Risk factors for SARS-CoV-2 seropositivity in a health care worker population during the early pandemic.

BACKGROUND: While others have reported severe acute respiratory syndrome-related coronavirus 2(SARS-CoV-2) seroprevalence studies in health care workers (HCWs), we leverage the use of a highly sensitive coronavirus antigen microarray to identify a group of seropositive health care workers who were missed by daily symptom screening that was instituted prior to any epidemiologically significant local outbreak. Given that most health care facilities rely on daily symptom screening as the primary method to identify SARS-CoV-2 among health care workers, here, we aim to determine how demographic, occupational, and clinical variables influence SARS-CoV-2 seropositivity among health care workers. METHODS: We designed a cross-sectional survey of HCWs for SARS-CoV-2 seropositivity conducted from May 15th to June 30th 2020 at a 418-bed academic hospital in Orange County, California. From an eligible population of 5,349 HCWs, study participants were recruited in two ways: an open cohort, and a targeted cohort. The open cohort was open to anyone, whereas the targeted cohort that recruited HCWs previously screened for COVID-19 or work in high-risk units. A total of 1,557 HCWs completed the survey and provided specimens, including 1,044 in the open cohort and 513 in the targeted cohort. Demographic, occupational, and clinical variables were surveyed electronically. SARS-CoV-2 seropositivity was assessed using a coronavirus antigen microarray (CoVAM), which measures antibodies against eleven viral antigens to identify prior infection with 98% specificity and 93% sensitivity. RESULTS: Among tested HCWs (n = 1,557), SARS-CoV-2 seropositivity was 10.8%, and risk factors included male gender (OR 1.48, 95% CI 1.05-2.06), exposure to COVID-19 outside of work (2.29, 1.14-4.29), working in food or environmental services (4.85, 1.51-14.85), and working in COVID-19 units (ICU: 2.28, 1.29-3.96; ward: 1.59, 1.01-2.48). Amongst 1,103 HCWs not previously screened, seropositivity was 8.0%, and additional risk factors included younger age (1.57, 1.00-2.45) and working in administration (2.69, 1.10-7.10). CONCLUSION: SARS-CoV-2 seropositivity is significantly higher than reported case counts even among HCWs who are meticulously screened. Seropositive HCWs missed by screening were more likely to be younger, work outside direct patient care, or have exposure outside of work.

Implementation and impact on length of stay of a post-discharge remote patient monitoring program for acutely hospitalized COVID-19 pneumonia patients.

Objective: In order to manage COVID-19 patient population and bed capacity issues, remote patient monitoring (RPM) is a strategy used to transition patients from inpatients to home. We describe our RPM implementation process for post-acute care COVID-19 pneumonia patients. We also evaluate the impact of RPM on patient outcomes, including hospital length of stay (LOS), post-discharge Emergency Department (ED) visits, and hospital readmission. Materials and Methods: We utilized a cloud-based RPM platform (Vivify Health) and a nurse-monitoring service (Global Medical Response) to enroll COVID-19 patients who required oxygen supplementation after hospital discharge. We evaluated patient participation, biometric alerts, and provider communication. We also assessed the program's impact by comparing RPM patient outcomes with a retrospective cohort of Control patients who similarly required oxygen supplementation after discharge but were not referred to the RPM program. Statistical analyses were performed to evaluate the 2 groups' demographic characteristics, hospital LOS, and readmission rates. Results: The RPM program enrolled 75 patients with respondents of a post-participation survey reporting high satisfaction with the program. Compared to the Control group (n = 150), which had similar demographics and baseline characteristics, the RPM group was associated with shorter hospital LOS (median 4.8 vs 6.1 days; P=.03) without adversely impacting return to the ED or readmission. Conclusion: We implemented a RPM program for post-acute discharged COVID-19 patients requiring oxygen supplementation. Our RPM program resulted in a shorter hospital LOS without adversely impacting quality outcomes for readmission rates and improved healthcare utilization by reducing the average LOS.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Implementation and Impact on Length of Stay of a Post-Discharge Remote Patient Monitoring Program for Acutely Hospitalized COVID-19 Pneumonia Patients

Objective In order to manage COVID-19 patient population and bed capacity issues, remote patient monitoring (RPM) is a strategy used to transition patients from inpatients to home. We describe our RPM implementation process for post-acute care COVID-19 pneumonia patients. We also evaluate the impact of RPM on patient outcomes, including hospital length of stay (LOS), post-discharge Emergency Department (ED) visits, and hospital readmission. >Materials and Methods We utilized a cloud-based RPM platform (Vivify Health) and a nurse-monitoring service (Global Medical Response) to enroll COVID-19 patients who required oxygen supplementation after hospital discharge. We evaluated patient participation, biometric alerts, and provider communication. We also assessed the program’s impact by comparing RPM patient outcomes with a retrospective cohort of Control patients who similarly required oxygen supplementation after discharge but were not referred to the RPM program. Statistical analyses were performed to evaluate the two groups’ demographic characteristics, hospital LOS, and readmission rates. Results The RPM program enrolled 75 patients with respondents of a post-participation survey reporting high satisfaction with the program. Compared to the Control group (n = 150), which had similar demographics and baseline characteristics, the RPM group was associated with shorter hospital LOS (median 4.8 vs 6.1 days;P =.03) without adversely impacting return to the ED or readmission. Conclusion We implemented a RPM program for post-acute discharged COVID-19 patients requiring oxygen supplementation. Our RPM program resulted in a shorter hospital LOS without adversely impacting quality outcomes for readmission rates and improved healthcare utilization by reducing the average LOS. LAY SUMMARY To improve hospital operations and bed utilization during the COVID-19 pandemic, we rapidly developed a remote patient monitoring (RPM) program as a strategy to facilitate the discharge of stable COVID-19 patients requiring supplemental oxygen and support their transition from the inpatient setting to home. We share our RPM implementation process and show that enrolled RPM patients were associated with shorter hospital length of stay (LOS) without any adverse impact on quality outcomes, such as return to the Emergency Department or readmission, compared to a cohort of control patients who were not enrolled in RPM. We also show that our RPM program had a high patient engagement rate and positive patient satisfaction. Our results demonstrate that RPM can be an essential part of the healthcare delivery model, as it could positively impact outcomes, healthcare utilization, and patient satisfaction.

Improved outcomes over time for adult COVID-19 patients with acute respiratory distress syndrome or acute respiratory failure.

BACKGROUND: COVID-19's pulmonary manifestations are broad, ranging from pneumonia with no supplemental oxygen requirements to acute respiratory distress syndrome (ARDS) with acute respiratory failure (ARF). In response, new oxygenation strategies and therapeutics have been developed, but their large-scale effects on outcomes in severe COVID-19 patients remain unknown. Therefore, we aimed to examine the trends in mortality, mechanical ventilation, and cost over the first six months of the pandemic for adult COVID-19 patients in the US who developed ARDS or ARF. METHODS AND FINDINGS: The Vizient Clinical Data Base, a national database comprised of administrative, clinical, and financial data from academic medical centers, was queried for patients ≥ 18-years-old with COVID-19 and either ARDS or ARF admitted between 3/2020-8/2020. Demographics, mechanical ventilation, length of stay, total cost, mortality, and discharge status were collected. Mann-Kendall tests were used to assess for significant monotonic trends in total cost, mechanical ventilation, and mortality over time. Chi-square tests were used to compare mortality rates between March-May and June-August. 110,223 adult patients with COVID-19 ARDS or ARF were identified. Mean length of stay was 12.1±13.3 days and mean total cost was $35,991±32,496. Mechanical ventilation rates were 34.1% and in-hospital mortality was 22.5%. Mean cost trended downward over time (p = 0.02) from $55,275 (March) to $18,211 (August). Mechanical ventilation rates trended down (p<0.01) from 53.8% (March) to 20.3% (August). Overall mortality rates also decreased (p<0.01) from 28.4% (March) to 13.7% (August). Mortality rates in mechanically ventilated patients were similar over time (p = 0.45), but mortality in patients not requiring mechanical ventilation decreased from March-May compared to June-July (13.5% vs 4.6%, p<0.01). CONCLUSIONS: This study describes the outcomes of a large cohort with COVID-19 ARDS or ARF and the subsequent decrease in cost, mechanical ventilation, and mortality over the first 6 months of the pandemic in the US.

Stratifying Deterioration Risk by Acuity at Admission Offers Triage Insights for Coronavirus Disease 2019 Patients.

OBJECTIVES: Triaging patients at admission to determine subsequent deterioration risk can be difficult. This is especially true of coronavirus disease 2019 patients, some of whom experience significant physiologic deterioration due to dysregulated immune response following admission. A well-established acuity measure, the Rothman Index, is evaluated for stratification of patients at admission into high or low risk of subsequent deterioration. DESIGN: Multicenter retrospective study. SETTING: One academic medical center in Connecticut, and three community hospitals in Connecticut and Maryland. PATIENTS: Three thousand four hundred ninety-nine coronavirus disease 2019 and 14,658 noncoronavirus disease 2019 adult patients admitted to a medical service between January 1, 2020, and September 15, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Performance of the Rothman Index at admission to predict in-hospital mortality or ICU utilization for both general medical and coronavirus disease 2019 populations was evaluated using the area under the curve. Precision and recall for mortality prediction were calculated, high- and low-risk thresholds were determined, and patients meeting threshold criteria were characterized. The Rothman Index at admission has good to excellent discriminatory performance for in-hospital mortality in the coronavirus disease 2019 (area under the curve, 0.81-0.84) and noncoronavirus disease 2019 (area under the curve, 0.90-0.92) populations. We show that for a given admission acuity, the risk of deterioration for coronavirus disease 2019 patients is significantly higher than for noncoronavirus disease 2019 patients. At admission, Rothman Index-based thresholds segregate the majority of patients into either high- or low-risk groups; high-risk groups have mortality rates of 34-45% (coronavirus disease 2019) and 17-25% (noncoronavirus disease 2019), whereas low-risk groups have mortality rates of 2-5% (coronavirus disease 2019) and 0.2-0.4% (noncoronavirus disease 2019). Similarly large differences in ICU utilization are also found. CONCLUSIONS: Acuity level at admission may support rapid and effective risk triage. Notably, in-hospital mortality risk associated with a given acuity at admission is significantly higher for coronavirus disease 2019 patients than for noncoronavirus disease 2019 patients. This insight may help physicians more effectively triage coronavirus disease 2019 patients, guiding level of care decisions and resource allocation.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Development and external validation of a prognostic tool for COVID-19 critical disease.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes. The purpose of this study is to develop and externally validate a prognostic model/clinical tool for predicting COVID-19 critical disease at presentation to medical care. METHODS: This is a retrospective study of a prognostic model for the prediction of COVID-19 critical disease where critical disease was defined as ICU admission, ventilation, and/or death. The derivation cohort was used to develop a multivariable logistic regression model. Covariates included patient comorbidities, presenting vital signs, and laboratory values. Model performance was assessed on the validation cohort by concordance statistics. The model was developed with consecutive patients with COVID-19 who presented to University of California Irvine Medical Center in Orange County, California. External validation was performed with a random sample of patients with COVID-19 at Emory Healthcare in Atlanta, Georgia. RESULTS: Of a total 3208 patients tested in the derivation cohort, 9% (299/3028) were positive for COVID-19. Clinical data including past medical history and presenting laboratory values were available for 29% (87/299) of patients (median age, 48 years [range, 21-88 years]; 64% [36/55] male). The most common comorbidities included obesity (37%, 31/87), hypertension (37%, 32/87), and diabetes (24%, 24/87). Critical disease was present in 24% (21/87). After backward stepwise selection, the following factors were associated with greatest increased risk of critical disease: number of comorbidities, body mass index, respiratory rate, white blood cell count, % lymphocytes, serum creatinine, lactate dehydrogenase, high sensitivity troponin I, ferritin, procalcitonin, and C-reactive protein. Of a total of 40 patients in the validation cohort (median age, 60 years [range, 27-88 years]; 55% [22/40] male), critical disease was present in 65% (26/40). Model discrimination in the validation cohort was high (concordance statistic: 0.94, 95% confidence interval 0.87-1.01). A web-based tool was developed to enable clinicians to input patient data and view likelihood of critical disease. CONCLUSIONS AND RELEVANCE: We present a model which accurately predicted COVID-19 critical disease risk using comorbidities and presenting vital signs and laboratory values, on derivation and validation cohorts from two different institutions. If further validated on additional cohorts of patients, this model/clinical tool may provide useful prognostication of critical care needs.

Novel therapeutic approaches for COVID-19 in chronic kidney disease and transplant.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the novel virus responsible for the current worldwide pandemic. The scientific and healthcare communities have made every effort to discover and implement treatment options at a historic pace. Patients with kidney disease are uniquely vulnerable to an infectious pandemic because of their need to be in frequent contact with the healthcare system for life-sustaining renal replacement therapy whether it be by dialysis or transplant. RECENT FINDINGS: The use of targeted viral therapies, extracorporeal therapies, immunosuppressive therapy and public health interventions are important in the management of patients with COVID-19 but require special consideration in patients with kidney disease because of the complexity of their condition. SUMMARY: Here, we discuss some of the major efforts made to prevent spread and emerging treatment options for this virus, as they pertain to patients with kidney disease.

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing.