scholarly journals Correction to: Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α

2021 ◽  
Author(s):  
Paolo Frisoni ◽  
Margherita Neri ◽  
Stefano D’Errico ◽  
Letizia Alfieri ◽  
Diana Bonuccelli ◽  
...  
Keyword(s):  
Viral Load ◽  
Cytokine Storm ◽  
Histopathological Findings ◽  
Tnf Α

scholarly journals Cell wall N-glycan of Candida albicans ameliorates early hyper- and late hypo-immunoreactivity in sepsis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Masataka Kawakita ◽  
Taiki Oyama ◽  
Ikuma Shirai ◽  
Shuto Tanaka ◽  
Kotaro Akaki ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Severe Infection ◽  
Cytokine Storm ◽  
Immune Exhaustion ◽  
Sepsis Model ◽  
Yeast Strains ◽  
Immune Paralysis ◽  
Tnf Α ◽  
Immunosuppressive Cytokine ◽  
Ifn Γ

AbstractSevere infection often causes a septic cytokine storm followed by immune exhaustion/paralysis. Not surprisingly, many pathogens are equipped with various anti-inflammatory mechanisms. Such mechanisms might be leveraged clinically to control septic cytokine storms. Here we show that N-glycan from pathogenic C. albicans ameliorates mouse sepsis through immunosuppressive cytokine IL-10. In a sepsis model using lipopolysaccharide (LPS), injection of the N-glycan upregulated serum IL-10, and suppressed pro-inflammatory IL-1β, TNF-α and IFN-γ. The N-glycan also improved the survival of mice challenged by LPS. Analyses of structurally defined N-glycans from several yeast strains revealed that the mannose core is key to the upregulation of IL-10. Knocking out the C-type lectin Dectin-2 abrogated the N-glycan-mediated IL-10 augmentation. Furthermore, C. albicans N-glycan ameliorated immune exhaustion/immune paralysis after acute inflammation. Our results suggest a strategy where the immunosuppressive mechanism of one pathogen can be applied to attenuate a severe inflammation/cytokine storm caused by another pathogen.

Montelukast - Its Immunomodulatory and Antiviral Action in COVID-19

2021 ◽  
Vol 8 (21) ◽  
pp. 1731-1732
Author(s):  
Prashant Ramesh Chakkarwar
Keyword(s):  
Tissue Factor ◽  
Inflammatory Cytokines ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Cytokine Storm ◽  
Oak Ridge ◽  
Montelukast Sodium ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Coronavirus disease-19 (COVID-19) is the deadliest pandemic that the whole world is facing today. COVID-19 is different from normal flu by its two lethal manifestations which includes deadly pneumonia which may lead to acute respiratory distress syndrome (ARDS) due to hyper-inflammation of alveolar tissues and pulmonary intravascular coagulopathy (PIC).1,2 It is noteworthy here to mention that both these lethal manifestations of COVID-19 are due to abnormally high levels of pro-inflammatory cytokines like interleukin (IL) - 1β, IL - 6, and tumour necrosis factor (TNF) - α, termed as “cytokine storm.”3,4 There is a certain link between pro-inflammatory cytokines like IL - 1β, IL - 6, and TNF - α and its pro-coagulatory influence on coagulation pathway mediated by tissue factor that binds and activate factor VII, leading to formation of tissue factor – VII a complexes which results in the activation of clotting factor X and IX.4 Recently the researchers in China and some European countries have found raised level of pro-inflammatory cytokines particularly IL - 6 in severe cases of COVID-19. They also found raised D-dimer, fibrinogen levels and prothrombin time in moderate to severe COVID-19 cases.5,6 Both of these lethal manifestations of COVID-19 – ARDS and PIC are linked to raised levels of pro-inflammatory cytokines, particularly, IL - 6. It is not very clear that the pro-inflammatory action of cytokines is mediated through leukotrienes as the biochemical assay for leukotrienes are not widely available but possibility of this probable mechanism cannot be ruled out. Hence, development of any molecule with ability to inhibit pro-inflammatory cytokines, particularly IL-6 may be able to tame the lethal nature of COVID-19, and may ultimately reduce the mortality of this deadly pandemic. Montelukast sodium is such molecule which has capacity to inhibit proinflammatory cytokines such as IL - 1β, IL - 6, and TNF - α.7 Montelukast sodium is leukotriene receptor antagonist that inhibits the cysteinyl leukotriene type-1 receptor. Leukotrienes modulate the production of pro-inflammatory cytokines.8 Its antagonist action on leukotriene receptors can inhibit the production of these pro-inflammatory cytokines. Even recent in silico study by Jacobson at Oak Ridge National Lab, was found that excess bradykinin production may be responsible for pulmonary, cardiac, neurological and nephrological lethal manifestations of COVID-19.9 Crimi et al.10 already found that Montelukast is effective to control bradykinin induced bronchoconstriction. Thus, theoretically, montelukast seems to be best molecule to deal with deadly manifestation of COVID-19 even if we go by cytokine storm hypothesis or bradykinin hypothesis.

scholarly journals Probable Neuropsychological & Cognitive Complications due to Cytokine Storm in Patients With COVID-19

2021 ◽  
Vol 0 (0) ◽  
pp. 1-37
Author(s):  
Zahra Keshtgar ◽  
◽  
GH. Reza Chalabianloo ◽  
Niloofar Esmaeili ◽  
◽  
...  
Keyword(s):  
Nervous System ◽  
Case Reports ◽  
Case Series ◽  
Executive Dysfunction ◽  
Inflammatory Factors ◽  
Cytokine Storm ◽  
Case Control Studies ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Tnf Α

Introduction: COVID-19 (coronavirus disease 2019) was identified in China in December 2019 for the first time and is rapidly spreading throughout the world as a pandemic. As COVID-19 causes mild to severe acute respiratory syndrome, most studies in this context have focused on pathogenesis primarily in the respiratory system. However, evidence shows that the central nervous system (CNS) may also be affected by COVID-19. Since COVID-19 is spreading, it is imperative to study its possible cognitive effects in patients suffering and recovering from COVID-19. Methods: The articles used in this study were searched by keywords such as Cytokine storm and covid-19, covid-19 and executive dysfunction, cognitive disorder and covid-19, CNS and covid 19, Coronavirus, Neuroinvasion in science direct, Scopus, PubMed, Embase, and Web of Science databases based on Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. The study will assess all observational studies published between December 2019 and April 2021 in peer-reviewed journals, including cross-sectional, cohort, case-control studies, case reports and case series. The search result was 106 articles, of which 73 articles related to Covid-19, the stages of infection by this virus, its effect on the nervous system and neurological symptoms, the cytokine storm caused by this infection, and the possible cognitive consequences caused by this virus in patients, has been reviewed. Other articles were not checked due to their limited relevance to the topic under discussion. Results: Studies show that neurons may be directly affected by SARS-CoV-1 and SARS-CoV-2. Furthermore, various studies indicate that systemic inflammation (so-called "cytokine storm") is also responsible for brain damage induced by infection with SARS-CoV-1 and SARS-CoV-2. Such a way that this patients showed elevated levels of interleukin (IL-), 6, 8, and 10 and of tumor necrosis factor-alpha (TNF- α) in their blood. Conclusion: Various cognitive defects following an increase level of cytokines such as TNF-α and IL-6,8 have been observed. Therefore, due to the increase level of these pro-inflammatory factors in the brains of these patients, cognitive deficits can be expected, which need further investigation.

Hydrocortisone vs Tocilizumab Effects on Cytokine Storm in Critically Ill Patients with COVID-19.

2020 ◽  
Author(s):  
Maria Vargas ◽  
Pasquale Buonanno ◽  
Carmine Iacovazzo ◽  
Gaetano Di Spigna ◽  
Daniela Spalletti ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Severe Pneumonia ◽  
Cytokine Storm ◽  
Tnf Α ◽  
Speed Up ◽  
The Impact ◽  
Late Stages

Abstract Introduction: Patients with severe pneumonia due COVID-19 are reported to have substantially lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines. In the late stages of COVID-19, cytokine storms are the mainly cause of disease progression and death. We performed a prospective observational study to evaluate the impact of tocilizumab and hydrocortisone on cytokine storm in critically ill patients with COVID-19.Methods: We included all adult patients with laboratory-confirmed COVID-19 infection and severe respiratory failure admitted to our ICU from March 10 to April 30. As therapeutic options, patients received tocilizumab od hydrocortisone. The primary end point was the evaluation of cytokine storm in terms of variation of the IL-6 and IL-6R, sgp130 and TNF-α concentrations during time to different treatment.Results: Eight patients received tocilizumab while 15 patients received hydrocortisone. IL-6 levels were lower in the hydrocortisone group with statistical significance was found at the days 2, 3, 8 and 9. The levels of IL-6R were lower during the days in the hydrocortisone group with statistical significance at days 1, 2, 3, 4, 5, 6, 8 and 10. Hydrocortisone group had higher levels of TNF-α at days 2, 3 and 4. The levels of sgo130 between tocilizumab and hydrocortisone groups were not statistically different during the days.Conclusions: In critically ill patients with severe COVID-19, the use of hydrocortisone allowed a better control of the cytokine storms, was further associated to less days of curarization, pronation and length of stay in ICU, and speed up the time to get negative RT-PCR swab.

Nutritional Status Impairments in HIV-Infected Patients Are Associated with Increased TNF-α and IL-6 Serum Levels but Not with Viral Load

Infection ◽  
2001 ◽  
Vol 29 (5) ◽  
pp. 257-261 ◽  
Author(s):  
M.C.G. Galhardo ◽  
M.G.C. de Carvalho ◽  
I. Georg ◽  
M. Perez ◽  
M.G. Morgado ◽  
...  
Keyword(s):  
Viral Load ◽  
Nutritional Status ◽  
Serum Levels ◽  
Tnf Α

scholarly journals Early control of viral load by favipiravir promotes survival to Ebola virus challenge and prevents cytokine storm in non-human primates

2021 ◽  
Vol 15 (3) ◽  
pp. e0009300
Author(s):  
Stéphanie Reynard ◽  
Emilie Gloaguen ◽  
Nicolas Baillet ◽  
Vincent Madelain ◽  
Jérémie Guedj ◽  
...  
Keyword(s):  
Viral Load ◽  
Ebola Virus ◽  
Virus Disease ◽  
Strongly Correlated ◽  
Cytokine Storm ◽  
Biological Functions ◽  
Crucial Importance ◽  
Immunological Parameters ◽  
Virus Challenge ◽  
Response To Stress

Ebola virus has been responsible for two major epidemics over the last several years and there has been a strong effort to find potential treatments that can improve the disease outcome. Antiviral favipiravir was thus tested on non-human primates infected with Ebola virus. Half of the treated animals survived the Ebola virus challenge, whereas the infection was fully lethal for the untreated ones. Moreover, the treated animals that did not survive died later than the controls. We evaluated the hematological, virological, biochemical, and immunological parameters of the animals and performed proteomic analysis at various timepoints of the disease. The viral load strongly correlated with dysregulation of the biological functions involved in pathogenesis, notably the inflammatory response, hemostatic functions, and response to stress. Thus, the management of viral replication in Ebola virus disease is of crucial importance in preventing the immunopathogenic disorders and septic-like shock syndrome generally observed in Ebola virus-infected patients.

scholarly journals The Activin/FLRG pathway associates with poor COVID-19 outcomes in hospitalized patients

2021 ◽  
Author(s):  
Megan McAleavy ◽  
Qian Zhang ◽  
Peter J. Ehmann ◽  
Jianing Xu ◽  
Matthew F. Wipperman ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Viral Load ◽  
Hospital Admission ◽  
Activin A ◽  
Severe Form ◽  
Cytokine Storm ◽  
Acute Respiratory Disease ◽  
Hamster Model ◽  
All Cause Mortality ◽  
Nf Kappab

A subset of hospitalized COVID-19 patients, particularly the aged and those with co-morbidities, develop the most severe form of the disease, characterized by Acute Respiratory Disease Syndrome (ARDS), coincident with experiencing a “cytokine storm." Here, we demonstrate that cytokines which activate the NF-kappaB pathway can induce Activin A. Patients with elevated Activin A, Activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that Activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of Activin. To evaluate this, the role for Activin A was examined in a hamster model of SARS-CoV2 infection, via blockade of Activin A signaling. The hamster model demonstrated that use of an anti-ActivinA antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of Activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.

scholarly journals Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α

2021 ◽  
Author(s):  
Paolo Frisoni ◽  
Margherita Neri ◽  
Stefano D’Errico ◽  
Letizia Alfieri ◽  
Diana Bonuccelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cells ◽  
Multiple Organ ◽  
Current Evidence ◽  
Control Group ◽  
Cytokine Storm ◽  
Tissue Localization ◽  
Tnf Α ◽  
Capillary Endothelial Cells ◽  
Inflammatory Cytokine Response

AbstractThis study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1β, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1β in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Clinical, Virological, and Immunological Profiles of DENV, ZIKV, and/or CHIKV-Infected Brazilian Patients

Intervirology ◽  
2020 ◽  
Vol 63 (1-6) ◽  
pp. 33-45
Author(s):  
Juan Camilo Sánchez-Arcila ◽  
Jessica Badolato-Correa ◽  
Thiara Manuele Alves de Souza ◽  
Iury Amâncio Paiva ◽  
Luciana Santos Barbosa ◽  
...  
Keyword(s):  
Viral Load ◽  
Inverse Correlation ◽  
Interleukin 10 ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Infected Adult ◽  
Chemokine Ligand ◽  
And Migration

<b><i>Background:</i></b> Arboviruses co-circulating within a population that are transmitted by the same vector have the potential to cause coinfections. Coinfections with dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) have been occurring in Brazil, but it is not well-understood how human responses vary during mono- or coinfections and whether they play different roles in pathogenesis. <b><i>Methods:</i></b> We investigated the clinical, virological, and immunological status during patients’ acute infections, focusing on the CCL/CXC chemokines, proinflammatory, as well as anti-inflammatory cytokines levels quantified by ELISAs. Viral load was determined by qRT-PCR in serum samples from 116 acute DENV, ZIKV, CHIKV, DENV/ZIKV, and CHIKV/ZIKV-infected adult patients from Brazil. <b><i>Results:</i></b> Most of the acute patients displayed fever, headache, prostration, and myalgia, regardless of the type of arbovirus infection. Zika viral load was higher in CHIKV/ZIKV coinfected patients compared with ZIKV or DENV/ZIKV infections. All infected individuals presented increased concentrations of C-X-C motif chemokine ligand 10/interferon protein-10 (CXCL10/IP-10), C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and tumor necrosis factor alpha (TNF-α) compared to healthy donors. Interestingly, the ZIKV group separated from CHIKV/ZIKV due to higher levels of interleukin-10 (IL-10) and lower levels of TNF-α. While DENV/ZIKV differentiated from CHIKV due to their higher levels of CCL2/MCP-1, in CHIKV- and CHIKV/ZIKV-infected patients, levels of CXC10/IP-10, CCL2/MCP-1, and migration inhibitory factor (MIF) were associated with CHIKV viral load. By contrast, in DENV/ZIKV- and CHIKV/ZIKV-infected patients, levels of CXCL10/IP-10, CCL2/MCP-1, and TNF-α showed a significant inverse correlation with ZIKV viral load. <b><i>Conclusions:</i></b> From all the circulating mediators measured, we detected differences of IL-10, TNF-α, and CCL2/MCP-1 between arbovirus groups. We hypothesize that CXC10/IP-10, CCL2/MCP-1, and MIF in the CHIKV-infected group could regulate the CHIKV viral load, while CXC10/IP-10, CCL2/MCP-1, and TNF-α in DENV/ZIKV, and CHIKV/ZIKV groups, could regulate ZIKV viral load.

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