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1.
Small Methods ; 5(5): e2001108, 2021 05.
Article in English | MEDLINE | ID: covidwho-1930144

ABSTRACT

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3 C2 Tx MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Hemoperfusion/methods , Nanostructures/administration & dosage , SARS-CoV-2/immunology , Titanium/administration & dosage , Adsorption , COVID-19/transmission , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/virology , Humans , Interleukin-6/immunology , Nanostructures/chemistry , SARS-CoV-2/isolation & purification , Titanium/chemistry
3.
Front Immunol ; 12: 781100, 2021.
Article in English | MEDLINE | ID: covidwho-1686474

ABSTRACT

Multiple studies have investigated the role of blood circulating proteins in COVID-19 disease using the Olink affinity proteomics platform. However, study inclusion criteria and sample collection conditions varied between studies, leading to sometimes incongruent associations. To identify the most robust protein markers of the disease and the underlying pathways that are relevant under all conditions, it is essential to identify proteins that replicate most widely. Here we combined the Olink proteomics profiles of two newly recruited COVID-19 studies (N=68 and N=98) with those of three previously published COVID-19 studies (N=383, N=83, N=57). For these studies, three Olink panels (Inflammation and Cardiovascular II & III) with 253 unique proteins were compared. Case/control analysis revealed thirteen proteins (CCL16, CCL7, CXCL10, CCL8, LGALS9, CXCL11, IL1RN, CCL2, CD274, IL6, IL18, MERTK, IFNγ, and IL18R1) that were differentially expressed in COVID-19 patients in all five studies. Except CCL16, which was higher in controls, all proteins were overexpressed in COVID-19 patients. Pathway analysis revealed concordant trends across all studies with pathways related to cytokine-cytokine interaction, IL18 signaling, fluid shear stress and rheumatoid arthritis. Our results reaffirm previous findings related to a COVID-19 cytokine storm syndrome. Cross-study robustness of COVID-19 specific protein expression profiles support the utility of affinity proteomics as a tool and for the identification of potential therapeutic targets.


Subject(s)
Blood Proteins/metabolism , COVID-19/blood , Cytokines/blood , Transcriptome/genetics , Aged , Biomarkers/blood , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Cytokines/metabolism , Female , Gene Expression Profiling , Humans , Inflammation/blood , Male , Middle Aged , Proteomics , SARS-CoV-2/immunology , Signal Transduction
4.
Cytokine ; 151: 155804, 2022 03.
Article in English | MEDLINE | ID: covidwho-1630370

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a "cytokine storm". IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. Il-32 was never evaluated before in COVID-19 patients stratifying as mild-moderate and severe patients. A total of 64 COVID-19 patients, 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1ß, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32, while IL-6 resulted the better variables for discriminate severe group. The best model performance for severe group was obtained by the combination of IL-32, IL-6, IFN-γ, and CRP serum concentration showing an AUC = 0.83. A cut off of 15 pg/ml of IL-6 greatly discriminate survivor from death patients. New insights related to the cytokine storm in COVID-19 patients, highlighting different severity of disease infection.


Subject(s)
COVID-19/blood , Cytokines/blood , Interleukin-8/blood , Interleukins/blood , Lung/immunology , Aged , Biomarkers/blood , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokines/immunology , Female , Humans , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-8/immunology , Interleukins/immunology , Lymphocyte Count/methods , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Prospective Studies , SARS-CoV-2/immunology
5.
Iran J Immunol ; 18(4): 331-337, 2021 12.
Article in English | MEDLINE | ID: covidwho-1594484

ABSTRACT

BACKGROUND: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. OBJECTIVE: To determine the association of serum cytokine levels with COVID-19 severity. METHODS: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico. RESULTS: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables. CONCLUSION: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Interleukin-10/metabolism , Interleukin-6/metabolism , COVID-19/pathology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Female , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Mexico , Patient Acuity
6.
J Clin Invest ; 132(3)2022 02 01.
Article in English | MEDLINE | ID: covidwho-1555937

ABSTRACT

BACKGROUNDSevere coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune response, which can result in cytokine-release syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19-associated ARDS have elevated free serum levels of the cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT; also known as TNFSF14). Such patients may benefit from LIGHT-neutralization therapy.METHODSThis randomized, double-blind, multicenter, proof-of-concept trial enrolled adults hospitalized with COVID-19-associated pneumonia and mild to moderate ARDS. Patients received standard of care plus a single dose of a human LIGHT-neutralizing antibody (CERC-002) or placebo. The primary endpoint was the proportion of patients receiving CERC-002 who remained alive and free of respiratory failure through day 28. Safety was assessed via adverse event monitoring.RESULTSFor most of the 83 enrolled patients, standard of care included systemic corticosteroids (88.0%) or remdesivir (57.8%). A higher proportion of patients remained alive and free of respiratory failure through day 28 after receiving CERC-002 (83.9%) versus placebo (64.5%; P = 0.044), including in patients 60 years of age or older (76.5% vs. 47.1%, respectively; P = 0.042). Mortality rates were 7.7% (CERC-002) and 14.3% (placebo) on day 28 and 10.8% and 22.5%, respectively, on day 60. Treatment-emergent adverse events were less frequent with CERC-002 than placebo.CONCLUSIONFor patients with COVID-19-associated ARDS, adding CERC-002 to standard-of-care treatment reduces LIGHT levels and might reduce the risk of respiratory failure and death.TRIAL REGISTRATIONClinicalTrials.gov NCT04412057.FUNDINGAvalo Therapeutics.


Subject(s)
Antibodies, Monoclonal/administration & dosage , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 14/antagonists & inhibitors , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones/administration & dosage , Adult , Alanine/administration & dosage , Alanine/analogs & derivatives , COVID-19/blood , COVID-19/mortality , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/mortality , Disease-Free Survival , Double-Blind Method , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Survival Rate , Tumor Necrosis Factor Ligand Superfamily Member 14/blood
7.
Front Immunol ; 12: 771609, 2021.
Article in English | MEDLINE | ID: covidwho-1551509

ABSTRACT

An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and mortality in patients with COVID-19. Longitudinal analysis of cytokine release can expand our understanding of the initial stages of disease development and help to identify early markers serving as predictors of disease severity. In this study, we performed a comprehensive analysis of 46 cytokines (including chemokines and growth factors) in the peripheral blood of a large cohort of COVID-19 patients (n=444). The patients were classified into five severity groups. Longitudinal analysis of all patients revealed two groups of cytokines, characterizing the "early" and "late" stages of the disease course and the switch between type 1 and type 2 immunity. We found significantly increased levels of cytokines associated with different severities of COVID-19, and levels of some cytokines were significantly higher during the first three days from symptom onset (DfSO) in patients who eventually required intensive care unit (ICU) therapy. Additionally, we identified nine cytokines, TNF-α, IL-10, MIG, IL-6, IP-10, M-CSF, G-CSF, GM-CSF, and IFN-α2, that can be used as good predictors of ICU requirement at 4-6 DfSO.


Subject(s)
Antibodies, Viral/blood , COVID-19/mortality , Cytokine Release Syndrome/blood , Cytokines/blood , SARS-CoV-2/immunology , Severity of Illness Index , Acute-Phase Reaction/blood , Antibodies, Viral/immunology , COVID-19/pathology , Critical Care/statistics & numerical data , Cytokine Release Syndrome/pathology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Prognosis , RNA, Viral/analysis
8.
J Mol Neurosci ; 72(1): 27-36, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1544564

ABSTRACT

The pandemic caused by severe acute respiratory syndrome coronavirus 2 and the related disorder i.e. "coronavirus disease 2019" (COVID-19) has 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. We aimed to assess expression levels of nine cytokine coding genes in COVID-19 patients admitted in a hospital. We collected clinical data of patients from their medical reports. Then, we assessed expression of genes using real-time PCR. Expression levels of IFN-G, IL-2, IL-4, IL-6, IL-17, TGF-B, IL-8, and IL-1B were significantly higher in COVID-19 patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression level of TNF-A was not different between COVID-19 patients and healthy controls. Expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 patients and controls. The area under curve (AUC) values ranged from 0.94 for IFN-G to 1.0 for IL-2 and IL-1B. After combining the transcript levels of all cytokines, AUC, sensitivity, and specificity values reached 100%, 100%, and 99%, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 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 available clinical/demographic data including age, gender, ICU admission, or erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) levels. This study provides further evidence for contribution of "cytokine storm" in the pathobiology of moderate/severe forms of COVID-19.


Subject(s)
COVID-19/blood , Cytokine Release Syndrome/blood , Cytokines/genetics , Pandemics , RNA, Messenger/blood , Adult , Aged , Aged, 80 and over , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/epidemiology , Case-Control Studies , Critical Care , Cytokine Release Syndrome/etiology , Female , Gene Expression Regulation , Humans , Iran/epidemiology , Male , Middle Aged , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Severity of Illness Index
9.
J Med Virol ; 93(12): 6519-6524, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544297

ABSTRACT

The COVID-19 pandemic, which has ravaged our world for more than a year, still shapes our agenda with a scale of intensity that fluctuates over time. In our study, we aimed to determine the correlation between serum migration inhibitory factor (MIF) level and disease severity in COVID-19 with different prognoses. Between 15 October 2020 and 20 January 2021, 110 patients over the age of 18 who were diagnosed with COVID-19 and 40 volunteer healthcare personnel were included in our study. MIF levels were measured by enzyme-linked immunosorbent assay. In the comparison of serum MIF values in the patient and control group, it was observed that the MIF level was significantly higher in patients with both moderate and severe COVID-19 levels compared to the control group (p = 0.001, 0.001). In the comparison of serum MIF values of moderate to severe COVID-19 patients, it was observed that MIF level was higher in severe patients (p = 0.001). In the receiver operating characteristic curve analysis performed to differentiate between severe and moderate COVID-19 patients with MIF levels, the area under the curve was observed as 0.78. When the cutoff value of the MIF level was taken as 4.455 ng/ml, the sensitivity was 83% and the specificity was 62%. Failure to adequately balance the pro-inflammatory cytokines synthesized in COVID-19 with anti-inflammatory effect is the most important reason for the aggravation of the disease course. Playing a role in pro-inflammatory cytokine synthesis, MIF can provide important information about the disease prognosis in the early period.


Subject(s)
COVID-19/pathology , Cytokine Release Syndrome/blood , Intramolecular Oxidoreductases/blood , Macrophage Migration-Inhibitory Factors/blood , Macrophages/immunology , SARS-CoV-2/immunology , Case-Control Studies , Cytokine Release Syndrome/pathology , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Macrophage Activation/immunology , Male , Middle Aged , Prognosis , Severity of Illness Index
10.
J Clin Lab Anal ; 36(1): e24064, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525450

ABSTRACT

BACKGROUND: The unresolved COVID-19 pandemic considerably impacts the health services in Iraq and worldwide. Consecutive waves of mutated virus increased virus spread and further constrained health systems. Although molecular identification of the virus by polymerase chain reaction is the only recommended method in diagnosing COVID-19 infection, radiological, biochemical, and hematological studies are substantially important in risk stratification, patient follow-up, and outcome prediction. AIM: This narrative review summarized the hematological changes including the blood indices, coagulative indicators, and other associated biochemical laboratory markers in different stages of COVID-19 infection, highlighting the diagnostic and prognostic significance. METHODS: Literature search was conducted for multiple combinations of different hematological tests and manifestations with novel COVID-19 using the following key words: "hematological," "complete blood count," "lymphopenia," "blood indices," "markers" "platelet" OR "thrombocytopenia" AND "COVID-19," "coronavirus2019," "2019-nCoV," OR "SARS-CoV-2." Articles written in the English language and conducted on human samples between December 2019 and January 2021 were included. RESULTS: Hematological changes are not reported in asymptomatic or presymptomatic COVID-19 patients. In nonsevere cases, hematological changes are subtle, included mainly lymphocytopenia (80.4%). In severe, critically ill patients and those with cytokine storm, neutrophilia, lymphocytopenia, elevated D-dimer, prolonged PT, and reduced fibrinogen are predictors of disease progression and adverse outcome. CONCLUSION: Monitoring hematological changes in patients with COVID-19 can predict patients needing additional care and stratify the risk for severe course of the disease. More studies are required in Iraq to reflect the hematological changes in COVID-19 as compared to global data.


Subject(s)
COVID-19/blood , COVID-19/etiology , Cytokine Release Syndrome/blood , Pregnancy Complications, Infectious/blood , Biomarkers/blood , Blood Coagulation , Cytokine Release Syndrome/virology , Female , Hematologic Tests , Humans , Leukocyte Count , Lymphopenia/blood , Lymphopenia/virology , Pregnancy , Pregnancy Complications, Infectious/virology , Severity of Illness Index
11.
Clin Microbiol Rev ; 34(3)2021 06 16.
Article in English | MEDLINE | ID: covidwho-1501524

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a rapidly evolving pandemic worldwide with at least 68 million COVID-19-positive cases and a mortality rate of about 2.2%, as of 10 December 2020. About 20% of COVID-19 patients exhibit moderate to severe symptoms. Severe COVID-19 manifests as acute respiratory distress syndrome (ARDS) with elevated plasma proinflammatory cytokines, including interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor α (TNF-α), C-X-C motif chemokine ligand 10 (CXCL10/IP10), macrophage inflammatory protein 1 alpha (MIP-1α), and chemokine (C-C motif) ligand 2 (CCL2), with low levels of interferon type I (IFN-I) in the early stage and elevated levels of IFN-I during the advanced stage of COVID-19. Most of the severe and critically ill COVID-19 patients have had preexisting comorbidities, including hypertension, diabetes, cardiovascular diseases, and respiratory diseases. These conditions are known to perturb the levels of cytokines, chemokines, and angiotensin-converting enzyme 2 (ACE2), an essential receptor involved in SARS-CoV-2 entry into the host cells. ACE2 downregulation during SARS-CoV-2 infection activates the angiotensin II/angiotensin receptor (AT1R)-mediated hypercytokinemia and hyperinflammatory syndrome. However, several SARS-CoV-2 proteins, including open reading frame 3b (ORF3b), ORF6, ORF7, ORF8, and the nucleocapsid (N) protein, can inhibit IFN type I and II (IFN-I and -II) production. Thus, hyperinflammation, in combination with the lack of IFN responses against SARS-CoV-2 early on during infection, makes the patients succumb rapidly to COVID-19. Therefore, therapeutic approaches involving anti-cytokine/anti-cytokine-signaling and IFN therapy would favor the disease prognosis in COVID-19. This review describes critical host and viral factors underpinning the inflammatory "cytokine storm" induction and IFN antagonism during COVID-19 pathogenesis. Therapeutic approaches to reduce hyperinflammation and their limitations are also discussed.


Subject(s)
COVID-19/pathology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Interferon Type I/blood , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/blood , COVID-19/therapy , Comorbidity , Humans , Immunity, Innate/immunology , Immunization, Passive/methods , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Spike Glycoprotein, Coronavirus/metabolism
12.
Br J Haematol ; 196(4): 923-927, 2022 02.
Article in English | MEDLINE | ID: covidwho-1488181

ABSTRACT

Patients who are severely affected by coronavirus disease 2019 (COVID-19) may develop a delayed onset 'cytokine storm', which includes an increase in interleukin-6 (IL-6). This may be followed by a pro-thrombotic state and increased D-dimers. It was anticipated that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID-19. However, clinical trials with TCZ have recorded an increase in D-dimer levels. In contrast to TCZ, colchicine reduced D-dimer levels in patients with COVID-19. To understand how the two anti-inflammatory agents have diverse effects on D-dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID-19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL-6, α-Defensin (α-Def), a pro-thrombotic peptide, and D-dimers. In contrast, treatment with colchicine reduced α-Def and Di-dimer levels. In vitro studies show that IL-6 stimulated the release of α-Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL-6; raising the possibility that the increase in IL-6 in patients with COVID-19 treated with TCZ triggers the release of α-Def, which promotes pro-thrombotic events reflected in an increase in D-dimer levels.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Colchicine/therapeutic use , Fibrin Fibrinogen Degradation Products/analysis , alpha-Defensins/immunology , Aged , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Female , Fibrin Fibrinogen Degradation Products/immunology , Humans , Interleukin-6/blood , Interleukin-6/immunology , Male , Middle Aged , Neutrophils/drug effects , Neutrophils/immunology
13.
Hamostaseologie ; 41(5): 379-385, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1483188

ABSTRACT

In 2019 first reports about a new human coronavirus emerged, which causes common cold symptoms as well as acute respiratory distress syndrome. The virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe thrombotic events including deep vein thrombosis, pulmonary embolism, and microthrombi emerged as additional symptoms. Heart failure, myocardial infarction, myocarditis, and stroke have also been observed. As main mediator of thrombus formation, platelets became one of the key aspects in SARS-CoV-2 research. Platelets may also directly interact with SARS-CoV-2 and have been shown to carry the SARS-CoV-2 virus. Platelets can also facilitate the virus uptake by secretion of the subtilisin-like proprotein convertase furin. Cleavage of the SARS-CoV-2 spike protein by furin enhances binding capabilities and virus entry into various cell types. In COVID-19 patients, platelet count differs between mild and serious infections. Patients with mild symptoms have a slightly increased platelet count, whereas thrombocytopenia is a hallmark of severe COVID-19 infections. Low platelet count can be attributed to platelet apoptosis and the incorporation of platelets into microthrombi (peripheral consumption) and severe thrombotic events. The observed excessive formation of thrombi is due to hyperactivation of platelets caused by the infection. Various factors have been suggested in the activation of platelets in COVID-19, such as hypoxia, vessel damage, inflammatory factors, NETosis, SARS-CoV-2 interaction, autoimmune reactions, and autocrine activation. COVID-19 does alter chemokine and cytokine plasma concentrations. Platelet chemokine profiles are altered in COVID-19 and contribute to the described chemokine storms observed in severely ill COVID-19 patients.


Subject(s)
Blood Platelets/physiology , Blood Platelets/virology , COVID-19/blood , Blood Platelets/immunology , COVID-19/complications , COVID-19/immunology , Chemokines/blood , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Host Microbial Interactions/immunology , Host Microbial Interactions/physiology , Humans , Models, Biological , Pandemics , Platelet Activation/immunology , Platelet Activation/physiology , SARS-CoV-2/pathogenicity , Thrombosis/blood , Thrombosis/etiology
15.
Immunopharmacol Immunotoxicol ; 43(6): 633-643, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1467231

ABSTRACT

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Purinergic Antagonists/therapeutic use , Receptors, Purinergic/drug effects , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Host-Pathogen Interactions , Humans , Ligands , Molecular Targeted Therapy , Multiple Organ Failure/immunology , Multiple Organ Failure/prevention & control , Multiple Organ Failure/virology , Purinergic Antagonists/adverse effects , Receptors, Purinergic/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction
16.
Int Immunopharmacol ; 101(Pt A): 108192, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1433412

ABSTRACT

The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group's demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Lovastatin/pharmacology , Adult , Anti-Inflammatory Agents/therapeutic use , COVID-19/blood , Case-Control Studies , Critical Care/methods , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokines/drug effects , Female , Hospitalization , Humans , Intensive Care Units , Interleukin-6/metabolism , Interleukin-8/metabolism , Lovastatin/therapeutic use , Male , Middle Aged , Receptors, Immunologic/metabolism , Sex Factors
17.
Biomed Pharmacother ; 145: 112243, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1432984

ABSTRACT

OBJECTIVE: In this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients. METHODS: A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n = 8) - Standard treatment; Gr. 2: Standard treatment + AFO-202 beta glucan (n = 8); and Gr. 3, Standard treatment + combination of AFO-202 and N-163 beta glucans (n = 8) for 30 days. RESULTS: There was no mortality or requirement of ventilation of the subjects in any of the groups. There was a decrease in D-Dimer values (751 ng/ml to 143.89 ng/ml) and IL-6 values (7.395-3.16 pg/ml) in Gr. 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202.5 ng/ml; IL-6 55.37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560.99 ng/dl to 79.615; IL-6: 26.18-3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25-0.5 pg/ml). The same trend was observed with ESR. LCR and LeCR increased while NLR decreased significantly in Gr. 3. CD4 + and CD8 + T cell count showed relatively higher increase in Gr.3. There was no difference in CRP within the groups. CONCLUSION: As these beta glucans are well known food supplements with a track record for safety, larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.


Subject(s)
Aureobasidium , COVID-19 , Cytokine Release Syndrome , Fibrin Fibrinogen Degradation Products/analysis , Interleukin-6/analysis , beta-Glucans/administration & dosage , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , Complementary Therapies/methods , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Dietary Supplements , Female , Humans , Immunologic Factors/administration & dosage , Male , Middle Aged , Pilot Projects , SARS-CoV-2 , Treatment Outcome
18.
J Steroid Biochem Mol Biol ; 213: 105964, 2021 10.
Article in English | MEDLINE | ID: covidwho-1433601

ABSTRACT

OBJECTIVE: We aimed to evaluate the vitamin D status of pregnant women with COVID-19, and the association between vitamin D level and severity of COVID-19. METHODS: In this case control study, 159 women with a single pregnancy and tested positive for SARS-CoV-2, and randomly selected 332 healthy pregnant women with similar gestational ages were included. COVID-19 patients were classified as mild, moderate, and severe. Vitamin D deficiency was defined as 25-hydroxycholecalciferol <20 ng/mL (50 nmol/L), and 25-OH D vitamin <10 ng/mL was defined as severe vitamin D deficiency, also 25-OH D vitamin level between 20-29 ng/mL (525-725 nmol/L) was defined as vitamin D insufficiency. RESULTS: Vitamin D levels of the pregnant women in the COVID-19 group (12.46) were lower than the control group (18.76). 25-OH D vitamin levels of those in the mild COVID-19 category (13.69) were significantly higher than those in the moderate/severe category (9.06). In terms of taking vitamin D supplementation, there was no statistically significant difference between the groups. However, it was observed that all of those who had severe COVID-19 were the patients who did not take vitamin D supplementation. CONCLUSION: The vitamin D levels are low in pregnant women with COVID-19. Also, there is a significant difference regarding to vitamin D level and COVID-19 severity in pregnant women. Maintenance of adequate vitamin D level can be useful as an approach for the prevention of an aggressive course of the inflammation induced by this novel coronavirus in pregnant women.


Subject(s)
COVID-19/diet therapy , Cytokine Release Syndrome/diet therapy , Dietary Supplements , Pregnancy Complications, Infectious/diet therapy , Vitamin D Deficiency/diet therapy , Vitamin D/administration & dosage , Adult , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Calcifediol/blood , Case-Control Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Female , Gestational Age , Humans , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Treatment Outcome , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/pathology , Vitamin D Deficiency/virology
19.
Int Immunopharmacol ; 100: 108163, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1415472

ABSTRACT

Zinc deficiency is associated with impaired antiviral response, cytokine releasing syndrome (CRS), and acute respiratory distress syndrome. Notably, similar complications are being observed during severe SARS-CoV-2 infection. We conducted a prospective, single-center, observational study in a tertiary university hospital (CUB-Hôpital Erasme, Brussels) to address the zinc status, the association between the plasma zinc concentration, development of CRS, and the clinical outcomes in PCR-confirmed and hospitalized COVID-19 patients. One hundred and thirty-nine eligible patients were included between May 2020 and November 2020 (median age of 65 years [IQR = 54, 77]). Our cohort's median plasma zinc concentration was 57 µg/dL (interquartile range [IQR] = 45, 67) compared to 74 µg/dL (IQR = 64, 84) in the retrospective non-COVID-19 control group (N = 1513; p < 0.001). Markedly, the absolute majority of COVID-19 patients (96%) were zinc deficient (<80 µg/dL). The median zinc concentration was lower in patients with CRS compared to those without CRS (-5 µg/dL; 95% CI = -10.5, 0.051; p = 0.048). Among the tested outcomes, zinc concentration is significantly correlated with only the length of hospital stay (rho = -0.19; p = 0.022), but not with mortality or morbidity. As such, our findings do not support the role of zinc as a robust prognostic marker among hospitalized COVID-19 patients who in our cohort presented a high prevalence of zinc deficiency. It might be more beneficial to explore the role of zinc as a biomarker for assessing the risk of developing a tissue-damaging CRS and predicting outcomes in patients diagnosed with COVID-19 at the early stage of the disease.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/etiology , SARS-CoV-2 , Zinc/blood , Aged , COVID-19/blood , Cytokine Release Syndrome/blood , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Zinc/physiology
20.
Cell Rep ; 37(1): 109793, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1415261

ABSTRACT

The mortality risk of coronavirus disease 2019 (COVID-19) patients has been linked to the cytokine storm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the inflammatory responses shared between COVID-19 and other infectious diseases that feature cytokine storms may therefore help in developing improved therapeutic strategies. Here, we use integrative analysis of single-cell transcriptomes to characterize the inflammatory signatures of peripheral blood mononuclear cells from patients with COVID-19, sepsis, and HIV infection. We identify ten hyperinflammatory cell subtypes in which monocytes are the main contributors to the transcriptional differences in these infections. Monocytes from COVID-19 patients share hyperinflammatory signatures with HIV infection and immunosuppressive signatures with sepsis. Finally, we construct a "three-stage" model of heterogeneity among COVID-19 patients, related to the hyperinflammatory and immunosuppressive signatures in monocytes. Our study thus reveals cellular and molecular insights about inflammatory responses to SARS-CoV-2 infection and provides therapeutic guidance to improve treatments for subsets of COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/immunology , HIV Infections/blood , Leukocytes, Mononuclear/metabolism , SARS-CoV-2/immunology , Sepsis/blood , Transcriptome , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokines/blood , Data Analysis , Datasets as Topic , HIV Infections/immunology , HIV-1/immunology , Humans , Inflammation/blood , Leukocytes, Mononuclear/immunology , Sepsis/immunology , Single-Cell Analysis
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