AUTHOR=Al-kuraishy Hayder M. , Al-Gareeb Ali Ismail , Mostafa-Hedeab Gomaa , Kasozi Keneth Iceland , Zirintunda Gerald , Aslam Akhmed , Allahyani Mamdouh , Welburn Susan Christina , Batiha Gaber El-Saber TITLE=Effects of β-Blockers on the Sympathetic and Cytokines Storms in Covid-19 JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.749291 DOI=10.3389/fimmu.2021.749291 ISSN=1664-3224 ABSTRACT=

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative virus in the development of coronavirus disease 2019 (Covid-19) pandemic. Respiratory manifestations of SARS-CoV-2 infection such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) leads to hypoxia, oxidative stress, and sympatho-activation and in severe cases leads to sympathetic storm (SS). On the other hand, an exaggerated immune response to the SARS-CoV-2 invasion may lead to uncontrolled release of pro-inflammatory cytokine development of cytokine storm (CS). In Covid-19, there are interactive interactions between CS and SS in the development of multi-organ failure (MOF). Interestingly, cutting the bridge between CS and SS by anti-inflammatory and anti-adrenergic agents may mitigate complications that are induced by SARS-CoV-2 infection in severely affected Covid-19 patients. The potential mechanisms of SS in Covid-19 are through different pathways such as hypoxia, which activate the central sympathetic center through carotid bodies chemosensory input and induced pro-inflammatory cytokines, which cross the blood-brain barrier and activation of the sympathetic center. β2-receptors signaling pathway play a crucial role in the production of pro-inflammatory cytokines, macrophage activation, and B-cells for the production of antibodies with inflammation exacerbation. β-blockers have anti-inflammatory effects through reduction release of pro-inflammatory cytokines with inhibition of NF-κB. In conclusion, β-blockers interrupt this interaction through inhibition of several mediators of CS and SS with prevention development of neural-cytokine loop in SARS-CoV-2 infection. Evidence from this study triggers an idea for future prospective studies to confirm the potential role of β-blockers in the management of Covid-19.