Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2565
N. Mesfin, A. Han, Michael A. Garcia, S. Johnson, R. Wiener
Rationale: During the early phase of the Covid-19 pandemic, there has been significant uncertainty and heightened fear regarding the poor prognosis of COVID-19 and the disproportionate impact on minorities and socioeconomically disadvantaged groups. Prior studies have demonstrated that baseline characteristics including older age, white race, female gender, and poor functional status are all associated with the decision to forego resuscitative efforts during critical illness. We sought to understand if demographic characteristics are stronger predictors for the decision to forgo resuscitative efforts than comorbid condition or severity of critical illness during COVID-19 pandemic. Methods: A retrospective study was conducted on all adults admitted to Boston Medical Center (BMC) ICU between March 1 and June 7 with confirmed Covid-19 infection. Patients were dichotomized into two groups: patients with code status conversion to DNAR and patients that remained full code during the entirety of their critical illness. Univariate analysis and logistic regression was performed to identify variables associated with code status conversion. Results: A total of 281 patients were hospitalized in the ICU with COVID-19 infection and 70% (n = 198) remained full code while 29.5% (n = 83) instituted DNAR orders. Older age was associated with decision to institute DNAR order (65 years-old SD±15 v 58 years-old SD±15, p < 0.001). The other demographic factors including gender, race, language preference, and insurance status were not associated with decision to institute DNAR order. The comorbid conditions of cardiopulmonary disease, chronic kidney disease, or malignancy were not associated with decision to institute DNAR. The intra-critical illness factors including need for invasive mechanical ventilation (IMV) (OR 5.2 95% CI 2.6-11.2), need for continuous renal replacement therapy (CRRT) (OR 3.8 95% CI 1.8-8) and admission SOFA score (5 SD ± 3.5 v 7 SD ± 4, p < 0.001) were associated with decision to institute DNAR order. Conclusion: This preliminary study suggests that at the height of the Covid-19 pandemic and height of uncertainty, factors associated with the decision to forgo resuscitative efforts are primarily intra-critical illness factors as opposed to baseline demographic characteristics. A larger multi-center study is required to confirm the findings from a single-center safety net hospital.
理由:在Covid-19大流行的早期阶段，对Covid-19预后不良以及对少数民族和社会经济弱势群体的不成比例的影响存在很大的不确定性和加剧的恐惧。先前的研究表明，包括年龄较大、白人种族、女性和较差的功能状态在内的基线特征都与危重疾病期间放弃复苏努力的决定有关。我们试图了解在COVID-19大流行期间，人口统计学特征是否比合并症或危重疾病严重程度更能预测放弃复苏努力的决定。方法:对3月1日至6月7日在波士顿医学中心(BMC) ICU收治的所有确诊感染Covid-19的成年人进行回顾性研究。患者被分为两组:代码状态转换为DNAR的患者和在整个危重疾病期间保持完整代码的患者。进行单变量分析和逻辑回归，以确定与代码状态转换相关的变量。结果:共有281例COVID-19感染患者在ICU住院，其中70% (n = 198)保持完整代码，29.5% (n = 83)建立了DNAR订单。年龄越大与决定采用DNAR顺序相关(65岁SD±15 vs 58岁SD±15,p <0.001)。其他人口统计学因素包括性别、种族、语言偏好和保险状况与决定建立DNAR顺序无关。心肺疾病、慢性肾脏疾病或恶性肿瘤的合并症与决定采用DNAR无关。危重期疾病因素包括需要有创机械通气(IMV) (OR 5.2 95% CI 2.6-11.2)、需要持续肾脏替代治疗(OR 3.8 95% CI 1.8-8)和入院SOFA评分(5 SD±3.5 v 7 SD±4,p <0.001)与制定DNAR顺序的决定相关。结论:本初步研究表明，在Covid-19大流行的高峰期和不确定性的高峰期，与放弃复苏努力的决定相关的因素主要是危重疾病因素，而不是基线人口统计学特征。需要更大的多中心研究来证实单中心安全网医院的研究结果。
{"title":"Predictors to Forgo Resuscitative Efforts During Covid-19 Critical Illness at the Height of the Pandemic.","authors":"N. Mesfin, A. Han, Michael A. Garcia, S. Johnson, R. Wiener","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2565","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2565","url":null,"abstract":"Rationale: During the early phase of the Covid-19 pandemic, there has been significant uncertainty and heightened fear regarding the poor prognosis of COVID-19 and the disproportionate impact on minorities and socioeconomically disadvantaged groups. Prior studies have demonstrated that baseline characteristics including older age, white race, female gender, and poor functional status are all associated with the decision to forego resuscitative efforts during critical illness. We sought to understand if demographic characteristics are stronger predictors for the decision to forgo resuscitative efforts than comorbid condition or severity of critical illness during COVID-19 pandemic. Methods: A retrospective study was conducted on all adults admitted to Boston Medical Center (BMC) ICU between March 1 and June 7 with confirmed Covid-19 infection. Patients were dichotomized into two groups: patients with code status conversion to DNAR and patients that remained full code during the entirety of their critical illness. Univariate analysis and logistic regression was performed to identify variables associated with code status conversion. Results: A total of 281 patients were hospitalized in the ICU with COVID-19 infection and 70% (n = 198) remained full code while 29.5% (n = 83) instituted DNAR orders. Older age was associated with decision to institute DNAR order (65 years-old SD±15 v 58 years-old SD±15, p < 0.001). The other demographic factors including gender, race, language preference, and insurance status were not associated with decision to institute DNAR order. The comorbid conditions of cardiopulmonary disease, chronic kidney disease, or malignancy were not associated with decision to institute DNAR. The intra-critical illness factors including need for invasive mechanical ventilation (IMV) (OR 5.2 95% CI 2.6-11.2), need for continuous renal replacement therapy (CRRT) (OR 3.8 95% CI 1.8-8) and admission SOFA score (5 SD ± 3.5 v 7 SD ± 4, p < 0.001) were associated with decision to institute DNAR order. Conclusion: This preliminary study suggests that at the height of the Covid-19 pandemic and height of uncertainty, factors associated with the decision to forgo resuscitative efforts are primarily intra-critical illness factors as opposed to baseline demographic characteristics. A larger multi-center study is required to confirm the findings from a single-center safety net hospital.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116962785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2553
G. Palmer, N. Meyer, F. Jamous
Rationale: We aim to describe the clinical characteristics and outcomes of patients who received Tocilizumab for COVID-19 pneumonia at our institution between March 20 and October 26, 2020. Methods: In this single center, retrospective, observational study, we identified 55 adults admitted with COVID-19 pneumonia who received Tocilizumab. Demographic data, symptoms, laboratory values, treatments, and clinical outcomes were collected. Data was compared between those who received Tocilizumab and all patients admitted with COVID-19. Primary outcome was 28-day mortality. Secondary outcomes included role of concomitant steroid use and change in eosinophil counts, ferritin, AST, CRP and D-Dimer values. Results: Of the 589 patients admitted with COVID-19 pneumonia, 55 received Tocilizumab as part of their treatment course. Patient demographics of those who received Tocilizumab include a mean age of 58 years with 73% male, 51% with diabetes, and 58% with hypertension. 4/55 (7.3%) were immunocompromised. Common presenting symptoms on admission were fever (62%), cough (78%) and dyspnea (89%). 35/55 (64%) were admitted to the ICU during their hospitalization;their mean P/F ratio was 127. Tocilizumab was administered on average admission day 4 (1-19). A second dose was given to 17 (31%) of patients, with 11 given the following day. Average hospital length of stay (LOS) postadministration was 17 days. Average white blood cell (WBC) count on day of Tocilizumab administration was 11, with an absolute lymphocyte count of 0.96. Mean IL-6 on hospital admission was 48.3. Two days post Tocilizumab administration there was a peak in ferritin, percent eosinophils, and AST. Both two-and five-day post-Tocilizumab CRP levels decreased while D-Dimer increased (Table 1). All Tocilizumab patients received antibiotics. In addition, three received hydroxychloroquine, 16 Remdesivir, and 51 convalescent plasma. 31 (56%) received steroids. On Day 2, those who did not receive steroids had, on average, more than double the percent of eosinophils in their blood (3.21% vs 1.53%). This difference decreased by Day 5. In time period of interest, COVID-19 admission mortality was 63/589 (10.6%) and 40/77 (52%) for mechanically ventilated patients. For Tocilizumab recipients, 25/55 patients were mechanically ventilated and 12/25 (48%) died. Overall, 28-day mortality was 11/55 (20%), with hospital mortality up to 16/55 (29%). This was similar to our larger cohort ICU mortality of 29.3%. Conclusion: Tocilizumab recipients in our cohort had a mortality similar to overall COVID ICU mortality. It appeared to be well tolerated except for an increase in eosinophilia if with no concomitant steroid use.
{"title":"Tocilizumab Administration for COVID-19 Pneumonia: A Single Center Experience Description","authors":"G. Palmer, N. Meyer, F. Jamous","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2553","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2553","url":null,"abstract":"Rationale: We aim to describe the clinical characteristics and outcomes of patients who received Tocilizumab for COVID-19 pneumonia at our institution between March 20 and October 26, 2020. Methods: In this single center, retrospective, observational study, we identified 55 adults admitted with COVID-19 pneumonia who received Tocilizumab. Demographic data, symptoms, laboratory values, treatments, and clinical outcomes were collected. Data was compared between those who received Tocilizumab and all patients admitted with COVID-19. Primary outcome was 28-day mortality. Secondary outcomes included role of concomitant steroid use and change in eosinophil counts, ferritin, AST, CRP and D-Dimer values. Results: Of the 589 patients admitted with COVID-19 pneumonia, 55 received Tocilizumab as part of their treatment course. Patient demographics of those who received Tocilizumab include a mean age of 58 years with 73% male, 51% with diabetes, and 58% with hypertension. 4/55 (7.3%) were immunocompromised. Common presenting symptoms on admission were fever (62%), cough (78%) and dyspnea (89%). 35/55 (64%) were admitted to the ICU during their hospitalization;their mean P/F ratio was 127. Tocilizumab was administered on average admission day 4 (1-19). A second dose was given to 17 (31%) of patients, with 11 given the following day. Average hospital length of stay (LOS) postadministration was 17 days. Average white blood cell (WBC) count on day of Tocilizumab administration was 11, with an absolute lymphocyte count of 0.96. Mean IL-6 on hospital admission was 48.3. Two days post Tocilizumab administration there was a peak in ferritin, percent eosinophils, and AST. Both two-and five-day post-Tocilizumab CRP levels decreased while D-Dimer increased (Table 1). All Tocilizumab patients received antibiotics. In addition, three received hydroxychloroquine, 16 Remdesivir, and 51 convalescent plasma. 31 (56%) received steroids. On Day 2, those who did not receive steroids had, on average, more than double the percent of eosinophils in their blood (3.21% vs 1.53%). This difference decreased by Day 5. In time period of interest, COVID-19 admission mortality was 63/589 (10.6%) and 40/77 (52%) for mechanically ventilated patients. For Tocilizumab recipients, 25/55 patients were mechanically ventilated and 12/25 (48%) died. Overall, 28-day mortality was 11/55 (20%), with hospital mortality up to 16/55 (29%). This was similar to our larger cohort ICU mortality of 29.3%. Conclusion: Tocilizumab recipients in our cohort had a mortality similar to overall COVID ICU mortality. It appeared to be well tolerated except for an increase in eosinophilia if with no concomitant steroid use.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127887539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2535
M. Stutz, A. Leonhard, S. Pearson, C. Ward, P. Osorio, P. Herbst, K. Wolfe, A. Pohlman, J.B. Hall, B. Patel, J. Kress
Rationale:Early mobilization and physical rehabilitation improve functional outcomes and are essential to high quality critical care. Despite its importance, it is common for rehabilitation to be deferred in the critically ill due to a variety of barriers, including infection with SARS-CoV-2. We present a single academic center's experience providing physical and occupational therapy to critically ill patients infected with SARS-CoV-2. Methods:All patients with Coronavirus Disease 2019 (COVID-19) associated illness admitted to the intensive care unit (ICU) from March 1st to July 31st, 2020 were identified in this retrospective chart review. Patients who received at least one therapy treatment session were included in the study. Results:Three-hundred and seventy-nine physical and occupational therapy sessions were conducted with 116 patients. The majority (85%) of patients were admitted to the ICU for hypoxemic respiratory failure. The median number of treatment sessions during ICU admission per patient was 2, (IQR: 1-4). The median time from ICU admission to first PT session was 4 days (IQR, 3-5). The median percentage of ICU days with physical and occupational therapy treatment was 33% (IQR, 21-50). The median session length was 25 minutes (IQR, 25-30min). Sitting was achieved in 353 sessions, (93%) standing was achieved in 261 sessions (69%), walking was achieved in 185 sessions (48%), and sitting in the bedside chair 118 times (31%).Patients with respiratory failure completed therapy sessions while receiving mechanical ventilation (21% of sessions), high flow nasal cannula (45% of sessions), non-invasive positive pressure ventilation by helmet and facemask (7% of sessions), and ECMO (12% of sessions). Patients requiring vasoactive medications (4%) and continuous renal replacement therapy (6%) were also treated by physical and occupational therapy. Delirium, determined by confusion assessment method (CAM-ICU), was frequently encountered by the physical and occupational therapy teams and was not an absolute barrier (32%) (Table 1). Discharge destinations included: home (n=57, 61%), acute rehabilitation units (n=16, 17%), long term acute care hospitals (n=9, 10%), sub-acute care centers (n=8, 8%), and skilled nursing facilities (n=4, 4%). No members of the therapy team were diagnosed with SARS-CoV-2 during the study period. Conclusions:This report demonstrates the feasibility of conducting physical and occupational therapy in COVID-19 specific ICUs. Providing therapy services appeared to be safe for patients and members of the therapy team, as adverse events were rare and no therapist was diagnosed with COVID-19.
{"title":"Feasibility of Physical and Occupational Therapy in Critically Ill Patients with COVID-19 Infection","authors":"M. Stutz, A. Leonhard, S. Pearson, C. Ward, P. Osorio, P. Herbst, K. Wolfe, A. Pohlman, J.B. Hall, B. Patel, J. Kress","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2535","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2535","url":null,"abstract":"Rationale:Early mobilization and physical rehabilitation improve functional outcomes and are essential to high quality critical care. Despite its importance, it is common for rehabilitation to be deferred in the critically ill due to a variety of barriers, including infection with SARS-CoV-2. We present a single academic center's experience providing physical and occupational therapy to critically ill patients infected with SARS-CoV-2. Methods:All patients with Coronavirus Disease 2019 (COVID-19) associated illness admitted to the intensive care unit (ICU) from March 1st to July 31st, 2020 were identified in this retrospective chart review. Patients who received at least one therapy treatment session were included in the study. Results:Three-hundred and seventy-nine physical and occupational therapy sessions were conducted with 116 patients. The majority (85%) of patients were admitted to the ICU for hypoxemic respiratory failure. The median number of treatment sessions during ICU admission per patient was 2, (IQR: 1-4). The median time from ICU admission to first PT session was 4 days (IQR, 3-5). The median percentage of ICU days with physical and occupational therapy treatment was 33% (IQR, 21-50). The median session length was 25 minutes (IQR, 25-30min). Sitting was achieved in 353 sessions, (93%) standing was achieved in 261 sessions (69%), walking was achieved in 185 sessions (48%), and sitting in the bedside chair 118 times (31%).Patients with respiratory failure completed therapy sessions while receiving mechanical ventilation (21% of sessions), high flow nasal cannula (45% of sessions), non-invasive positive pressure ventilation by helmet and facemask (7% of sessions), and ECMO (12% of sessions). Patients requiring vasoactive medications (4%) and continuous renal replacement therapy (6%) were also treated by physical and occupational therapy. Delirium, determined by confusion assessment method (CAM-ICU), was frequently encountered by the physical and occupational therapy teams and was not an absolute barrier (32%) (Table 1). Discharge destinations included: home (n=57, 61%), acute rehabilitation units (n=16, 17%), long term acute care hospitals (n=9, 10%), sub-acute care centers (n=8, 8%), and skilled nursing facilities (n=4, 4%). No members of the therapy team were diagnosed with SARS-CoV-2 during the study period. Conclusions:This report demonstrates the feasibility of conducting physical and occupational therapy in COVID-19 specific ICUs. Providing therapy services appeared to be safe for patients and members of the therapy team, as adverse events were rare and no therapist was diagnosed with COVID-19.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130184034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2530
L. Pinilla, I. Benítez, A. Carratalá, A. Moncusí-Moix, C. Gort-Paniello, M. Molinero, Jessica González, G. Torres, M. Bernal, S. Picó, Cristina Doncel, R. Almansa, N. Jorge, E. Bustamante, J. M. Gomez, M. Gonzalez-Rivera, D. Micheloud, P. Ryan, L. Tamayo, C. Aldecoa, R. Ferrer, A. Ceccato, L. Fernández, A. Motos, J. Riera, R. Menéndez, D. Garcia, Peñuelas, A. Torres, J. Bermejo-Martín, F. Barbé, D. Gonzalo-Calvo
RATIONALE: The identification of minimally invasive and easily-accessible biomarkers to support the management of coronavirus disease 2019 (COVID-19) in hospitalized patients constitutes a hot topic in clinical research. MicroRNAs (miRNAs) have been proposed as clinical indicators to assist in medical decision-making. Here, we aimed to examine the circulating miRNA profile of hospitalized COVID-19 patients and to evaluate its potential as a source of biomarkers for the management of the disease. METHODS: Observational, prospective and multicenter study which included 84 patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, recruited during the first pandemic wave in Spain (March-May 2020). Patients were stratified according to disease severity: hospitalized patients admitted to the clinical wards without requiring critical care (n = 47) and hospitalized patients admitted to the ICU (n = 37). An additional study considering ICU non-survivors (n=17) and survivors (n = 20) was performed. Expression profiling of 41 miRNAs was performed in plasma samples using RT-qPCR. The panel included miRNAs associated with: i) immune/inflammatory response;ii) lung damage;iii) respiratory viral infections;iv) myocardial damage;v) coagulation. Quality control was performed using spike-ins and hemolysis tests. Predictive models were constructed using a variable selection process based on LASSO regression. RESULTS: Ten circulating miRNAs were deregulated in ICU compared to ward patients. LASSO analysis identified a signature of three miRNAs that displayed an optimal discrimination ability to distinguish between ICU and ward patients (AUC = 0.88) (Figure 1A). Among ICU patients, six miRNAs were downregulated when comparing nonsurvivors to survivors. A signature based on two miRNAs was found to be a relevant predictor of mortality during ICU stay (AUC = 0.84) (Figure 1B). The discrimination potential of the miRNA signature was higher than the observed for clinical laboratory parameters such as leukocyte counts (including neutrophil count, lymphocyte count and the neutrophil-tolymphocyte ratio), CRP or D-dimer (maximum AUC for these variables = 0.76). CONCLUSIONS: The severity of COVID-19 impacts on the circulating miRNA profile. The results suggest the potential usefulness of the circulating miRNA signature for the management of the disease over contemporaneous tests, at least in ICU patients.
{"title":"Circulating microRNAs as Biomarkers of COVID-19 Severity","authors":"L. Pinilla, I. Benítez, A. Carratalá, A. Moncusí-Moix, C. Gort-Paniello, M. Molinero, Jessica González, G. Torres, M. Bernal, S. Picó, Cristina Doncel, R. Almansa, N. Jorge, E. Bustamante, J. M. Gomez, M. Gonzalez-Rivera, D. Micheloud, P. Ryan, L. Tamayo, C. Aldecoa, R. Ferrer, A. Ceccato, L. Fernández, A. Motos, J. Riera, R. Menéndez, D. Garcia, Peñuelas, A. Torres, J. Bermejo-Martín, F. Barbé, D. Gonzalo-Calvo","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2530","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2530","url":null,"abstract":"RATIONALE: The identification of minimally invasive and easily-accessible biomarkers to support the management of coronavirus disease 2019 (COVID-19) in hospitalized patients constitutes a hot topic in clinical research. MicroRNAs (miRNAs) have been proposed as clinical indicators to assist in medical decision-making. Here, we aimed to examine the circulating miRNA profile of hospitalized COVID-19 patients and to evaluate its potential as a source of biomarkers for the management of the disease. METHODS: Observational, prospective and multicenter study which included 84 patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, recruited during the first pandemic wave in Spain (March-May 2020). Patients were stratified according to disease severity: hospitalized patients admitted to the clinical wards without requiring critical care (n = 47) and hospitalized patients admitted to the ICU (n = 37). An additional study considering ICU non-survivors (n=17) and survivors (n = 20) was performed. Expression profiling of 41 miRNAs was performed in plasma samples using RT-qPCR. The panel included miRNAs associated with: i) immune/inflammatory response;ii) lung damage;iii) respiratory viral infections;iv) myocardial damage;v) coagulation. Quality control was performed using spike-ins and hemolysis tests. Predictive models were constructed using a variable selection process based on LASSO regression. RESULTS: Ten circulating miRNAs were deregulated in ICU compared to ward patients. LASSO analysis identified a signature of three miRNAs that displayed an optimal discrimination ability to distinguish between ICU and ward patients (AUC = 0.88) (Figure 1A). Among ICU patients, six miRNAs were downregulated when comparing nonsurvivors to survivors. A signature based on two miRNAs was found to be a relevant predictor of mortality during ICU stay (AUC = 0.84) (Figure 1B). The discrimination potential of the miRNA signature was higher than the observed for clinical laboratory parameters such as leukocyte counts (including neutrophil count, lymphocyte count and the neutrophil-tolymphocyte ratio), CRP or D-dimer (maximum AUC for these variables = 0.76). CONCLUSIONS: The severity of COVID-19 impacts on the circulating miRNA profile. The results suggest the potential usefulness of the circulating miRNA signature for the management of the disease over contemporaneous tests, at least in ICU patients.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128753779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2534
Aartik Sarma, S. Christenson, E. Mick, Catherine DeVoe, Thomas J Deiss, A. Pisco, R. Ghale, A. Byrne, Farzad Moazed, N. Spottiswoode, P. Sinha, B. Zha, P. Serpa, K. Ansel, Jennifer G. Wilson, A. Leligdowicz, E. Siegel, M. Sirota, J. Derisi, A. Jauregui, M. Matthay, C. Hendrickson, K. Kangelaris, M. Krummel, P. Woodruff, D. Erle, C. Calfee, C. Langelier
Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a rapid increase in the incidence of acute respiratory distress syndrome (ARDS). The distinct features of pulmonary biology in COVID-19 ARDS compared to other causes of ARDS, including other lower respiratory tract infections (LRTIs), are not well understood. Methods: Tracheal aspirates (TA) and plasma were collected within five days of intubation from mechanically ventilated adults admitted to one of two academic medical centers. ARDS and LRTI diagnoses and were verified by study physicians. Subjects were excluded if they received immunosuppression. TA from subjects with COVID-ARDS was compared to gene expression in TA from subjects with other causes of ARDS (OtherARDS) or mechanically ventilated control subjects without evidence of pulmonary pathology (NoARDS). Plasma concentrations of IL-6, IL-8, and protein C also were compared between these groups. Upstream regulator and pathway analysis was performed on significantly differentially expressed genes with Ingenuity Pathway Analysis (IPA). Subgroup analyses were performed to compare gene expression in COVID to ARDS associated with other viral LRTIs and bacterial LRTIs. The association of interferon-stimulated gene expression with SARS-CoV2 viral load was compared to the same association in nasopharyngeal swabs in a cohort of subjects with mild SARS-CoV2. Results: TA sequencing was available from 15 subjects with COVID, 32 subjects with other causes of ARDS (OtherARDS), and 5 mechanically ventilated subjects without evidence of pulmonary pathology (NoARDS). 696 genes were differentially expressed between COVID and OtherARDS (Figure 1A). IL-6, IL-8, B-cell receptor, and hypoxia inducible factor-1a signaling were attenuated in COVID compared to OtherARDS. Peroxisome proliferator-activated receptor (PPAR) and PTEN signaling were higher in COVID compared to OtherARDS (Figure 1B). Plasma levels of IL-6, IL-8, and protein C were not significantly different between COVID and OtherARDS. In subgroup analyses, IL-8 signaling was higher in COVID compared to viral LRTI, but lower than bacterial LRTI. Type I/III interferon was higher in COVID compared to bacterial ARDS, but lower compared to viral ARDS (Figure 1C). Compared to nasopharyngeal swabs from subjects with mild COVID-19, expression of several interferon stimulated genes was less strongly correlated with SARS-CoV2 viral load in TA (Figure 1D). IPA identified several candidate medications to treat COVID-19, including dexamethasone, G-CSF, and etanercept. Conclusions: TA sequencing identifies unique features of the host response in COVID-19. These differentially expressed pathways may represent potential therapeutic targets. An impaired interferon response in the lung may increase susceptibility to severe SARS-COV2.
{"title":"Tracheal Aspirate Sequencing Identifies Unique Features of Dysregulated Host Response in SARS-CoV2 Associated Acute Respiratory Distress Syndrome","authors":"Aartik Sarma, S. Christenson, E. Mick, Catherine DeVoe, Thomas J Deiss, A. Pisco, R. Ghale, A. Byrne, Farzad Moazed, N. Spottiswoode, P. Sinha, B. Zha, P. Serpa, K. Ansel, Jennifer G. Wilson, A. Leligdowicz, E. Siegel, M. Sirota, J. Derisi, A. Jauregui, M. Matthay, C. Hendrickson, K. Kangelaris, M. Krummel, P. Woodruff, D. Erle, C. Calfee, C. Langelier","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2534","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2534","url":null,"abstract":"Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a rapid increase in the incidence of acute respiratory distress syndrome (ARDS). The distinct features of pulmonary biology in COVID-19 ARDS compared to other causes of ARDS, including other lower respiratory tract infections (LRTIs), are not well understood. Methods: Tracheal aspirates (TA) and plasma were collected within five days of intubation from mechanically ventilated adults admitted to one of two academic medical centers. ARDS and LRTI diagnoses and were verified by study physicians. Subjects were excluded if they received immunosuppression. TA from subjects with COVID-ARDS was compared to gene expression in TA from subjects with other causes of ARDS (OtherARDS) or mechanically ventilated control subjects without evidence of pulmonary pathology (NoARDS). Plasma concentrations of IL-6, IL-8, and protein C also were compared between these groups. Upstream regulator and pathway analysis was performed on significantly differentially expressed genes with Ingenuity Pathway Analysis (IPA). Subgroup analyses were performed to compare gene expression in COVID to ARDS associated with other viral LRTIs and bacterial LRTIs. The association of interferon-stimulated gene expression with SARS-CoV2 viral load was compared to the same association in nasopharyngeal swabs in a cohort of subjects with mild SARS-CoV2. Results: TA sequencing was available from 15 subjects with COVID, 32 subjects with other causes of ARDS (OtherARDS), and 5 mechanically ventilated subjects without evidence of pulmonary pathology (NoARDS). 696 genes were differentially expressed between COVID and OtherARDS (Figure 1A). IL-6, IL-8, B-cell receptor, and hypoxia inducible factor-1a signaling were attenuated in COVID compared to OtherARDS. Peroxisome proliferator-activated receptor (PPAR) and PTEN signaling were higher in COVID compared to OtherARDS (Figure 1B). Plasma levels of IL-6, IL-8, and protein C were not significantly different between COVID and OtherARDS. In subgroup analyses, IL-8 signaling was higher in COVID compared to viral LRTI, but lower than bacterial LRTI. Type I/III interferon was higher in COVID compared to bacterial ARDS, but lower compared to viral ARDS (Figure 1C). Compared to nasopharyngeal swabs from subjects with mild COVID-19, expression of several interferon stimulated genes was less strongly correlated with SARS-CoV2 viral load in TA (Figure 1D). IPA identified several candidate medications to treat COVID-19, including dexamethasone, G-CSF, and etanercept. Conclusions: TA sequencing identifies unique features of the host response in COVID-19. These differentially expressed pathways may represent potential therapeutic targets. An impaired interferon response in the lung may increase susceptibility to severe SARS-COV2.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127498790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2538
D. Furfaro, M. Cummings, D. Abrams, J. Fountain, A. B. Thompson, L. G. Merchan, M. Murn, A. Rosen, J. Beitler, D. Brodie, M. O’Donnell
Rationale: Higher levels of circulating interleukin-6 (IL-6) and lower respiratory system compliance have each been associated with increased mortality in severe coronavirus 2019 (COVID-19). IL-6 levels are associated with disease severity and mortality in non-COVID-19-related acute respiratory distress syndrome (ARDS). The purpose of this study was to examine the relationship between IL-6 and respiratory mechanics in COVID-19-related ARDS. Methods: This retrospective cohort study took place at two Columbia University Irving Medical Center hospitals. We identified patients age >18 years with laboratory confirmed COVID-19, who were intubated from March 1st through April 30th, 2020, and met the Berlin definition of ARDS. Electronic medical records were reviewed for clinical data. Outcomes were censored at 90 days after intubation. For patients without IL-6 levels recorded on the initial day of intubation, serum samples were obtained from the Columbia University Biobank and tested using the Quantikine Human IL-6 Immunoassay. IL-6 values were log-transformed. The primary outcome was respiratory system compliance. Secondary outcomes were calculated ventilatory ratio, PaO2:FiO2 ratio, and mortality. Linear regression and logistic regression were used for statistical analyses. Results: During the study period, 483 patients had COVID-19-associated ARDS. Median time of follow up was 37 days (IQR 11-90). At 90 days, 260 (53.8%) patients were deceased, 206 (42.7%) had been discharged, and 17 (3.5%) were still admitted. Two hundred sixteen (44.7%) patients had available data on respiratory system compliance and serum IL-6 levels from the initial day of mechanical ventilation. The median IL-6 value was 204.1 pg/ml (IQR 110-469.7). Median compliance was 25.5 ml/cmH2O (IQR 21.4-33.3), median ventilatory ratio was 1.96 (IQR 1.51-2.57), and median PaO2:FiO2 ratio was 134 (IQR 87-196). In unadjusted linear regression, higher IL-6 was associated with lower respiratory system compliance (log [IL-6] coefficient-1.80, p = 0.001) (Figure 1). This relationship remained significant when adjusting for age, sex, body mass index, race, ethnicity, and Sequential Organ Failure Assessment (SOFA) score (coefficient-2.43, p<0.001). There was no significant association between IL-6 and ventilatory ratio (0.76 p=0.08) or PaO2:FiO2 ratio (-6.15 p=0.06). Higher IL-6 was associated with higher odds of death at 90 days (OR 1.35 per unit increase in log [IL-6], p-value 0.022) when adjusting for age, sex, body mass index, race, ethnicity, and SOFA score. Conclusion: In COVID-19-associated ARDS, higher levels of IL-6 were associated with lower respiratory system compliance even adjusting for measured confounders. Higher IL-6 was also associated with higher mortality.
{"title":"Interleukin-6 and Pulmonary Compliance in COVID-19-Related Acute Respiratory Distress Syndrome","authors":"D. Furfaro, M. Cummings, D. Abrams, J. Fountain, A. B. Thompson, L. G. Merchan, M. Murn, A. Rosen, J. Beitler, D. Brodie, M. O’Donnell","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2538","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2538","url":null,"abstract":"Rationale: Higher levels of circulating interleukin-6 (IL-6) and lower respiratory system compliance have each been associated with increased mortality in severe coronavirus 2019 (COVID-19). IL-6 levels are associated with disease severity and mortality in non-COVID-19-related acute respiratory distress syndrome (ARDS). The purpose of this study was to examine the relationship between IL-6 and respiratory mechanics in COVID-19-related ARDS. Methods: This retrospective cohort study took place at two Columbia University Irving Medical Center hospitals. We identified patients age >18 years with laboratory confirmed COVID-19, who were intubated from March 1st through April 30th, 2020, and met the Berlin definition of ARDS. Electronic medical records were reviewed for clinical data. Outcomes were censored at 90 days after intubation. For patients without IL-6 levels recorded on the initial day of intubation, serum samples were obtained from the Columbia University Biobank and tested using the Quantikine Human IL-6 Immunoassay. IL-6 values were log-transformed. The primary outcome was respiratory system compliance. Secondary outcomes were calculated ventilatory ratio, PaO2:FiO2 ratio, and mortality. Linear regression and logistic regression were used for statistical analyses. Results: During the study period, 483 patients had COVID-19-associated ARDS. Median time of follow up was 37 days (IQR 11-90). At 90 days, 260 (53.8%) patients were deceased, 206 (42.7%) had been discharged, and 17 (3.5%) were still admitted. Two hundred sixteen (44.7%) patients had available data on respiratory system compliance and serum IL-6 levels from the initial day of mechanical ventilation. The median IL-6 value was 204.1 pg/ml (IQR 110-469.7). Median compliance was 25.5 ml/cmH2O (IQR 21.4-33.3), median ventilatory ratio was 1.96 (IQR 1.51-2.57), and median PaO2:FiO2 ratio was 134 (IQR 87-196). In unadjusted linear regression, higher IL-6 was associated with lower respiratory system compliance (log [IL-6] coefficient-1.80, p = 0.001) (Figure 1). This relationship remained significant when adjusting for age, sex, body mass index, race, ethnicity, and Sequential Organ Failure Assessment (SOFA) score (coefficient-2.43, p<0.001). There was no significant association between IL-6 and ventilatory ratio (0.76 p=0.08) or PaO2:FiO2 ratio (-6.15 p=0.06). Higher IL-6 was associated with higher odds of death at 90 days (OR 1.35 per unit increase in log [IL-6], p-value 0.022) when adjusting for age, sex, body mass index, race, ethnicity, and SOFA score. Conclusion: In COVID-19-associated ARDS, higher levels of IL-6 were associated with lower respiratory system compliance even adjusting for measured confounders. Higher IL-6 was also associated with higher mortality.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127869143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2556
G. Singh, R. Crawford, J. Cunningham
Introduction-A significant number of intubated COVID-19 patients may develop worrisome hemorrhage related to trachea-bronchial mucosal and submucosal slough due to severe inflammation/necrosis related to COVID-19 pneumonia. The accumulation of debris in the endotracheal tube can progress to severe endotracheal tube obstruction ( ETO) necessitating high peak driving pressures with eventual loss of satisfactory ventilator volume delivery. Emergency endotracheal tube exchange under these circumstances can be an extremely high-risk undertaking both for the patient and caregivers. Method-Thirty mechanically ventilated COVID-19 patients deemed at high risk for ETO or who had already had a prior episodes of ETO were selected as candidates for bedside percutaneous tracheostomy. Those patients requiring high ventilator settings high ventilator ( i.e. FIO2 > 50 and PEEP more than 10 ) were also included in the study group. A disposable bronchoscope was utilized for direct visualization of appropriate tracheal puncture, guidewire passage, and final positioning of the tracheal tube. Results-All patients, including those individuals on high ventilator support attained the primary outcome of successful percutaneous tracheostomy without serous adverse events. Minor adverse events, such as brief periods of oxygen desaturation, were observed in 3 patients. Conclusion-Bedside percutaneous tracheostomy is a safe therapeutic option for patients with high risk for ETO due to trachea-bronchial mucosal and submucosal slough. Consideration for early, elective intervention may be justified due to high risks associated with urgent/emergency endotracheal tube exchange.
{"title":"Bedside Percutaneous Tracheostomy for Patients with COVID 19 with Endotracheal Obstruction","authors":"G. Singh, R. Crawford, J. Cunningham","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2556","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2556","url":null,"abstract":"Introduction-A significant number of intubated COVID-19 patients may develop worrisome hemorrhage related to trachea-bronchial mucosal and submucosal slough due to severe inflammation/necrosis related to COVID-19 pneumonia. The accumulation of debris in the endotracheal tube can progress to severe endotracheal tube obstruction ( ETO) necessitating high peak driving pressures with eventual loss of satisfactory ventilator volume delivery. Emergency endotracheal tube exchange under these circumstances can be an extremely high-risk undertaking both for the patient and caregivers. Method-Thirty mechanically ventilated COVID-19 patients deemed at high risk for ETO or who had already had a prior episodes of ETO were selected as candidates for bedside percutaneous tracheostomy. Those patients requiring high ventilator settings high ventilator ( i.e. FIO2 > 50 and PEEP more than 10 ) were also included in the study group. A disposable bronchoscope was utilized for direct visualization of appropriate tracheal puncture, guidewire passage, and final positioning of the tracheal tube. Results-All patients, including those individuals on high ventilator support attained the primary outcome of successful percutaneous tracheostomy without serous adverse events. Minor adverse events, such as brief periods of oxygen desaturation, were observed in 3 patients. Conclusion-Bedside percutaneous tracheostomy is a safe therapeutic option for patients with high risk for ETO due to trachea-bronchial mucosal and submucosal slough. Consideration for early, elective intervention may be justified due to high risks associated with urgent/emergency endotracheal tube exchange.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126500596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2532
C. Cosgriff, H. Giannini, D. Mathew, B. J. Anderson, T. Jones, C. Ittner, A. Weisman, A. Baxter, L. Kuri-Cervantes, M. Pampena, K. D’Andrea, R. Agyekum, T. Dunn, J. Reilly, M. Betts, E. Wherry, M. Shashaty, N. Meyer
Rationale: To utilize high-dimensional proteomic data to identify dysregulated pathways that are associated with COVID-19 disease severity and suggest potential therapeutic targets. Methods: We enrolled 161 COVID-19 inpatients admitted at two tertiary care hospitals. Plasma samples collected within 48 hours of admission were analyzed with the Olink Proximity Extension Assay;713 unique proteins were assayed. The WHO COVID-19 ordinal severity scale at enrollment was dichotomized into moderate (levels 3-4) and severe (levels 5-7). Normalized protein expression (NPX) values were generated in relation to a common pooled control plasma on each plate. The association between NPX values and disease severity on admission was estimated with logistic regression (LR) after adjustment for age, sex, race, and select comorbidities. Ingenuity Pathway Analysis (IPA) was employed after application of the Benjamini-Hochberg procedure with a false discovery rate of 5% to all proteins for which the NPX difference was +/-0.8 between groups. Predictive models of disease severity on hospital day 7 using all proteins as potential features were fit using elastic net LR (ENLR) and gradient boosting (GBM). Performance was estimated on a held-out test set (40% of the data) with area under the receiveroperator characteristic curve (AUROC). Results: Of 161 subjects, 85 (53%) were classified as having severe COVID-19. A total of 552 proteins were differentially expressed (Figure 1), and 31 of these proteins met criteria for inclusion in pathway analysis. IPA identified the triggering receptor expressed on myeloid cells 1 (TREM-1) signaling pathway (4 members, p=3.8E-3), the tumor microenvironment (TME) pathway (5 members, p=4.1E-3), and the interleukin 17 (IL-17) signaling pathway (4 members, p=1.8E-2). Interleukin 1 receptor-like 1, a member of the TREM-1 pathway, was the protein most associated with disease severity (OR=3.18, p=1.82E-08). Tumor necrosis factor ligand superfamily member 11 (TNFSF11), a member of the IL-17 signaling pathway was the only factor whose enrichment was associated with less severe disease (OR=0.39, p=2.3E-05). ENLR and GBM predicted disease severity on day 7 with AUROC values of 0.908 (0.828, 0.968) and 0.882 (0.788, 0.957), respectively. Conclusion: We identified pathways differentially expressed between patients with severe and nonsevere COVID-19 associated with immune function and angiogenesis. Several agents currently being investigated to treat severe COVID-19 act on these dysregulated pathways, and future investigations could test whether these proteins act as enrichment markers or response indicators. Integrating protein expression with cellular immune phenotype may help explain COVID-19 pathophysiology.
{"title":"Proteomic Analysis of COVID-19 Plasma Reveals Dysregulated TREM-1, I-17, and Tumor Microenvironment Pathways Associated with Disease Severity","authors":"C. Cosgriff, H. Giannini, D. Mathew, B. J. Anderson, T. Jones, C. Ittner, A. Weisman, A. Baxter, L. Kuri-Cervantes, M. Pampena, K. D’Andrea, R. Agyekum, T. Dunn, J. Reilly, M. Betts, E. Wherry, M. Shashaty, N. Meyer","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2532","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2532","url":null,"abstract":"Rationale: To utilize high-dimensional proteomic data to identify dysregulated pathways that are associated with COVID-19 disease severity and suggest potential therapeutic targets. Methods: We enrolled 161 COVID-19 inpatients admitted at two tertiary care hospitals. Plasma samples collected within 48 hours of admission were analyzed with the Olink Proximity Extension Assay;713 unique proteins were assayed. The WHO COVID-19 ordinal severity scale at enrollment was dichotomized into moderate (levels 3-4) and severe (levels 5-7). Normalized protein expression (NPX) values were generated in relation to a common pooled control plasma on each plate. The association between NPX values and disease severity on admission was estimated with logistic regression (LR) after adjustment for age, sex, race, and select comorbidities. Ingenuity Pathway Analysis (IPA) was employed after application of the Benjamini-Hochberg procedure with a false discovery rate of 5% to all proteins for which the NPX difference was +/-0.8 between groups. Predictive models of disease severity on hospital day 7 using all proteins as potential features were fit using elastic net LR (ENLR) and gradient boosting (GBM). Performance was estimated on a held-out test set (40% of the data) with area under the receiveroperator characteristic curve (AUROC). Results: Of 161 subjects, 85 (53%) were classified as having severe COVID-19. A total of 552 proteins were differentially expressed (Figure 1), and 31 of these proteins met criteria for inclusion in pathway analysis. IPA identified the triggering receptor expressed on myeloid cells 1 (TREM-1) signaling pathway (4 members, p=3.8E-3), the tumor microenvironment (TME) pathway (5 members, p=4.1E-3), and the interleukin 17 (IL-17) signaling pathway (4 members, p=1.8E-2). Interleukin 1 receptor-like 1, a member of the TREM-1 pathway, was the protein most associated with disease severity (OR=3.18, p=1.82E-08). Tumor necrosis factor ligand superfamily member 11 (TNFSF11), a member of the IL-17 signaling pathway was the only factor whose enrichment was associated with less severe disease (OR=0.39, p=2.3E-05). ENLR and GBM predicted disease severity on day 7 with AUROC values of 0.908 (0.828, 0.968) and 0.882 (0.788, 0.957), respectively. Conclusion: We identified pathways differentially expressed between patients with severe and nonsevere COVID-19 associated with immune function and angiogenesis. Several agents currently being investigated to treat severe COVID-19 act on these dysregulated pathways, and future investigations could test whether these proteins act as enrichment markers or response indicators. Integrating protein expression with cellular immune phenotype may help explain COVID-19 pathophysiology.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126066463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2544
M. Davila-Molina, K. Johnson, R. Durrance, D. Papademetriou, P. Ram, A. Mizoue, N. Shah, T. Sidhu, R. Elshafey, A. Astua
RATIONALE COVID-19 infection has affected 5 million lives, resulting in over 300,000 deaths worldwide. Those with respiratory failure requiring mechanical ventilation (MV) make up less than 10% of individuals, but account for the majority of fatalities.(1) Exploring characteristics of those extubated, strategies for treatment and resource allocation can be potentially implemented. METHODS A retrospective review of the initial 33 adult patients positive for COVID19 admitted to EHC, with respiratory failure and extubated from 3/8/2020 to 5/8/2020 was performed. Clinical characteristics were evaluated descriptively. RESULTS Successfully extubated patients averaged 56 years of age, males made up 91% of the population. Average BMI was 28.2 and hemoglobin A1C was 6.26. The mean maximum creatinine was 4.39 and max procalcitonin was 26. Mean admission and maximum D-dimer levels were 5,349 and 12,450 respectively, while mean admission CRP was 204. The mean days on nasal cannula, non-rebreather and CPAP prior to intubation were 5, 4, and 3, respectively, with overall mean time to intubation of 11.9 days and average length of stay of 20.6 days. The mean minimum PaO2 was 57.7 (most often on 100% FiO2) and max mean PEEP was 12.7. Total sedation days and total pressors days were calculated giving each pressor or sedative used the equivalence of 1 to provide an estimate of sedative and pressor requirements. The mean number of pressor days was 9.8;with a mean number of sedative days as 28. Survival after extubation at time of analyses was (21/33) 63%. CONCLUSION These results signal that these initial extubated patients were quite hypoxic and ventilated with a low PEEP strategy deviating from those suggested by surviving sepsis guidelines. They were in a hyperinflammatory state with moderate renal failure and propensity for infection, however, perhaps the BMI, low A1C scores, relatively fast decline in D dimers and ventilation with low PEEP strategy allowed them to be mechanically liberated. Classifying patient demographics and disease severity early can help identify patients likely to achieve successful extubation. The duration of preintubation oxygen support, duration of intubation, ideal vent settings, and realistic sedative requirements should be explored to optimize successful MV and extubation strategies.
{"title":"Clinical Characteristics of Initial Patients Successfully Extubated After Respiratory Failure Secondary to COVID-19 at Elmhurst Hospital Center (EHC)","authors":"M. Davila-Molina, K. Johnson, R. Durrance, D. Papademetriou, P. Ram, A. Mizoue, N. Shah, T. Sidhu, R. Elshafey, A. Astua","doi":"10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2544","DOIUrl":"https://doi.org/10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2544","url":null,"abstract":"RATIONALE COVID-19 infection has affected 5 million lives, resulting in over 300,000 deaths worldwide. Those with respiratory failure requiring mechanical ventilation (MV) make up less than 10% of individuals, but account for the majority of fatalities.(1) Exploring characteristics of those extubated, strategies for treatment and resource allocation can be potentially implemented. METHODS A retrospective review of the initial 33 adult patients positive for COVID19 admitted to EHC, with respiratory failure and extubated from 3/8/2020 to 5/8/2020 was performed. Clinical characteristics were evaluated descriptively. RESULTS Successfully extubated patients averaged 56 years of age, males made up 91% of the population. Average BMI was 28.2 and hemoglobin A1C was 6.26. The mean maximum creatinine was 4.39 and max procalcitonin was 26. Mean admission and maximum D-dimer levels were 5,349 and 12,450 respectively, while mean admission CRP was 204. The mean days on nasal cannula, non-rebreather and CPAP prior to intubation were 5, 4, and 3, respectively, with overall mean time to intubation of 11.9 days and average length of stay of 20.6 days. The mean minimum PaO2 was 57.7 (most often on 100% FiO2) and max mean PEEP was 12.7. Total sedation days and total pressors days were calculated giving each pressor or sedative used the equivalence of 1 to provide an estimate of sedative and pressor requirements. The mean number of pressor days was 9.8;with a mean number of sedative days as 28. Survival after extubation at time of analyses was (21/33) 63%. CONCLUSION These results signal that these initial extubated patients were quite hypoxic and ventilated with a low PEEP strategy deviating from those suggested by surviving sepsis guidelines. They were in a hyperinflammatory state with moderate renal failure and propensity for infection, however, perhaps the BMI, low A1C scores, relatively fast decline in D dimers and ventilation with low PEEP strategy allowed them to be mechanically liberated. Classifying patient demographics and disease severity early can help identify patients likely to achieve successful extubation. The duration of preintubation oxygen support, duration of intubation, ideal vent settings, and realistic sedative requirements should be explored to optimize successful MV and extubation strategies.","PeriodicalId":111156,"journal":{"name":"TP49. TP049 COVID: ARDS AND ICU MANAGEMENT","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134357334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-01DOI: 10.1164/AJRCCM-CONFERENCE.2021.203.1_MEETINGABSTRACTS.A2528
L. Mabrey, E. Morrell, P. Bhatraju, S. Sahi, S. Sakr, T. West, C. Mikacenic, M. Wurfel
Intro: Early innate immune responses are hypothesized to impact inflammation and therefore severity of disease and organ injury in COVID-19. Prior work in sepsis has identified CD14 as a marker of innate immune responses to bacterial infection and emerging evidence has implicated CD14 in COVID-19. CD14 exists in membrane bound and soluble (sCD14) form. A soluble N-terminal fragment of sCD14, sCD14 subtype (sCD14-ST, “Presepsin”) has been shown to have utility in diagnosis of sepsis and prognosis of associated organ failure and death. Goal: To determine the relationship between plasma sCD14 and sCD14-ST levels, COVID-19 status, and COVID-19 related outcomes in a cohort of prospectively enrolled critically ill patients admitted under suspicion for COVID-19. Methods: Critically ill patients under investigation for COVID-19 were prospectively enrolled between April 2020 and November 2020 at three hospitals affiliated with University of Washington. We ascertained COVID-19 status by SARS-CoV-2 RT-PCR upon admission. We measured plasma sCD14 and sCD14-ST levels in samples collected within 24 hours of admission. We tested for associations between biomarker levels and COVID-19 status using logistic regression adjusting for age, sex and APACHE III. In patients with COVID-19, we tested for associations between biomarker levels and disease severity and clinical outcomes using regression analyses adjusting for age, sex and APACHE III. Results: The cohort (n=222) mean age was 55 years, it was predominantly male (66%), in hospital mortality was 26%, and 50% of patients were positive by SARS-CoV-2 RT-PCR. Patients with COVID-19 had lower APACHE III scores (p: 0.013) than non-COVID-19. SCD14-ST levels were inversely associated with risk of SARS-CoV-2 positivity in multivariate regression (OR: 0.70, 95% CI: 0.57-0.84). Among patients with COVID-19, sCD14-ST levels were associated with higher APACHE III scores (beta: 7.3, 95% CI: 4.1-11), lower ventilatorfree days (beta:-1.6, 95% CI:-3.2 to-0.05) and higher risk for AKI (OR: 1.6, 95% CI: 1.0 to 2.7). SCD14-ST levels were not associated with these clinical outcomes in non-COVID-19 controls. In contrast to sCD14-ST levels, sCD14 levels did not differ between COVID-19 and non-COVID-19 patients and were not associated with COVID-19 clinical outcomes. Conclusions: In critically ill patients, sCD14-ST levels are inversely associated with risk of COVID-19 and positively associated with severity of disease and clinical outcomes among patients with COVID-19 while sCD14 levels were not associated with COVID-19 status or related outcomes. Early measurements of sCD14-ST levels could have prognostic utility in COVID-19.
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