More than 15 million people have been affected by coronavirus disease 2019 (COVID-19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID-19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the "ARAS loop") is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID-19, and beta-adrenergic blockers are proposed as a potential treatment option. Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo.

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More than 2.5 million people were affected by COVID-19 and it had caused around 175000 deaths as of April 23, 2020. Currently no effective treatment option is present for COVID-19 patients. Even though many drugs have been proposed, none of them showed its efficacy in clinical trials. In this article, I had briefly reviewed the current scenario of COVID-19 condition, and focused on the Adrenergic system- RAAS relation in COVID-19 and proposed a vicious Adrenergic system-RAAS-ACE2-SARS-CoV-2 (ARAS) loop. Hyperactivation of ARAS loop may be the underlying pathophysiological mechanism in COVID-19. I had proposed beta-adrenergic blockers as a potential treatment option for treating COVID-19. Beta-adrenergic blockers by its negative regulation of RAAS pathway may decrease ACE2 receptors expression and CD147 in various cells in the body including typeII pulmonary alveolar epithelial cells and decrease the SARS-CoV-2 virus cellular entry. Beta-adrenergic blocker may also exert beneficial affects through inhibition of NLRP3 inflammasome, and reduction of proinflammatory cytokines like IL-6, reduced expression of MUC5AC, and decreasing airway mucus secretion. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing the ARDS, pulmonary embolism, pulmonary edema, refractory hypoxemia, and Septic shock complications. Considering potential beneficial effects of beta-adrenergic blockers in COVID-19, retrospective and prospective clinical trials needs to conducted to check the validity of the hypothesis and clarify its role in COVID-19. I had speculated that Beta2-adrenergic agonists use in the nebulizers and norepinephrine use in the COVID-19 patients having septic shock may worsen the condition. I suggest that Beta-adrenergic blockers should be used in the treatment of COVID-19, and norepinephrine, beta2-adrenergic agonists should be avoided in COVID-19.

In this review article, the role of Warburg effect in various pathologies will be discussed using septic shock as the base model. I had proposed a slightly extended Warburg effect which I would like to call it as 'Warburg common pathogenesis model or Warburg differentiation dedifferentiation effect', which has the potential to explain septic shock and sepsis associated multi-organ dysfunction and many other major pathologies like SHT, PAH, CHF, DM, Asthma, ARDS, AKI implying most of the diseases may have a common pathogenesis as the underlying mechanism. Increased Nitric oxide (NO) in sepsis via iNOS or any respiratory poison in general irreversibly inhibits the mitochondrial respiration and shifts the metabolic phenotype of the cell from oxidative phosphorylation (OXPHOS) to glycolytic phenotype and the change in metabolic phenotype is followed by the change in cell phenotype from the normal adult dynamic differentiation state to irreversible dedifferentiation statesembryonic phenotype, synthetic / proliferative phenotype, and cancer phenotype. This dedifferentiated state switching can be seen as the cells local survival strategy in response to injuries, but returning to their primitive forms leads to disorder and ends in global collapse of the organ systems and organism which requires order in terms of differentiation. Treatment in most of pathologies should aim at reversing Warburg effect by activation of mitochondrial respiration thereby decreasing the aerobic glycolysis and changing the cell to its normal adult dynamic differentiation phenotype i.e. all the drugs will be used here as differentiation therapy. Adrenergic blockers and Ascorbic acid may be the main treatment options, which are already used by some research groups, other options will be discussed in this article. Even though high NO via iNOS was involved in most of the pathologies including sepsis, any substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect and irreversible dedifferentiation. A mild and reversible Warburg differentiation dedifferentiation effect may be necessary for normal functioning and the same effect in exaggerated and irreversible way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the diseases including septic shock.

COVID-19 is a severe acute respiratory syndrome caused by a novel strain of coronavirus (SARS-CoV-2) and is declared as a global pandemic by WHO as it caused severe damage to mankind by virus transmission from human to human with increased mortality rate worldwide. Corona virus is a spherical shaped and enveloped positive-sense single stranded RnA virus with a size of ~30 kilobase encoding various structural, non-structural proteins and accessory proteins. the entry of coronavirus into the host cells is mediated by spike proteins which efficiently allow SARS-CoV2 to replicate in host cell by evading immune surveillance like innate and adaptive immune responses in the host cells and ultimately leads to increased virulence and disease outcome. In the current review, we highlighted the molecular insights of SARS-CoV-2 and its infection mechanism in the host cell via host-viral protein interactions based on currently available data up to 16 th May 2020 and using various research literature databases. the detection of coronavirus is mainly by Rt-PCR and serological tests. there is no complete treatment for COVID-19, few methods like plasma therapy and remdesivir treatment are reported to show promising results in improving patient's health and decreasing mortality rate.