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HGNC Genes

SARS-CoV-2 proteins

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    LENZILUMAB EFFICACY AND SAFETY IN NEWLY HOSPITALIZED MESHD COVID-19 MESHD SUBJECTS: RESULTS FROM THE LIVE-AIR PHASE 3 RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL

    Authors: Zelalem Temesgen; Charles D. Burger; Jason Baker; Christopher Polk; Claudia Libertin; Colleen Kelley; Vincent C Marconi; Robert Orenstein; Cameron Durrant; Dale Chappell; Omar Ahmed; Gabrielle Chappell; Andrew Badley

    doi:10.1101/2021.05.01.21256470 Date: 2021-05-05 Source: medRxiv

    BACKGROUND: Severe COVID19 MESHD pneumonia MESHD results from a hyperinflammatory immune response (cytokine storm, CS), characterized by GM CSF HGNC mediated activation and trafficking of myeloid cells, leading to elevation of downstream inflammatory chemokines ( MCP1 HGNC, IL8 HGNC, IP10 HGNC), cytokines ( IL6 HGNC, IL1 HGNC), and other markers of systemic inflammation MESHD ( CRP HGNC, D dimer, ferritin). CS leads to fever MESHD, hypotension MESHD, coagulopathy MESHD, respiratory failure MESHD, ARDS, and death MESHD. Lenzilumab is a novel Humaneered anti-human GM CSF HGNC monoclonal antibody that directly binds GM CSF HGNC and prevents signaling through its receptor. The LIVE AIR Phase 3 randomized, double blind, placebo controlled trial investigated the efficacy and safety of lenzilumab to assess the potential for lenzilumab to improve the likelihood of ventilator free survival (referred to herein as survival without ventilation, SWOV), beyond standard supportive care, in hospitalized subjects with severe COVID-19 MESHD. METHODS: Subjects with COVID-19 MESHD (n=520), >18 years <94% oxygen saturation on room air and/or requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized to receive lenzilumab (600 mg, n=261) or placebo (n=259) via three intravenous infusions administered 8 hours apart. Subjects were followed through Day 28 following treatment. RESULTS: Baseline demographics were comparable between the two treatment groups: male, 64.7%; mean age, 60.5 years; mean BMI, 32.5 kg/m2; mean CRP HGNC, 98.36 mg/L; CRP HGNC was <150 mg/L in 77.9% of subjects. The most common comorbidities were obesity MESHD (55.1%), diabetes MESHD (53.4%), chronic kidney disease MESHD (14.0%), and coronary artery disease MESHD (13.6%). Subjects received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the likelihood of SWOV by 54% in the mITT population (HR: 1.54; 95% CI: 1.02 to 2.31, p=0.041) and by 90% in the ITT population (HR: 1.90; 1.02 to 3.52, nominal p=0.043) compared to placebo. SWOV also relatively improved by 92% in subjects who received both corticosteroids and remdesivir (1.92; 1.20 to 3.07, nominal p=0.0067); by 2.96-fold in subjects with CRP HGNC<150 mg/L and age <85 years (2.96; 1.63 to 5.37, nominal p=0.0003); and by 88% in subjects hospitalized <2 days prior to randomization (1.88; 1.13 to 3.12, nominal p=0.015). Survival was improved by 2.17-fold in subjects with CRP HGNC<150 mg/L and age <85 years (2.17; 1.04 to 4.54, nominal p=0.040). CONCLUSION: Lenzilumab significantly improved SWOV in hospitalized, hypoxic subjects with COVID-19 MESHD pneumonia MESHD over and above treatment with remdesivir and/or corticosteroids. Subjects with CRP HGNC<150 mg/L and age <85 years demonstrated an improvement in survival and had the greatest benefit from lenzilumab. NCT04351152

    Altered Transcript Levels of Cytokines in COVID-19 MESHD Patients

    Authors: Majid Samsami; Alireza Fatemi; Reza Jalili Khoshnoud; Karim Kohansal; Arezou Sayad; Shabnam Soghala; Shahram Arsang-Jang; Mohammad Taheri; Soudeh Ghafouri-Fard

    doi:10.21203/rs.3.rs-126215/v1 Date: 2020-12-10 Source: ResearchSquare

    The pandemic caused by severe acute respiratory syndrome coronavirus 2 MESHD and the related disorder i.e. “ coronavirus disease 2019 MESHD” ( COVID-19 MESHD) have encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder MESHD. We aimed to assess the expression levels of nine cytokine coding in COVID-19 MESHD patients admitted in a hospital. Expression levels of IFN-G HGNC, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-17 HGNC, TGF-B HGNC, IL-8 HGNC and IL-1B HGNC were significantly higher in COVID-19 MESHD patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 HGNC whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Expression of TNF-A HGNC was not different between COVID-19 MESHD patients and healthy controls. Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 MESHD patients and controls. The area under curve (AUC) values range from 0.94 for IFN-G HGNC to 1.0 for IL-2 HGNC and IL-1B HGNC. After combining the transcript levels of all cytokines, AUC, sensitivity and specificity values reached 1.0, 1.0 and 0.99, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 HGNC with AUC value of 0.68, had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the assessed clinical/demographic data including age, gender, ICU admission, or CRP HGNC/ESR levels. Our study provides further evidence for contribution of “cytokine storm” in the pathobiology of moderate/severe forms of COVID-19 MESHD.

    Clinical Value of Blood Markers to Assess the Severity of Coronavirus Disease 2019 MESHD

    Authors: Liuniu Xiao; Xiao Ran; Yan-Xia Zhong; Shu-Sheng Li

    doi:10.21203/rs.3.rs-89388/v1 Date: 2020-10-07 Source: ResearchSquare

    Background: Severe acute respiratory syndrome coronavirus type 2 MESHD (SARS-CoV-2) is threatening the world with the symptoms of seasonal influenza. This study was conducted to investigate the patient characteristics and clinical value of blood markers to assess the severity of coronavirus disease 2019 MESHD ( COVID-19 MESHD). Methods: 187 patients, diagnosed with COVID-19 MESHD (non-severe and severe cases) and admitted to hospital between January 27th and March 8th of 2020, were enrolled in the present study. Results: A higher proportion of clinical symptoms, including cough, expectoration, myalgia MESHD and fatigue MESHD were observed in non-severe group. Significant increased level of WBC count, neutrophils, CRP HGNC, IL-6 HGNC and IL-8 HGNC were noted in severe group. The level of neutrophils, CRP HGNC, IL-6 HGNC and IL-8 HGNC were significantly increased, while platelet was remarkely decreased in the severe group. The risk model based on lymphocyte, IL-6 HGNC, IL-8 HGNC, CRP HGNC and platelet had the highest area under the receiver operator characteristic curve (AUROC). The baseline of IL-6 HGNC, IL-8 HGNC and CRP HGNC was positively correlated with other parameters except lymphocyte, hemoglobin and platelet. While the baseline of platelet was negatively correlated with other parameters except lymphocyte and hemoglobin. Additionally, there was no connection between severity of COVID-19 MESHD and cultures of blood, sputum and catheter secretion. Conclusions: The present study suggested that IL-6 HGNC, IL-8 HGNC, CRP HGNC and platelet played a critical role in deterioration of COVID-19 MESHD with potential value for monitoring the severity of COVID-19 MESHD

    More severe hypercoagulation status, cytokine storm, and disease progression in coronavirus disease 2019 MESHD with persistent RT-PCR negative results: a multicenter prospective study

    Authors: Wei Du; Guochao Shi; Min Zhou; Yahui Liu; Gelei Lan; Xueqing Du; Chunrong Huang; Ranran Dai; Wei Chen

    doi:10.21203/rs.3.rs-85866/v1 Date: 2020-09-30 Source: ResearchSquare

    Purpose: Persistent negative results (at least 3 times) of reverse transcription–polymerase chain reaction (RT-PCR) from pharyngeal swabs are not rare in coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients, but their characteristics have not yet been well studied.Methods: PCR confirmed, serum antibody confirmed with persistent negative PCR results, and clinically diagnosed patients hospitalized in two medical centers during February and March 2020 were included. Differences in clinical, imaging and laboratory characteristics as well as factors affecting their prognosis were analyzed.Results: There were 114 PCR confirmed, 17 serology confirmed and 21 clinically diagnosed patients included. Time from onset of disease to the first PCR and admission were similar among the groups. Compared with PCR-confirmed patients, serology-confirmed patients were older and likely to have hypertension MESHD, vomiting MESHD, or symptoms of chest pain MESHD and dyspnea MESHD. Regarding imaging manifestations, serology-confirmed patients were more prone to pleural effusion MESHD. In addition, higher levels of C-reactive protein HGNC, neutrophil-to-lymphocyte ratio, total bilirubin, D-dimer, fibrinogen HGNC, troponin, interleukin-6 HGNC and IL-8 HGNC were also found. Although with similar mortality, serology confirmed patients were more likely to have disease progression. High levels of D-dimer and IL-6 HGNC were possibly the underlying factors leading to their worse prognosis. On the other hand, clinically diagnosed patients were more similar to PCR-confirmed patients.Conclusion: Serology confirmed COVID-19 MESHD patients with at least three negative PCR results had different clinical characteristics and were likely to have disease progression, possibly due to more severe hypercoagulation status MESHD and cytokine storm.

    Early initiation of Extracorporeal Blood 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 MESHD disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperinflammatory state, systemic coagulopathies MESHD and multiorgan involvement, in particular respiratory distress. We here describe our initial experience with treating of COVID-19 MESHD patients based on early initiation of extracorporeal blood purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 MESHD intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6 HGNC, IL-8 HGNC, TNF-α HGNC, C-Reactive Protein HGNC ( CRP HGNC), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen HGNC, 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 Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability MESHD (= elevated Fibrinogen HGNC or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea MESHD, 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 MESHD). 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 cells, stable levels of IL-6 HGNC (< 50 ng/mL) and a decrease of CRP HGNC and Fibrinogen HGNC. Conclusion: Means to monitor COVID-19 MESHD disease severity during hospitalisation are crucial to control disease progression 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 purification may prevent hyperinflammation, thromboembolism MESHD during hospitalisation and thus support clinical recovery. 

    Systemic Inflammation and Clinical Outcomes in COVID-19 MESHD: a retrospective study

    Authors: Meijia Wang; Zhenli Huang; Kun Tang; Pengfei Gao; Yanjiao Lu; Shanshan Wang; Tao Wang; Jungang Xie; Jianping Zhao

    doi:10.21203/rs.3.rs-27267/v1 Date: 2020-05-06 Source: ResearchSquare

    Background: COVID-19 MESHD causes epidemics and pandemics worldwide, but the role of pathophysiological parameters particularly systemic inflammation MESHD in COVID-19 MESHD has not been understood. We aimed to investigate clinical outcomes in view of systemic inflammation MESHD in COVID-19 MESHD.Methods:In this retrospective study, the demographic and clinical data of 225 confirmed COVID-19 MESHD cases on admission at Tongji Hospital from January 28 to February 15, 2020, were extracted and analyzed. These patients were categorized by inflammation MESHD state on the basis of the expression of inflammatory factors or classified as severe and non-severe according to 2019 American Thoracic Society / Infectious Disease Society of America guidelines.Results: Among 225 patients with confirmed COVID-19 MESHD, 155 patients (68.9%) categorized into hyperinflammation group and 70 (31.1%) were non- hyperinflammation group. Compared to non-hyperinflammation group, hyperinflammation group more frequently had chest tightness/dyspnea and lymphopenia MESHD, aberrant multiple indexes of organ function including the heart, liver, kidney, and coagulation, with higher level of C-reactive protein HGNC (hsCRP) as well as interleukin (IL)-6, IL-8 HGNC, tumour necrosis MESHD factor α ( TNF-α HGNC), etc. Hyperinflammation group were more likely to admit to intensive care unit (ICU) (52.3% vs 5.7%), receive ventilation (84.5% vs 10.0%) and be with higher mortality (44.5% vs 5.7%) than non-hyperinflammation group. The mortality of severe patients with hyperinflammation (60/99, 60.6%) was significantly higher than without hyperinflammation (2/20, 10.0%). Non-severe patients with hyperinflammation even tended to have higher mortality (9/56, 16.1%) than those in severe cases without hyperinflammation (2/20, 10%).Conclusion: Excessive systemic inflammation MESHD was correlated highly with poor clinical outcomes in COVID-19 MESHD, particularly in severe cases. Non-severe patients with hyperinflammation even tended to have higher mortality than those in severe cases without hyperinflammation.Trial registration: This is a retrospective observational study without a trial registration number.

    Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 MESHD Pneumonia

    Authors: Jing Gong; Hui Dong; Song Qing Xia; Yi Zhao Huang; Dingkun Wang; Yan Zhao; Wenhua Liu; Shenghao Tu; Mingmin Zhang; Qi Wang; Fuer Lu

    doi:10.1101/2020.02.25.20025643 Date: 2020-02-27 Source: medRxiv

    Aim: The new coronavirus pneumonia MESHD ( COVID-19 MESHD) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters MESHD on disease progression. This study analyzed blood inflammation MESHD indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation MESHD-related indicators with disease criticality was analyzed. Cut-off values for critically ill MESHD patients were speculated through the ROC curve. ResultsSignificantly, disease severity were associated with age (R=-0.564, P<0.001), interleukin-2 receptor ( IL2R HGNC) (R=-0.534, P<0.001), interleukin-6 HGNC ( IL-6 HGNC) (R=-0.535, P<0.001), interleukin-8 HGNC ( IL-8 HGNC) (R=-0.308, P<0.001), interleukin-10 HGNC ( IL-10 HGNC) (R=-0.422, P<0.001), tumor MESHD tumor HGNC necrosis MESHD factor ( TNF HGNC) (R=-0.322, P<0.001), C-reactive protein HGNC ( CRP HGNC) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=-0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). ConclusionWith following parameters such as age >67.5 years, IL2R HGNC >793.5U/mL, CRP HGNC >30.7ng/mL, ferroprotein >2252g/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 MESHD to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19 MESHD, and IL-6 HGNC, TNF HGNC and IL-8 HGNC might be promising therapeutic targets.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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