Faculty Bibliography

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.

The coronavirus disease 2019 (COVID-19) pandemic has stretched our healthcare system to the brink, highlighting the importance of efficient resource utilization without compromising healthcare provider safety. While advanced imaging is a great resource for diagnostic purposes, the risk of contamination and infection transmission is high and requires extensive logistical planning for intrahospital patient transport, healthcare provider safety, and post-imaging decontamination. This dilemma has necessitated the transition to more bedside imaging. More so than ever, during the current pandemic, the clinical utility and importance of point-of-care ultrasound (POCUS) cannot be overstressed. It allows for safe and efficient beside procedural guidance and provides front line providers with valuable diagnostic information that can be acted upon in real-time for immediate clinical decision-making. The authors have been routinely using POCUS for the management of COVID-19 patients both in the emergency department and in intensive care units turned into "COVID-units." In this article, we review the nuances of using POCUS in a pandemic situation and maximizing diagnostic output from this bedside technology. Additionally, we review various methods and diagnostic uses of POCUS which can replace conventional imaging and bridge current literature and common clinical practices in critically ill patients. We discuss practical guidance and pertinent review of the literature for the most relevant procedural and diagnostic guidance of respiratory illness, hemodynamic decompensation, renal failure, and gastrointestinal disorders experienced by many patients admitted to COVID-units.

COVID-19 has created significant strain on the supply of healthcare resources and, during the spring surge in New York City, many hospitals prepared resource allocation policies should the demand for ventilators exceed supply. In such circumstances, resources should remain allocated to patients most likely to survive. Understanding how these guidelines perform is an important consideration in disaster planning. Numerous allocation guidelines exist however nearly all utilize a Sequential Organ Failure Assessment (SOFA) score. We sought to evaluate the performance of ventilator reallocation by applying the New York State Ventilator Allocation Guidelines (NYVAG) to a large cohort of COVID-19 patients. Our retrospective cohort included 895 intubated COVID-19 patients admitted to an academic system in New York City. SOFA scores were calculated for every day of mechanical ventilation. Per NYVAG, patients would have their ventilator reallocated at 48 hours if their interval SOFA score increased, did not change from an initial SOFA of 8-11, or was greater than 11. At 120 hours it would be reallocated if their SOFA score worsened or was greater than 7. At 168 hours and every subsequent 48 hours it would be reallocated if their SOFA score worsened. Ventilator reallocation was simulated and no reallocation was made for any patient. The average SOFA (n=895) at the time of intubation was 7.1 +/- 3.6. At the 48-hour reassessment (average SOFA 8.2 +/- 3.6, n=759), 436 (57%) patients would have their ventilator reallocated, 145 (33%) of whom would later survive to discharge. At the 120-hour reassessment (average SOFA 7.8 +/- 3.6, n=264) 173 (66%) of the 264 remaining simulated ventilated patients would have their ventilators reallocated, 83 (48%) of whom would later survive to discharge. At the 168-hour reassessment (average SOFA 7.8 +/- 3.6, n=80) 66 (83%) of the 80 simulated remaining ventilated patients would have their ventilators reallocated. Overall, 685 patients (77%) of the starting cohort would have had their ventilator reallocated at some time during the first 168 hours of mechanical ventilation, 268 (40%) of whom survived to discharge. Our simulated study found that the application of NYVAG to the COVID-19 surge at one academic system would have resulted in a significant portion of ventilated patients having had their ventilators reallocated. This may be deeply concerning as a significant portion of patients ultimately survived to discharge. These results call for further confirmatory studies and have implications for optimal resource allocation strategies during pandemics

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.

BACKGROUND:Prolonged duration of mechanical ventilation is associated with higher mortality and increased patient complications; conventional physician-directed weaning methods are highly variable and permit significant time that weaning is inefficient and ineffective. OBJECTIVES/OBJECTIVE:The primary objective of this quality improvement project was to implement a registered nurse (RN)- and respiratory therapist (RT)-driven mechanical ventilation weaning protocol in a medical intensive care unit (ICU) at a tertiary care academic medical center. METHODS:This quality improvement project used a quasi-experimental design with a retrospective usual care group who underwent physician-directed (conventional) weaning (n = 51) and a prospective intervention group who underwent protocol-directed weaning (n = 54). Outcomes included duration of mechanical ventilation, ICU length of stay, reintubation rates, and RN and RT satisfaction with the weaning protocol. RESULTS:Patients in the RN- and RT-driven mechanical ventilation weaning protocol group had significantly lower duration of mechanical ventilation (74 vs 152 hours; P = .002) and ICU length of stay (6.7 vs 10.2 days; P = .031). There was no significant difference in reintubation rates between groups. Staff surveys indicate that both RN and RTs were satisfied with the process change. DISCUSSION/CONCLUSIONS:Implementation of a multidisciplinary mechanical ventilation weaning protocol is a safe and effective way to improve patient outcomes and empower ICU staff.

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.

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2.

The evolution of lung function, including assessment of small airways, was assessed in individuals enrolled in the World Trade Center Environmental Health Center (WTC-EHC). We hypothesized that a bronchodilator response at initial evaluation shown by spirometry or in small airways, as measured by forced oscillation technique (FOT), would be associated with improvement in large and small airway function over time. Standardized longitudinal assessment included pre and post bronchodilator (BD) spirometry (forced vital capacity, FVC; forced expiratory volume in 1 second, FEV₁) and FOT (resistance at 5 Hz, R₅; resistance at 5 minus 20 Hz, R_5-20). Longitudinal changes were assessed using linear mixed-effects modelling with adjustment for potential confounders (median follow-up 2.86 years; 95% measurements within 4.9 years). Data demonstrated: (1) parallel improvement in airflow and volume measured by spirometry and small airway function (R₅ and R_5-20) measured by FOT; (2) the magnitude of longitudinal improvement was tightly linked to the initial BD response; and (3) longitudinal values for small airway function on FOT were similar to residual abnormality observed post BD at initial visit. These findings suggest presence of reversible and irreversible components of small airway injury that are identifiable at initial presentation. These results have implications for treatment of isolated small airway abnormalities that can be identified by non-invasive effort independent FOT particularly in symptomatic individuals with normal spirometry indices. This study underscores the need to study small airway function to understand physiologic changes over time following environmental and occupational lung injury.