The role of dysregulated immune responses in COVID-19 pathogenesis

Tahaghoghi-Hajghorbani, Sahar; Zafari, Parisa; Masoumi, Elham; Rajabinejad, Misagh; Jafari-Shakib, Reza; Hasani, Bahare; Rafiei, Alireza

doi:10.1016/j.virusres.2020.198197

Cited by 67 publications

(65 citation statements)

References 85 publications

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“…A way to reduce the severity and mortality generated by acute respiratory distress syndrome (ARDS) produced by SARS-COV 2 is to strengthen the immune system. ARDS produces a dysregulation of the immunological system, and in the most severe cases, the release of pro-inflammatory cytokines and loss of T-cells in the infected organism [ 52 ]. There is evidence of the antiviral effect of Nrf2 on respiratory syncytial virus infection [ 53 ] and on SARS-COV 1 [ 54 ].…”

Section: Mechanisms Of Action Of Sfn On Immune Systemmentioning

confidence: 99%

Potential of Sulforaphane as a Natural Immune System Enhancer: A Review

Mahn

Castillo

2021

Molecules

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Brassicaceae are an outstanding source of bioactive compounds such as ascorbic acid, polyphenols, essential minerals, isothiocyanates and their precursors, glucosinolates (GSL). Recently, GSL gained great attention because of the health promoting properties of their hydrolysis products: isothiocyanates. Among them, sulforaphane (SFN) became the most attractive one owing to its remarkable health-promoting properties. SFN may prevent different types of cancer and has the ability to improve hypertensive states, to prevent type 2 diabetes–induced cardiomyopathy, and to protect against gastric ulcer. SFN may also help in schizophrenia treatment, and recently it was proposed that SFN has potential to help those who struggle with obesity. The mechanism underlying the health-promoting effect of SFN relates to its indirect action at cellular level by inducing antioxidant and Phase II detoxifying enzymes through the activation of transcription nuclear factor (erythroid-derived 2)-like (Nrf2). The effect of SFN on immune response is generating scientific interest, because of its bioavailability, which is much higher than other phytochemicals, and its capacity to induce Nrf2 target genes. Clinical trials suggest that sulforaphane produces favorable results in cases where pharmaceutical products fail. This article provides a revision about the relationship between sulforaphane and immune response in different diseases. Special attention is given to clinical trials related with immune system disorders.

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Section: Mechanisms Of Action Of Sfn On Immune Systemmentioning

confidence: 99%

Potential of Sulforaphane as a Natural Immune System Enhancer: A Review

Mahn

Castillo

2021

Molecules

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“…Both SARS-CoV-2- (such as viral mutations) and human-related factors (such as age, gender, genetic, immune status, comorbidities, obesity and smoking) contribute to the COVID-19 severity and outcomes [ 1 , 2 ]. Massive infiltration of lung alveoli with inflammatory cells such as monocytes, macrophages, lymphocytes, eosinophils and neutrophils occur during COVID-19 [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Contribution of STAT3 to the pathogenesis of COVID-19

Jafarzadeh

Nemati

Jafarzadeh

2021

Microbial Pathogenesis

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Hyper-inflammatory responses, lymphopenia, unbalanced immune responses, cytokine storm, large viral replication and massive cell death play fundamental roles in the pathogenesis of COVID-19. Extreme production of many kinds of pro-inflammatory cytokines and chemokines occur in severe COVID-19 that called cytokine storm. Signal transducer and activator of transcription-3 (STAT-3) present in the cytoplasm in an inactive form and can be stimulated by a vast range of cytokines, chemokines and growth factors. Thus, STAT-3 can participate in the induction of inflammatory responses during coronavirus infections. STAT-3 can also suppress anti-virus interferon response and induce unbalanced anti-virus adaptive immune response, through influencing Th17-, Th1-, Treg-, and B cell-mediated functions. Furthermore, STAT-3 can contribute to the M2 macrophage polarization, lung fibrosis and thrombosis. Moreover, STAT-3 may be directly targeted by some virus-derived protein and operate as a pro-viral or anti-viral element in a virus-specific process. Here, the possible contribution of STAT-3 to the pathogenesis of COVID-19 was explained, while providing potential approaches to target this transcription factor in an attempt for COVID-19 treatment.

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“…It has been suggested that doxycycline may have beneficial effects for people affected by the newly emerged coronavirus disease 2019 (COVID19) due to its antiviral and anti-inflammatory properties [ 52 , 53 ]. The latter seem particularly relevant, as dysregulation of the innate immune responses and the cytokine storm have been associated with severe COVID19 cases [ 54 ]. This notion may be supported by observational reports of apparent benefits of the use of doxycycline for treatment of COVID19 patients [ 55 ], despite the fact that the in vitro calculated ratios of Cmax/IC 50 and Cmax/IC 90 seemed too low to reach effective concentrations in human plasma to inhibit growth of SARS-CoV-2 in [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Effects of Doxycycline on Replication of Feline Coronavirus

Dunowska

Ghosh

2021

Pathogens

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Feline infectious peritonitis (FIP) is a sporadic fatal disease of cats caused by a virulent variant of feline coronavirus (FCoV), referred to as FIP virus (FIPV). Treatment options are limited, and most of the affected cats die or are euthanized. Anecdotally, doxycycline has been used to treat FIP-affected cats, but there are currently no data to support or discourage such treatment. The aim of this study was to establish whether doxycycline inhibits replication of FIPV in vitro. The virus was cultured in Crandell-Rees feline kidney cells with various concentrations of doxycycline (0 to 50 µg/mL). The level of FIPV in cultures was determined by virus titration and FCoV-specific reverse-transcription quantitative PCR. Cell viability was also monitored. There was no difference in the level of infectious virus or viral RNA between doxycycline-treated and untreated cultures at 3, 12- and 18-hours post-infection. However, at 24 h, the growth of FIPV was inhibited by approximately two logs in cultures with >10 µg/mL doxycycline. This inhibition was dose-dependent, with inhibitory concentration 50% (IC50) 4.1 µg/mL and IC90 5.4 µg/mL. Our data suggest that doxycycline has some inhibitory effect on FIPV replication in vitro, which supports future clinical trials of its use for the treatment of FIP-affected cats.

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The role of dysregulated immune responses in COVID-19 pathogenesis

Cited by 67 publications

References 85 publications

Potential of Sulforaphane as a Natural Immune System Enhancer: A Review

Potential of Sulforaphane as a Natural Immune System Enhancer: A Review

Contribution of STAT3 to the pathogenesis of COVID-19

In Vitro Effects of Doxycycline on Replication of Feline Coronavirus

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