Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Almulaiky, Yaaser Q.; Cruz‐Martins, Natália; Batiha, Gaber El‐Saber

doi:10.1016/j.ejphar.2021.174196

Cited by 55 publications

(50 citation statements)

References 68 publications

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“…It was suggested that montelukast can directly impact on COVID-19 [92], by having an anti-viral effect, or by suppression of heightened cytokine release in response to the virus [93][94][95][96]. Montelukast can block Cysteinyl-leukotriene in different organs or indirectly through inhibition of the NF-κB signaling pathway [97].…”

mentioning

confidence: 99%

TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy

Laubscher

Lourens

Venter

et al. 2021

JCM

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An important component of severe COVID-19 disease is virus-induced endothelilitis. This leads to disruption of normal endothelial function, initiating a state of failing normal clotting physiology. Massively increased levels of von Willebrand Factor (VWF) lead to overwhelming platelet activation, as well as activation of the enzymatic (intrinsic) clotting pathway. In addition, there is an impaired fibrinolysis, caused by, amongst others, increased levels of alpha-(2) antiplasmin. The end result is hypercoagulation (proven by thromboelastography® (TEG®)) and reduced fibrinolysis, inevitably leading to a difficult-to-overcome hypercoagulated physiological state. Platelets in circulation also plays a significant role in clot formation, but they themselves may also drive hypercoagulation when they are overactivated due to the interactions of their receptors with the endothelium, immune cells or circulating inflammatory molecules. From the literature it is clear that the role of platelets in severely ill COVID-19 patients has been markedly underestimated or even ignored. We here highlight the value of early management of severe COVID-19 coagulopathy as guided by TEG®, microclot and platelet mapping. We also argue that the failure of clinical trials, where the efficacy of prophylactic versus therapeutic clexane (low molecular weight heparin (LMWH)) were not always successful, which may be because the significant role of platelet activation was not taken into account during the planning of the trial. We conclude that, because of the overwhelming alteration of clotting, the outcome of any trial evaluating an any single anticoagulant, including thrombolytic, would be negative. Here we suggest the use of the degree of platelet dysfunction and presence of microclots in circulation, together with TEG®, might be used as a guideline for disease severity. A multi-pronged approach, guided by TEG® and platelet mapping, would be required to maintain normal clotting physiology in severe COVID-19 disease.

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mentioning

confidence: 99%

TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy

Laubscher

Lourens

Venter

et al. 2021

JCM

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“…One of possible explanations of differential susceptibility among carriers of different GSTP1 alleles may be the variations in regulatory roles of GSTP1. It is noteworthy to mention that, apart from its well-established role in detoxification and antioxidant protection, GSTP1 also exhibits leukotriene synthase activity, thus influencing pulmonary and extrapulmonary manifestations of COVID-19 ( Al-Kuraishy et al, 2021 ). Still, the data on the effect of different GSTP1 genetic variants on LTC4 synthesis are lacking.…”

Section: Discussionmentioning

confidence: 99%

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19

Ćorić

Milošević

Djukić

et al. 2021

Front. Mol. Biosci.

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Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

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“…Pharmacological approach may also be applied to treat acute uncomplicated cases. However, more treatment options are required, thus necessitating the search for newer therapeutic agents ( 20 , 21 ). Presently, the WHO and other stakeholders are faced with the task to discover effective therapeutic agents to combat SARS-CoV-2 or make possible the fast development of vaccine(s) that prevent the disease.…”

Section: Covid-19 Transmissionmentioning

confidence: 99%

Maternal Transmission of SARS-CoV-2: Safety of Breastfeeding in Infants Born to Infected Mothers

et al. 2021

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Coronavirus disease 2019 (COVID-19) is a recent epidemic disease caused by severe acute respiratory syndrome virus type 2 (SARS-CoV-2). In pregnancy, SARS-Cov-2 infection creates additional alarm due to concerns regarding the potential for transmission from the mother to the baby during both the antenatal and postpartum times. In general, breastfeeding is seldom disallowed because of infection of the mother. However, there are few exceptions with regards to certain infectious organisms with established transmission evidence from mother to infant and the link of infection of a newborn with significant morbidity and mortality. It is confirmed that pregnant women can become infected with SARS-CoV-2, although the debate on the possible vertical transmission of SARS-CoV-2 infection during pregnancy is still open. In this regard, the literature is still poor. On the contrary, the information on the safety of breastfeeding even during infections seems reassuring when the mother takes the necessary precautions. However, there are still answered questions regarding the precautions to be taken during breastfeeding by COVID-19 patients. This paper reviews the existing answers to these and many other questions. This review therefore presents a summary of the present-day understanding of infection with SARS-CoV-2 and discusses the answers around the maternal transmission of COVID-19 and the potential threat of breastfeeding to babies born to infected pregnant mothers. In conclusion, intrauterine transmission of SARS-CoV-2 infection is less likely to occur during pregnancy. Most studies suggest that COVID-19 is not transmitted through breast milk. Correspondingly, COVID-19-infected neonates might acquire the infection via the respiratory route because of the postnatal contact with the mother rather than during the prenatal period. International organizations encourage breastfeeding regardless of the COVID-19 status of the mother or child as long as proper hygienic and safety measures are adhered to so as to minimize the chance of infant infection by droplets and direct contact with the infected mother. Pasteurized donor human milk or infant formula as supplemental feeding can be quite beneficial in the case of mother–infant separation till breastfeeding is safe.

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Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

Cited by 55 publications

References 68 publications

TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy

TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19

Maternal Transmission of SARS-CoV-2: Safety of Breastfeeding in Infants Born to Infected Mothers

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