Faculty Bibliography

INTRODUCTION: Hospitals experienced substantial stress during the COVID-19 pandemic-threats to standard operations- but it is not well known how this stress manifested at individual hospitals. We aimed to understand patterns of hospital stress over time, where stress was located within hospitals, and correlations between individual stress measures.
METHOD(S): We conducted a weekly hospital stress survey from November 2020 through May 2021 among site leaders from the SCCM Discovery Severe Acute Respiratory Infection - Preparedness (SARI-PREP) multicenter prospective cohort study. The survey assessed hospital stress ordinally and also assessed ED and ICU stress and deviations from standard operating procedures. Pairwise comparisons of strain measures were calculated by Pearson's correlation coefficients (r).
RESULT(S): Eight hospitals across three health systems in New York, California, and Washington contributed 190 hospital-weeks of data. Sites reported unavailability of some hospital resources resulting in potentially avoidable patient harm during 3.5% of hospital-weeks (with at least one such week at four hospitals); alterations in care processes and/or staffing which were fully compensated for during 57.9% of weeks; and no stress during 38.6% of weeks. During one December 2020 week, hospital stress, ICU stress, and care deviations were all present at 100% of reporting sites. The most common care deviations were increased hospital staffing (39.5%) and cancelling elective surgeries (18.6%). Hospital stress and care deviations were highly correlated (r = 0.81, p < 0.0001). Stress was more common in ICUs (72.4%) than EDs (14.3%), and ICU and ED stress were not correlated (r = 0.19, p = 0.05). While ED stress rose and abated earlier, ICU stress and care deviations persisted (range 2-13 weeks longer) as local case rates declined.
CONCLUSION(S): Hospital stress during the pandemic varied in degree and type both within and among hospitals over time. Care deviations were common but potentially avoidable patient harm was rare. Systematic national assessments of hospital stress, both during and between pandemics, could inform more rapid, proactive public health responses to novel threats. Areas for further study include impacts from persistent low-level stress and longer-term consequences for hospitals and their communities

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.
METHOD(S): 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%.
CONCLUSION(S): 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

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

OBJECTIVES/OBJECTIVE:To evaluate the impact of ICU surge on mortality and to explore clinical and sociodemographic predictors of mortality. DESIGN/METHODS:Retrospective cohort analysis. SETTING/METHODS:NYC Health + Hospitals ICUs. PATIENTS/METHODS:Adult ICU patients with coronavirus disease 2019 admitted between March 24, and May 12, 2020. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Hospitals reported surge levels daily. Uni- and multivariable analyses were conducted to assess factors impacting in-hospital mortality. Mortality in Hispanic patients was higher for high/very high surge compared with low/medium surge (69.6% vs 56.4%; p = 0.0011). Patients 65 years old and older had similar mortality across surge levels. Mortality decreased from high/very high surge to low/medium surge in, patients 18-44 years old and 45-64 (18-44 yr: 46.4% vs 27.3%; p = 0.0017 and 45-64 yr: 64.9% vs 53.2%; p = 0.002), and for medium, high, and very high poverty neighborhoods (medium: 69.5% vs 60.7%; p = 0.019 and high: 71.2% vs 59.7%; p = 0.0078 and very high: 66.6% vs 50.7%; p = 0.0003). In the multivariable model high surge (high/very high vs low/medium odds ratio, 1.4; 95% CI, 1.2-1.8), race/ethnicity (Black vs White odds ratio, 1.5; 95% CI, 1.1-2.0 and Asian vs White odds ratio 1.5; 95% CI, 1.0-2.3; other vs White odds ratio 1.5, 95% CI, 1.0-2.3), age (45-64 vs 18-44 odds ratio, 2.0; 95% CI, 1.6-2.5 and 65-74 vs 18-44 odds ratio, 5.1; 95% CI, 3.3-8.0 and 75+ vs 18-44 odds ratio, 6.8; 95% CI, 4.7-10.1), payer type (uninsured vs commercial/other odds ratio, 1.7; 95% CI, 1.2-2.3; medicaid vs commercial/other odds ratio, 1.3; 95% CI, 1.1-1.5), neighborhood poverty (medium vs low odds ratio 1.6, 95% CI, 1.0-2.4 and high vs low odds ratio, 1.8; 95% CI, 1.3-2.5), comorbidities (diabetes odds ratio, 1.6; 95% CI, 1.2-2.0 and asthma odds ratio, 1.4; 95% CI, 1.1-1.8 and heart disease odds ratio, 2.5; 95% CI, 2.0-3.3), and interventions (mechanical ventilation odds ratio, 8.8; 95% CI, 6.1-12.9 and dialysis odds ratio, 3.0; 95% CI, 1.9-4.7) were significant predictors for mortality. CONCLUSIONS:Patients admitted to ICUs with higher surge scores were at greater risk of death. Impact of surge levels on mortality varied across sociodemographic groups.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.