Anticoagulant and antiarrhythmic effects of heparin in the treatment of COVID‐19 patients

Rodrigues, Francisco Sandro Menezes; Tavares, José Roberto; Pires-Oliveira, Marcelo; Carvalho, Rafael Guzella de; Errante, Paolo Ruggero; Taha, Murched Omar; Fagundes, Djalma José; Caricati‐Neto, Afonso

doi:10.1111/jth.14902

Cited by 27 publications

(31 citation statements)

References 10 publications

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“…In these circumstances, the antiviral against virus RNA, Remdesivir, has been a potential therapy against SARS-CoV-2 without definitive results 36 . Heparin has also been used in the treatment of patients with COVID-19, and it has been actively used since it combats coagulopathies, which are most likely caused by the immune system decompensation when facing COVID-19 37 .…”

Section: Discussionmentioning

confidence: 99%

IL-4/IL-13 remodeling pathway of COVID-19 lung injury

Paula

Azevedo

Nagashima

et al. 2020

Sci Rep

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The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the mechanisms of both pandemic pneumonias need clarification. Thus, our goal was to analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury. Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC). Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages were observed in the COVID-19 group compared to both the H1N1 and the CONTROL groups. A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-CoV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. Understanding and managing the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.

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Section: Discussionmentioning

confidence: 99%

IL-4/IL-13 remodeling pathway of COVID-19 lung injury

Paula

Azevedo

Nagashima

et al. 2020

Sci Rep

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“… Arjmand et al, 2020 , Lin et al, 2017 , Li et al, 2011 , Liu et al, 2004 , Liu et al, 2020 , Liu et al, 2019 , Lowe et al, 2017 , Luo et al, 2020 , Maggio and Corsini, 2020 , Magalhães et al, 1985 , Magrone et al, 2020 , Mani et al, 2020 , Mohammed et al, 2020 , Matsuyama et al, 2014 , Mecha et al, 2013 , Menezes‐Rodrigues et al, 2020 , Millet and Whittaker, 2018 , Millet et al, 2016 , Brodkiewicz et al, 2020 , Ming and Yin, 2013 , Nelson et al, 2003 , Mousavizadeh and Ghasemi, 2020 , Nikhat and Fazil, 2020 , O'Keefe et al, 2010 , Panraksa et al, 2017 , Pandey, 2011 , Park et al, 2013 , Park et al, 2017 , Calabrese et al, 2000 , Paris et al, 1994 , Patel et al, 2008 , Peng et al, 2000 , Perwitasari et al, 2015 , Rathinavel et al, 2020 , Rendina et al, 2014 , Cameron and Castro, 2001 , Rothan et al, 2019 , Roh, 2012 , Ryu et al, 2010b , Saavedra, 2020 , Sadaie et al, 2004 , Sahebkar et al, 2016 , Shaito et al, 2020 , Shao et al, 2013 , Shen et al, 1996 , Shin and Seong, 2017 , Shin et al, 2013 , Song and Choi, 2011 , Su et al, 2020 , Su et al, 2020 , Cao et al, 2013 , Tyagi et al, 2016 , Utsunomiya et al, 1997 , Vankadari and Wilce, 2020 , Wang et al, 2011 , Cao et al, 2013 ...…”

Section: Uncited Referencesmentioning

confidence: 99%

Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

et al. 2021

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Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack of proper & specific target-oriented pharmacologically safe prophylactic agents or drugs, and or any effective vaccine. drug development is urgently required to back in the normalcy in the community and to combat this pandemic. Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. We have highlighted this target-oriented novel drug delivery strategy, based on their pathophysiological implication on SARS-CoV-2 infection, as evident from earlier SARS-CoV-1, MERS, and influenza virus infection via host cell entry, priming, fusion, and endocytosis. An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target. As, few of them had shown promising anti-viral response in both preclinical and clinical study with acceptable therapeutic safety-index. Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection, when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell.

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“…Complement and platelet activation, increased tissue factors and endothelial damage are considered as main causes of the COVID-19-associated vascular thrombosis. These changes can be interpreted as the consequence of overshooting inflammation due to hyperactivation of the innate immune system [ 4 , 5 , 6 , 7 , 8 , 9 ]. In addition to its anti-inflammatory actions, melatonin promotes the release of tissue factor pathway inhibitor (TFPI) from intracellular stores or from glycosyl phosphatidylinositol anchored TFPI present on endothelial membranes [ 152 ].…”

Section: The Outcomes Of Covid-19 Are Potentially Linked To Melatomentioning

confidence: 99%

“…To date, no real breakthrough has been achieved by antiviral strategies in terms of reducing mortality from COVID-19. Some moderate success has been obtained by supportive treatments with anticoagulants [ 4 , 5 , 6 ] or anti-inflammatory agents, such as the IL-6 receptor blocker tocilizumab [ 7 , 8 , 9 ]. This situation is not totally surprising with regard to the history of anti-viral drug development.…”

Section: Introductionmentioning

confidence: 99%

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Tan¹,

Hardeland

2020

Molecules

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Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen’s spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host’s tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

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Anticoagulant and antiarrhythmic effects of heparin in the treatment of COVID‐19 patients

Cited by 27 publications

References 10 publications

IL-4/IL-13 remodeling pathway of COVID-19 lung injury

IL-4/IL-13 remodeling pathway of COVID-19 lung injury

Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

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