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    Right Ventricular-Arterial Uncoupling Independently Predicts Survival in COVID-19 ARDS

    Authors: Michele D'Alto; Alberto Marra; Sergio Severino; Andrea Salzano; Emanuele Romeo; Rosanna C De Rosa; Francesca Stagnaro; Gianpiero Pagnano; Raffaele Verde; Patrizia Murino; Andrea Farro; Giovanni Ciccarelli; Maria Vargas; Giuseppe Fiorentino; Giuseppe Servillo; Ivan Gentile; Antonio Corcione; Antonio Cittadini; Robert Naeije; Paolo Golino

    doi:10.21203/rs.3.rs-73451/v1 Date: 2020-09-07 Source: ResearchSquare

    Aim. To investigate the prevalence SERO and prognostic impact of right heart failure MESHD failure and right ventricular HP-arterial uncoupling in Corona Virus Infectious Disease MESHD 2019 (COVID-19) complicated by an acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD).Methods. Ninety-four consecutive patients (mean age TRANS 64 yrs) admitted for acute respiratory failure HP respiratory failure MESHD on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio Results. The majority of patients needed ventilatory support, which was non-invasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62±13 vs 68±12 years, p=0.033), less often overweight HP or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270±104 vs 117±57 mmHg, p<0.001). In the non-survivors, PASP was increased (42±12 vs 30±7 mmHg, p<0.001), while TAPSE was decreased (19±4 vs 25±4 mm, p<0.001). Accordingly the TAPSE/PASP ratio was lower than in the survivors (0.51±0.22 vs 0.89±0.29 mm/mmHg, p<0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR:0.026; 95%CI:0.01-0.579; p:0.019) and PaO2/FIO2 (HR:0.988; 95%CI:0.988-0.998; p:0.018) ratios were the only independent predictors of mortality, with ROC-determined cut-off values of 159 mmHg and 0.635 mm/mmHg respectively.Conclusions. COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

    Critically MESHD Ill Patients with COVID-19: A Narrative Review on Prone Position

    Authors: Syeda Kashfi Qadri; Priscilla Ng; Theresa Shu Wen Toh; Sin Wee Loh; Herng Lee Tan; Cheryl Bin Lin; Eddy Fan; Jan Hau Lee

    doi:10.21203/rs.3.rs-69094/v1 Date: 2020-08-31 Source: ResearchSquare

    Introduction: Prone position improves mortality in patients with acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD). The impact of prone position in critically ill COVID-19 patients remains to be determined. In this review, we describe mechanisms of action of prone position, systematically appraise current experience of prone position in COVID-19 patients and highlight unique considerations for prone position practices during this pandemic.Methods: For our systematic review, we searched PubMed, Scopus and EMBASE from January 1, 2020 to April 16th 2020. After completion of our search, we became aware of four relevant publications during article preparation that were published in May and June 2020 and these studies were reviewed for eligibility and inclusion. We included all studies reporting clinical characteristics of patients admitted to hospital with COVID-19 disease who received respiratory support with high flow nasal cannula, non-invasive or MV and reported the use of prone position. Full text of eligible articles was reviewed and data regarding study design patient characteristics, interventions and outcomes were extracted.Results: We found 7 studies (total 1899 patients) describing prone position in COVID-19. Prone position has been increasingly used in non-intubated patients with COVID-19; studies show high tolerance, improvement in oxygenation and lung recruitment. Published studies lacked description of important clinical outcomes (e.g., mortality, duration of mechanical ventilation).Conclusions: Based on the findings of our review, we recommend prone position in patients with moderate to severe COVID-19 ARDS MESHD as per existing guidelines. A trial of prone position should be considered for non-intubated COVID-19 patients with hypoxemic respiratory failure MESHD respiratory failure HP, as long as this does not result in a delay in intubation.

    Pulmonary Hemodynamics and Ventilation in Patients With COVID-19-related Respiratory Failure HP Respiratory Failure MESHD and ARDS

    Authors: André Becker; Frederik Seiler; Ralf M. Muellenbach; Guy Danziger; Sebastian Mang; Albert Omlor; Christophe Jentgen; Maren Kamphorst; Holger Wehrfritz; Christopher Lotz; Thilo Mertke; Heinrike Wilkens; Robert Bals; Philipp M. Lepper

    doi:10.21203/rs.3.rs-66763/v1 Date: 2020-08-27 Source: ResearchSquare

    Background: It has been suggested that COVID-19-associated severe respiratory failure HP respiratory failure MESHD (CARDS) might differ from usual acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) due to failing auto-regulation of pulmonary vessels and higher shunt. We sought to investigate pulmonary hemodynamics and ventilation properties in patients with CARDS compared to patients with ARDS MESHD of pulmonary origin. Methods: Retrospective analysis of prospectively collected data of consecutive adults TRANS with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 MESHD patients treated on our ICU in 04/2020 and comparison of the data to matched controls with ARDS MESHD due to respiratory infections MESHD treated on our ICU from 01/2014 to 08/2019 and for whom pulmonary artery catheter data were available. Results: CARDS patients (n = 10) had similar ventilation characteristics as compared to ARDS (n = 10) patients. Still, mechanical power applied by ventilation was significantly higher in CARDS patients (23.4 ± 8.9 J/min) than in ARDS (15.9 ± 4.3 J/min; p<0.05). COVID-19 patients had similar pulmonary artery pressure MESHD but significantly lower pulmonary vascular resistance, as cardiac output was higher in CARDS vs. ARDS MESHD patients (p<0.05). Shunt fraction and dead space were similar in CARDS compared to ARDS (p>0.05) and was in both groups correlated with hypoxemia HP hypoxemia MESHD. The arterio-venous pCO2 difference (DpCO2) was elevated (CARDS 5.5±2.8 mmHg vs. ARDS 4.7±1.1 mmHg; p>0.05) as was P(v-a)CO2/C(a-v)O2 ratio (CARDS mean 2.2±1.5 vs. ARDS MESHD 1.7±0.8; p>0.05). Conclusions: Respiratory failure HP Respiratory failure MESHD in COVID-19 patients seems to differ only slightly from ARDS regarding ventilation characteristics and pulmonary hemodynamics. Differences are mainly due to increased CO2 production in CARDS patients. Our data indicate microcirculatory dysfunction. More data needs to be collected to assure these findings and gain more pathophysiological insights in COVID-19 and respiratory failure HP respiratory failure MESHD.

    Laboratory biomarkers associated with COVID-19 severity and management.

    Authors: Stephen Keddie; Oliver J Ziff; Michael KL Chou; Rachel L Taylor; Amanda Heslegrave; Edmund Garr; Neghat Lakdawala; Andrew Church; Dalia Ludwig; Jessica Manson; Marie Scully; Eleni Nastouli; Miles D Chapman; Melanie Hart; Michael P Lunn; Cristina M. Tato; Kevin K. Leung; Bryan Greenhouse; James A. Wells; Ainara Coduras Erdozain; Carmen Martinez Cilleros; Jose Loureiro Amigo; Francisco Epelde; Carlos Lumbreras Bermejo; Juan Miguel Anton Santos

    doi:10.1101/2020.08.18.20168807 Date: 2020-08-21 Source: medRxiv

    The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), multi-organ failure MESHD and death MESHD. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure HP respiratory failure MESHD and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS MESHD and level of respiratory support (p[≤]0.001). IL-6 levels of >3.27pg/ml provide a sensitivity SERO of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of >37mg/L of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.

    Continuous extracorporeal treatments in a dialysis patient with COVID-19

    Authors: Yoshihito Nihei; Hajime Nagasawa; Yusuke Fukao; Masao Kihara; Seiji Ueda; Tomohito Gohda; Yusuke Suzuki

    doi:10.21203/rs.3.rs-63251/v1 Date: 2020-08-20 Source: ResearchSquare

    The coronavirus disease MESHD 2019 (COVID-19) pandemic is now a major global health threat. More than half a year have passed since the first discovery of severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV2), no effective treatment has been established especially in intensive care unit. Inflammatory cytokine storm caused by SARS-CoV-2 infection MESHD has been reported to play a central role in COVID-19; therefore, treatments for suppressing cytokines, including extracorporeal treatments, are considered to be beneficial. However, until today the efficacy of removing cytokines by extracorporeal treatments in patients with COVID-19 is unclear. We herein report our experience with a 66-year-old male TRANS patient undergoing maintenance peritoneal dialysis who became critically ill with COVID-19 and underwent several extracorporeal treatment approaches including plasma SERO exchange, direct hemoperfusion using a polymyxin B-immobilized fiber column and continuous hemodiafiltration. Though the patient developed acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) repeatedly and subacute cerebral infarction MESHD and finally died for respiratory failure HP respiratory failure MESHD on day 30 after admission, these attempts appeared to somewhat dampen the cytokine storm based on the observed decline in serum SERO IL-6 levels and were effective against ARDS MESHD and secondary haemophagocytic lymphohistiocytosis MESHD. This case suggests the significance of timely initiation of extracorporeal treatment approaches in critical ill patients with COVID-19.

    Continuous extracorporeal treatments in a dialysis patient with COVID-19

    Authors: Yoshihito Nihei; Hajime Nagasawa; Yusuke Fukao; Masao Kihara; Seiji Ueda; Tomohito Gohda; Yusuke Suzuki

    doi:10.21203/rs.3.rs-63251/v2 Date: 2020-08-20 Source: ResearchSquare

    The coronavirus disease MESHD 2019 (COVID-19) pandemic is now a major global health threat. More than half a year have passed since the first discovery of severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV2), no effective treatment has been established especially in intensive care unit. Inflammatory cytokine storm caused by SARS-CoV-2 infection MESHD has been reported to play a central role in COVID-19; therefore, treatments for suppressing cytokines, including extracorporeal treatments, are considered to be beneficial. However, until today the efficacy of removing cytokines by extracorporeal treatments in patients with COVID-19 is unclear. Herein, we report our experience with a 66-year-old male TRANS patient undergoing maintenance peritoneal dialysis who became critically ill with COVID-19 and underwent several extracorporeal treatment approaches including plasma SERO exchange, direct hemoperfusion using a polymyxin B-immobilized fiber column and continuous hemodiafiltration. Though the patient developed acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) repeatedly and subacute cerebral infarction MESHD and finally died for respiratory failure HP respiratory failure MESHD on day 30 after admission, these attempts appeared to dampen the cytokine storm based on the observed decline in serum SERO IL-6 levels and were effective against ARDS MESHD and secondary haemophagocytic lymphohistiocytosis MESHD. This case suggests the significance of timely initiation of extracorporeal treatment approaches in critically ill MESHD patients with COVID-19.

    Alveolitis MESHD in severe SARS-CoV-2 pneumonia MESHD pneumonia HP is driven by self-sustaining circuits between infected alveolar MESHD macrophages and T cells

    Authors: Rogan A Grant; Luisa Morales-Nebreda; Nikolay S Markov; Suchitra Swaminathan; Estefany R Guzman; Darryl A Abbott; Helen K Donnelly; Alvaro Donayre; Isaac A Goldberg; Zasu M Klug; Nicole Borkowski; Ziyan Lu; Hermon Kihshen; Yuliya Politanska; Lango Sichizya; Mengjia Kang; Ali Shilatifard; Chao Qi; A Christine Argento; Jacqueline M Kruser; Elizabeth S Malsin; Chiagozie O Pickens; Sean Smith; James M Walter; Anna E Pawlowski; Daniel Schneider; Prasanth Nannapaneni; Hiam Abdala-Valencia; Ankit Bharat; Cara J Gottardi; GR Scott Budinger; Alexander A Misharin; Benjamin David Singer; Richard G Wunderink; - The NU SCRIPT Study Investigators

    doi:10.1101/2020.08.05.238188 Date: 2020-08-05 Source: bioRxiv

    Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) develop severe pneumonia HP pneumonia MESHD and the acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus MESHD differs from other types of pneumonia HP pneumonia MESHD. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure HP respiratory failure MESHD and 252 patients with known or suspected pneumonia HP pneumonia MESHD from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection MESHD at the onset of mechanical ventilation, the alveolar MESHD space is persistently enriched in alveolar MESHD macrophages and T cells without neutrophilia HP. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar MESHD macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar MESHD macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis MESHD in which alveolar MESHD macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation MESHD.

    Elevated oxygen demand in a case of COVID-19 with severe ARDS MESHD: a point for optimal oxygenation therapy including ECMO management

    Authors: Taku Oshima; Takehiko Oami; Mana Yamashiro; Akiko Higashi; Yosuke Hayashi; Natsumi Suga; Shin Takayanagi; Seiichiro Sakao; Taka-aki Nakada

    doi:10.21203/rs.3.rs-51286/v1 Date: 2020-07-30 Source: ResearchSquare

    Background: Coronavirus disease MESHD 2019 (COVID-19) caused by SARS-CoV-2 has become a global pandemic, and those developing critically ill conditions have been reported to have mortality in the range of 39% to 61%. Due to the lack of definitive treatments, mechanical ventilation and supportive oxygenation therapy are key management strategies for the survival of patients with acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD). Optimizing oxygenation therapy is mandatory to treat patients with severe respiratory failure HP respiratory failure MESHD, to sufficiently compensate for the oxygen (O2) demand. We experienced a case of severe ARDS MESHD due to COVID-19 successfully treated with extracorporeal membrane oxygenation (ECMO) after increasing oxygen delivery according to O2 consumption measurement by indirect calorimetryCase Presentation: A 29-year-old obese MESHD but otherwise healthy man was hospitalized for treatment of COVID-19 pneumonia HP pneumonia MESHD presenting with a 4-day history of persisting cough HP cough MESHD, high fever HP, and dyspnea HP dyspnea MESHD. Mechanical ventilation, nitric oxide inhalation, and prone positioning were initiated in the ICU against severe respiratory dysfunction MESHD. Indirect calorimetry on the 3rd and 6th ICU days revealed persistent elevation of oxygen consumption (VO2) of 380 mL/min. Veno-venous ECMO was initiated on the 7th ICU day after further deterioration of respiratory failure MESHD respiratory failure HP. Periodic events of SpO2 decline due to effortful breathing was not resolved by neuromuscular blockade in attempt to reduce O2 consumption. Increasing the ECMO flow induced hemolysis MESHD and hyperkalemia HP hyperkalemia MESHD despite the use of large bore cannulas and ECMO circuit free of clots and defects. The hemoglobin management level was elevated from 10 g/dL to 13 g/dL to increase blood SERO oxygen capacity, enabling the reduction of ECMO flow while attenuating respiratory effort and maintaining SpO2. Lung protective ventilation strategy and prone positioning were continued for successful weaning from ECMO on the 16th ICU day, and the ventilator on the 18th ICU day.Conclusion: The present case of severe ARDS MESHD due to COVID-19 was successfully treated with ECMO. Enhancing oxygen delivery was crucial to compensate for the elevated O2 demand. Measuring O2 consumption by indirect calorimetry can elucidate the oxygen demand for optimizing the oxygenation therapy for successful management and survival of critically ill COVID-19 patients. 

    60-day survival of critically ill COVID-19 first comers

    Authors: Corinna N. Lang; V. Zotzmann; B. Schmid; M. Berchtold-Herz; S. Utzolino; P.M. Biever; T. Pottgießer; D. Duerschmied; C. Bode; T. Wengenmayer; D.L. Staudacher

    doi:10.21203/rs.3.rs-50651/v1 Date: 2020-07-29 Source: ResearchSquare

    Background: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease MESHD 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed resources allocated to critically ill COVID-19 patients and their outcomes. Methods: Retrospectively, we enrolled SARS-CoV2 PCR positive patients with respiratory failure HP respiratory failure MESHD from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany. Results: Thirty-four COVID-19 patients were admitted to the ICU in the defined interval with medium age TRANS of 67±13 (31-86) years. 6/34 (17.6%) were female TRANS. All patients suffered from moderate or severe acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. 96% required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. 60-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death MESHD were multi-organ failure MESHD (52.9%), refractory ARDS MESHD (17.6%) and intracerebral hemorrhage MESHD (17.6%). Conclusions: Treatment of critically ill COVID-19 patients is protracted and resource intense. In a context without resources shortage, 50% of critically ill COVID-19 survived up to 60 days.

    Happy Hypoxia MESHD: Higher NO in red blood SERO cells of COVID-19 patients

    Authors: Esmaeil Moratz; Majid Malekmohammad; Hamidreza Jamaati; Parisa Adimi Naghan; Mohammadreza Hashemian; Payam Tabarsi; Maohammad Varahram; Hamidreza Zaheri; Efsun Gonca Uğur Chousein; Gert Folkerts; Ian Adcock

    doi:10.21203/rs.3.rs-49770/v1 Date: 2020-07-27 Source: ResearchSquare

    Background: Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) that causes coronavirus disease MESHD 2019 (COVID-19) has spread to almost 100 countries, infected over 10M patients and resulted in 505K deaths worldwide as of 30th June 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute Respiratory Distress HP Respiratory Distress MESHD Syndrome ( ARDS MESHD) with multi-functional failure as a result of a cytokine storm with increased serum SERO levels of cytokines. The pathogenesis of the respiratory failure HP respiratory failure MESHD in COVID-19 is yet unknown, but diffuse alveolar damage MESHD with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia MESHD has been seen in the COVID-19 patients however, patients present with a distinct phenotype. Intracellular levels of NO playing important role in the vasodilation of small vessels.Objectives: To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects.Methods: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood SERO samples were harvested from patients and intracellular levels of NO in 1 million red blood SERO cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA).Results: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P≤0.05). As a further control for whether hypoxia MESHD induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic MESHD patients. No significant differences in NO levels were seen between the hypoxic MESHD and non-hypoxic control group.Conclusions: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future studies should examine whether intracellular NO would be increased in large number of COVID-19 patients for usage of possible NO therapy in severe patients. 

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