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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

Percutaneous Dilational Tracheostomy for Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation

Angel, Luis F; Amoroso, Nancy E; Rafeq, Samaan; Mitzman, Brian; Goldenberg, Ronald; Shekar, Saketh Palasamudram; Troxel, Andrea B; Zhang, Yan; Chang, Stephanie H; Kwak, Paul; Amin, Milan R; Sureau, Kimberly; Nafday, Heidi B; Thomas, Sarun; Kon, Zachary; Sommer, Philip M; Segal, Leopoldo N; Moore, William H; Cerfolio, Robert
OBJECTIVES/OBJECTIVE:To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN/METHODS:Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING/METHODS:Critical care units at two large metropolitan hospitals in New York City. PATIENTS/METHODS:Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS/METHODS:Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS/RESULTS:Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS:In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.
PMID: 33826583
ISSN: 1530-0293
CID: 4839312

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

Early Outcomes From Early Tracheostomy for Patients With COVID-19

Kwak, Paul E; Connors, Joseph R; Benedict, Peter A; Timen, Micah R; Wang, Binhuan; Zhang, Yan; Youlios, Stephanie; Sureau, Kimberly; Persky, Michael J; Rafeq, Samaan; Angel, Luis; Amin, Milan R
Importance/UNASSIGNED:Decision-making in the timing of tracheostomy in patients with coronavirus disease 2019 (COVID-19) has centered on the intersection of long-standing debates on the benefits of early vs late tracheostomy, assumptions about timelines of infectivity of the novel coronavirus, and concern over risk to surgeons performing tracheostomy. Multiple consensus guidelines recommend avoiding or delaying tracheostomy, without evidence to indicate anticipated improvement in outcomes as a result. Objective/UNASSIGNED:To assess outcomes from early tracheostomy in the airway management of patients with COVID-19 requiring mechanical ventilation. Design, Setting, and Participants/UNASSIGNED:A retrospective medical record review was completed of 148 patients with reverse transcriptase-polymerase chain reaction-confirmed COVID-19 requiring mechanical ventilation at a single tertiary-care medical center in New York City from March 1 to May 7, 2020. Interventions/UNASSIGNED:Open or percutaneous tracheostomy. Main Outcomes and Measures/UNASSIGNED:The primary outcomes were time from symptom onset to (1) endotracheal intubation, (2) tracheostomy; time from endotracheal intubation to tracheostomy; time from tracheostomy to (1) tracheostomy tube downsizing, (2) decannulation; total time on mechanical ventilation; and total length of stay. Results/UNASSIGNED:Participants included 148 patients, 120 men and 28 women, with an overall mean (SD) age of 58.1 (15.8) years. Mean (SD; median) time from symptom onset to intubation was 10.57 (6.58; 9) days; from symptom onset to tracheostomy, 22.76 (8.84; 21) days; and from endotracheal intubation to tracheostomy, 12.23 (6.82; 12) days. The mean (SD; median) time to discontinuation of mechanical ventilation was 33.49 (18.82; 27) days; from tracheostomy to first downsize, 23.02 (13.76; 19) days; and from tracheostomy to decannulation, 30.16 (16.00; 26) days. The mean (SD; median) length of stay for all patients was 51.29 (23.66; 45) days. Timing of tracheostomy was significantly associated with length of stay: median length of stay was 40 days in those who underwent early tracheostomy (within 10 days of endotracheal intubation) and 49 days in those who underwent late tracheostomy (median difference, -8; 95% CI, -15 to -1). In a competing risks model with death as the competing risk, the late tracheostomy group was 16% less likely to discontinue mechanical ventilation (hazard ratio, 0.84; 95% CI, 0.55 to 1.28). Conclusions and Relevance/UNASSIGNED:This cohort study from the first 2 months of the pandemic in New York City provides an opportunity to reconsider guidelines for tracheostomy for patients with COVID-19. Findings demonstrated noninferiority of early tracheostomy and challenges recommendations to categorically delay or avoid tracheostomy in this patient population. When aligned with emerging evidence about the timeline of infectivity of the novel coronavirus, this approach may optimize outcomes from tracheostomy while keeping clinicians safe.
PMID: 33331855
ISSN: 2168-619x
CID: 4718022

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

Lower airway dysbiosis affects lung cancer progression

Tsay, Jun-Chieh J; Wu, Benjamin G; Sulaiman, Imran; Gershner, Katherine; Schluger, Rosemary; Li, Yonghua; Yie, Ting-An; Meyn, Peter; Olsen, Evan; Perez, Luisannay; Franca, Brendan; Carpenito, Joseph; Iizumi, Tadasu; El-Ashmawy, Mariam; Badri, Michelle; Morton, James T; Shen, Nan; He, Linchen; Michaud, Gaetane; Rafeq, Samaan; Bessich, Jamie L; Smith, Robert L; Sauthoff, Harald; Felner, Kevin; Pillai, Ray; Zavitsanou, Anastasia-Maria; Koralov, Sergei B; Mezzano, Valeria; Loomis, Cynthia A; Moreira, Andre L; Moore, William; Tsirigos, Aristotelis; Heguy, Adriana; Rom, William N; Sterman, Daniel H; Pass, Harvey I; Clemente, Jose C; Li, Huilin; Bonneau, Richard; Wong, Kwok-Kin; Papagiannakopoulos, Thales; Segal, Leopoldo N
In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in group IIIB-IV TNM stage lung cancer and is associated with poor prognosis, as shown by decreased survival among subjects with early stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with IIIB-IV stage disease. In addition, this lower airway microbiota signature was associated with upregulation of IL-17, PI3K, MAPK and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL-17 inflammatory phenotype and activation of checkpoint inhibitor markers.
PMID: 33177060
ISSN: 2159-8290
CID: 4663012

Multi-institutional retrospective analysis of adverse events following rigid tracheobronchoscopy

Fortin, Marc; Yarmus, Lonny; Rendina, Erino Angelo; Rafeq, Samaan; Andrade, Rafael; Michaud, Gaetane; Kazakov, Jordan; Arias, Sixto; Ciccone, Anna Maria; Ortiz, Ricardo; Liberman, Moishe
BACKGROUND AND OBJECTIVE/OBJECTIVE:Rigid tracheobronchoscopy (RTB) has seen an increasing interest over the last decades with the development of the field of IPM but no benchmark exists for complication rates in RTB. We aimed to establish benchmarks for complication rates in RTB. METHODS:A multicentric retrospective analysis of RTB performed between 2009 and 2015 in eight participating centres was performed. RESULTS:A total of 1546 RTB were performed over the study period. One hundred and thirty-one non-lethal complications occurred in 103 procedures (6.7%, 95% CI: 5.5-8.0%). The periprocedural mortality rate was 1.2% (95% CI: 0.6-1.8%). The 30-day mortality rate was 5.6% (95% CI: 4.5-6.8%). Complication rate increases further when procedures were performed in an emergency setting. Procedures in patients with MAO are associated with a higher 30-day mortality (8.1% vs 2.7%, P < 0.01) and a different complication profile when compared to procedures performed for BAS. CONCLUSION/CONCLUSIONS:RTB is associated with a 6.7% non-lethal complication rate, a 1.2% periprocedural mortality rate and a 5.6% 30-day mortality in a large multicentre cohort of patients with benign and malignant airway disease.
PMID: 32537884
ISSN: 1440-1843
CID: 4484482

ATS Core Curriculum 2020. Adult Pulmonary Medicine

Channick, Colleen L; Garrison, Garth; Huie, Tristan J; Narewski, Erin; Caplan-Shaw, Caralee; Cho, Josalyn; Rafeq, Samaan; Alalawi, Raed; Alashram, Rami; Bailey, Kristina L; Carmona, Eva M; Habib, Naomi; Kapolka, Rebecca; Krishnan, Amita; Lammi, Matthew R; Peck, Tyler; Pennington, Kelly M; Rali, Parth; Small, Bronwyn L; Swenson, Colin; Witkin, Alison; Hayes, Margaret M
The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).
PMCID:8015759
PMID: 33870311
ISSN: 2690-7097
CID: 4846682

Novel Percutaneous Tracheostomy for Critically Ill Patients with COVID-19

Angel, Luis; Kon, Zachary N; Chang, Stephanie H; Rafeq, Samaan; Shekar, Saketh Palasamudram; Mitzman, Brian; Amoroso, Nancy; Goldenberg, Ronald; Sureau, Kimberly; Smith, Deane; Cerfolio, Robert J
BACKGROUND:COVID-19 is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a super-spreading event due to aerosolization that unduly risks healthcare workers. METHODS:Patients with severe COVID-19 that were on mechanical ventilation ≥ 5 days were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. This improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. RESULTS:From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan's campus of which 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 days (SD ±5 days). Currently, thirty-two (33%) patients do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized and 8 (8%) were decannulated. Forty (41%) patients remain on full ventilator support, while 19 (19%) are weaning from mechanical ventilation. Seven (7%) died as result of respiratory and multiorgan failure. Tracheostomy related bleeding was the most common complication (5 patients). None of health care providers have developed symptoms or tested positive for COVID-19. CONCLUSIONS:Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for healthcare workers.
PMID: 32339508
ISSN: 1552-6259
CID: 4411932