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INTRODUCTION: Despite a heavy burden of disease, resource-limited settings remain underrepresented in pandemic research. Critical illness epidemiology for both COVID-19 and non-COVID-19 bystander patients may differ compared to well-resourced settings. METHOD(S): We performed a retrospective cohort study of patients admitted to intensive care units (ICU) at two public hospitals in the KwaZulu-Natal Department of Health in South Africa preceding and during the COVID-19 pandemic. We used multivariable logistic regression to analyze the association between three patient cohorts (pre-pandemic non-COVID-19, pandemic non-COVID-19, and pandemic COVID-19) and pandemic variant wave and the primary outcome of ICU mortality, adjusted for patient-level factors and ICU capacity strain. RESULT(S): 1,132 patients were admitted to the ICU during the pandemic study period (180 [15.9%] with COVID-19 and 952 [84.1%] without COVID-19) and 803 patients were admitted to the ICU during the pre-pandemic period. The pre-pandemic and pandemic non-COVID-19 cohorts were similar. Compared to the non-COVID-19 cohorts, the pandemic COVID-19 cohort had older age, higher rates of chronic cardiovascular disease and diabetes, less extrapulmonary organ dysfunction, and longer ICU length of stay. Study hospitals experienced greater ICU referral burden, turnover, occupancy, and acuity during the pandemic. Compared to the pre-pandemic non-COVID-19 cohort, the pandemic non-COVID-19 cohort had similar odds of ICU mortality (OR 1.05, 95% CI 0.78-1.42, p = 0.75) while the pandemic COVID-19 cohort had significantly increased odds of ICU mortality (OR 6.43, 95% CI 3.88-10.65, p < 0.0005). Compared to the ancestral strain-dominant wave, during the beta variant-dominant wave neither the pandemic non-COVID-19 cohort (OR 1.33, 95% CI 0.67-2.63, p = 0.41) nor the pandemic COVID-19 cohort (OR 2.29, 95% CI 0.84-6.23, p = 0.10) had statistically different odds of ICU mortality. CONCLUSION(S): Pre-pandemic and pandemic non- COVID-19 ICU patients were broadly similar in clinical characteristics and outcomes, while pandemic COVID-19 ICU patients had important clinical differences and had significantly higher mortality after adjusting for patient-level factors and capacity strain. Study hospitals experienced increased ICU capacity strain during the pandemic.
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Background. Tocilizumab (TCZ) was approved by the Food and Drug Administration under emergency use authorization for treatment of COVID-19 in patients requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Despite multiple clinical trials, there remain unanswered questions surrounding TCZ use. Methods. This multi-hospital retrospective cohort study included patients who received TCZ for COVID-19 between January 29th, 2021 and June 30th, 2021 at five University of Pennsylvania Health System (UPHS) hospitals. Patients were eligible for TCZ per UPHS criteria if they scored >= 5 on the World Health Organization (WHO) ordinal scale for <= 24 hours and experienced < 14 days of acute COVID-19 symptoms. Descriptive statistics were performed to characterize usage within the health system. Results. This study evaluated 134 patients who received TCZ for the treatment of COVID-19. TCZ was ordered a median of 22 hours (interquartile range [IQR], 13.2 - 41.5) after hospital admission. A majority of patients (76.1%) were admitted to the intensive care unit and a small portion (12.7%) had a WHO ordinal scale that was >5 at time of TCZ order entry. All patients received concomitant dexamethasone therapy at a total prednisone equivalent of 400 mg (IQR, 335.6 - 480). Overall 33.6% of patients experienced an adverse event (ADE) within 30 days of TCZ administration (Table 1). Most common ADEs included bacterial infection (29.9%), hepatitis (6.7%), and fungal infection (3%);other etiologies of ADEs were not accounted for. All-cause mortality (Table 2) at day 30 occurred in 20.9% of patients and median time from TCZ administration to mortality was 12.5 days (IQR 5 - 18.3). Ninety-six patients in the cohort (71.6%) were discharged by day 30. Of the subgroup discharged by day 30, the majority (70.8%) were discharged to home. Conclusion. Patients who received TCZ for severe COVID-19 experienced 20.9% mortality;mortality was higher among those with higher ordinal scale at the time of TCZ dosing. A large portion of patients (70.8%) were discharged to home within 30 days. One third of patients experienced an adverse event, primarily bacterial or fungal infection. Our experience may be useful in counseling patients about anticipated effects of TCZ.
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OBJECTIVES: We designed a prospective cohort study to systematically study patients with severe acute respiratory infection (SARI) and improve hospital preparedness (SARI-PREP). The goal of this project is to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with SARI clinical outcomes and severity. METHODS: In collaboration with the Society of Critical Care Medicine Discovery Research Network and the National Emerging Special Pathogen Training and Education Center (NETEC), SARIPREP is an ongoing, prospective, observational, multi-center cohort study of hospitalized patients with respiratory viral infections. We collected patient demographics, signs, symptoms, and medications;microbiology, imaging, and other diagnostics;mechanical ventilation, hospital procedures, and other interventions;and clinical outcomes. Hospital leadership completed a weekly hospital stress survey. Respiratory, blood, and urine biospecimens were collected from patients on days 0, 3, 7-14 after study enrollment and at hospital discharge. MEASUREMENTS AND MAIN RESULTS: SARI-PREP enrollment began on April 4, 2020 and currently includes 674 patients. Here we report results from the first 400 patients: 216 are from the University of Washington Hospitals, Seattle WA, 142 from New York University, New York NY and 42 from University of Southern California, Los Angeles, CA. Almost all tested positive for SARS-CoV-2 infection (n=397), whereas 3 patients tested positive for an alternative viral pathogen. The mean (±SD) age of the patients was 57±16 years;72% were men, 62% were White, 14% were Asian, 12% were Black, and 31% were Hispanic. Most of the patients were admitted to the intensive care unit (96%). The median (interquartile range) hospital length of stay was 22 (9-46) days. Rates of invasive mechanical ventilation (72%) and renal replacement therapy (19%) were common and the rate of hospital mortality was 35%. CONCLUSIONS: Initial SARI-PREP analysis indicates enrollment of a diverse population of hospitalized patients primarily with SARSCoV-2 infection. The demographics and clinical outcomes of our cohort mirror other large critically ill cohorts of COVID-19 patients. Results of a concomitant, weekly, hospital stress assessment are reported separately.
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INTRODUCTION: To describe the epidemiology of Coronavirus Disease 2019 (COVID-19)-related critical illness at a diverse academic health system. METHODS: We performed a single-health system, multihospital retrospective cohort study of patients with COVID- 19-related critical illness who were admitted to an intensive care unit (ICU) at any of five hospitals within the University of Pennsylvania Health System. We report descriptive statistics for patient demographics, comorbidities, acute physiology parameters, receipt of ICU therapies, hospital outcomes, and survivorship. Using multivariable linear and logistic regression, we evaluated trends over time in all-cause 28-day in-hospital mortality, the primary outcome, and in patient acuity, and we evaluated candidate prognostic risk factors for association with mortality. RESULTS: 468 patients with COVID-19-related critical illness had a median age of 65 years (interquartile range [IQR] 54-74), were more likely male (57.7%), were more likely Black race (52.8%), and had a high co-morbidity burden (71.8% with ≥ 2 points on the Charlson Comorbidity Index). At least once during their hospitalization, 319 (68.2%) patients were treated with mechanical ventilation and 121 (25.9%) with vasopressors. Outcomes were notable for 29.9% all-cause 28-day in-hospital mortality (37.0% among those who received mechanical ventilation and 14.8% among those who did not receive mechanical ventilation), 8-day (IQR 3-17) median ICU length of stay, 13-day (IQR 7-25) median hospital length of stay, and 10.8% all-cause 30-day readmission rate. Mortality decreased over time from 43.5% (95% confidence interval 31.3%-53.8%) to 19.2% (11.6%- 26.7%) between the first and last 15-day periods in the fully adjusted model. Risk factors at ICU admission prognostic for mortality included increasing age, peripheral vascular disease, low or high body mass index, abnormal mental status, hypoxemia, tachypnea, and thrombocytopenia. CONCLUSIONS: Among patients with COVID-19-related critical illness admitted to the ICU at an academic health system in the U.S., a finite set of patient-level factors were prognostic for mortality and mortality decreased over time.