Targeting inflammatory cytokine storm to fight against COVID-19 associated severe complications

Hirawat, Rishabh; Saifi, Mohd Aslam; Godugu, Chandraiah

doi:10.1016/j.lfs.2020.118923

Cited by 34 publications

(27 citation statements)

References 149 publications

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“…However, accumulating evidence show that in addition to facilitating its fusion to the cell membrane, the location of the spike protein on SARS-CoV-2 also makes it a direct target for host immune responses [31]. With respect to immune responses induced by SARS-CoV-2 infection, it is now established that this may involve an exaggerated inflammation, also known as cytokine storm [33][34][35]. Recently, we reported induction of increased release of pro-inflammatory cytokines in human peripheral blood mononuclear cells stimulated with a recombinant SARS-CoV-2 spike protein sub-unit S1, further confirming the role of the spike protein in COVID-19 cytokine storm [36].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia

Olajide

Iwuanyanwu

Adegbola

2020

Preprint

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The emergence of SARS‐CoV‐2 has resulted in a global pandemic. In addition to respiratory complications as a result of SARS‐CoV‐2 illness, accumulating evidence suggests that neurological and neuropsychiatric symptoms are associated with the disease caused by the virus. In this study, we investigated the effects of the SARS‐CoV‐2 spike glycoprotein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNFα, IL-6, IL-1β and iNOS/NO. SARS‐CoV‐2 spike glycoprotein S1 increased protein expressions of phospho-p65 and phospho-IκB, as well as enhancing DNA binding and transcriptional activity of NF-κB. Pro-inflammatory effects of the glycoprotein effects were reduced in the presence of BAY11-7082 (1 μM). The presence of SARS‐CoV‐2 spike glycoprotein S1 in BV-2 microglia increased the protein expression of NLRP3, as well as caspase-1 activity. However, pre-treatment with CRID3 (1 μM) or BAY11-7082 (1 μM) resulted in the inhibition of NLRP3 inflammasome/caspase-1. It was also observed that CRID3 attenuated SARS‐CoV‐2 spike glycoprotein S1-induced increase in IL-1β production. Increased protein expression of p38 MAPK was observed in BV-2 microglia stimulated with the spike glycoprotein S1, and was reduced in the presence of SKF 86002. These results have provided the first evidence demonstrating SARS-CoV-2 spike S1 glycoprotein-induced neuroinflammation in BV-2 microglia. We propose that promotion of neuroinflammation by this glycoprotein is mediated through activation of NF-κB, NLRP3 inflammasome and p38 MAPK. These results are significant because of their relevance to our understanding of neurological and neuropsychiatric symptoms observed in patients infected with SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia

Olajide

Iwuanyanwu

Adegbola

2020

Preprint

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“…A striking finding was the development of sinus bradycardia in 98.4% of the patients of the second wave without clinically detectable myocardial necrosis or after treatment with medications affecting heart rate. The average time for development of bradycardia was 5 and 10 days from admission and onset of symptoms, respectively (23), which is significantly shorter compared to other cohorts (5). The development of bradycardia in our patients may reflect the activation of the cholinergic nervous system in an effort to regulate the inflammatory response (24).…”

Section: Discussionmentioning

confidence: 61%

“…In patients with COVID-19, dysfunctional endothelium may display a hypercoagulant/prothrombotic/pro-oxidant state and impairs microvascular reactivity (26). The latter, together with the increased levels of inflammatory mediators, enhances mechanical stress of cardiomyocytes and metabolic demands of conduction muscle cells, promoting metabolic instability and conduction disorders (23,27,28).…”

Section: Discussionmentioning

confidence: 99%

Clinical course and outcomes of critically ill COVID-19 patients in two successive pandemic waves

Chalkias

Pantazopoulos

Papagiannakis³

et al. 2021

Preprint

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Rationale: The progress of COVID-19 from moderate to severe may be precipitous, while the heterogenous characteristics of the disease pose challenges to the management of these patients. Objectives: To characterize the clinical course and outcomes of critically ill patients with COVID-19 during two successive waves. Methods: We leveraged the multi-center SuPAR in Adult Patients With COVID-19 (SPARCOL) study and collected data from consecutive patients requiring admission to the intensive care unit from April 1st to November 30th, 2020. Measurements and Main Results: Of 252 patients, 81 (32%) required intubation and mechanical ventilation. Of them, 17 (20.9%) were intubated during the first wave, while 64 (79%) during the second wave. The most prominent difference between the two waves was the overall survival (first wave 58.9% vs. second wave 15.6%, adjusted p-value=0.006). This difference is reflected in the prolonged hospitalization during the first wave. The mean ICU length of stay (19.1 vs. 11.7 days, p=0.022), hospital length of stay (28.5 vs. 17.1 days, p=0.012), and days on ventilator (16.7 vs. 11.5, p=0.13) were higher during the first wave. A significant difference between the two waves was the development of bradycardia. In the first wave, 2 (11.7%) patients developed sinus bradycardia only after admission to the intensive care unit, while in the second wave, 63 (98.4%) patients developed sinus bradycardia during hospitalization. Conclusions: Survival of critically ill patients with COVID-19 was significantly lower during the second wave. The majority of these patients developed sinus bradycardia during hospitalization.

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“…(2020) reported that increasing blood viscosity by the inflammatory mediators and immunoglobulins may be the reason for DIC [ 38 ]. Indeed, clinical laboratory studies of COVID-19 patients have reported significant elevation of serum levels of pro-inflammatory cytokines (IL-6, IFN-γ and TNF-α) especially in critically ill patients admitted to the ICU [ 39 ]. Consequently, inflammatory mediators, primarily IL-6, can serve as useful prognostic biomarkers for the severity of COVID-19 disease [ 40 , 41 ].…”

Section: Cytokine Stormmentioning

confidence: 99%

Promising drug repurposing approach targeted for cytokine storm implicated in SARS-CoV-2 complications

Shawki

Elsayed

Mantawy

et al. 2021

Immunopharmacology and Immunotoxicology

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A global threat has emerged in 2019 due to the rapid spread of Coronavirus disease (COVID-19). As of January 2021, the number of cases worldwide reached 103 million cases and 2.22 million deaths which were confirmed as the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This global pandemic galvanized the scientific community to study the causative virus (SARS-CoV2) pathogenesis, transmission, and clinical symptoms. Remarkably, the most common complication associated with this disease is the cytokine storm which is responsible for COVID-19 mortality. Thus, targeting the cytokine storm with new medications is needed to hamper COVID-19 complications where the most prominent strategy for the treatment is drug repurposing. Through this strategy, several steps are skipped especially those required for testing drug safety and thus may help in reducing the dissemination of this pandemic. Accordingly, the aim of this review is to outline the pathogenesis, clinical features, and immune complications of SARS-CoV2 in addition to suggesting several repurposed drugs with their plausible mechanism of action for possible management of severe COVID-19 cases.

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Targeting inflammatory cytokine storm to fight against COVID-19 associated severe complications

Cited by 34 publications

References 149 publications

SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia

SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia

Clinical course and outcomes of critically ill COVID-19 patients in two successive pandemic waves

Promising drug repurposing approach targeted for cytokine storm implicated in SARS-CoV-2 complications

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