The effect of ramatroban on cytokine and thrombotic storms in Covid-19

Immunity Inflam & Disease

et al. 2023

Self Cite

Coronavirus disease 2019 (Covid-19) is caused by a novel severe acute respiratory syndrome coronavirus virus type 2 (SARS-CoV-2) leading to the global pandemic worldwide. Systemic complications in Covid-19 are mainly related to the direct SARS-CoV-2 cytopathic effects, associated hyperinflammation, hypercytokinemia, and the development of cytokine storm (CS). As well, Covid-19 complications are developed due to the propagation of oxidative and thrombotic events which may progress to a severe state called oxidative storm and thrombotic storm (TS), respectively. In addition, inflammatory and lipid storms are also developed in Covid-19 due to the activation of inflammatory cells and the release of bioactive lipids correspondingly. Therefore, the present narrative review aimed to elucidate the interrelated relationship between different storm types in Covid-19 and the development of the mixed storm (MS). In conclusion, SARS-CoV-2 infection induces various storm types including CS, inflammatory storm, lipid storm, TS and oxidative storm. These storms are not developing alone since there is a close relationship between them. Therefore, the MS seems to be more appropriate to be related to severe Covid-19 than CS,

Section: Lipid Storm In Covid‐19mentioning

confidence: 99%

Section: Lipid Storm In Covid‐19mentioning

confidence: 99%

Mixed storm in SARS‐CoV‐2 infection: A narrative review and new term in the Covid‐19 era

Alomair

Immunity Inflam & Disease

et al. 2023

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“…Taken together, there is an intricate relationship between SARS-CoV-2 infection and associated inflammatory response with complications of ACS due to erosion/rupture of coronary atherosclerotic plaque. 132,133 As mentioned earlier, COVID-19-induced hypoxia by ARDS, SARS-CoV-2-induced cardiomyocyte injury, cardiomyocyte interstitial injury, and cytokine storm may together affect coronary microcirculation. These changes lead to the induction of T2MI through-provoking release of the clotting factor and von-Willebrand factor with inhibition of endothelial anticoagulant activity.…”

Section: Covid-19 and Acsmentioning

confidence: 93%

The potential role of SARS‐CoV‐2 infection in acute coronary syndrome and type 2 myocardial infarction (T2MI): Intertwining spread

Alsaidan

Immunity Inflam & Disease

et al. 2023

Self Cite

Coronavirus disease 2019 (COVID‐19) is a novel pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It has been shown that SARS‐CoV‐2 infection‐induced inflammatory and oxidative stress and associated endothelial dysfunction may lead to the development of acute coronary syndrome (ACS). Therefore, this review aimed to ascertain the link between severe SARS‐CoV‐2 infection and ACS. ACS is a spectrum of acute myocardial ischemia due to a sudden decrease in coronary blood flow, ranging from unstable angina to myocardial infarction (MI). Primary or type 1 MI (T1MI) is mainly caused by coronary plaque rupture and/or erosion with subsequent occlusive thrombosis. Secondary or type 2 MI (T2MI) is due to cardiac and systemic disorders without acute coronary atherothrombotic disruption. Acute SARS‐CoV‐2 infection is linked with the development of nonobstructive coronary disorders such as coronary vasospasm, dilated cardiomyopathy, myocardial fibrosis, and myocarditis. Furthermore, SARS‐CoV‐2 infection is associated with systemic inflammation that might affect coronary atherosclerotic plaque stability through augmentation of cardiac preload and afterload. Nevertheless, major coronary vessels with atherosclerotic plaques develop minor inflammation during COVID‐19 since coronary arteries are not initially and primarily targeted by SARS‐CoV‐2 due to low expression of angiotensin‐converting enzyme 2 in coronary vessels. In conclusion, SARS‐CoV‐2 infection through hypercytokinemia, direct cardiomyocyte injury, and dysregulation of the renin‐angiotensin system may aggravate underlying ACS or cause new‐onset T2MI. As well, arrhythmias induced by anti‐COVID‐19 medications could worsen underlying ACS.

“…Molecular docking studies revealed that SARS‐CoV‐2 activates integrin and PKC, which trigger Ca 2+ release through activation of Ca 2+ channels 57,58 . The fusion protein of the SARS‐CoV‐2 spike protein is enhanced by Ca 2+.…”

Section: Role Of Ryanodine Receptors and Dantrolene In Covid‐19mentioning

confidence: 99%

“…55,56 Molecular docking studies revealed that SARS-CoV-2 activates integrin and PKC, which trigger Ca 2+ release through activation of Ca 2+ channels. 57,58 The fusion protein of the SARS-CoV-2 spike protein is enhanced by Ca 2+. 59,60 These findings suggest that Ca 2+ is necessary for binding, entry and invasion of SARS-CoV-2.…”

Section: Role Of Dantrolene In Severe Acute Respiratory Syndrome Coro...mentioning

confidence: 99%

Dantrolene and ryanodine receptors in COVID‐19: The daunting task and neglected warden

Alkazmi

et al. 2023

Clin Exp Pharma Physio

Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca 2+ release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), because Ca 2+ is necessary for viral replication, maturation and release. DTN can inhibit the proliferation of SARS-CoV-2, indicating its potential role in reducing entry and pathogenesis of SARS-CoV-2. DTN may increase clearance of SARS-CoV-2 and promote coronavirus disease 2019 (COVID-19) recovery by shortening the period of infection. DTN inhibits N-methyl-D-aspartate (NMDA) mediated platelets aggregations and thrombosis. Therefore, DTN may inhibit thrombosis and coagulopathy in COVID-19 through suppression of platelet NMDA receptors. Moreover, DTN has a neuroprotective effect against SARS-CoV-2 infection-induced brain injury through modulation of NMDA receptors, which are involved in excitotoxicity, neuronal injury and the development of neuropsychiatric disorders. In conclusion, DTN by inhibiting RyRs may attenuate inflammatory disorders in SARS-CoV-2 infection and associated cardio-pulmonary complications. Therefore, DNT could be a promising drug therapy against COVID-19. Preclinical and clinical studies are warranted in this regards.