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SARS-CoV-2 proteins

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    CERC-002, a human anti-LIGHT mAb reduces respiratory failure MESHD and death MESHD in hospitalized COVID-19 MESHD ARDS MESHD patients

    Authors: David S. Perlin; Garry A. Neil; Colleen Anderson; Inbal Zafir-Lavie; Lori Roadcap; Shane Raines; Carl Ware; Jeffrey Wilkins

    doi:10.1101/2021.04.03.21254748 Date: 2021-04-07 Source: medRxiv

    Background Severe COVID-19 MESHD infection is associated with dysregulated MESHD immune response which, in a substantial minority of patients, results in cytokine release syndrome ( CRS MESHD) and acute respiratory distress syndrome MESHD ( ARDS MESHD). Inhibition of cytokines or cytokine-associated signal transduction is a promising strategy to ameliorate ARDS MESHD associated with CRS. We and others have previously shown that serum free LIGHT ( TNFSF14 HGNC) levels are markedly elevated in patients with COVID-19 MESHD pneumonia MESHD/ARDS10,11, suggesting that LIGHT neutralization may offer therapeutic benefit to COVID-19 MESHD ARDS MESHD patients. Methods We conducted a randomized, double-blind, placebo-controlled, multi-center, proof-of-concept clinical trial of CERC-002 in adults with mild to moderate ARDS MESHD associated with COVID-19 MESHD (n=83). Enrolled patients received a single dose of CERC-002 or placebo, in addition to standard of care that included high dose corticosteroids. The primary efficacy endpoint was alive and free of respiratory failure MESHD status through Day 28. Secondary outcomes included alive status at Day 28, free of invasive ventilation through Day 28, and serum free LIGHT levels. Results In patients hospitalized with COVID-19 MESHD associated pneumonia MESHD and mild to moderate ( ARDS MESHD), CERC-002 increased the rate of alive and free of respiratory failure MESHD status through Day 28 as compared to placebo (83.9% vs 64.5%; p=0.044). Efficacy was highest in the prespecified subgroup of patients 60 years old and older (76.5% vs 47.1%; p=0.042), the population most vulnerable to severe complications and death MESHD with COVID-19 MESHD infection. Through both the initial 28-day and 60-day follow-up periods, reductions of approximately 50% in mortality were observed for CERC-002 compared to placebo (7.7% vs 14.3% at Day 28 and 10.8% vs 22.5% at Day 60). Importantly, this improvement was incremental to standard of care including high dose steroids and remdesivir 88.0% and 57.8%, respectively). In addition, serum LIGHT levels but not IL-6 HGNC levels were markedly reduced in patients treated with CERC-002. Conclusions The data presented herein demonstrate that CERC-002 markedly reduces the risk of respiratory failure MESHD and death incremental MESHD to standard of care including high dose corticosteroids and reduces LIGHT levels in patients with COVID-19 MESHD ARDS MESHD. (ClinicalTrials.gov number NCT04412057).

    IL-6 HGNC and D-Dimer at Admission Predicts Cardiac Injury MESHD and Early Mortality during SARS-CoV-2 Infection MESHD

    Authors: Daoyuan Si; Beibei Du; Bo Yang; Lina Jin; Lujia Ni; Qian Zhang; Zhongfan Zhang; Mohammed Ali Azam; Patrick F.H Lai; Stephane Masse; Huan Sun; Xingtong Wang; Slava Epelman; Patrick R Lawler; Ping Yang; Kumaraswamy Nanthakumar

    doi:10.1101/2021.03.22.21254077 Date: 2021-03-29 Source: medRxiv

    BACKGROUND: We recently described mortality of cardiac injury MESHD in COVID-19 MESHD patients. Admission activation of immune, thrombotic MESHD biomarkers and their ability to predict cardiac injury MESHD and mortality patterns in COVID-19 MESHD is unknown. METHODS: This retrospective cohort study included 170 COVID-19 MESHD patients with cardiac injury MESHD at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS: Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death MESHD were elevate levels of interleukin 6 HGNC ( IL-6 HGNC) (p<0.0001), Tumor Necrosis Factor-a HGNC Tumor Necrosis Factor-a MESHD ( TNF-a HGNC) (p=0.0025), and C-reactive protein HGNC ( CRP HGNC) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic MESHD pathway activation. Increasing cTnI HGNC levels were associated with those of increasing IL-6 HGNC (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS: In COVID-19 MESHD patients with cardiac injury MESHD, admission IL-6 HGNC and D-dimer predicted subsequent elevation of cTnI HGNC and early death MESHD, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury MESHD.

    Tocilizumab Effect in COVID-19 MESHD Hospitalized Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials

    Authors: Waleed Tharwat Aletreby; Basheer Abdulrahman; Ahmed Fouad Mady; Alfateh Mohammed Noor; Mohammed H Lhmdi; Fahad Faqihi; Abdulrahman M Alharthy; Mohammed A Al-Odat; Dimitrios Karakitsos; Ziad Memish

    doi:10.1101/2021.03.15.21253581 Date: 2021-03-17 Source: medRxiv

    Since the emergence of the first cases of COVID-19 MESHD viral pneumonia MESHD late 2019 several studies evaluated the benefits of different treatment modalities. Early in the pandemic, the interleukin 6 HGNC (IL-6) receptor antibody Tocilizumab was considered in view of the cytokine release syndrome associated with COVID-19 MESHD infection. Several early observational studies showed beneficial effect of treatment with Tocilizumab on mortality, however, results from well-designed randomized clinical trials (RCT) were contradicting. ObjectivesTo perform a systematic literature review and meta-analysis of RCTs utilizing Tocilizumab in the treatment of COVID-19 MESHD pneumonia MESHD, with in-hospital mortality as a primary objective, while secondary objectives included composite outcome of mortality, intubation, or ICU admission, another secondary outcome was super added infection. MethodThis was a random effects model (DerSimonian and Laird) model of relative risk (RR), along with corresponding 95% confidence intervals, p values, and forest plots of both primary and secondary outcomes. A fixed effect sensitivity test was performed for the primary outcome, in addition to subgroup and meta-regression analyses with predefined criteria. ResultsThe primary outcome of mortality showed statistically insignificant reduction of mortality with Tocilizumab (RR = 0.9, 95% CI: 0.8 - 1.01; p = 0.09) although with an unmistakable apparent clinical benefit. There was a significant reduction in the RR of the secondary composite outcome (RR = 0.83, 95% CI: 0.76 - 0.9; p < 0.001), and no difference between groups in super-added infection (RR = 0.77, 95% CI: 0.51 - 1.19; p = 0.24). Treatment protocol allowing a second dose was the only significant predictor of improved mortality in the meta-regression analysis. Certainty of evidence was reduced to moderate for the primary outcome and the secondary outcome of clinical deterioration, while it was reduced to low for the secondary outcome of super-added infection. ConclusionModerate certainty of evidence suggest no statistically significant improvement of 28-30 day all-cause mortality of hospitalized COVID-19 MESHD patients treated with TCZ, although there may be clinically important value. Moderate certainty of evidence suggest lowered relative risk of a composite outcome of death MESHD or clinical deterioration, while, low grade evidence indicate no increase in the risk of super-added infection associated with TCZ treatment. A protocol allowing two doses of TCZ shows evidence of improved mortality as compared to a strictly single dose protocol.

    Targeting of the NLRP3 HGNC Inflammasome for early COVID-19 MESHD

    Authors: Carlo Marchetti; Kara Mould; Isak W. Tengesdal; William J. Janssen; Charles A. Dinarello

    doi:10.1101/2021.02.24.432734 Date: 2021-02-24 Source: bioRxiv

    Following entry and replication of Severe Acute Respiratory Syndrome-coronavirus MESHD 2 (SARS-CoV-2) into ACE2 expressing cells, the infected cells undergo lysis releasing more virus but also cell contents. In the lung, constitutive cytokines such as IL-1 HGNC are released together with other cell contents. A cascade of inflammatory cytokines ensues, including chemokines and IL-1{beta}, triggering both local as well as systemic inflammation MESHD. This cascade of inflammatory cytokines in patients with COVID-19 MESHD is termed Cytokine Release Syndrome ( CRS MESHD), and is associated with poor outcomes and death MESHD. Many studies reveal that blocking IL-1{beta HGNC} activities in COVID-19 MESHD patients reduces disease severity and deaths MESHD. Here we report highly significant circulating levels of IL-1{beta HGNC}, IL-1 Receptor antagonist HGNC, IL-6 HGNC, TNF HGNC, IL-10 HGNC and soluble urokinase plasminogen activator receptor HGNC in COVID-19 MESHD patients with mild or no symptoms. We also report that in circulating myeloid cells from the same patients, there is increased expression of the NOD-, LRR- and pyrin domain-containing 3 ( NLRP3 HGNC) early in the infection. We observed increased NLRP3 HGNC gene expression in myeloid cells correlated with IL-1{beta HGNC} gene expression and also with elevated circulating IL-1{beta HGNC} levels. We conclude that early in SARS-CoV-2 infection MESHD, NLRP3 HGNC activation takes place and initiates the CRS. Thus, NLRP3 HGNC is a target to reduce the organ damage of inflammatory cytokines of the CRS.

    Combination therapy of Tocilizumab and steroid for management of COVID-19 MESHD associated cytokine release syndrome: A single center experience from Pune, Western India

    Authors: Ameet Dravid; Reema Kashiva; Zafer Khan; Danish Memon; Aparna Kodre; Prashant Potdar; Milind Mane; Rakesh Borse; Vishal Pawar; Dattatraya Patil; Debashis Banerjee; Kailas Bhoite; Reshma Pharande; Suraj Kalyani; Prathamesh Raut; Madhura Bapte; Anshul Mehta; M Sateesh Reddy; Krushnadas Bhayani; S S Laxmi; P D Vishnu; Shipra Srivastava; Shubham Khandelwal; Sailee More; Rohit Shinde; Mohit Pawar; Amol Harshe; Sagar Kadam; Uma Mahajan; Gaurav Joshi; Dilip Mane

    doi:10.1101/2021.02.04.21249959 Date: 2021-02-06 Source: medRxiv

    Background: Cytokine release syndrome ( CRS MESHD) or cytokine storm is thought to be the cause of inflammatory lung damage MESHD, worsening pneumonia MESHD and death MESHD in patients with COVID-19 MESHD. Steroids (Methylprednisolone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor HGNC antagonist, are approved for the treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroids in COVID-19 MESHD associated CRS. Methods: This retrospective cohort study was conducted at a tertiary level private hospital in Pune, India between 2nd April and 2nd November 2020. All patients administered TCZ and steroids for treatment of CRS were included. The primary endpoint was the incidence of all-cause mortality. Secondary outcomes studied were the need for mechanical ventilation and incidence of infectious complications. Baseline and time-dependent risk factors significantly associated with death MESHD were identified by Relative risk estimation. Results: Out of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. Median age of the cohort was 57 (IQR: 46.5, 66) years. Almost 72 % patients had preexisting co-morbidities. Median time to TCZ administration since onset of symptoms was 9 days (IQR: 7, 11). 63% patients needed intensive care unit (ICU) admission. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Infectious complications like hospital acquired pneumonia MESHD, bloodstream bacterial and fungal infections MESHD were observed in 2.13 %, 2.13 % and 0.06 % patients respectively. Age [≥] 60 years (p=0.014), presence of co-morbidities like hypertension MESHD (p = 0.011), IL-6 HGNC [≥] 100 pg/ml (p = 0.002), D-dimer [≥] 1000 ng/ml (p < 0.0001), CT severity index [≥] 18 (p < 0.0001) and systemic complications like lung fibrosis MESHD (p = 0.019), cardiac arrhythmia MESHD (p < 0.0001), hypotension MESHD (p < 0.0001) and encephalopathy MESHD (p < 0.0001) were associated with increased risk of death MESHD. Conclusions: Combination therapy of TCZ and Steroids is likely to be safe and effective in the management of COVID-19 MESHD associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled clinical trials.

    Administration of tocilizumab to patients with high concentrations of IL-6 HGNC in the course of COVID-19 MESHD is associated with a better prognosis

    Authors: Robert Flisiak; Jerzy Jaroszewicz; Magdalena Rogalska; Tadeusz Lapinski; Aleksandra Berkan-Kawinska; Beata Bolewska; Magdalena Tudrujek-Zdunek; Dorota Kozielewicz; Marta Rorat; Piotr Leszczynski; Krzysztof Klos; Justyna Kowalska; Pawel Pabjan; Anna Piekarska; Iwona Mozer-Lisewska; Krzysztof Tomasiewicz; Malgorzata Pawlowska; Krzysztof Simon; Joanna Polanska; Dorota Zarebska-Michaluk

    doi:10.1101/2021.01.28.21249932 Date: 2021-02-01 Source: medRxiv

    Background Despite the direct viral activity, the pathogenesis of coronavirus disease 2019 MESHD ( COVID-19 MESHD) includes an overproduction of cytokines including interleukin 6 HGNC ( IL-6 HGNC). Therefore tocilizumab (TCZ), a monoclonal antibody against IL-6 HGNC receptors, became considered as a possible therapeutic option. Methods Patients were selected from the SARSTer national database, which included 2332 individuals with COVID-19 MESHD and the current study included 825 adult patients with moderate to severe course. The retrospective analysis was performed in 170 patients treated with TCZ and 655 without this medication or any other anti-cytokine therapy. The end-points of treatment effectiveness were a rate of death, need for mechanical ventilation, and clinical improvement. Results Patients treated with TCZ were balanced compared to non-TCZ regarding gender, age, BMI, and prevalence of coexisting conditions. The reduced death rate was demonstrated in patients treated with TCZ and baseline IL-6 HGNC >100 pg/ml (hazard ratio [HR]: 0.27, 95% confidence interval [CI]:0.10-0.78), or those needing oxygen supplementations who worsened within 7 days of hospitalization (HR: 0.38, 95% CI:0.16-0.88). The best effectiveness of TCZ was achieved in patients with a combination of baseline IL-6>100 pg/ml and either SpO2[≤]90% (HR for death MESHD, mechanical ventilation, and clinical improvement after 21 or 28 days: 0.07, 0.14, 5.53, 5.18 respectively) or requiring oxygen supplementation (HR for death MESHD and clinical improvement after 21 or 28 days, 0.18, 2.66, 2.85 respectively). Conclusions Tocilizumab administered for COVID-19 MESHD in patients with a baseline concentration of IL-6>100 pg/ml is associated with reduced mortality and faster clinical improvement, particularly if there is a need for oxygen supplementation due to SpO2[≤]90%.

    Clinical utility of Corona Virus Disease MESHD-19 serum IgG, IgM, and neutralizing antibodies and inflammatory markers

    Authors: Ernst J Schaefer; Florence Comite; Latha Dulipsingh; Maxine Lang; Jessica Jimison; Martin M Grajower; Nathan E Lebowitz; Andrew S Geller; Margaret R Diffenderfer; Lihong He; Gary Breton; Michael L Dansinger; Ben Saida; Chong Yuan

    doi:10.1101/2021.01.19.21249604 Date: 2021-01-20 Source: medRxiv

    Most deaths MESHD from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD occur in older subjects. We assessed age effects and clinical utility of serum SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies and serum inflammatory markers. Serum IgG, IgM, and neutralizing antibody levels were measured using chemiluminescence assays from Diazyme (Poway, CA), while serum interleukin-6 HGNC ( IL-6 HGNC), C reactive protein HGNC ( CRP HGNC), and ferritin were measured with immunoassays obtained from Roche (Indianapolis, IN). In 79,005 subjects, IgG and IgM levels were positive ([≥]1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively. In antibody positive subjects, median IgG levels were 3.93 AU/mL if <45 years of age, 10.18 AU/mL if 45-64 years of age, and 10.85 AU/mL if [≥]65 years of age (p<0.0001). In SARS-CoV-2 RNA positive cases, family members and exposed subjects (n=1,111), antibody testing was found to be valuable for case finding, and persistent IgM levels were associated with chronic symptoms. In non-hospitalized and hospitalized subjects assessed for SARS-CoV-2 RNA (n=278), median IgG levels in AU/mL were 0.05 in negative subjects (n=100), 14.83 in positive outpatients (n=129), and 30.61 in positive hospitalized patients (n=49, p<0.0001). Neutralizing antibody levels correlated significantly with IgG (r=0.875; p<0.0001). Two or more of the criteria of IL-6 HGNC [≥]10 pg/mL, CRP HGNC [≥]10 mg/L, and/or IgM >1.0 AU/mL occurred in 97.7% of inpatients versus 1.8% of outpatients (>50-fold relative risk, C statistic 0.986, p<0.0001). Our data indicate that: 1) IgG levels are significantly higher in positive older subjects, possibly to compensate for decreased cellular immunity with aging; 2) IgG levels are important for case finding in family clusters; 3) IgG levels are significantly correlated with neutralizing antibody levels; 4) persistently elevated IgM levels are associated with chronic disease MESHD; and 5) markedly elevated IL-6 HGNC, hs- CRP HGNC, and/or positive IgM accurately identify SARS-CoV-2 RNA positive subjects requiring hospitalization.

    Detection of SARS-Cov-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 MESHD patients.

    Authors: Diego A. Rodriguez Serrano; Emilia Roy-Vallejo; Nelly D. Zurita Cruz; Alexandra Martin Ramirez; Sebastian C. Rodriguez-Garcia; Nuria Arevalillo-Fernandez; Jose Maria Galvan-Roman; Leticia Fontan Garcia-Rodrigo; Lorena Vega Piris; Marta Chicot Llano; David Arribas Mendez; Begona Gonzalez de Marcos; Julia Hernando Santos; Ana Sanchez Azofra; Elena Avalos Perez-Urria; Pablo Rodriguez-Cortes; Laura Esparcia; Ana Marcos-Jimenez; Santiago Sanchez-Alonso; Irene Llorente; Joan B. Soriano; Carmen Suarez Fernandez; Rosario Garcia-Vicuna; Julio Ancochea; Jesus Sanz; Cecilia Munoz-Calleja; Rafael de la Camara; Alfonso Canabal Berlanga; Isidoro Gonzalez-Alvaro; Laura Cardenoso

    doi:10.1101/2021.01.14.21249372 Date: 2021-01-15 Source: medRxiv

    Background COVID-19 MESHD has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19 MESHD. Methods and FindingsRetrospective observational study including 193 patients admitted for COVID-19 MESHD. Detection of SARS-CoV-2 RNA in serum (CoVemia) was performed with samples collected at 48-72 hours of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19 MESHD. CoVemia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with CoVemia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia MESHD (p < 0.001) and higher LDH (p < 0.001), IL-6 HGNC (p = 0.021), C-reactive protein HGNC ( CRP HGNC; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant CoVemia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35 % specificity. Relevant CoVemia predicted death during hospitalization (OR 9.2 [3.8 - 22.6] for Roche, OR 10.3 [3.6 - 29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant CoVemia (HR = 9.87 [4.13-23.57] for TFS viremia MESHD and HR = 7.09 [3.3-14.82] for Roche viremia MESHD) as the best markers to predict mortality. ConclusionsCoVemia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 MESHD patients. CoVemia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 MESHD and better predictive accuracy. AUTHOR SUMMARY COVID-19 MESHD shows a very heterogeneous clinical picture. In addition, it has overloaded national health services worldwide. Therefore, early identification of patients with poor prognosis is critical to improve the use of limited health resources. In this work, we evaluated whether baseline SARS-CoV2 RNA detection in blood (CoVemia) is associated with worse outcomes. We studied almost 200 patients admitted to our hospital and about 50-60% of them showed positive CoVemia. Patients with positive CoVemia were older and had more severe disease; CoVemia was also more frequent in patients requiring admission to the ICU. Moreover, we defined "relevant CoVemia", as the amount of viral load that better predicted mortality obtaining 95% sensitivity and 35% specificity. In addition, relevant CoVemia was a better predictor than other biomarkers such as LDH, lymphocyte count, interleukin-6 HGNC, and indexes used in ICU such as qSOFA and CURB65. In summary, detection of CoVemia is the best biomarker to predict death MESHD in COVID-19 MESHD patients. Furthermore, it is easy to be implemented and is reproducible with two techniques (Roche and Thermo Fisher Scientific) that are currently used for diagnosis in nasopharyngeal swabs samples.

    Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 MESHD patients

    Authors: Jorge A. Masso-Silva PhD; Alexander Moshensky BS; Michael T. Y. Lam MD PhD; Mazen Odish MD; Arjun Patel MBBS; Le Xu PhD; Emily Hansen MS; Samantha Trescott BS; Celina Nguyen BS; Roy Kim BS; Katherine Perofsky MD; Samantha Perera N/A; Lauren Ma BS; Josephine Pham N/A; Mark Rolfsen MD; Jarod Olay MS; John Shin BS; Jennifer M. Dan MD PhD; Robert Abbott PhD; Sydney Ramirez MD PhD; Thomas H. Alexander MD MHSc; Grace Y. Lin MD; Ana Lucia Fuentes MD; Ira N. Advani BS; Deepti Gunge BS; Victor Pretorius MBChB MD; Atul Malhotra MD; Xin Sun PhD; Jason Duran MD PhD; Shane Crotty PhD; Nicole G. Coufal MD PhD; Angela Meier MD PhD; Laura E. Crotty Alexander MD

    doi:10.1101/2021.01.14.21249831 Date: 2021-01-15 Source: medRxiv

    BackgroundIncreased inflammation MESHD is a hallmark of COVID-19 MESHD, with pulmonary and systemic inflammation MESHD identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases MESHD and acute respiratory distress syndrome MESHD ( ARDS MESHD), a primary cause of morbidity and mortality in COVID-19 MESHD. Changes in multiple neutrophil functions and circulating cytokine levels over time during COVID-19 MESHD may help define disease severity and guide care and decision making. MethodsBlood was obtained serially from critically ill COVID-19 MESHD patients for 11 days. Neutrophil oxidative burst, neutrophil extracellular trap formation (NETosis), phagocytosis and cytokine levels were assessed ex vivo. Lung tissue was obtained immediately post-mortem for immunostaining. ResultsElevations in neutrophil-associated cytokines IL-8 HGNC and IL-6 HGNC, and general inflammatory cytokines IP-10 HGNC, GM-CSF HGNC, IL-1b HGNC, IL-10 and TNF MESHD, were identified in COVID-19 MESHD plasma both at the first measurement and at multiple timepoints across hospitalization (p < 0.0001). Neutrophils had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis correlated with both leukocytosis and neutrophilia MESHD. Neutrophils and NETs were identified within airways and alveoli in the lung parenchyma of 40% of SARS-CoV-2 infected lungs MESHD. While elevations in IL-8 HGNC and ANC correlated to COVID-19 MESHD disease severity, plasma IL-8 HGNC levels alone correlated with death MESHD. ConclusionsCirculating neutrophils in COVID-19 MESHD exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 HGNC and circulating neutrophil function may be potential COVID-19 MESHD disease biomarkers.

    Efficacy of Doxycycline in treating COVID-19 MESHD Positive Patients: A Case Series

    Authors: Zohreh Akhoundi Meybody; Mohammad Bagher Owlia; Sina Owlia; Seyed Rohollah Mousavinasab

    doi:10.21203/rs.3.rs-141875/v3 Date: 2021-01-06 Source: ResearchSquare

    Background: Given the high morbidity and mortality caused by Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), scientific research is necessary to achieve a proper treatment regimen. Since doxycycline is effective in reducing inflammatory factors, including IL-6 HGNC and TNF-alpha HGNC that play an important role in initiating cytokine storms and probably causing death MESHD in patients with COVID-19 MESHD, its use is associated with low side effects and can be used orally, the present study was attempted to evaluate the efficacy of doxycycline in the treatment of inpatients and outpatients with COVID-19 MESHD.Methods: This descriptive and prospective study was performed on inpatients and outpatients were diagnosed with COVID-19 MESHD based on polymerase chain reaction (PCR) test from nasopharyngeal secretions or computerized tomography scan (CT Scan). Patients who met the inclusion criteria received doxycycline at a dose of 100 mg every 12 hours for 7 days and then were evaluated on the baseline day and on days 3, 7, and 14 after admission for cough, Shortness of breath MESHD, temperature and oxygen saturation.Results:  Out of 21 patients, 11 patients were male and 10 patients were female. Cough, SOB, temperature, and O2 sat improved in both of outpatients and inpatients compared to baseline. In general, the results showed that doxycycline was more effective in improving cough, SOB, temperature, and O2 sat in outpatients than inpatients. Conclusion:  It can be concluded that doxycycline with the dose and duration prescribed in our study could play an effective role in the treatment of patients with COVID-19 MESHD

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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