Antonio Vitiello

and 2 more

Dear Editor,SARS-CoV-2 (COVID-19) is responsible for the current global pandemic. At the date, no antivirals directed against the virus or effective vaccines are available. (1) It is essential to recognise the risk factors and components that may play a protective role. There is no clear evidence on the correlation between changes in the Renin-angiotensin system (RAS) by ACE-is, ARB or DRis and COVID-19 infection.(2) (3) (4) Randomised controlled trials are needed to verify the involvement of COVID-19 viral infection and chronic treatment with these drugs. A possible scientific hypothesis to investigate is the role of the neprilisin inhibitor Sacubitril in association with valsartan in the more severe stages of COVID-19 infection. The challenge to defeat the current pandemic poses several objectives, among them try to give added values to therapeutic solutions, in this direction the association sacubitril/valsartan has already demonstrated the therapeutic efficacy in the treatment of chronic symptomatic heart failure with reduced ejection fraction in several studies (5), indirectly the therapeutic benefits of cardiovascular type are also directed to a decrease in the risk of infection and complications from COVID-19. Furthermore, there is evidence of a significant increase in NT-proBNP in COVID-19 patients. (6) Studies show that higher NT-proBNP was an independent risk factor for death in patients with severe COVID-19, (7) moreover, NT-proBNP is associated with proinflammatory effects. (8) (9) Sacubitril through its mechanism of action increases neprylisin-degraded peptides, such as natriuretic peptides (NP), ANP and BNP, (10) evidence associates these peptides with anti antiflammatory, antihypertrophic and antifibrotic effects, recent evidence shows that IL-1𝛽 secretion is strongly inhibited by the BNP/NPR-1/cGMP axis to all molecular mechanisms closely controlling its production and release, NF-kB, ERK 1/2, and all elements of the NALP3/ASC/Caspase-1 inflammasomic cascade, and that NALP3 inflammatory inhibition is directly related to the deregulatory effect of BNP on the activation of NF-kB/ERK ½,(11) also the decrease of NT-proBNP by Sacubitril is known. Valsartan in association, by blocking the AT-1r receptor of ang II, decreases profibrotic and proinflammatory activity mediated by AT-1r, and indirectly increases the action of ang II on AT-2r with antifibrotic, antifibrotic effects. Based on the evidence and in relation to our generated hypothesis, we believe that a use of sacubitril/valsartan in the most severe stages of COVID-19 infection could have therapeutic efficacy, with anti-inflammatory and antifibrotic effects mediated by natriuretic peptides. Clinical studies are required to confirm this hypothesis.
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Antonio Vitiello

and 1 more

At date, research is moving for a direct SARS-CoV-2 antiviral, which will be, probably, the ideal solution to defeat the virus. In the meantime, evidences have shown that effective improvements for health status of infected patients can be found in the decrease or stop of the hyper inflammatory state. Experts have divided the SARS-CoV-2 infection in three phases. In the last one, phase 3, the most severe, the immune system goes an overdrive status and, as consequence, it launches a large-scale assault versus all the tissues. This phenomenon is known as “cytokine storm” and it can lead to a damage of organs and, in some cases to death. Several studies showed that blocking the cytokine storm or acting advance with a prevention of the phenomenon, can be effective; studies are ongoing to evaluate agents that can be able to reduce this hyperinflammatory state, as, for example, IL-6 or IL-1 inhibitors. However, other drugs that are able to block the cytokine cascade can also be considered. In this article is reported the scientific and molecular motivation related to the use of colchicine as monotherapy or in association in all three phases of infection by SARS-CoV-2 modulating the inflammatory state. Colchicine can be considered safe and effective for the treatment and prevention of Cytokine Storm in patients affected by SARS-CoV-2 infection, in particular as a remedy added to other therapeutical agents. In fact, colchicine, probably, provides a bigger benefit to all current agents and its safety profile is superior to the one provided by other drugs, such as corticosteroids and immunosuppressive drugs.
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Antonio Vitiello

and 1 more

Beckgroung: The global pandemic Sars-Cov-2 (COVID-19) is causing thousands of deaths worldwide, and is one of the greatest health challenges ever faced in human history. Sars-Cov-2 infection can cause fatal lung injuries caused by a generalized inflammatory state associated with multi-organ dysfunction. Objective: In this context, it is essential to recognize the factors that increase the risk of viral infection. People with pre-existing conditions, such as diabetes, are at greater risk of complications and death caused by COVID-19. Materials and Method: Old age, possible chronic drug therapies, kidney failure, hyperglycemia, heart disease, are predictive factors of a bad outcome for the diabetic patient. The regulation of glycaemia and the adoption of appropriate measures are critical aspects to be taken into consideration for the diabetic patient in this pandemic period, especially in the patient with ongoing infection. Results: In the latter, the use of drugs used to fight COVID-19 infection, such as antivirals or immunomodulants, must be well controlled to avoid possible drug interactions and major complications. People with diabetes fall into the category of fragile and at-risk population, and if a COVID-19 infection is also ongoing the patient must be managed optimally, trying to fight the virus but also without neglecting homeostasis and glycemic control. Conclusion: This analysis highlights current knowledge and challenges for the prevention and management of patients with diabetes and COVID-19 infection.
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Antonio Vitiello

and 4 more

Antonio Vitiello

and 3 more

Francesco Ferrara

and 4 more

Objectives:Literature data have shown that decreasing the SARS-CoV-2-induced hyperinflammatory state is essential for fighting the virus in an emergency and avoiding death. Many authors have divided the SARS-CoV-2 infection into three phases, of which the second and third are purely inflammatory. For this reason, while the development of antiviral drugs and vaccines is increasing, the best pharmacological goal is the decrease in proinflammatory molecules. Design: In phase 3, the most serious, there is an overdrive state of the immune system with consequent assault against all tissues and lung damage. Sars cov 2 pneumonia is characterized by “cytokine storm” and can lead to death. Acting in advance and with combination therapy aimed at blocking the inflammatory cascade can be effective. Results: Many drugs are being tested in evaluating these effects such as IL-6 or IL-1 inhibitors, chloroquine / hydroxycloroquine and colchicine which is proving its effectiveness especially in association in the last two stages of SARS-CoV-2 infection. modulating the inflammatory state and allowing to use an effective combined terepia with drugs at non-lethal dosages. Colchicine is considered safe and effective for the treatment and prevention of the cytokine storm in patients suffering from SARS-CoV-2 infection and is certainly an added remedy to other therapeutic agents with a safety profile superior to that provided by others. drugs. Conclusion:The aim of this study is to explain the pharmacological rationale behind the use of a combination therapy as an effective and safe remedy to decrease pneumonia and the consequent death from Sars CoV 2.
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Francesco Ferrara

and 4 more

Reduction of pulmonary fibrotic status and reduction of hyperinflammation is essential to combat SARS-CoV-2 and avoid death. Many authors have divided the SARS-CoV-2 infection into three stages, the second and third of which are purely inflammatory and fibrotic. Waiting for the development of antiviral drugs and vaccines to give good results, the best pharmacological goal is the reduction of proinflammatory molecules. This leads to less formation of fibrotic tissue and to the resolution of the patient’s respiratory problems. In fact, in phase 3, the most serious, there is a state of overexpression of the immune system with consequent assault on all tissues and damage to the lungs. Sars cov 2 pneumonia is characterized by “cytokine storm” and can lead to death. Acting early and with pirfenidone combination therapy can be effective. The IL-6 or IL-1 inhibitors, chloroquine / hydroxychloroquine and colchicine, which are demonstrating their anti-inflammatory efficacy, when combined with an anti-inflammatory and antifibrotic agent, such as pirfenidone, can have a winning result. The effective combined terepia allows to use non-lethal dosages and affects all the pathological steps induced by the virus. Pirfenidone has been used for years in lung diseases and has been shown to have good clinical success and good safety and tolerability.The purpose of this study is to explain the pharmacological logic behind the use of a combination therapy as an effective and safe remedy to reduce pneumonia and the consequent death from Sars CoV 2. Keywords: pirfenidone, fibrotic, inflammation, cythokine, interleukin, Sars-CoV-2.