Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Alveolitis in severe SARS-CoV-2 pneumonia MESHD pneumonia HP is driven by self-sustaining circuits between infected alveolar 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 MESHD Coronavirus-2 (SARS-CoV-2) develop severe pneumonia MESHD pneumonia HP and the acute respiratory distress HP syndrome MESHD (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia MESHD pneumonia HP. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure HP and 252 patients with known or suspected pneumonia MESHD pneumonia HP 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 space is persistently enriched in alveolar macrophages and T cells without neutrophilia HP. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation MESHD.

    COVID19: An Opinion on Animal Infections MESHD and Role of Veterinarians in One Health Perspective

    Authors: SWAGATIKA PRIYADARSINI; ROHIT SINGH; ARUN SOMAGOND; PUJA MECH

    id:10.20944/preprints202008.0069.v1 Date: 2020-08-03 Source: Preprints.org

    Coronavirus disease MESHD is the current cause of global concern. The massive outbreak of COVID-19 has led the World Health Organization (WHO) to declare this as a pandemic situation. The Severe Acute Respiratory Syndrome MESHD Coronavirus-2 (SARSCoV-2) is responsible for COVID-19 leading to acute respiratory distress HP and substantial mortality in humans. However, the first laboratory confirmation of SARS-CoV-2 in a pet dog in Hong Kong has shown the possibility of human-to-animal transmission TRANS (zooanthroponotic) of the virus. Thereafter, many animals including cat, tiger, lion and mink have also been reported to acquire the virus in several countries. In this situation the role of veterinarian assumes important in treating the animals, helping in food security, disease MESHD diagnosis, surveillance and boosting the economy of livestock stakeholders at the grassroot level. In the absence of any selective vaccine or drug against SARS-CoV-2, the world is anticipated to triumph over this pandemic with collaborative, multisectoral, and transdisciplinary approach linking human, animal and environmental health. This article gives an insight into the confirmed SARS-CoV-2 outbreaks in animals, including the factors behind the shuffling of the virus among variety of species and also emphasizes on the role of veterinarian in managing and safeguarding public health so as to pave the way for adopting one health approach in order to conserve biodiversity.

    Montelukast in Hospitalized Patients Diagnosed with COVID-19

    Authors: Ahsan Khan; Christian Misdary; Nikhil Yegya-Raman; Sinae Kim; Navaneeth Narayanan; Sheraz Siddiqui; Padmini Salgame; Jared Radbel; Frank De Groote; Carl Michel; Janice Mehnert; Caleb Hernandez; Thomas Braciale; Jyoti Malhotra; Michael A. Gentile; Salma K. Jabbour

    doi:10.21203/rs.3.rs-52430/v1 Date: 2020-08-01 Source: ResearchSquare

    Background Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists such as montelukast have been shown to reduce both cytokine release and lung inflammation MESHD in preclinical models of viral influenza and acute respiratory distress HP syndrome MESHD, we hypothesized that therapy with montelukast would reduce clinical deterioration MESHD as measured by the COVID-19 Ordinal Scale.Methods We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used “clinical deterioration” as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration MESHD between the montelukast and non-montelukast groups were compared using the Fisher’s exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration MESHD.Results A total of 92 patients were analyzed, 30 received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast. Patients receiving montelukast experienced significantly fewer events of clinical deterioration MESHD compared to patients not receiving montelukast (10% vs 32%, p = 0.022). Sensitivity SERO analysis among those without asthma MESHD asthma HP showed a trend toward fewer clinical deterioration MESHD events in the montelukast group than non-montelukast groups (11% vs 33%, p = 0.077). Sensitivity SERO analysis among those who did not receive azithromycin showed fewer clinical deterioration MESHD events in the montelukast group vs. non-montelukast groups (8% vs 32%, p = 0.030).Conclusions Our findings suggest that montelukast associates with a reduction in clinical deterioration MESHD for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale. Montelukast may have activity in COVID-19 infection MESHD, and future efforts should evaluate this potential therapy.

    Covid-19-associated coagulopathy (CoAC): thrombin burst and insufficient fibrinolysis leading to bad outcome.

    Authors: Marco Ranucci; Clementina Sitzia; Ekaterina Baryshnikova; Umberto Di Dedda; Rosanna Cardani; Fabio Martelli; Massimiliano Corsi Romanelli

    doi:10.21203/rs.3.rs-52214/v1 Date: 2020-08-01 Source: ResearchSquare

    Background: COVID-19 associated coagulopathy is characterized by a pro-thrombotic state. However, the nature of this pattern has not been comprehensively studied. We investigated the coagulation pattern of patients with COVID-19 acute respiratory distress HP syndrome MESHD (ARDS) comparing survivors to not survivors. Methods: Prospective cohort study conducted in the Intensive Care Unit (ICU) of a University Hospital . Twenty COVID-19 ARDS patients received measurements of markers of thrombin generation (prothrombin fragment 1+2, PF 1+2); fibrinolysis activation (tissue plasminogen activator, tPA) and inhibition (plasminogen activator inhibitor-2, PAI-2); fibrin synthesis (fibrinopeptide A) and fibrinolysis magnitude (plasmin-antiplasmin complex, PAP, and D-dimers). Measurements were done at the ICU admission and after 10-14 days. Results: The general pattern showed an increased thrombin generation, modest or null release of t-PA, and increased levels of PAI-2, Fibrinopeptide A, PAP and D-dimers. At baseline, non survivors had a significantly (P=0.014) higher PAI-2/PAP ratio than survivors (109, interquartile range [IQR] 18.1-216, vs. 8.7, IQR 2.9-12.6). At follow-up, thrombin generation was significantly (P=0.025) reduced in survivors (PF 1+2 from 396 pg/mL, IQR 185-585 to 237 pg/mL, IQR 120-393), whereas it increased in non-survivors. Fibrinolysis inhibition at follow-up remained stable in survivors, and increased in non-survivors, leading to a significant (P=0.026) difference in PAI-2 levels (161 pg/mL, IQR 50-334, vs. 1,088 pg/mL, IQR 177-1,565). Conclusions: Severe patterns of COVID-19 infection MESHD (ARDS) are characterized by a thrombin burst, triggered by the release of IL-6 and other cytokines, and the consequent release of Tissue Factor. Mechanisms of fibrinolysis regulation appear unbalanced toward fibrinolysis inhibition. In survivors, this pattern ameliorates, whereas in non-survivors it worsens, leading to the environment for clinically relevant thrombi generation, that was found in 58% of non-surviving patients. Trial registration: clinicaltrials.gov (NCT04441502).

    Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: a systematic review and meta-analysis

    Authors: Hany Hasan Elsayed; Aly Sherif Hassaballa; Taha Aly Ahmed; Mohamed Gumaa; Hazem Youssef Sharkawy

    doi:10.21203/rs.3.rs-52224/v1 Date: 2020-08-01 Source: ResearchSquare

    Background: COVID 19 is the most recent cause of Adult respiratory distress syndrome MESHD Adult TRANS respiratory distress HP syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries.Methods: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from June 8 2019 to June 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection MESHD treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age TRANS and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365Findings: Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death MESHD after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p=0.23) (95% CI = 0.94-1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p=0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43-0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age TRANS had no statistically significant effect on mortality (p= 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p=0.714 and Begg&Mazumdar test with p=0.334Interpretation: The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.

    Tocilizumab shortens time on mechanical ventilation and length of hospital stay in patients with severe COVID-19: a retrospective cohort study.

    Authors: Johannes Eimer; Jan Vesterbacka; Anna-Karin Svensson; Bertil Stojanovic; Charlotta Wagrell; Anders Sonnerborg; Piotr Nowak

    doi:10.1101/2020.07.29.20164160 Date: 2020-07-30 Source: medRxiv

    Background: Hyperinflammation is a key feature of the pathogenesis of COVID-19 with a central role of the interleukin-6 pathway. We aimed to study the impact of the IL-6 receptor antagonist tocilizumab on the outcome of patients admitted to the intensive care unit (ICU) with acute respiratory distress HP syndrome MESHD (ARDS) related to COVID-19. Methods: Eighty-seven patients with confirmed SARS-CoV-2 infection MESHD and moderate to severe ARDS were included (n tocilizumab = 29, n controls = 58). A matched cohort was created using a propensity score. The primary endpoint was 30-day all-cause mortality, secondary endpoints included ventilation-free days and length of stay. Results: No difference was found in 30-day all-cause mortality in patients treated with tocilizumab compared to controls (17.2% vs. 32.8%, p = 0.2; HR = 0.52 [0.19 - 1.39], p = 0.19). Ventilator-free days were 19.0 (IQR 12.5 - 20.0) versus 9 (IQR 0.0 - 18.5; p = 0.04), respectively. A higher rate of freedom from mechanical ventilation at 30 days was achieved in patients receiving tocilizumab (HR 2.83 [1.48 - 5.40], p < 0.002). Median length of stay in ICU and total length of stay were reduced by 8 and 9.5 days in patients treated with tocilizumab. Similar results were obtained in the analysis of the propensity score matched cohort. Conclusions: Treatment of critically ill patients with ARDS due to COVID-19 with tocilizumab was not associated with reduced 30-day all-cause mortality, but shorter duration on ventilatory support as well as shorter overall length of stay in hospital and in ICU.

    Fighting COVID-19 spread among nursing home residents even in absence of molecular diagnosis: a retrospective cohort study.

    Authors: Alessio Strazzulla; Paul Tarteret; Maria Concetta Postorino; Marie Picque; Astrid de Pontfarcy; Nicolas Vignier; Catherine Chakvetadze; Coralie Noel; Cecile Drouin; Zine Eddine Benguerdi; Sylvain Diamantis

    doi:10.21203/rs.3.rs-51305/v1 Date: 2020-07-30 Source: ResearchSquare

    Background Access to molecular diagnosis was limited out-of-hospital in France during the 2020 coronavirus disease MESHD 2019 (COVID-19) epidemic. This study describes the evolution of COVID-19 outbreak in a nursing home in absence of molecular diagnosis. Methods A monocentric prospective study was conducted in a French nursing home from March 17th, 2020 to June 11th, 2020. Because of lack of molecular tests for severe acute respiratory syndrome MESHD 2 (SARS-Cov2) infection MESHD, probable COVID-19 cases were early identified considering only respiratory and not-respiratory symptoms and therefore preventing measures and treatments were enforced. Once available, serology tests were performed at the end of the study.A chronologic description of new cases and deaths MESHD was made together with a description of COVID-19 symptoms. Data about personal characteristics and treatments were collected and the following comparisons were performed: i) probable COVID-19 cases vs asymptomatic TRANS residents; ii) SARS-Cov2 seropositive residents vs seronegative residents. Results Overall, 32/66 (48.5%) residents and 19/39 (48.7%) members of health-care personnel were classified as probable COVID-19 cases. A total of 34/61 (55.7%) tested residents resulted seropositive. Death MESHD occurred in 4/66 (6%) residents. Diagnosis according to symptoms had 65% of sensitivity SERO, 78% of specificity, 79% of positive predictive value SERO and 64% of negative predictive value SERO.In resident population, the following symptoms were registered: 15/32 (46.8%) lymphopenia MESHD lymphopenia HP, 15/32 (46.8%) fever MESHD fever HP, 8/32 (25%) fatigue MESHD fatigue HP, 8/32 (25%) cough MESHD cough HP, 6/32 (18.8%) diarrhoea, 4/32 (12.5%) severe respiratory distress HP requiring oxygen therapy, 4/32 (12.5%) fall HP, 3/32 (9.4%) conjunctivitis MESHD conjunctivitis HP, 2/32 (6.3%) abnormal pulmonary noise at chest examination and 2/32 (6,25%) abdominal pain MESHD abdominal pain HP. Probable COVID-19 cases were older (81.3 vs 74.9; p=0.007) and they had higher prevalence SERO of atrial fibrillation MESHD atrial fibrillation HP (8/32, 25% vs 2/34, 12%; p=0.030); insulin treatment (4/34, 12% vs 0, 0%; p=0.033) and positive SARS-Cov2 serology (22/32, 69% vs 12/34, 35%; p=0.001) than asymptomatic TRANS residents. Seropositive residents had lower prevalence SERO of diabetes (4/34, 12% vs 9/27, 33%; p=0.041) and angiotensin-converting-enzyme inhibitors’ intake (1/34, 1% vs 5/27, 19%; p=0.042). Conclusions During SARS-Cov2 epidemic, early detection of respiratory and not-respiratory symptoms allowed to enforce extraordinary measures. They achieved limiting contagion and deaths MESHD among nursing home residents, even in absence of molecular diagnosis.

    Cell type-specific immune dysregulation HP in severely ill COVID-19 patients

    Authors: Changfu Yao; Stephanie A Bora; Tanyalak Parimon; Tanzira Zaman; Oren A Friedman; Joseph A Palatinus; Nirmala S Surapaneni; Yuri P Matusov; Giuliana Cerro Chiang; Alexander G Kassar; Nayan Patel; Chelsi ER Green; Adam W Aziz; Harshpreet Suri; Jo Suda; Andres A Lopez; Gislaine A Martins; Barry R Stripp; Sina A Gharib; Helen S Goodridge; Peter Chen

    doi:10.1101/2020.07.23.20161182 Date: 2020-07-24 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury MESHD called acute respiratory distress HP syndrome MESHD (ARDS) that causes progressive respiratory failure HP requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection MESHD, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood SERO mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease MESHD (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies HP within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease MESHD course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease MESHD course in COVID-19.

    Chronic Hemodialysis Patients have better outcomes with COVID-19 - a retrospective cohort study

    Authors: Ashutossh Naaraayan; Abhishek Nimkar; Amrah Hasan; Sushil Pant; Momcilo Durdevic; Henrik Elenius; Corina Nava Suarez; Prasanta Basak; Kameswari Lakshmi; Michael Mandel; Stephen Jesmajian

    doi:10.1101/2020.07.22.20159202 Date: 2020-07-24 Source: medRxiv

    Introduction Several comorbid conditions, have been identified as risk factors in patients with COVID-19. However, there is a dearth of data describing the impact of COVID-19 infection MESHD in patients with end-stage renal disease MESHD on hemodialysis (ESRD-HD). Methods This retrospective case series analyzed 362 adult TRANS patients consecutively hospitalized with confirmed COVID-19 illness between March 12, 2020 and May 13, 2020, at a teaching hospital in the New York City metropolitan area. Primary outcome was severe pneumonia MESHD pneumonia HP as defined by the World Health Organization. Secondary outcomes were: 1) the Combined Outcome of Acute respiratory distress HP syndrome MESHD or in-hospital Death MESHD (COAD), and 2) the need for High-levels of Oxygen supplementation (HiO2). Results Patients with ESRD-HD had lower odds for poor outcomes including severe pneumonia MESHD pneumonia HP [Odds Ratio (OR) 0.4, Confidence Interval (CI) (0.2-0.9) p=.04], HiO2 [OR 0.3, CI (0.1-0.8) p=.02] and COAD [OR 0.4, CI (0.2-1.05) p=.06], when compared to patients without ESRD. In contrast, higher odds for severe pneumonia MESHD pneumonia HP, COAD and HiO2 were seen with advancing age TRANS. African-Americans were over-represented in the hospitalized patient cohort, when compared to their representation in the community (35% vs 18%). Hispanics had higher odds for severe-illness and HiO2 when compared to Caucasians. Conclusions Patients with ESRD-HD had a milder course of illness with a lower likelihood of severe pneumonia MESHD pneumonia HP and a lesser need for aggressive oxygen supplementation when compared to patients not on chronic dialysis. This protective effect, might have a pathophysiologic basis and needs to be further explored.

    Sequential use of hemadsorption using Cytosorb® and Biosky® filter- technology in a COVID-19 patient suffering from severe ARDS 

    Authors: Matthias Mezger; Ingo Eitel; Stephan Ensminger; Dirk Pogorzalek; Zhipan Huang; Tobias Graf

    doi:10.21203/rs.3.rs-47352/v1 Date: 2020-07-22 Source: ResearchSquare

    In March 2020, the World Health Organization (WHO) declared the novel coronavirus disease MESHD (COVID- 19) pandemic. Here, we present the case of a patient who was admitted to our hospital with acute respiratory distress HP syndrome MESHD (ARDS) following infection MESHD with COVID-19. After initial stabilization through restrictive fluid management, hemadsorption using Cytosorb® was performed and finally temporary extubation of the patient was possible. However, the patient again clinically deteriorated and needed ventilation and finally ECMO-support and high catecholamine application. Whilst being on VV- ECMO, hemadsorption using Biosky® MG 350 filter was performed. In this manuscript, after a brief overview of the role of hemadsorption in ARDS, a detailed case presentation is followed by a critical discussion of the current literature.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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