ABSTRACT
Introduction: Although the mechanism of neurological complications after COVID-19 vaccination has not been precisely explained, it could be attributed to the inflammatory state triggered by COVID-19 vaccine as in the course of COVID-19 viral infection. This condition induces disseminated intravascular coagulation (DIC) in combination with vascular endothelial dysfunction, leading to stroke of the large vessels. This hypothesis may be the main cause of DIC, especially in mRNA-based vaccines, whose mechanism involves delivery of the mRNA code of the spike protein to human cells. Cellular synthesis of the spike protein stimulates the immune system to recognize and store it for future attack. Based on this hypothesis, the inflammatory state triggered by the vaccine can be considered the main pathway for neurological complications of COVID-19 vaccine. Objective(s): The aim of this work is to analyse the incidence of ischaemic stroke risk following administration of the ComirnatyTM vaccine in ASST GOM Niguarda, an Italian hospital based in Milan, and to compare it with data from FAERS database. Method(s): The Reporting Odds Ratio (ROR) was calculated in order to evaluate a possible correlation between the risk of ischaemic stroke and ComirnatyTM vaccine administration in the period of January- December 2021. For this purpose, we consulted FAERS public domain database that allows you to search information relating to adverse events reported to the FDA. Result(s): From reports of adverse events of ComirnatyTM vaccinated patients at ASST GOM Niguarda hospital, it was observed that after administration of this vaccine there is a correlation with the risk of developing ischaemic stroke mainly in over 65 years old patients (OR = 1.26;95% CI 0.17-9.13;z = 0.230;p value = 0.8182) when comparing the data with other vaccines. These data match the data obtained from FAERS (OR: 1.29;95% CI 0.85-1.96;z = 1.205;p value = 0.228), confirming the data collected in ASST GOM Niguarda. Conclusion(s): The data extrapolated from this analysis conducted at ASST GOM Niguarda mirror those obtained from the FAERS database with a comparable significance index (p value). In conclusion, the possible correlation between ComirnatyTM vaccine administration and the development of ischaemic stroke as an adverse event was confirmed.
ABSTRACT
Introduction: Although the mechanism of neurological complications after COVID-19 vaccination has not been precisely explained, it could be attributed to the inflammatory state triggered by COVID-19 vaccine as in the course of COVID-19 viral infection. This condition induces disseminated intravascular coagulation (DIC) in combination with vascular endothelial dysfunction, leading to stroke of the large vessels. This hypothesis may be the main cause of DIC, especially in mRNA-based vaccines, whose mechanism involves delivery of the mRNA code of the spike protein to human cells. Cellular synthesis of the spike protein stimulates the immune system to recognize and store it for future attack. Based on this hypothesis, the inflammatory state triggered by the vaccine can be considered the main pathway for neurological complications of COVID-19 vaccine. Objective: The aim of this work is to analyse the incidence of ischaemic stroke risk following administration of the ComirnatyTM vaccine in ASST GOM Niguarda, an Italian hospital based in Milan, and to compare it with data from FAERS database. Methods: The Reporting Odds Ratio (ROR) was calculated in order to evaluate a possible correlation between the risk of ischaemic stroke and Comirnaty™ vaccine administration in the period of January-December 2021. For this purpose, we consulted FAERS public domain database that allows you to search information relating to adverse events reported to the FDA. Results: From reports of adverse events of ComirnatyTM vaccinated patients at ASST GOM Niguarda hospital, it was observed that after administration of this vaccine there is a correlation with the risk of developing ischaemic stroke mainly in over 65 years old patients (OR = 1.26;95% CI 0.17-9.13;z = 0.230;p value = 0.8182) when comparing the data with other vaccines. These data match the data obtained from FAERS (OR: 1.29;95% CI 0.85-1.96;z = 1.205;p value = 0.228), confirming the data collected in ASST GOM Niguarda. Conclusion: The data extrapolated from this analysis conducted at ASST GOM Niguarda mirror those obtained from the FAERS database with a comparable significance index (p value). In conclusion, the possible correlation between ComirnatyTM vaccine administration and the development of ischaemic stroke as an adverse event was confirmed.
ABSTRACT
Background: ACE2 is a carboxypeptidase homolog to the dipeptidase ACE but with different substrate specificity;while ACE principally acts as a carboxydipeptidase (peptidyldipeptidase) removing the C-terminal dipeptide from Ang I to form Ang II, ACE2 functions exclusively as a carboxypeptidase removing a single C-terminal amino acid from Ang II generating Ang- (1-7) or, much less efficiently, from Ang I forming Ang-(1-9). ACE and ACE2 than playing a key role in regulating the renin–angiotensin–aldosterone system (RAAS). In the normal lung, ACE2 mRNA is mainly expressed by type II alveolar epithelial cells and endothelial cells, but the level of expression increases in response to inflammation while is downregulated in response to SARS-CoV infection. ACE2, mRNA and protein, is highly expressed in the gastrointestinal tract, with the higher expression detected in epithelial cells of the ileum and the colon where mediates the absorption of amino acids. ACE2 expression in the intestine undergoes regulation in response to a variety of factors including intestinal microbiota and inflammation. Furthermore, previous studies have suggested that insulinotropic factor glucagon like peptide (GLP)-1 might regulate ACE2 expression in the heart, suggesting a potential interaction of GLP1 with ACE2. GPBAR1, G Protein Bile Acid Receptor, is robustly expressed in the gastrointestinal tract and its activation in the intestine promotes the release of GLP-1. Aim: to investigate the possible interaction between bile acids via GPBAR1 and the expression of ACE2 in the gastrointestinal tract. Materials and Methods: HT29 cells treated with TNF-α + IL-1β and mouse models of colitis were used to assess ACE2 expression and treatment with BAR501, a GPBAR1 agonist, was used to investigate its modulation. Results: The inflammatory stimulus increased the expression of Ace2 in HT29 cells and in colon of mice according to the data obtained in human samples from patient with IBD. GPBAR1 agonism by BAR501 relieved inflammation both in vitro and in vivo but in vitro this effect induced down-regulation of ACE2 while in vivo administration of BAR501 increased ACE2 expression. In mouse model of colitis, inflammation up-regulated also the GLP-1 gene expression that was further increased by BAR501 and instead, the administration of Exendina- 3, a GLP-1R antagonist was able to block the up-regulation of Ace2 expression exerted by BAR501. Conclusions: In conclusion, our results demonstrate that both in vivo and in vitro activation of GPBAR1 by a selective agonist exerts an anti-inflammatory effect. On the other hand, in vivo activation of GPBAR1 in the colon induces the release of GLP-1, which mediates some of the anti-inflammatory effects exerted by the receptor, and induces further upregulation of Ace2 by GPBAR1/GLP-1/GLP-1R axis.(Figure Presented)