Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
    displaying 11 - 20 records in total 243
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    The folate antagonist methotrexate diminishes replication of the coronavirus SARS-CoV-2 and enhances the antiviral efficacy of remdesivir in cell culture models

    Authors: Kim M Stegmann; Antje Dickmanns; Sabrina Gerber; Vella Nikolova; Luisa Klemke; Valentina Manzini; Denise Schloesser; Cathrin Bierwirth; Julia Freund; Maren Sitte; Raimond Lugert; Gabriela Salinas; Dirk Goerlich; Bernd Wollnik; Uwe Gross; Matthias Dobbelstein

    doi:10.1101/2020.07.18.210013 Date: 2020-07-20 Source: bioRxiv

    The search for successful therapies of infections MESHD with the coronavirus SARS-CoV-2 is ongoing. We tested inhibition of host cell nucleotide synthesis as a promising strategy to decrease the replication of SARS-CoV-2-RNA, thus diminishing the formation of virus progeny. Methotrexate (MTX) is an established drug for cancer therapy and to induce immunosuppression. The drug inhibits dihydrofolate reductase and other enzymes required for the synthesis of nucleotides. Strikingly, the replication of SARS-CoV-2 was inhibited by MTX in therapeutic concentrations around 1 M, leading to more than 1000-fold reductions in virus progeny in Vero C1008 (Vero E6) as well as Calu-3 cells. Virus replication was more sensitive to equivalent concentrations of MTX than of the established antiviral agent remdesivir. MTX strongly diminished the synthesis of viral structural proteins and the amount of released virus RNA. Virus replication and protein synthesis were rescued by folinic acid (leucovorin) and also by inosine, indicating that purine depletion is the principal mechanism that allows MTX to reduce virus RNA synthesis. The combination of MTX with remdesivir led to synergistic impairment of virus replication, even at 300 nM MTX. The use of MTX in treating SARS-CoV-2 infections MESHD still awaits further evaluation regarding toxicity and efficacy in infected organisms, rather than cultured cells. Within the frame of these caveats, however, our results raise the perspective of a two-fold benefit from repurposing MTX for treating COVID-19. Firstly, its previously known ability to reduce aberrant inflammatory responses might dampen respiratory distress HP. In addition, its direct antiviral activity described here would limit the dissemination of the virus. SIGNIFICANCEO_LIMTX is one of the earliest cancer drugs to be developed, giving rise to seven decades of clinical experience. It is on the World Health Organizations List of Essential Medicines, can be administered orally or parenterally, and its costs are at single digit {euro} or $ amounts/day for standard treatment. In case of its successful further preclinical evaluation for treating SARS-CoV-2 infections MESHD, its repurposing to treat COVID-19 would thus be feasible, especially under low-resource conditions. C_LIO_LIAdditional drugs exist to interfere with the synthesis of nucleotides, e.g. additional folate antagonists, inhibitors of GMP synthetase, or inhibitors of dihydroorotate dehydrogenase (DHODH). Such inhibitors have been approved as drugs for different purposes and might represent further therapeutic options against infections MESHD with SARS-CoV-2 C_LIO_LIRemdesivir is currently the most established drug for treating COVID-19. Our results argue that MTX and remdesivir, even at moderate concentrations, can act in a synergistic fashion to repress virus replication to a considerably greater extent than either drug alone. C_LIO_LICOVID-19, in its severe forms, is characterized by pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD, and additional organ involvements. These manifestations are not necessarily a direct consequence of virus replication and cytopathic effects, but rather a result of an uncontrolled inflammatory and immune response. Anti-inflammatory drugs such as glucocorticoids are thus being evaluated for treating COVID-19. However, this bears the risk of re-activating virus spread by suppressing a sufficient and specific immune response. In this situation, it is tempting to speculate that MTX might suppress both excessive inflammation MESHD as well as virus replication at the same time, thus limiting both the pathogenesis of pneumonia MESHD pneumonia HP and also the spread of virus within a patient. C_LI

    Can Adenosine Fight COVID-19 Acute Respiratory Distress HP Syndrome MESHD?

    Authors: Carmela Falcone; Massimo Caracciolo; Pierpaolo Correale; Sebastiano Macheda; Eugenio Giuseppe Vadalà; Stefano La Scala; Marco Tescione; Roberta Danieli; Anna Ferrarelli; Maria Grazia Tarsitano; Lorenzo Romano; Antonino De Lorenzo

    id:10.20944/preprints202007.0426.v1 Date: 2020-07-19 Source: Preprints.org

    Some COVID-19 patients develop interstitial pneumonia MESHD pneumonia HP that can evolve into Acute Respiratory Distress HP Syndrome MESHD (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity MESHD obesity HP. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia MESHD / reperfusion models and could also be exploited in acute lung injury MESHD, with hypoxia MESHD. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure HP, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.

    Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19

    Authors: Chang Su; Zhenxing Xu; Katherine Hoffman; Parag Goyal; Monika M Safford; Jerry Lee; Sergio Alvarez-Mulett; Luis Gomez-Escobar; David R Price; John S Harrington; Lisa K Torres; Fernando J Martinez; Thomas R Campion Jr.; Rainu Kaushal; Augustine M.K. Choi; Fei Wang; Edward J Schenck

    doi:10.1101/2020.07.16.20155382 Date: 2020-07-18 Source: medRxiv

    Rationale. COVID-19-associated respiratory failure HP offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Prior studies of Acute Respiratory Distress HP Syndrome MESHD (ARDS) have identified subphenotypes with differential outcomes. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Objectives. To identify and characterize distinct subphenotypes of COVID-19 critical illness MESHD defined by the post-intubation trajectory of Sequential Organ Failure Assessment (SOFA) score. Methods. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Statistical tests defined trajectory subphenotype predictive markers. Measurements and Main Results. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p=0.033; intermediate stratum, 29.3% vs. 8.0%, p=0.002; severe stratum, 53.7% vs. 22.2%, p<0.001). Worsening and recovering subphenotypes were replicated in the validation cohort. Routine laboratory tests, vital signs, and respiratory variables rather than demographics and comorbidities were predictive of the worsening and recovering subphenotypes. Conclusions. There are clear worsening and recovering subphenotypes of COVID-19 respiratory failure HP after intubation, which are more predictive of outcomes than baseline severity of illness. Organ dysfunction trajectory may be well suited as a surrogate for research in COVID-19 respiratory failure HP.

    HIGH VERSUS STANDARD DOSES OF CORTICOSTEROIDS IN COVID-19 PATIENTS WITH AN ACUTE RESPIRATORY DISTRESS HP SYNDROME MESHD: a controlled observational comparative study.

    Authors: Enric Monreal; Susana Sainz de la Maza; Elena Natera-Villalba; Alvaro Beltran-Corbellini; Fernando Rodriguez-Jorge; Jose Ignacio Fernandez-Velasco; Paulette Walo-Delgado; Alfonso Muriel; Javier Zamora; Araceli Alonso-Canovas; Jesus Fortun; Luis Manzano; Beatriz Montero-Errasquin; Lucienne Costa-Frossard; Jaime Masjuan; Luisa Maria Villar

    doi:10.1101/2020.07.17.20156315 Date: 2020-07-17 Source: medRxiv

    INTRODUCTION: Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease MESHD 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. METHODS: All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress HP syndrome MESHD (ARDS). Patients were allocated to the high doses (HD, 250mg/day or more of methylprednisolone) of corticosteroids or the standard doses (SD, 1.5mg/kg/day or more of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death MESHD and the risk of developing a severe ARDS. RESULTS: 573 patients were included: 428 (74.7%) men, with a median (IQR) age TRANS of 64 (54-73) years. In HD cohort, a worse baseline respiratory situation was observed and male TRANS sex, older age TRANS and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58-3.83, p<0.001) and with an increased risk of needing MV or death MESHD (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly TRANS patients. CONCLUSION: Our real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

    Early initiation of Extracorporeal Blood SERO Purification using the AN69ST (oXiris®) hemofilter as a treatment modality for COVID - 19 patients: a single-centre case series

    Authors: Petar Ugurov; Dijana Popevski; Tanja Gramosli; Dashurie Neziri; Dragica Vuckova; Emil Stoicovski; Lidija Veljanovska-Kiridjievska; Katerina Ignevska; Sanja Mehandziska; Elena Ambarkova; Rodney Alexander Rosalia; Zan Mitrev

    doi:10.21203/rs.3.rs-44717/v1 Date: 2020-07-17 Source: ResearchSquare

    Introduction: Our understanding of the COVID-19 disease MESHD has been steadily evolving since the original outbreak in December 2019. Advanced disease MESHD is characterised by a hyperinflammatory state, systemic coagulopathies and multiorgan involvement, in particular respiratory distress HP. We here describe our initial experience with treating of COVID-19 patients based on early initiation of extracorporeal blood SERO purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females TRANS. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease MESHD severity following admission to our dedicated COVID-19 intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6, IL-8, TNF-α, C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood SERO Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability HP (= elevated Fibrinogen or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea, hypoxia MESHD, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure HP). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome MESHD. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood SERO cells, stable levels of IL-6 (< 50 ng/mL) and a decrease of CRP and Fibrinogen. Conclusion: Means to monitor COVID-19 disease MESHD severity during hospitalisation are crucial to control disease progression MESHD and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood SERO purification may prevent hyperinflammation, thromboembolism MESHD thromboembolism HP during hospitalisation and thus support clinical recovery. 

    Lung ultrasound and computed tomography to monitor COVID-19 pneumonia MESHD pneumonia HP in critically ill patients: a two-center prospective cohort study

    Authors: Micah Heldeweg; Jorge A. Lopez Matta; Mark E. Haaksma; Jasper M. Smit; Carlos V. Elzo Kraemer; Harm-Jan S. de Grooth; E. de Jonge; L.J. Meijboom; Leo M.A. Heunks; David J. van Westerloo; Pieter Roel Tuinman

    doi:10.21203/rs.3.rs-44726/v1 Date: 2020-07-17 Source: ResearchSquare

    Background: Lung ultrasound can adequately monitor disease MESHD severity in pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia MESHD pneumonia HP in critically ill patients. Methods: Adult TRANS patients with COVID-19 pneumonia MESHD pneumonia HP admitted to the intensive care unit of two academic hospitals who underwent a 12-zone lung ultrasound and a chest CT examination were included. Baseline characteristics, and outcomes including composite endpoint death MESHD or ICU stay >30 days were recorded. Lung ultrasound and CT images were quantified as a Lung Ultrasound Score Involvement index (LUSI) and CT Severity Involvement index (CTSI). Primary outcome was the correlation, agreement, and concordance between LUSI and CTSI. Secondary outcome was the association of LUSI and CTSI with the composite endpoints.Results: We included 55 ultrasound examinations in 34 patients, which were 88% were male TRANS, with a mean age TRANS of 63 years and mean P/F ratio of 151. The correlation between LUSI and CTSI was strong (r=0.795), with an overall 15% bias, and limits of agreement ranging -40 to 9.7. Concordance between changes in sequentially measured LUSI and CTSI was 81%. In the univariate model, high involvement on LUSI and CTSI were associated with a composite endpoint. In the multivariate model, LUSI was the only remaining independent predictor.Conclusions: Lung ultrasound can be used as an alternative for chest CT in monitoring COVID-19 pneumonia MESHD pneumonia HP in critically ill patients as it can quantify pulmonary involvement, register changes over the course of the disease MESHD, and predict death MESHD or ICU stay >30 days.Trial registration: NTR, NL8584. registered 01 May 2020 - retrospectively registered, https://www.trialregister.nl/trial/8584

    Acute Demyelinating Encephalomyelitis MESHD (ADEM) in COVID-19 infection MESHD: A Case Series.

    Authors: Michaela McCuddy; Praful Kelkar; Yu Zhao; David Wicklund

    doi:10.1101/2020.07.15.20126730 Date: 2020-07-17 Source: medRxiv

    Objective: To report three patients infected with COVID-19 with severe respiratory syndrome MESHD requiring intubation, who developed acute demyelinating encephalomyelitis MESHD (ADEM). Method: Patient data were obtained from medical records from the North Memorial Health Hospital, Robbinsdale, MN, USA Results: Three patients (two men and one woman, aged TRANS 38 - 63) presented with fatigue MESHD fatigue HP, cough MESHD cough HP and fever MESHD fever HP leading to development of acute respiratory distress HP syndrome MESHD secondary to COVID-19 infection MESHD requiring intubation and ventilatory support. Two patients were unresponsive, one with strong eye deviation to the left and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection MESHD, including negative COVID-19 PCR. All three of the patients received Convalescent plasma SERO therapy for COVID-19. All patients were treated with intravenous corticosteroids and improved, although two responded minimally. Two patients treated with IVIG showed no further improvement. Conclusion: Neurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune mediated complication of COVID-19 infection MESHD, which may be responsive to corticosteroid treatment. Early recognition of this complication and treatment is important to avoid long term complications.

    Early Improvement of Acute Respiratory Distress HP Syndrome MESHD in Patients with COVID-19: Insights from the Data of ICU Patients in Chongqing, China

    Authors: Zhu Zhan; Xin Yang; Hu Du; Chuanlai Zhang; Yuyan Song; Xiaoyun Ran; An Zhang; Mei Yang

    doi:10.1101/2020.07.15.20154047 Date: 2020-07-16 Source: medRxiv

    Acute respiratory distress HP syndrome MESHD (ARDS) may be the main cause of death MESHD in patients with coronavirus disease MESHD 2019 (COVID-19). Herein, we retrospect clinical features, outcomes and ARDS characteristics of 75 intensive care unit (ICU) patients with COVID-19 in Chongqing, China. We found a 5.3% case fatality rate of the ICU patients in Chongqing. 93% patients developed ARDS during the intensive care, and more than half were moderate. However, most of the patients (55%) supported with high flow nasal cannula (HFNC) oxygen therapy, but not mechanical ventilation. Nearly one third of patients with ARDS got an early improvement (eiARDS), and the rate is much higher than the other causes of ARDS in a previous study. Patients with eiARDS had a higher survival rate and lower length of ICU stay. The age TRANS (< 55 years) is an independent predictor for the eiARDS, and stratification of COVID-19 patients by age TRANS is recommended.

    Risks Of Ventilator-Associated Pneumonia MESHD Pneumonia HP And Invasive Pulmonary Aspergillosis MESHD Invasive Pulmonary Aspergillosis HP In Patients With Viral Acute Respiratory Distress HP Syndrome MESHD Related or Not To Coronavirus 19 Disease MESHD

    Authors: Keyvan Razazi; Romain ARRESTIER; Anne-Fleur Haudebourg; Brice Benelli; Guillaume Carteaux; Jean-Winoc Decousser; Slim Fourati; Paul-Louis Woerther; Frederic Schlemmer; Anais Charles-Nelson; Françoise Botterel; Nicolas De Prost; Armand Mekontso-Dessap

    doi:10.21203/rs.3.rs-44275/v1 Date: 2020-07-16 Source: ResearchSquare

    Background The goal of this study was to assess risk factors of ventilator-associated pneumonia MESHD pneumonia HP (VAP) and invasive pulmonary aspergillosis MESHD invasive pulmonary aspergillosis HP in patients with SARS-CoV-2 infection MESHD.Methods. We conducted a monocenter retrospective study comparing the prevalence SERO of VAP and invasive aspergillosis MESHD between patients with COVID-19 related acute respiratory distress HP syndrome MESHD (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).Results. We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 hours. At ICU admission, there were significantly fewer bacterial coinfections MESHD documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p<0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS : 58 (64%) vs. 36 (44%), p=0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death MESHD and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p<0.01].The prevalence SERO of multi-drug resistant bacteria (MDR) related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p=0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p<0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis MESHD in C-ARDS than in NC-ARDS  [2 (2%) vs. 12 (15%), p=0.003], but there was no difference in Aspergillus colonization.Conclusions. In this retrospective case-control study, we evidenced a higher prevalence SERO of VAP and MDR-VAP in C-ARDS than in NC-ARDS, and a lower risk for invasive aspergillosis MESHD in the former group.

    Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission TRANS associated with increased mortality in Western Europe and the United States

    Authors: Yuan Hu; Lee W Riley

    doi:10.1101/2020.07.13.20152959 Date: 2020-07-15 Source: medRxiv

    Mechanisms underlying the acute respiratory distress HP syndrome MESHD (ARDS)-like clinical manifestations leading to deaths MESHD in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility TRANS and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection MESHD may trigger a hyperinflammatory response similar to the antibody SERO-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies SERO against the first infection MESHD. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.

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MeSH Disease
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Transmission
Seroprevalence


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