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MeSH Disease


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    The spatio-temporal landscape of lung pathology in SARS-CoV-2 infection MESHD

    Authors: Andre F Rendeiro; Hiranmayi Ravichandran; Yaron Bram; Steven Salvatore; Alain Borczuk; Olivier Elemento; Robert Edward Schwartz; Lilian Inoue; Joao Paulo Kitajima; Mayra Kuroki; Cibele Masotti; Tatiana Marques; Alice Reis; Luiz Fernando Reis; Bibiana Santos; Ernande dos Santos; David Schlesinger; Cecilia Sena; Talita Spadaccini; Lucas Taniguti; Surendra Parmar; Dominic Sparkes; Lucy Rivett; Nick K Jones; Sushmita Sridhar; Sally Forest; Tom Dymond; Kayleigh Grainger; Chris Workman; Effrossyni Gkrania-Klotsas; Nicholas M Brown; Michael Weekes; Stephen Baker; Sharon J Peacock; Theodore Gouliouris; Ian G. Goodfellow; Daniela de Angelis; M. Estee Torok

    doi:10.1101/2020.10.26.20219584 Date: 2020-10-27 Source: medRxiv

    Recent studies have provided insights into the pathology and immune response to coronavirus disease 2019 MESHD ( COVID-19 MESHD). However thorough interrogation of the interplay between infected cells and the immune system at sites of infection is lacking. We use high parameter imaging mass cytometry targeting the expression of 36 proteins, to investigate at single cell resolution, the cellular composition and spatial architecture of human acute lung injury MESHD including SARS-CoV-2. This spatially resolved, single-cell data unravels the disordered structure of the infected and injured lung alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia MESHD pneumonia HP and COVID-19 MESHD, respectively. We provide evidence that SARS-CoV-2 infects MESHD predominantly alveolar epithelial MESHD cells and induces a localized hyper-inflammatory cell state associated with lung damage MESHD. By leveraging the temporal range of COVID-19 MESHD severe fatal disease in relation to the time of symptom onset TRANS, we observe increased macrophage extravasation, mesenchymal cells, and fibroblasts abundance concomitant with increased proximity between these cell types as the disease progresses, possibly as an attempt to repair the damaged lung tissue. This spatially resolved single-cell data allowed us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. This spatial single-cell landscape enabled the pathophysiological characterization of the human lung from its macroscopic presentation to the single-cell, providing an important basis for the understanding of COVID-19 MESHD, and lung pathology in general.

    Tocilizumab in nonventilated patients hospitalized with Covid-19 MESHD pneumonia HP pneumonia MESHD

    Authors: Carlos Salama; Jian Han; Linda Yau; William G. Reiss; Benjamin Kramer; Jeffrey D. Neidhart; Gerard J. Criner; Emma Kaplan-Lewis; Rachel Baden; Lavannya Pandit; Miriam L. Cameron; Julia Garcia-Diaz; Victoria Chávez; Martha Mekebeb-Reuter; Ferdinando Lima Menezes; Reena Shah; Maria F. González-Lara; Beverly Assman; Jamie Freedman; Shalini V. Mohan; Felix Frueh; Brett L Hurst; Hong Wang; Klaudia I Kocurek; Frank M Raushel; Jair L. Siqueira-Neto; Thomas D Meek; James H McKerrow

    doi:10.1101/2020.10.21.20210203 Date: 2020-10-23 Source: medRxiv

    Background: Coronavirus disease 2019 MESHD ( Covid-19 MESHD) pneumonia HP pneumonia MESHD is often associated with hyperinflammation. Safety and efficacy of the anti-interleukin-6 receptor antibody SERO tocilizumab was evaluated in patients hospitalized with Covid-19 MESHD pneumonia HP pneumonia MESHD. Methods: Nonventilated patients hospitalized with Covid-19 MESHD pneumonia MESHD pneumonia HP were randomized (2:1) to tocilizumab (8 mg/kg intravenous) or placebo plus standard care. Sites enrolling high-risk and minority populations were emphasized. The primary endpoint was cumulative proportion of patients requiring mechanical ventilation or who had died by Day 28. Results: Of 389 randomized patients, 249 patients received tocilizumab and 128 received placebo in the modified intent-to-treat population (Hispanic/Latino, 56.0%; Black/African American, 14.9%; American Indian/Alaska Native, 12.7%; White, 12.7%; other/unknown, 3.7%). The cumulative proportion (95% confidence interval [CI]) of patients requiring mechanical ventilation or who had died by Day 28 was 12.0% (8.52% to 16.86%) and 19.3 % (13.34% to 27.36%) for the tocilizumab and placebo arms, respectively (log-rank P=0.0360; hazard ratio, 0.56 [95% CI, 0.33 to 0.97]). Median time to clinical failure up to Day 28 favored tocilizumab over placebo (hazard ratio 0.55 [95% CI, 0.33 to 0.93]). All-cause mortality by Day 28 was 10.4% with tocilizumab and 8.6% with placebo (weighted difference, 2.0% [95% CI, -5.2% to 7.8%). In the safety population, serious adverse events occurred in 15.2% of tocilizumab patients (38/250 patients) and 19.7% of placebo patients (25/127). Conclusions: This trial demonstrated the efficacy and safety of tocilizumab over placebo in reducing the likelihood of progression to requiring mechanical ventilation or death MESHD in nonventilated patients hospitalized with Covid-19 MESHD pneumonia MESHD pneumonia HP.

    Diagnostic utility of a Ferritin-to-Procalcitonin Ratio to differentiate patients with COVID-19 MESHD from those with Bacterial Pneumonia HP: A multicenter study

    Authors: Amal A. Gharamti; Fei Mei; Katherine C. Jankousky; Jin Huang; Peter Hyson; Daniel B. Chastain; Jiawei Fan; Sharmon Osae; Wayne W. Zhang; Jose G. Montoya; Kristine M. Erlandson; Sias J. Scherger; Carlos Franco-Paredes; Andres F. Henao-Martinez; Leland Shapiro

    doi:10.1101/2020.10.20.20216309 Date: 2020-10-22 Source: medRxiv

    Importance: There is a need to develop tools to differentiate COVID-19 MESHD from bacterial pneumonia HP pneumonia MESHD at the time of clinical presentation before diagnostic testing is available. Objective: To determine if the Ferritin-to-Procalcitonin ratio (F/P) can be used to differentiate COVID-19 MESHD from bacterial pneumonia MESHD pneumonia HP. Design: This case-control study compared patients with either COVID-19 MESHD or bacterial pneumonia MESHD pneumonia HP, admitted between March 1 and May 31, 2020. Patients with COVID-19 MESHD and bacterial pneumonia co-infection MESHD pneumonia HP co-infection were excluded. Setting: A multicenter study conducted at three hospitals that included UCHealth and Phoebe Putney Memorial Hospital in the United States, and Yichang Central People Hospital in China. Participants: A total of 242 cases with COVID-19 MESHD infection and 34 controls with bacterial pneumonia MESHD pneumonia HP. Main Outcomes and Measures: The F/P in patients with COVID-19 MESHD or with bacterial pneumonia HP pneumonia MESHD were compared. Receiver operating characteristic analysis determined the sensitivity SERO and specificity of various cut-off F/P values for the diagnosis of COVID-19 MESHD versus bacterial pneumonia HP pneumonia MESHD. Results: Patients with COVID-19 MESHD pneumonia MESHD pneumonia HP had a lower mean age TRANS (57.11 vs 64.4 years, p=0.02) and a higher BMI (30.74 vs 27.15 kg/m2, p=0.02) compared to patients with bacterial pneumonia MESHD pneumonia HP. Cases and controls had a similar proportion of women (47% vs 53%, p=0.5) and COVID-19 MESHD patients had a higher prevalence SERO of diabetes mellitus MESHD diabetes mellitus HP (32.6% vs 12%, p=0.01). The median F/P was significantly higher in patients with COVID-19 MESHD (4037.5) compared to the F/P in bacterial pneumonia MESHD pneumonia HP (802, p<0.001). An F/P greater than or equal to 877 used to diagnose COVID-19 MESHD resulted in a sensitivity SERO of 85% and a specificity of 56%, with a positive predictive value SERO of 93.2%, and a likelihood ratio of 1.92. In multivariable analyses, an F/P greater than or equal to 877 was associated with greater odds of identifying a COVID-19 MESHD case (OR: 11.27, CI: 4-31.2, p<0.001). Conclusions and Relevance: An F/P greater than or equal to 877 increases the likelihood of COVID-19 MESHD pneumonia MESHD pneumonia HP compared to bacterial pneumonia MESHD pneumonia HP. Further research is needed to determine if obtaining ferritin and procalcitonin simultaneously at the time of clinical presentation has improved diagnostic value. Additional questions include whether an increased F/P and/or serial F/P associates with COVID-19 MESHD disease severity or outcomes.

    Validation of expert system enhanced deep learning algorithm MESHD for automated screening for COVID- Pneumonia HP on chest X-rays

    Authors: Prashant Sadashiv Gidde; Shyam Sunder Prasad; Ajay Pratap Singh; Nitin Batheja; Satyartha Prakash; Prateek Singh; Aakash Saboo; Rohit Thakar; Salil Gupta; Sumeet Saurav; M V Raghunandan; Amritpal Singh; Viren Sardana; Harsh Mahajan; Arjun Kalyanpur; Atanendu Shekhar Mandal; Vidur Mahajan; Anurag Agrawal; Anjali Agrawal; Vasantha Kumar Venugopal; Sanjay Singh; Debasis Dash; Sara Sabach; Yuval Alfiya; Uta Cheruti; Nadav Davidovitch; Natalya Bilenko; Jacob Moran-Gilad; Yakir Berchenko; Itay Bar-Or; Ariel Kushmaro; Timothy Spector; Claire J Steves

    doi:10.1101/2020.10.20.20213793 Date: 2020-10-21 Source: medRxiv

    The coronavirus disease of 2019 ( COVID-19 MESHD) pandemic exposed a limitation of artificial intelligence (AI) based medical image interpretation systems. Early in the pandemic, when need was greatest, the absence of sufficient training data prevented effective deep learning (DL) solutions. Even now, there is a need for Chest-X-ray (CxR) screening tools in low and middle income countries (LMIC), when RT-PCR is delayed, to exclude COVID-19 MESHD pneumonia MESHD pneumonia HP (Cov-Pneum) requiring transfer to higher care. In absence of local LMIC data and poor portability of CxR DL algorithms, a new approach is needed. Axiomatically, it is faster to repurpose existing data than to generate new datasets. Here, we describe CovBaseAI, an explainable tool which uses an ensemble of three DL models and an expert decision system (EDS) for Cov-Pneum diagnosis, trained entirely on datasets from the pre- COVID-19 MESHD period. Portability, performance SERO, and explainability of CovBaseAI was primarily validated on two independent datasets. First, 1401 randomly selected CxR from an Indian quarantine-center to assess effectiveness in excluding radiologic Cov-Pneum that may require higher care. Second, a curated dataset with 434 RT-PCR positive cases of varying levels of severity and 471 historical scans containing normal studies and non-COVID pathologies, to assess performance SERO in advanced medical settings. CovBaseAI had accuracy of 87% with negative predictive value SERO of 98% in the quarantine-center data for Cov-Pneum. However, sensitivity SERO varied from 0.66 to 0.90 depending on whether RT-PCR or radiologist opinion was set as ground truth. This tool with explainability feature has better performance SERO than publicly available algorithms trained on COVID-19 MESHD data but needs further improvement.

    Tocilizumab is associated with reduction in inflammation MESHD and improvement in P/F ratio in critically sick COVID19 MESHD patients

    Authors: Muhammad Asim Rana; Mubashar Sultan Hashmi; Muhammad Muneeb Ullah Saif; Muhammad Faisal Munir; Ahad Qayyum; Rizwan Pervaiz; Muhammad Mansoor Hafeez; Graham Cooke; Timothy B Hallett; Katharina D Hauck; Peter J White; Mark R Thursz; Shevanthi Nayagam; Brendan Flannery; Ricardo Gilead Baibich; Iris Bigler; Matan Malul; Rotem Rishti; Asher Brenner; Yair E. Lewis; Eran Friedler; Yael Gilboa; Sara Sabach; Yuval Alfiya; Uta Cheruti; Nadav Davidovitch; Natalya Bilenko; Jacob Moran-Gilad; Yakir Berchenko; Itay Bar-Or; Ariel Kushmaro; Timothy Spector; Claire J Steves

    doi:10.1101/2020.10.20.20210195 Date: 2020-10-21 Source: medRxiv

    Introduction: Coronavirus disease 2019 MESHD was initially detected in China and has been declared a global pandemic by World Health Organization on March 11, 2020. In the majority of patients, SARS-CoV-2 causes a mild to moderate illness characterized by fever MESHD fever HP and respiratory symptoms MESHD, with or without evidence of pneumonia HP pneumonia MESHD. The recent studies suggest that anti-cytokine targeted therapies might be associated with benefit for patients with severe COVID-19 MESHD especially in improving respiratory failure HP respiratory failure MESHD. Tocilizumab, a monoclonal antibody SERO against interleukin 6 (IL6) receptor, is associated with clinical benefit for COVID-19 MESHD patients as it inhibits IL6 and decreases inflammation MESHD. Methods: As Tocilizumab has been an important part of our treatment and a strict criterion was followed to administer Tocilizumab, a retrospective study design used to assess the beneficial effects of Tocilizumab in improvement of ratio partial pressure of arterial Oxygen and fraction of inspired Oxygen (PaO2/FiO2 or P/F ratio) and C- reactive protein (CRP) in COVID19 MESHD patients has been done. 60 patients were taken for this study by using convenient sampling technique the data of demographics, laboratory results, and clinical outcomes i.e. improvement of respiratory failure MESHD respiratory failure HP depicted in the form of PF Ratio were obtained from the medical records, Statistical analysis was done with SPSS, version 21.0. Results: Sixty patients (47 males TRANS and 13 females TRANS) with COVID-19 MESHD were included in this study, the mean age TRANS of patients was 53.83 (14-81) years. After administration of Tocilizumab the lab parameters were changed as CRP decreased down to .40 (9.6-73) mg/L but other parameters were not affected. The PF ratio improved in COVID-19 MESHD patients after administration of Tocilizumab the median of PF Ratio before treatment was 108 (52-362) and improved up to 128 (37-406) after Tocilizumab therapy. Conclusion: In summary, Tocilizumab appears to be associated with improvement in P/F Ratio and CRP in COVID19 MESHD patients but other markers did not improve in response to Tocilizumab therapy in severely ill COVID-19 MESHD patients.

    Effective Deep Learning Approaches for Predicting COVID-19 MESHD Outcomes from Chest Computed Tomography Volumes

    Authors: Anusua Trivedi; Anthony Ortiz; Jocelyn Desbiens; Caleb Robinson; Marian Blazes; Sunil Gupta; Rahul Dodhia; Pavan Bhatraju; W. Conrad Liles; Aaron Lee; Juan M Lavista Ferres; Jane Eddleston; Chris Brookes; Christopher Harrison; Weiqi Liu; Tianyi Liu; Jin-Wen Song; Liangliang Sun; Fan Yang; Xin Zhang; Bo Zhang; Ming Shi; Fanping Meng; Yanning Song; Yongpei Yu; Jiqiu Wen; Qi Li; Qing Mao; Markus Maeurer; Alimuddin Zumla; Chen Yao; Weifen Xie; Fu-Sheng Wang; Anthony Atala; Ali Ghodsizad; Joshua M Hare

    doi:10.1101/2020.10.15.20213462 Date: 2020-10-20 Source: medRxiv

    The rapid evolution of the novel coronavirus SARS-CoV-2 pandemic has resulted in an urgent need for effective clinical tools to reduce transmission TRANS and manage severe illness. Numerous teams are quickly developing artificial intelligence approaches to these problems, including using deep learning to predict COVID-19 MESHD diagnosis and prognosis from computed tomography (CT) imaging data. In this work, we assess the value of aggregated chest CT data for COVID-19 MESHD prognosis compared to clinical metadata alone. We develop a novel patient-level algorithm to aggregate the chest CT volume into a 2D representation that can be easily integrated with clinical metadata to distinguish Novel Coronavirus Pneumonia HP ( COVID-19 MESHD+) from other cases of viral pneumonia MESHD pneumonia HP and normal healthy chest CT volumes with state-of-the-art performance SERO. Furthermore, we present a multitask model for joint segmentation of different classes of pulmonary lesions MESHD present in COVID-19 MESHD infected lungs MESHD that can outperform individual segmentation models for each task. We directly compare this multitask segmentation approach to combining feature-agnostic volumetric CT classification feature maps with clinical metadata for predicting mortality. These approaches enable the automated extraction of clinically relevant features from chest CT volumes for risk stratification of COVID-19 MESHD+ patients.

    Intravenous Mesenchymal Stem Cells in Extracorporeal Oxygenation Patients with Severe COVID-19 MESHD Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome

    Authors: Sunjay Kaushal; Aisha Khan; Kristopher Deatrick; Derek K Ng; Abigail Snyder; Aakash Shah; Lina V Caceres; Ketty Bacallao; Melania Bembea; Allen Everett; Jie Zhu; David Kaczorowski; Ronson Madathil; Ali Tabatabai; Geoffrey Rosenthal; Adriana Brooks; Bangon Longsomboon; Rachana Mishra; Progyaparamita Saha; Yvenie Desire; Russell Saltzman; Kim G Hankey; Sixto A Arias; Folusakin Ayoade; Jairo A. Tovar; Rejane Lamazares; Hayley B Gershengorn; Fontaine J Magali; Matthias Loebe; Kristin Mullins; Muthukumar Gunasekaran; Vela Karakeshishyan; Dushyantha T Jayaweera; Anthony Atala; Ali Ghodsizad; Joshua M Hare

    doi:10.1101/2020.10.15.20122523 Date: 2020-10-20 Source: medRxiv

    Background: There is an ongoing critical need to improve therapeutic strategies for COVID-19 MESHD pneumonia MESHD pneumonia HP, particularly in the most severely affected patients. Adult TRANS mesenchymal stem cell (MSC) infusions have the potential to benefit critically ill MESHD patients with acute respiratory syndrome SARS-COV-2 infection MESHD SARS-COV-2 infection MESHD, but clinical data supporting efficacy are lacking. Methods: We conducted a case-control study of critically ill MESHD patients with laboratory-confirmed COVID-19 MESHD, severe acute respiratory distress syndrome MESHD respiratory distress syndrome HP ( ARDS MESHD). To evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ECMO) support. Patients (n=9) were administered with up to 3 infusions of intravenous (IV) MSCs and compared to a local ECMO control group (n=31). The primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance. Findings: MSC infusions (12 patients) were well tolerated and no side effects occurred. Of ECMO patients receiving MSC infusions, 2 out of 9 died (22.2%; 95%CI: 2.8%, 60.0%) compared with a mortality of 15 of 31 (48.4%; 95%CI: 30.2%, 66.9%; p = 0.25) in the ECMO control group. Isolated plasma SERO exosomes containing the SARS-COV-2 Spike protein decreased after MSC infusions between day 14 or 21 after administration (p=0.003 and p=0.005, respectively) and was associated with a decrease in COVID-19 MESHD IgG Spike protein titer at same time points (p = 0.006 and p=0.007, respectively). Control ECMO patients receiving convalescent plasma SERO did not clear COVID-19 MESHD IgG over the same time frame. Interpretation: Together these findings suggest that MSC IV infusion is well tolerated in patients with a broad range of severity including the most severe COVID-19 MESHD ARDS requiring ECMO. These data also raise the possibility that MSCs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial.

    Correlation between Chest CT Severity Scores and the Clinical Parameters of Adult TRANS Patients with COVID-19 MESHD pneumonia HP pneumonia MESHD

    Authors: Ghufran Saeed; Waqar Gaba; Asad Shah; Abeer Al Helali; Emadullah Raidullah; Ameirah Al Ali; Mohammed Elghazali; Deena Ahmed; Shaikha Al Kaabi; Safaa Almazrouei; Juan M Lavista Ferres; Jane Eddleston; Chris Brookes; Christopher Harrison; Weiqi Liu; Tianyi Liu; Jin-Wen Song; Liangliang Sun; Fan Yang; Xin Zhang; Bo Zhang; Ming Shi; Fanping Meng; Yanning Song; Yongpei Yu; Jiqiu Wen; Qi Li; Qing Mao; Markus Maeurer; Alimuddin Zumla; Chen Yao; Weifen Xie; Fu-Sheng Wang; Anthony Atala; Ali Ghodsizad; Joshua M Hare

    doi:10.1101/2020.10.15.20213058 Date: 2020-10-20 Source: medRxiv

    Purpose Our aim is to correlate the clinical condition of patients with COVID-19 MESHD infection with the 25 Point CT severity score by Chang et al (devised for assessment of ARDS in patients with SARS in 2005). Material and Methods Data of consecutive symptomatic patients who were suspected to have COVID-19 MESHD infection and presented to our hospital, was collected from March to April 2020. All patients underwent two consecutive RT-PCR tests and had a non-contrast HRCT scan done at presentation. From the original cohort of 1062 patients, 160 patients were excluded leaving a total number of 902 patients. Results The mean age TRANS was 44.2 +/- 11.9 years [85.3% males TRANS, 14.7 % females TRANS]. CT severity score found to be positively correlated with lymphopenia MESHD lymphopenia HP, increased serum SERO CRP, d-dimer and ferritin levels (p < 0.0001). The oxygen requirements as well as length of hospital stay were increasing with the increase of scan severity. Conclusion The 25-point CT severity score correlates well with the COVID-19 MESHD clinical severity. Our data suggest that chest CT scoring system can aid in predicting COVID-19 MESHD disease outcome and significantly correlates with lab tests and oxygen requirements.


    Authors: Cristina Calvo; Agustin Remesal; Sara Murias; Fatima Ara-Montojo; Enrique Otheo; Francisco J Sanz-Santaeufemia; Alvaro Villaroya; Cinta Moraleda; Alfredo Tagarro; Jean Michel Heraud; C. Jessica E. Metcalf; Benjamin L Rice; Javier Colomina; David Navarro

    doi:10.1101/2020.10.17.20214296 Date: 2020-10-20 Source: medRxiv

    Objectives: SARS-CoV-2 infection MESHD in adults TRANS with rheumatic diseases MESHD ( RD MESHD) is a cause for concern. Data in the pediatric population are practically absent. We aimed to describe the prevalence SERO of patients with RD MESHD and their complications among children TRANS admitted with COVID-19 MESHD in the Spanish national cohort EPICO-AEP; a multicenter prospective national study. Methods: Children TRANS <18 years old with RD MESHD and COVID-19 MESHD enrolled in EPICO-AEP were included in this study. Results: By June 30th 2020, 350 children TRANS were admitted in secondary and tertiary hospitals of Spain with SARS-CoV-2 infection MESHD. A total of 8 patients presented RD MESHD (2.2% of those hospitalized). All were female TRANS. The median age TRANS was 12.1 years (IQR 8.3-14.5). The diagnosis related with COVID-19 MESHD were febrile syndrome and/or upper respiratory infection MESHD (4 cases) and pneumonia HP pneumonia MESHD (4 cases). One of the 8 (12.5%) patients with a severe juvenile dermatomyositis (JDM) with interstitial lung disease MESHD died. Juvenile idiopathic arthritis MESHD arthritis HP ( JIA MESHD) was the most frequent diagnosis in 3/8 (37.5%) patients. In 5/8 (62.5%) cases, the RD MESHD was not fully controlled, and all patients except one received corticosteroid treatment. Conclusions: Children TRANS with RD MESHD have accounted for 2.2% of hospitalized patients with COVID-19 MESHD in our series. The evolution has been moderately favorable, with one deceased. In case of active disease and use of corticosteroids patients should be managed with caution. Key words: COVID-19 MESHD, children TRANS, rheumatic diseases MESHD, corticosteroids.


    Authors: Ali A El Solh; Gianfranco Umberto Meduri; Yolanda Lawson; MIchael Carter; Kari A Mergenhagen; Ce Cheng; Qin Zhou; Chenyu Sun; Manuel M Vicente; Angela Fernandes; Ana M Dias; Ivan-Christian Kurolt; Alemka Markotic; Dragan Primorac; Adriana Soares; Luis Malheiro; Irena Trbojevic-Akmacic; Miguel Abreu; Rui Sarmento e Castro; Silvia Bettinelli; Annapaola Callegaro; Marco Arosio; Lorena Sangiorgio; Luca Lorini; Xavier Castells; Juan P Horcajada; Salome Pinho; Massimo Allegri; Clara Barrios; Gordan Lauc

    doi:10.1101/2020.10.16.20214130 Date: 2020-10-20 Source: medRxiv

    Background: Mortality attributable to coronavirus disease-19 MESHD ( COVID-19 MESHD) 2 infection occurs mainly through the development of viral pneumonia HP pneumonia MESHD-induced acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD). Research Question: The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS MESHD using the Veterans Affairs Corporate Data Warehouse. Study Design and Methods: Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 MESHD infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS MESHD and 30-day mortality from ARDS MESHD, respectively. Results: The cohort was comprised predominantly of men (94.5%) with a median age TRANS of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS MESHD. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS MESHD were body mass index (BMI)[≥] 40 kg/m2, diabetes MESHD, lymphocyte counts<700x109/L, LDH>450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock HP. Use of an anticoagulant was associated with two-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone. Conclusions: Among those hospitalized for COVID-19 MESHD, nearly one in ten progressed to ARDS. Septic shock HP, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 MESHD should be placed at a minimum on prophylactic doses of anticoagulation.

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