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HGNC Genes

SARS-CoV-2 proteins

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    Innate immune deficiencies in patients with COVID-19 MESHD

    Authors: Marine Peyneau; Vanessa Granger; Paul-Henri Wicky; Dounia Khelifi-Touhami; Jean-Francois Timsit; Francois-Xavier Lescure; Yazdan Yazdanpanah; Alexy Tran-Dihn; Philippe Montravers; Renato Monteiro; Sylvie Chollet-Martin; Margarita Hurtado-Nedelec; Luc de Chaisemartin

    doi:10.1101/2021.03.29.21254560 Date: 2021-03-31 Source: medRxiv

    COVID-19 MESHD can cause acute respiratory distress syndrome MESHD ( ARDS MESHD), leading to death in a significant number of individuals. Evidence of a strong role of the innate immune system is accumulating, but the precise cells and mechanism involved remain unclear. In this study, we investigated the links between circulating innate phagocyte phenotype and functions and severity in COVID-19 MESHD patients. Eighty-four consecutive patients were included, 44 of which were in intensive care units (ICU). We performed an in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, myeloid cell functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Resulting parameters were linked to disease severity and prognosis. Both ICU and non-ICU patients had circulating neutrophils and monocytes with an activated phenotype, as well as elevated concentrations of soluble activation markers (calprotectin, myeloperoxidase HGNC, neutrophil extracellular traps, MMP9 HGNC, sCD14) in their plasma. ICU MESHD patients were characterized by increased CD10 HGNClow CD13 HGNClow immature neutrophils, LOX-1 HGNC+ and CCR5 HGNC+ immunosuppressive neutrophils, and HLA-DRlow CD14 HGNClow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity and poor outcome. Moreover, neutrophils and monocytes of ICU patients had impaired antimicrobial functions, which correlated with organ dysfunction MESHD, severe infections, and mortality. Our study reveals a marked dysregulation MESHD of innate immunity in COVID-19 MESHD patients, which was correlated with severity and prognosis. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 MESHD severe infections and pleads for targeted therapeutic options.

    Disruptions to schistosomiasis programmes due to COVID-19 MESHD: an analysis of potential impact and mitigation strategies

    Authors: KLODETA KURA; Diepreye Ayabina; Jaspreet Toor; T. Deirdre Hollingsworth; Roy M Anderson

    doi:10.1101/2020.10.26.20219543 Date: 2020-10-27 Source: medRxiv

    Background: The 2030 goal for schistosomiasis MESHD is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-aged children ( SAC MESHD) a central pillar of the strategy. However, due to COVID-19 MESHD, many mass treatment campaigns for schistosomiasis MESHD have been halted with uncertain implications for the programmes. Method: We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni MESHD and S. haematobium. Results: In moderate and some high prevalence settings, the disruption may delay the goal by up to two years. In some high prevalence settings EPHP is not achievable with current strategies, and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and stage of the programme. Conclusions: Schistosomiasis MDA programmes in medium and high prevalence areas should restart as soon as is feasible, and mitigation strategies may be required in some settings.

    First Wave of COVID-19 MESHD Hospital Admissions in Denmark: A Nationwide Population-Based Cohort Study

    Authors: Jon Gitz Holler; Robert Eriksson; Tomas Østergaard Jensen; Maarten Van Wijhe; Thea Kølsen Fischer; Ole Schmeltz Søgaard; Simone Bastrup Israelsen; Rajesh Mohey; Thilde Fabricius; Frederik Jøhnk; Lothar Wiese; Stine Johnsen; Christian Søborg; Henrik Nielsen; Ole Kirk; Birgitte Lindegaard Madsen; Zitta Barrella Harboe

    doi:10.21203/rs.3.rs-66082/v1 Date: 2020-08-26 Source: ResearchSquare

    Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 MESHD ( COVID-19 MESHD), is a worldwide emergency. Demographic, clinical and laboratory factors associated with mortality in Danish patients hospitalised with  COVID-19 MESHD is limited.Methods: National health registries were used to identify all hospitalized patients with a COVID-19 MESHD diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis.Results: Among 2,431 hospitalised patients with COVID-19 MESHD between February 27th and July 8th (median age 69 years [IQR 53–80], 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU MESHD admission was lower for females (7.9%) than for males (16.7%), (p < 0.001). Age, high CCI, elevated C-reactive protein HGNC ( CRP HGNC), ferritin, D-dimer, lactate dehydrogenase (LDH), urea, creatinine, lymphopenia MESHD, neutrophilia, and thrombocytopenia MESHD within 24-hours of admission were independently associated with death within the first week in the multivariate analysis. Conditional upon surviving the first week, male sex, age, high CCI, elevated CRP HGNC, LDH, creatinine, urea and neutrophil count were associated with death MESHD within 30 days. Males presented with more pronounced laboratory abnormalities on admission. Conclusions: Advanced age, male sex, comorbidity, higher levels of systemic inflammation MESHD and cell-turnover were prognostic factors for mortality. Age was the strongest predictor for death MESHD, moderate to high level of comorbidity were associated with a nearly two-fold increase in mortality. Mortality was significantly higher for males after surviving the first week.  

    Rationale and Study Design of an Early Care, Therapeutic Education, and Psychological Intervention for the Management of Post-intensive Care Syndrome and Chronic Pain MESHD After Coronavirus Disease 2019 MESHD ( PAIN MESHD-COVID): Study protocol for a randomized controlled trial

    Authors: Antonio Ojeda; Andrea Calvo; Tomas Cuñat; Ricard Mellado Artigas; Oscar Comino-Trinidad; Jorge Aliaga; Marilyn Arias; Maribel Ahuir; Carlos Ferrando; Christian Dürsteler

    doi:10.21203/rs.3.rs-54199/v2 Date: 2020-08-05 Source: ResearchSquare

    Background: Critically ill MESHD patients with COVID-19 MESHD disease are an especially susceptible population to develop Post-intensive Care Syndrome ( PICS MESHD) due to acute respiratory distress syndrome MESHD ( ARDS MESHD). Patients can suffer acute severe pain MESHD and may have long-term deterioration in mental, cognitive, and functional health after discharge. However, few controlled trials are evaluating interventions for the prevention and treatment of PICS. The study hypothesis is that a specific care program based on early therapeutic education and a psychological intervention improves the quality of life of patients at risk of developing PICS and chronic pain MESHD after COVID-19 MESHD disease. The primary objective is to determine if the program is superior to standard-of-care on health-related life quality at six months after hospital discharge. The secondary objectives are to determine if the intervention is superior to standard care, evaluating the health-related life quality, the incidence of chronic pain MESHD and the degree of functional limitation, the incidence of anxiety MESHD, depression MESHD, and post- traumatic stress syndrome MESHD at 3 and 6 months after hospital discharge.Methods: The PAINCOVID trial is a unicentric randomized, controlled, patient blinded superiority trial with two parallel groups. The primary endpoint is the health-related quality of life at six months after hospital discharge, and randomization will be performed with a 1:1 allocation. This paper details the methodology and statistical analysis plan of the trial and was submitted before outcome data were available.The sample size calculated is 84 patients, 42 for each arm. Estimating a loss of follow up of 20%, a sample size of 102 patients is necessary (51 each group). Discussion: This is the first randomized clinical trial assessing the effectiveness of an early care therapeutic education, and psychological intervention for the management of PICS and Chronic Pain MESHD after COVID-19 MESHD. The intervention will serve as a sample of the need to implement early care programs on early stages, having an incalculable impact given the current scenario of the pandemic.Trial registration: This study is being in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board Comité Ético de Investigación Clínica del Hospital Clinic de Barcelona (approval number: HCB/2020/0549) and was registered on May 9, 2020 at  clinicaltrials.gov (NCT04394169).

    Early Improvement of Acute Respiratory Distress Syndrome in Patients with COVID-19 MESHD: 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 syndrome MESHD ( ARDS MESHD) may be the main cause of death MESHD in patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD). Herein, we retrospect clinical features, outcomes and ARDS characteristics of 75 intensive care unit (ICU) patients with COVID-19 MESHD in Chongqing, China. We found a 5.3% case fatality rate of the ICU MESHD patients in Chongqing. 93% patients developed ARDS MESHD 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 MESHD got an early improvement (eiARDS), and the rate is much higher than the other causes of ARDS MESHD in a previous study. Patients with eiARDS had a higher survival rate and lower length of ICU stay. The age (< 55 years) is an independent predictor for the eiARDS, and stratification of COVID-19 MESHD patients by age is recommended.

    Identifying main and interaction effects of risk factors to predict intensive care admission in patients hospitalized with COVID-19 MESHD: a retrospective cohort study in Hong Kong

    Authors: Jiandong Zhou; Gary Tse; Sharen Lee; Tong Liu; William KK Wu; zhidong cao; Dajun Zeng; Ian CK Wong; Qingpeng Zhang; Bernard MY Cheung

    doi:10.1101/2020.06.30.20143651 Date: 2020-07-02 Source: medRxiv

    Background: The coronavirus disease 2019 MESHD ( COVID-19 MESHD) has become a pandemic, placing significant burdens on the healthcare systems. In this study, we tested the hypothesis that a machine learning approach incorporating hidden nonlinear interactions can improve prediction for Intensive care unit (ICU) admission. Methods: Consecutive patients admitted to public hospitals between 1st January and 24th May 2020 in Hong Kong with COVID-19 MESHD diagnosed by RT-PCR were included. The primary endpoint was ICU admission. Results: This study included 1043 patients (median age 35 (IQR: 32-37; 54% male). Nineteen patients were admitted to ICU (median hospital length of stay (LOS): 30 days, median ICU LOS: 16 days). ICU MESHD patients were more likely to be prescribed angiotensin converting enzyme inhibitors/angiotensin receptor blockers, anti-retroviral drugs lopinavir/ritonavir and remdesivir, ribavirin, steroids, interferon-beta HGNC and hydroxychloroquine. Significant predictors of ICU admission were older age, male sex, prior coronary artery disease MESHD, respiratory diseases MESHD, diabetes MESHD, hypertension MESHD and chronic kidney disease MESHD, and activated partial thromboplastin time, red cell count, white cell count, albumin and serum sodium. A tree-based machine learning model identified most informative characteristics and hidden interactions that can predict ICU admission. These were: low red cells with 1) male, 2) older age, 3) low albumin, 4) low sodium or 5) prolonged APTT. A five-fold cross validation confirms superior performance of this model over baseline models including XGBoost, LightGBM, random forests, and multivariate logistic regression. Conclusions: A machine learning model including baseline risk factors and their hidden interactions can accurately predict ICU admission in COVID-19 MESHD.

    Fat mass prevalence and influence on nutritional status in ICU COVID-19 MESHD patients

    Authors: Antonino De Lorenzo; Maria Grazia Tarsitano; Carmela Falcone; Laura Di Renzo; Lorenzo Romano; Sebastiano Macheda; Anna Ferrarelli; Demetrio Labate; Marco Tescione; Federico Bilotta; Paola Gualtieri

    doi:10.21203/rs.3.rs-33974/v1 Date: 2020-06-06 Source: ResearchSquare

    Background: Obesity and steatosis MESHD are associated with COVID-19 MESHD severe pneumonia MESHD. Elevated levels of pro-inflammatory cytokines and reduced immune response are typical of these patients. In particular, adipose tissue is the organ playing the crucial role. So, it is necessary to evaluate fat mass and not simpler body mass index (BMI), because BMI leaves a portion of the obese MESHD population unrecognized. The aim is to evaluate the relationship between FM% and immune-inflammatory response, after 10th days in ICU.Methods: Prospective observational study in single cohort of 22 adult patients, affected by COVID-19 MESHD pneumonia MESHD and admitted to the Intensive Care Unit (ICU) and classified (10) lean and (12) obese MESHD, according to Percentage of Fat Mass (FM%) and age (De Lorenzo classification). Patients were analyzed at admission in ICU and at 10th day.Results: Obese have steatosis MESHD, impaired hepatic function MESHD, compromise immune response and higher inflammation MESHD. In addition, they have a reduced prognostic nutritional index ( PNI HGNC), nutritional survival index for ICU MESHD patients.Conclusion: This is the first study evaluating FM% in COVID-19 MESHD patient. We underlined obese MESHD characteristic with likely poorly prognosis and an important misclassification of obesity MESHD. A not negligible number of patients with normal BMI could actually have an excess of adipose tissue and therefore have an unfavorable outcome such as an obese MESHD. Is fundamental personalized patients nutrition basing on disease phases.

    COVID-19 MESHD: the key role of pulmonary capillary leakage. An observational cohort study

    Authors: Maddalena Alessandra Wu; Tommaso Fossali; Laura Pandolfi; Luca Carsana; Davide Ottolina; Vanessa Frangipane; Roberto Rech; Antonella Tosoni; Andrea Agarossi; Chiara Cogliati; Federica Meloni; Beatrice Marchini; Manuela Nebuloni; Emanuele Catena; Riccardo Colombo

    doi:10.1101/2020.05.17.20104877 Date: 2020-05-21 Source: medRxiv

    Background: COVID-19 MESHD induces progressive hypoxemic respiratory failure MESHD and acute respiratory distress syndrome MESHD, mostly due to a dysregulated MESHD inflammatory response. Since the first observations of COVID-19 MESHD patients, significant hypoalbuminemia MESHD was detected. This study aimed to investigate the hypothesis that hypoalbuminemia MESHD in COVID-19 MESHD patients is due to pulmonary capillary leakage and to test its correlation with indicators of respiratory function. Methods: 174 COVID-19 MESHD patients, 92 admitted to the Intermediate Medicine ward (IMW), and 82 to the Intensive Care Unit (ICU) at Luigi Sacco Hospital in Milan were included in this study. Findings: Serum albumin concentration was decreased in the whole cohort, with ICU MESHD patients displaying lower values than IMW patients [20 (18-23) vs 28 (24-33) g/L, p<0.0001]. Lower albumin values were found in patients belonging to a more compromised group (lower PaO2 to FiO2 ratio and worst chest X-ray findings). In a subset of 26 patients, analysis of bronchoalveolar lavage fluid (BALF) highlighted high protein concentrations, which were correlated to Interleukin-8 HGNC and Interleukin-10 HGNC BALF concentration. The length of hospitalisation [20 (15-29) vs 8 (5-14) days, p<0.0001] and death MESHD rate (52.4% vs 21.7%, p<0.0001) were higher in ICU than in IMW patients, while a strict relation between hypoalbuminemia MESHD and 30 day-survival was detected in the whole cohort. Electron microscopy examinations of eight out of ten autopsy lung tissues showed diffuse loosening of interendothelial junctional complex. Interpretation: The degree of hypoalbuminemia MESHD can be considered as a useful severity marker in hospitalised COVID-19 MESHD patients. Pulmonary capillary leak syndrome MESHD secondary to the hyperinflammatory state plays a key role in the pathogenesis of COVID-19 MESHD respiratory dysfunction MESHD and should be regarded as a therapeutic target.

    Epidemiological and clinical features of 201 COVID-19 MESHD patients in Changsha city, Hunan, China

    Authors: Jian Zhou; Jing-jing Sun; Zi-qin Cao; Wan-chun Wang; Kang Huang; Fang Zheng; Yuan-lin Xie; Di-xuan Jiang; Zhi-guo Zhou

    doi:10.21203/rs.3.rs-27266/v1 Date: 2020-05-06 Source: ResearchSquare

    Background: In December 2019, a cluster of coronavirus Disease MESHD coronavirus Disease 2019 MESHD ( COVID-19 MESHD) occurred in Wuhan, Hubei Province, China. With the advent of the Chinese Spring Festival, this disease spread rapidly throughout the country. The information about the clinical characteristics of COVID-19 MESHD patients outside of Wuhan is limited.Methods: All of the patients with confirmed COVID-19 MESHD were admitted to the First Hospital of Changsha City, the designated hospital for COVID-19 MESHD assigned by the Changsha City Government. The clinical and epidemiological characteristics, data of laboratory, radiological picture, treatment, and outcomes records of 201 COVID-19 MESHD patients were collected using electronic medical records.Results: This study population consisted of 201 hospitalized patients with laboratory-confirmed COVID-19 MESHD in Changsha by April 28, 2020. The median age of the patients was 45 years (IQR 34–59). About half (50.7%) of the patients were male, and most of the infected MESHD patients were staff (96 [47.8%]). Concerning the epidemiologic history, the number of patients linked to Wuhan was 92 (45.8%). The most common symptoms were fever MESHD (125 [62.2%]), dry cough MESHD (118 [58.7%]), fatigue MESHD (65 [32.3%]), and pharyngalgia (31 [15.4%]). One hundred and forty-four (71.6%) enrolled patients showed bilateral pneumonia MESHD. Fifty-four (26.9%) patients showed unilateral involvement, and three (1.5%) patients showed no abnormal signs or symptoms. The laboratory findings differed significantly between the Intensive Care Unit (ICU) and non-ICU groups. Compared with non-ICU patients, ICU MESHD patients had depressed MESHD white blood cell (WBC), neutrocytes, lymphocytes, and prolonged prothrombin time (PT). Moreover, higher plasma levels of erythrocyte sedimentation rate (ESR), C-reactive protein HGNC ( CRP HGNC), procalcitonin (PCT), alanine aminotransferase (ALA), aspartate aminotransferase ( AST HGNC), creatine kinase (CK), creatine kinase-MB (CK-MB), creatinine (CREA), and lactate dehydrogenase (LDH) were detected in the ICU group.Conclusions: In this single-center study of 201 COVID-19 MESHD patients in Changsha, China, 22.4% of patients were admitted to ICU. Based on our findings, we propose that the risk of cellular immune deficiency MESHD, hepatic injury MESHD, and kidney injury MESHD should be monitored. Previous reports focused on the clinical features of patients from Wuhan, China. With the global epidemic of COVID-19 MESHD, we should pay more attention to the clinical and epidemiological characteristics of patients outside of Wuhan.

    An outbreak of intestinal schistosomiasis, alongside increasing urogenital schistosomiasis prevalence, in primary school children on the shoreline of Lake Malawi, Mangochi District, Malawi

    Authors: Sekeleghe Kayuni; Angus M. O’Ferrall; Hamish Baxter; Josie Hesketh; Bright Mainga; David Lally; Mohammad H. Al-Harbi; E. James LaCourse; Lazarus Juziwelo; Janelisa Musaya; Peter Makaula; John Russell Stothard

    doi:10.21203/rs.3.rs-26662/v3 Date: 2020-05-03 Source: ResearchSquare

    Background: Intestinal schistosomiasis was not considered endemic in Lake Malawi until November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis MESHD was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis MESHD by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis MESHD is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed.Methods: During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis MESHD were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Samama (n = 80) and Mchoka (n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) (n = 60) and Koche (n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis MESHD, and B. pfeifferi, conducted across a further 8 shoreline schools (n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations.Results: In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by ‘positive’ urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% Confidence Interval (CI): 27.5–35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (Relative Risk (RR) = 1.7, 95% CI: 1.4–2.2) and Mchoka (RR = 2.7, 95% CI: 1.7–4.3) schools were observed. Intestinal schistosomiasis MESHD was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0% to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis MESHD was 24.0% (95% CI: 20.3–27.7). Conclusions: We notify that intestinal schistosomiasis MESHD, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 MESHD ( COVID-19 MESHD) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control. 

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SARS-CoV-2 Proteins


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