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Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome

Sulaiman, Imran; Chung, Matthew; Angel, Luis; Tsay, Jun-Chieh J; Wu, Benjamin G; Yeung, Stephen T; Krolikowski, Kelsey; Li, Yonghua; Duerr, Ralf; Schluger, Rosemary; Thannickal, Sara A; Koide, Akiko; Rafeq, Samaan; Barnett, Clea; Postelnicu, Radu; Wang, Chang; Banakis, Stephanie; Pérez-Pérez, Lizzette; Shen, Guomiao; Jour, George; Meyn, Peter; Carpenito, Joseph; Liu, Xiuxiu; Ji, Kun; Collazo, Destiny; Labarbiera, Anthony; Amoroso, Nancy; Brosnahan, Shari; Mukherjee, Vikramjit; Kaufman, David; Bakker, Jan; Lubinsky, Anthony; Pradhan, Deepak; Sterman, Daniel H; Weiden, Michael; Heguy, Adriana; Evans, Laura; Uyeki, Timothy M; Clemente, Jose C; de Wit, Emmie; Schmidt, Ann Marie; Shopsin, Bo; Desvignes, Ludovic; Wang, Chan; Li, Huilin; Zhang, Bin; Forst, Christian V; Koide, Shohei; Stapleford, Kenneth A; Khanna, Kamal M; Ghedin, Elodie; Segal, Leopoldo N
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.
PMID: 34465900
ISSN: 2058-5276
CID: 4998422

Evaluation of the lower airway microbiota in patients with severe sars-cov2 [Meeting Abstract]

Barnett, C R; Sulaiman, I; Tsay, J; Wu, B; Krolikowski, K; Li, Y; Postelnicu, R; Carpenito, J; Rafeq, S; Clemente, J C; Angel, L F; Mukherjee, V; Pradhan, D; Brosnahan, S; Lubinsky, A S; Yeung, S; Jour, G; Shen, G; Chung, M; Khanna, K; Ghedin, E; Segal, L N
RATIONALE:Secondary infections with bacterial pathogens are thought to be responsible for poor outcomes in the 1918 Spanish and H1N1 pandemics. We postulate that poor prognosis in patients with SARS-CoV2 may be associated with uncontrollable viral replication, co-infection with a secondary pathogen, and over exuberant host immune response. We seek to evaluate whether there is an association between distinct features of the lower airway microbiota and poor clinical outcome in patients with SARS-CoV2.
METHOD(S):We collected lower airway samples in 148 patients from NYU admitted between 3/10/2020 and 5/10/2020 with severe respiratory failure requiring mechanical ventilation and that underwent bronchoscopy for airway clearance and/or tracheostomy. Clinical outcome was defined as dead vs alive. DNA was isolated in parallel using zymoBIOMICSTM DNA/RNA Miniprep Kit (Cat: R2002) as per manufacturer's instructions. The V4 region of the 16S rRNA gene marker was sequenced using Illumina MiSeq. Sequences were analyzed using the Quantitative Insights into Microbial Ecology (QIIME version 1.9.1) pipeline. Total bacterial load was evaluated in lower airway samples using digital droplet PCR targeting the 16S rRNA gene.
RESULT(S):Of the 148 patients included, 114 survived (77%) and 34 (23%) died. Among those with poor clinical outcome, there was a non-statistically significant trend towards higher age and BMI. Patients who died more commonly had chronic kidney disease and prior cerebrovascular accidents, and more often required dialysis. There was no statistically significant difference in the rate of positive bacterial respiratory or blood cultures among those that survived vs. those that died (75 vs. 73% and 43 vs 38%, respectively). Topographical analysis of the 16S RNA microbiome shows compositional differences between the upper and lower airways based on beta diversity comparisons. When comparing across clinical outcomes, the alpha diversity was lower in the dead group but there was no statistically significant difference in overall community composition (beta diversity). Taxonomic differential enrichment analysis using DESeq analysis showed that oral commensals were enriched in the group that survived. Patients that died had a higher bacterial load in their lower airways than those who survived.
CONCLUSION(S):Using samples obtained via bronchoscopy we identified lower airway microbiota signatures associated with mortality among critical patients infected with SARS-CoV2. Taxonomic signals identified as associated with poor prognosis did not reveal bacterial taxa commonly classified as respiratory pathogens. This data is not supportive of the hypothesis that secondary untreated bacterial co-infections are responsible for increased mortality in patients with severe SARS-CoV-2
EMBASE:635309029
ISSN: 1535-4970
CID: 4915522

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome

Sulaiman, Imran; Chung, Matthew; Angel, Luis; Koralov, Sergei; Wu, Benjamin; Yeung, Stephen; Krolikowski, Kelsey; Li, Yonghua; Duerr, Ralf; Schluger, Rosemary; Thannickal, Sara; Koide, Akiko; Rafeq, Samaan; Barnett, Clea; Postelnicu, Radu; Wang, Chang; Banakis, Stephanie; Perez-Perez, Lizzette; Jour, George; Shen, Guomiao; Meyn, Peter; Carpenito, Joseph; Liu, Xiuxiu; Ji, Kun; Collazo, Destiny; Labarbiera, Anthony; Amoroso, Nancy; Brosnahan, Shari; Mukherjee, Vikramjit; Kaufman, David; Bakker, Jan; Lubinsky, Anthony; Pradhan, Deepak; Sterman, Daniel; Heguy, Adriana; Uyeki, Timothy; Clemente, Jose; de Wit, Emmie; Schmidt, Ann Marie; Shopsin, Bo; Desvignes, Ludovic; Wang, Chan; Li, Huilin; Zhang, Bin; Forst, Christian; Koide, Shohei; Stapleford, Kenneth; Khanna, Kamal; Ghedin, Elodie; Weiden, Michael; Segal, Leopoldo
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.
PMCID:8010736
PMID: 33791687
ISSN: n/a
CID: 4830952

Use of a Multidisciplinary Mechanical Ventilation Weaning Protocol to Improve Patient Outcomes and Empower Staff in a Medical Intensive Care Unit

Gunther, Ingrid; Pradhan, Deepak; Lubinsky, Anthony; Urquhart, Annie; Thompson, Julie A; Reynolds, Staci
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.
PMID: 33961373
ISSN: 1538-8646
CID: 4897792

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome

Sulaiman, Imran; Chung, Matthew; Angel, Luis; Tsay, Jun-Chieh J; Wu, Benjamin G; Yeung, Stephen T; Krolikowski, Kelsey; Li, Yonghua; Duerr, Ralf; Schluger, Rosemary; Thannickal, Sara A; Koide, Akiko; Rafeq, Samaan; Barnett, Clea; Postelnicu, Radu; Wang, Chang; Banakis, Stephanie; Perez-Perez, Lizzette; Jour, George; Shen, Guomiao; Meyn, Peter; Carpenito, Joseph; Liu, Xiuxiu; Ji, Kun; Collazo, Destiny; Labarbiera, Anthony; Amoroso, Nancy; Brosnahan, Shari; Mukherjee, Vikramjit; Kaufman, David; Bakker, Jan; Lubinsky, Anthony; Pradhan, Deepak; Sterman, Daniel H; Weiden, Michael; Hegu, Adriana; Evans, Laura; Uyeki, Timothy M; Clemente, Jose C; De Wit, Emmie; Schmidt, Ann Marie; Shopsin, Bo; Desvignes, Ludovic; Wang, Chan; Li, Huilin; Zhang, Bin; Forst, Christian V; Koide, Shohei; Stapleford, Kenneth A; Khanna, Kamal M; Ghedin, Elodie; Segal, Leopoldo N
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.
PMCID:7924286
PMID: 33655261
ISSN: n/a
CID: 4801472

Uninterrupted Continuous and Intermittent Nebulizer Therapy in a COVID-19 Patient Using Sequential Vibratory Mesh Nebulizers: A Case Report

Elnadoury, Ola; Beattie, Jason; Lubinsky, Anthony S
Interruptions in continuous nebulized pulmonary vasodilators, such as epoprostenol, can potentially result in clinical deterioration in respiratory status. Coadministration of other intermittent nebulized therapies may require opening the ventilator circuit to facilitate administration. However, in patients with SARS-CoV2 infection, it is preferred to avoid opening the circuit whenever feasible to prevent aerosolization of the virus and exposure of health care workers. In this study, we describe a unique method of administering continuous epoprostenol nebulization and intermittent nebulized antibiotics, mucolytics, and bronchodilators, using Aerogen vibrating mesh nebulizers without interruptions in epoprostenol or opening the ventilator circuit. This technique set up consisted of stacking two Aerogen nebulizer cups, each with its own controller. This approach was successful in allowing concomitant delivery of intermittent and continuous nebulized therapy without interruptions. To our knowledge, this method has not been previously described in the literature and may be helpful to bedside clinicians facing a similar clinical scenario.
PMID: 32852238
ISSN: 1941-2703
CID: 4629732

Where to start? A single center retrospective analysis of early liberation from mechanical ventilation in vv ECMO patients with acute respiratory failure [Meeting Abstract]

Gunther, I; Toy, B; Andriotis, A; Hagedorn, J; Morgenstern, T; Staccone, L; Smith, D; Lubinsky, A
Intro: The optimal strategy for weaning of respiratory support during lung recovery of patients requiring VV ECMO for acute respiratory failure is unknown. We hypothesized that earlier liberation from the ventilator in these patients may correlate with improved outcomes.
Method(s): We retrospectively reviewed all VV ECMO patients at our center from November 2015 to May 2019. Patients who were on VV ECMO as bridge to transplant or for isolated intraoperative indications were excluded. The final study population included 18 patients; 6 were liberated from mechanical ventilation prior to ECMO decannulation and 12 were decannulated from ECMO, but remained mechanically ventilated. Demographics and outcomes were compared between the two groups.
Result(s): Patients liberated from the ventilator prior to ECMO were treated for asthma, pneumonia and vasculitis (33% each) versus predominantly pneumonia (58%), had a lower rate of pre-existing lung disease (17% vs 33%), and lower APACHE II scores (median of 21 vs 24). These patients had longer duration of ECMO (220 vs 205 hours), less ventilator days (5 vs 20.5 days), higher average Richmond Agitation Scores (-1 vs -3), fewer days until they were able to get out of bed (4.5 vs 15 days), shorter ICU stays (16 vs 29 days), and were more likely to survive to hospital discharge (100% vs 67%).
Conclusion(s): Early ventilator liberation of patients on VV ECMO was associated with improved outcomes. Our study is limited by small sample size, retrospective design, and potential for confounding due to baseline differences between groups
EMBASE:631095458
ISSN: 1538-943x
CID: 4387222

Maintaining quality outcomes with a rapidly growing ECMO program [Meeting Abstract]

Toy, B; Angel, L; Beaulieu, T; Hill, F; Kon, Z; Moazami, N; Sullivan, B; Lubinsky, A; Smith, D
Introduction: Our institution's Adult ECMO Program started in 2015 and continues to see exponential growth with an average of 89% annual increase in volume. When demand for ECMO exceeds available resources, the multiple teams, resources and processes involved in the care of these patients are challenged to provide excellent outcomes. Our program made specific changes to accommodate increased volume while maintaining quality. Our growth directly impacted staff exposure and expertise, locations of ECMO care, emergent bedside cannulations, and utilization of equipment and supplies.
Result(s): Our team coordinated comprehensive training courses to increase the number of ECMO-credentialed physicians and advanced practice providers. We then focused on improving bedside cannulations. We provided cannulation didactic and simulation training for a cohort of critical care nurses, created a single ECMO Perfusion activation number, and increased available primed circuits. We also rebuilt our cannulation carts, using an exchange process for immediate replenishment of supplies. All carts were streamlined to one lay out and were expanded across the hospital in five different locations. We increased our equipment inventory from 9 to 15 consoles and introduced a more cost-effective ECMO system. Last, we implemented ECMO safety rounds, a biweekly bedside audit of existing safety measures that also allowed for real-time staff education.
Conclusion(s): Our patient outcomes continue to meet the national ELSO benchmarks for survival rates. As our growth continues, all areas require ongoing assessment and evaluation to maintain best practices. With proper planning and resources, quality patient outcomes can be maintained
EMBASE:631095447
ISSN: 1538-943x
CID: 4387242

Creating a cohort of nursing experts to assist in emergent bedside cannulations [Meeting Abstract]

Toy, B; Vera, S; Dinally, K; Drus, K; Lubinsky, A; Smith, D
INTRO: Our Adult ECMO Program cannulates most of our patients in the operating room (OR). However, in the past year, our bedside cannulation volume increased from 13 to 27 across six inpatient units. Because we expect cannulations outside of the OR to increase, the Adult Langone Emergency Response Team (ALERT) nurses were identified as the ideal providers to assist in bedside cannulations.
METHOD(S): Our ECMO Team developed a cannulation program to meet the educational needs of the 20 ALERT nurses. The ECMO Directors and Coordinator held a two hour didactic course, reviewing cannulation procedures, ECMO configurations and nursing roles in a bedside cannulation. We distributed pre & post self-assessments to evaluate the nurses' confidence levels. The ECMO Team then invited ALERT nurses to observe planned cannulations, providing an ideal setting for learning and reflection of the cannulation process. ALERT nurses identified areas for improvement that could aid in emergent initiation of ECMO outside of the OR. The program concluded with a one hour simulation session that provided an opportunity for both teams to clarify expectations of future cannulations.
RESULT(S): Using the Wilcoxon Signed-rank test, we found a statistically significant improvement in pre & post self-assessment scores (p-value <0.001). Direct feedback from ALERT nurses included further clarification for ECMO team activation process, terminology of surgical supplies and additional resources needed to support a bedside cannulation. The program allowed for both teams to strengthen their collaboration that will ultimately result in improved workflow, communication and patient outcomes
EMBASE:631095151
ISSN: 1538-943x
CID: 4387272

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations

Kazachkov, Mikhail; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Bar-Aluma, Bat-El; Spalink, Christy L; Barnes, Erin P; Amoroso, Nancy E; Balou, Stamatela M; Bess, Shay; Chopra, Arun; Condos, Rany; Efrati, Ori; Fitzgerald, Kathryn; Fridman, David; Goldenberg, Ronald M; Goldhaber, Ayelet; Kaufman, David A; Kothare, Sanjeev V; Levine, Jeremiah; Levy, Joseph; Lubinsky, Anthony S; Maayan, Channa; Moy, Libia C; Rivera, Pedro J; Rodriguez, Alcibiades J; Sokol, Gil; Sloane, Mark F; Tan, Tina; Kaufmann, Horacio
BACKGROUND:Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS:We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS:Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS:Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
PMCID:6084453
PMID: 30053970
ISSN: 1532-3064
CID: 3216612