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      The novel aspirin as breakthrough drug for COVID-19: a narrative review

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          Abstract

          Abstract Introduction: Aspirin has justifiably been called the first miracle drug. In this article, we highlight the history of Aspirin, a novel mechanism of action, and its use in cardiovascular and other diseases. Also included is a brief statement of emerging new applications. Objective: We highlight principal mechanisms by which Aspirin inhibits acute inflammation and alters platelet-biology; therefore, hypothesized that Aspirin might prove highly beneficial as a novel therapeutic drug for combating severe acute inflammation and thrombosis associated with the cytokine storm in COVID -19 patients. The communiqué also suggests possible strategies for maximizing the gain of Aspirin as a wonder-drug of the future. Discussion: Interestingly, some fascinating studies demonstrated Aspirin's superior benefits with dangerous side effects. Aspirin inhibits COX-1 (cyclooxygenase-1). Its impact on COX-2 is more delicate because it “turns off” COX-2's production of prostaglandins but “switches on” the enzymatic ability to produce novel protective lipid mediators. The established mechanism of action of Aspirin is the inhibition of prostaglandin synthesis. However, further evidence showed that aspirin-elicited nitric oxide exerts anti-inflammatory effects in the microcirculation by inhibiting leukocyte–endothelium interactions. Interestingly, aspirin-triggered lipoxin formation may provide a novel mechanism underlying Aspirin's clinical benefits. Interestingly, Aspirin reduces the risk of a cardiovascular event by about 30 percent. Also, Aspirin has been associated with a reduced risk of colorectal cancer, and possibly a few other digestive tract cancers. Conclusion: The current emerging interest is to conduct further study to provide evidence for Aspirin as the novel therapeutic drug for combating severe acute inflammation and thrombosis associated with the cytokine storm in COVID-19 patients. Besides, the most wanted is The RECOVERY II (Randomized Evaluation of COVID-19 Therapy II) trial to be established as a randomized clinical trial to test the effectiveness of low-dose Aspirin as an anti-inflammatory and antithrombotic treatment in COVID-19 patients.

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          Most cited references134

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          A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

          Abstract Background No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. Methods We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao 2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao 2) to the fraction of inspired oxygen (Fio 2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. Results A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. Conclusions In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.)
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            Incidence of thrombotic complications in critically ill ICU patients with COVID-19

            Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
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              Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

              Abstract Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS‐CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin‐converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS‐CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                ijm
                Iberoamerican Journal of Medicine
                Iberoam J Med
                Hospital San Pedro (Logroño, La Rioja, Spain )
                2695-5075
                2695-5075
                2020
                : 2
                : 4
                : 335-350
                Affiliations
                [3] orgnameNHS Foundation Trust Nethermayne-Basildon orgdiv1Basildon & Thurrock University Hospitals orgdiv2Department of Geriantology United Kingdom
                [2] Kainifing orgnameAmerican International University West Africa orgdiv1Department of Pharmacology Gambia
                [1] Shisong Northwestern Region orgnameSt Elizabeth Catholic General Hospital orgdiv1Department of Surgery Cameroon
                [5] Logroño orgnameHospital San Pedro orgdiv1Emergency Department Spain
                [4] Baghdad orgnameUniversity of Baghdad orgdiv1College of Science orgdiv2Department of Biotechnology Irak
                Article
                S2695-50752020000400014 S2695-5075(20)00200400014
                10.5281/zenodo.3970519
                3bb9d601-7d40-47ba-9ae7-7e5fbe546b09

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 30 June 2020
                : 28 July 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 135, Pages: 16
                Product

                SciELO Spain

                Categories
                Review

                Aspirin,Cytokine storm,Systemic inflammatory response,COVID-19,Steroids,SARS-CoV-2,Nonsteroidal anti-inflammatory drugs

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