People with diabetes represent a population at greater risk of infection and complications from Sars-Cov-2 (COVID-19), Diabetes represents one of the most important comorbidities related to the severity of viral infection causing an increased risk of serious complications such as severe acute respiratory syndrome and multi-organ dysfunction associated with a hyperinflammatory state. Glycemic normalization in patients with diabetes must be managed in the best possible way even during COVID-19 infection to avoid serious complications. However, for some antidiabetic agents such as DPP-4 inhibitors (gliptins) there is evidence of efficacy against COVID-19 extra pancreatic glycemic normalization. The objective of this article is to provide an overview of current evidence on the potential therapeutic benefits of gliptins to combat Sars-Cov-2 infection.
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.
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.
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.
During the SARS-Cov-2 pandemic, it is essential to identify the risk factors that can cause a higher probability of infection and, therefore, worsen the patient's health. In fact, the known risk factors include already existing diseases and associated pharmacological treatments. A patient with multiple sclerosis takes immunomodulatory drugs and certainly has a high risk. Evidence and literature have shown that SARS-Cov-2 infection causes severe lung damage due to a poorly functioning immune system and overexpression of cytokines. Therefore the management of multiple sclerosis treatments in immunomodulating therapy must be carefully monitored. This article on the one hand analyzes and recalls the safety profile of all drugs for multiple sclerosis, on the other the recommendations adopted by different countries are highlighted, trying to understand if the suspension of MS treatment must actually materialize in order not to incur lethal covid pneumonia.
Introduction The new coronavirus, called SARS-CoV-2, is responsible for the recent outbreak of serious respiratory diseases worldwide. The state of the global pandemic is still being declared and the virus has already claimed thousands of victims. Therapies are urgently needed to contain its rapid spread and reduce high mortality rates, no direct antiviral is yet available and several clinical trials are underway. In addition, no vaccines are currently available and any development in this direction may take several months. Experts in the field have divided SARS-Cov-2 infection into three phases. Materials and methods This article explores the scientific hypothesis based on pharmacological and molecular knowledge to consider drugs that modulate the RAS system as therapeutic agents that can help the body fight SARS-CoV-2 infection. Results It is known from the 2003 SARS epidemic that the critical receptor for SARS-CoV entry into host cells is the angiotensin 2 conversion enzyme (ACE2), the strain involved in the current SARS-CoV-2 epidemic is similar to the SARS-CoV variety involved in the 2002-2003 SARS epidemic. ACE-2 is part of the RAS system, modulating this enzyme could be effective. Conclusions A scientific hypothesis is described, in the absence of studies and clinical data, based on therapeutic treatments that modulate RAS, and current knowledge of the mechanism of penetration of SARS-CoV-2 into cells, and the role of ACE-2 in the inflammatory state of the infection.
The global pandemic from Sars-cov-2 has down caused thousands of deaths worldwide, triggering a health crisis in the various countries involved, with few precedents in history. To date there are no vaccines for prophylaxis, and there are no antivirals directed against the virus. Among the therapeutic options that have shown effectiveness is passive immunization with immune plasma from convalescent patients cured of the infection. Plasma collected from patients cured of Sars-cov-2 infection is rich in antibodies that neutralized the pathogen. Plasma therapy has already demonstrated its efficacy in other epidemics, such as Sars-Cov and MERS. To date, there are limited data for its use in sars-Cov-2 infection, both for prophylaxis and treatment, but the few existing data bode well for the scientific world. Many questions are still unresolved, when to administer it? At what dosage? When is it most appropriate to take the plasma from the cured patient? Are there different answers depending on gender and age? Certainly in view of the high number of patients infected and cured by Sars-Cov-2, there could be a high amount of plasma from donor patients. In this article we want to give an overview on a current and important topic in the perspective of the battle against the new Sars-Cov-2, analysing the therapeutic successes in past epidemics, the clinical data currently available, the future prospect and an expert opinion.
Immunosuppressive therapies, such as multiple sclerosis, are a risk for people with this condition because they can expose them to a greater risk of Sars-CoV-2 infection. For these reasons, recommendations from agencies, patient associations and scientific societies follow one another quickly so that therapy is guaranteed with good efficacy and without risk, choosing from the many drugs available in multiple formulations.
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.
In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as Tumor Necrosis Factor (TNF). In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature. Keywords: TNF inhibitors, SARS-Cov-2, immunomodulating, infection, hyperinflammatory
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.