes data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. Adult patients hospitalized from February 15th, 2020, to September 30th, 2021, were included. Multivariable regression analyses were utilized to assess the association between pre-hospital use of ASA and the primary outcome of overall hospital mortality. RESULTS: 21,579 patients were included from 185 hospitals (predominantly US-based, 71.3%), with 4691 (21.7%) receiving pre-hospital ASA. Patients receiving ASA, compared to those without pre-admission ASA use, were generally older (median 70 vs. 59 years), more likely to be male (58.7 vs. 56.0%), caucasian (57.4 vs. 51.6%), and more commonly had higher rates of medical comorbidities. In multivariable analyses, patients receiving pre-hospital ASA had lower mortality (HR: 0.89, 95% CI 0.82-0.97, p=0.01) and reduced hazard for progression to severe disease or death (HR: 0.91, 95% CI 0.84-0.99, p=0.02) and more hospital free days (1.00 days, 95% CI 0.66-1.35, p=0.01) compared to those without pre-hospital ASA use. The overall direction and significance of the results remained the same in sensitivity analysis, after adjusting the multivariable model for time since pandemic. CONCLUSIONS: In this large international cohort, pre-hospital use of ASA was associated with a lower hazard for death in hospitalized patients with COVID-19. Randomized controlled trials may be warranted to assess the utility of pre-hospital use of ASA.

The Cosmos Collaborative: A Vendor-Facilitated Electronic Health Record Data Aggregation Platform.

OBJECTIVE: Learning healthcare systems use routinely collected data to generate new evidence that informs future practice. While implementing an electronic health record (EHR) system can facilitate this goal for individual institutions, meaningfully aggregating data from multiple institutions can be more empowering. Cosmos is a cross-institution, single EHR vendor-facilitated data aggregation tool. This work aims to describe the initiative and illustrate its potential utility through several use cases. METHODS: Cosmos is designed to scale rapidly by leveraging preexisting agreements, clinical health information exchange networks, and data standards. Data are stored centrally as a limited dataset, but the customer facing query tool limits results to prevent patient reidentification. RESULTS: In 2 years, Cosmos grew to contain EHR data of more than 60 million patients. We present practical examples illustrating how Cosmos could further efforts in chronic disease surveillance (asthma and obesity), syndromic surveillance (seasonal influenza and the 2019 novel coronavirus), immunization adherence and adverse event reporting (human papilloma virus and measles, mumps, rubella, and varicella vaccination), and health services research (antibiotic usage for upper respiratory infection). DISCUSSION: A low barrier of entry for Cosmos allows for the rapid accumulation of multi-institutional and mostly de-duplicated EHR data to power research and quality improvement queries characteristic of learning healthcare systems. Limitations are being vendor-specific, an "all or none" contribution model, and the lack of control over queries run on an institution's healthcare data. CONCLUSION: Cosmos provides a model for within-vendor data standardization and aggregation and a steppingstone for broader intervendor interoperability.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

Telemedicine Visits During COVID-19 Improved Clinic Show Rates.

OBJECTIVE: We aimed to explore the impact of telehealth in the setting of COVID-19 on patient access to ambulatory rheumatologic care at our academic public health system and to determine whether telemedicine visits had a beneficial impact on access to our rheumatology ambulatory clinics. METHODS: We compared completed, no-show, and cancellation rates between in-person clinic visits and telemedicine appointments over a 10-week time period before Ohio's initial executive order responding to COVID-19 (premandate period) and a 10-week time period afterward (postmandate period). Scheduling and appointment data were retrospectively extracted from the medical center's electronic health record. RESULTS: During the premandate period, when all visits were in-person, the total number of completed visits was 930. The percentages of cancellations, no-shows, and completed appointments of all appointment activities were 31.43%, 13.12%, and 55.46%, respectively. During the postmandate period, when telemedicine visits were added, the overall total number of completed visits was 1038. The percentages of cancellations, no-shows, and completed appointments of all appointment activities were 53.45%, 13.91%, and 32.64%, respectively, for in-person appointments and 0.12%, 8.48%, and 91.39%, respectively, for telemedicine appointments. CONCLUSION: Telemedicine during the COVID-19 pandemic resulted in higher rates of completed appointments and lower rates of missed appointments in the rheumatology outpatient clinic compared with in-person visits during and prior to the pandemic.

Mechanisms of socioeconomic differences in COVID-19 screening and hospitalizations.

BACKGROUND: Social and ecological differences in early SARS-CoV-2 pandemic screening and outcomes have been documented, but the means by which these differences have arisen are not well understood. OBJECTIVE: To characterize socioeconomic and chronic disease-related mechanisms underlying these differences. DESIGN: Observational cohort study. SETTING: Outpatient and emergency care. PATIENTS: 12900 Cleveland Clinic Health System patients referred for SARS-CoV-2 testing between March 17 and April 15, 2020. INTERVENTIONS: Nasopharyngeal PCR test for SARS-CoV-2 infection. MEASUREMENTS: Test location (emergency department, ED, vs. outpatient care), COVID-19 symptoms, test positivity and hospitalization among positive cases. RESULTS: We identified six classes of symptoms, ranging in test positivity from 3.4% to 23%. Non-Hispanic Black race/ethnicity was disproportionately represented in the group with highest positivity rates. Non-Hispanic Black patients ranged from 1.81 [95% confidence interval: 0.91-3.59] times (at age 20) to 2.37 [1.54-3.65] times (at age 80) more likely to test positive for the SARS-CoV-2 virus than non-Hispanic White patients, while test positivity was not significantly different across the neighborhood income spectrum. Testing in the emergency department (OR: 5.4 [3.9, 7.5]) and cardiovascular disease (OR: 2.5 [1.7, 3.8]) were related to increased risk of hospitalization among the 1247 patients who tested positive. LIMITATIONS: Constraints on availability of test kits forced providers to selectively test for SARS-Cov-2. CONCLUSION: Non-Hispanic Black patients and patients from low-income neighborhoods tended toward more severe and prolonged symptom profiles and increased comorbidity burden. These factors were associated with higher rates of testing in the ED. Non-Hispanic Black patients also had higher test positivity rates.

On the Front (Phone) Lines: Results of a COVID-19 Hotline.

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease of 2019 (COVID-19) have presented immense challenges for health care systems. Many regions have struggled to adapt to disruptions to health care practice and use systems that effectively manage the demand for services. METHODS: This was a cohort study using electronic health records at a health care system in northeast Ohio that examined the effectiveness of the first 5 weeks of a 24/7 physician-staffed COVID-19 hotline including social care referrals for patients required to self-isolate. We describe clinical diagnosis, patient characteristics (age, sex race/ethnicity, smoking status, insurance status), and visit disposition. We use logistic regression to evaluate associations between patient characteristics, visit disposition and subsequent emergency department use, hospitalization, and SARS-Cov-2 PCR testing. PARTICIPANTS: In 5 weeks, 10,112 patients called the hotline (callers). Of these, 4213 (42%) were referred for a physician telehealth visit (telehealth patients). Mean age of callers was 42 years; 67% were female, 51% white, and 46% were on Medicaid/uninsured. RESULTS: Common caller concerns included cough, fever, and shortness of breath. Most telehealth patients (79%) were advised to self-isolate at home, 14% were determined to be unlikely to have COVID-19, 3% were advised to seek emergency care, and 4% had miscellaneous other dispositions. A total of 287 patients (7%) had a subsequent emergency department visit, and 44 (1%) were hospitalized with a COVID-19 diagnosis. Of the callers, 482 (5%) had a COVID-19 test reported, with 69 (14%) testing positive. Among patients advised to stay at home, 83% had no further face-to-face visits. In multivariable results, only a physician recommendation to seek emergency care was associated with emergency department use (odds ratio = 4.73, 95% confidence interval = 1.37-16.39, P = .014). Only older age was associated with having a positive test result. Patients with social needs and interest in receiving help were offered services to meet their needs including food deliveries (n = 92), behavioral health telephone visits (n = 49), and faith-based comfort calls from pastoral care personnel (n = 37). CONCLUSIONS AND RELEVANCE: Robust, physician-directed telehealth services can meet a wide range of clinical and social needs during the acute phase of a pandemic, conserving scarce resources such as personal protective equipment and testing supplies and preventing the spread of infections to patients and health care workers.

SARS-CoV-2 Infection among Serially Tested Emergency Medical Services Workers.

BACKGROUND: Emerging research has examined the prevalence of severe acute respiratory syndrome virus 2 (SARS-CoV-2) infections in numerous settings, but a critical gap in knowledge is an understanding of the rate of infection among first responders. METHODS: We conducted a prospective serial serologic survey by recruiting public first responders from Cleveland area emergency medical services agencies and fire departments. Volunteers submitted a nasopharyngeal swab for SARS-CoV-2 PCR testing and serum samples to detect the presence of antibodies to SARS-CoV-2 on two visits scheduled approximately 3 weeks apart. RESULTS: 296 respondents completed a first visit and 260 completed the second. While 71% of respondents reported exposure to SARS-CoV-2, only 5.4% (95% CI 3.1-8.6) had positive serologic testing. No subjects had a positive PCR. On the first visit, eight (50%) of the test-positive subjects had no symptoms and only one (6.2%) sought healthcare or missed school or work. None of the subjects that tested negative on the first visit were positive on their second. CONCLUSIONS: While our results show a relatively low rate of test positivity for SARS-CoV-2 amongst first responders, most were either asymptomatic or mildly symptomatic. The potential risk of asymptomatic transmission both between first responders and from first responders to vulnerable patients requires more study.