Research

12 pages, 1832 KiB

Open AccessArticle

DNA Hypomethylation Is Associated with Increased Inflammation in Peripheral Blood Neutrophils of Children with Autism Spectrum Disorder: Understanding the Role of Ubiquitous Pollutant Di(2-ethylhexyl) Phthalate

by Ali A. Alshamrani, Samiyah Alshehri, Sana S. Alqarni, Sheikh F. Ahmad, Hanan Alghibiwi, Naif O. Al-Harbi, Saleh A. Alqarni, Laila Y. Al-Ayadhi, Sabry M. Attia, Ali S. Alfardan, Saleh A. Bakheet and Ahmed Nadeem

Metabolites 2023, 13(3), 458; https://doi.org/10.3390/metabo13030458 - 22 Mar 2023

Cited by 3 | Viewed by 1527

Abstract

Autism spectrum disorder (ASD) is a multidimensional disorder in which environmental, immune, and genetic factors act in concert to play a crucial role. ASD is characterized by social interaction/communication impairments and stereotypical behavioral patterns. Epigenetic modifications are known to regulate genetic expression through [...] Read more.

Autism spectrum disorder (ASD) is a multidimensional disorder in which environmental, immune, and genetic factors act in concert to play a crucial role. ASD is characterized by social interaction/communication impairments and stereotypical behavioral patterns. Epigenetic modifications are known to regulate genetic expression through various mechanisms. One such mechanism is DNA methylation, which is regulated by DNA methyltransferases (DNMTs). DNMT transfers methyl groups onto the fifth carbon atom of the cytosine nucleotide, thus converting it into 5-methylcytosine (5mC) in the promoter region of the DNA. Disruptions in methylation patterns of DNA are usually associated with modulation of genetic expression. Environmental pollutants such as the plasticizer Di(2-ethylhexyl) phthalate (DEHP) have been reported to affect epigenetic mechanisms; however, whether DEHP modulates DNMT1 expression, DNA methylation, and inflammatory mediators in the neutrophils of ASD subjects has not previously been investigated. Hence, this investigation focused on the role of DNMT1 and overall DNA methylation in relation to inflammatory mediators (CCR2, MCP-1) in the neutrophils of children with ASD and typically developing healthy children (TDC). Further, the effect of DEHP on overall DNA methylation, DNMT1, CCR2, and MCP-1 in the neutrophils was explored. Our results show that the neutrophils of ASD subjects have diminished DNMT1 expression, which is associated with hypomethylation of DNA and increased inflammatory mediators such as CCR2 and MCP-1. DEHP further causes downregulation of DNMT1 expression in the neutrophils of ASD subjects, probably through oxidative inflammation, as antioxidant treatment led to reversal of a DEHP-induced reduction in DNMT1. These data highlight the importance of the environmental pollutant DEHP in the modification of epigenetic machinery such as DNA methylation in the neutrophils of ASD subjects. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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12 pages, 2751 KiB

Open AccessArticle

Disequilibrium in the Thioredoxin Reductase-1/Thioredoxin-1 Redox Couple Is Associated with Increased T-Cell Apoptosis in Children with Autism

by Samiyah Alshehri, Ahmed Nadeem, Sheikh F. Ahmad, Sana S. Alqarni, Naif O. Al-Harbi, Laila Y. Al-Ayadhi, Sabry M. Attia, Saleh A. Alqarni and Saleh A. Bakheet

Metabolites 2023, 13(2), 286; https://doi.org/10.3390/metabo13020286 - 16 Feb 2023

Cited by 2 | Viewed by 1325

Abstract

Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant [...] Read more.

Autism spectrum disorder (ASD) is a neuropsychiatric childhood disorder that affects social skill and language development, and is characterized by persistent stereotypic behaviors, restricted social interests, and impaired language/social skills. ASD subjects have dysregulated immune responses due to impairment in inflammatory and antioxidant signaling in immune cells, such as T cells. Thioredoxin reductase-1 (TrxR1) and thioredoxin-1 (Trx1) play a crucial role in the maintenance of redox equilibrium in several immune cells, including T cells. T-cell apoptosis plays a crucial role in the pathogenesis of several inflammatory diseases. However, it remains to be explored how the TrxR1/Trx1 redox couple affects T-cells apoptosis in ASD and typically developing control (TDC) groups. Therefore, this single-center cross-sectional study explored the expression/activity of TrxR1/Trx1, and Bcl2, 7-AAD/annexin V immunostaining in T cells of ASD (n = 25) and TDC (n = 22) groups. Further, effects of the LPS were determined on apoptosis in TDC and ASD T cells. Our data show that T cells have increased TrxR1 expression, while having decreased Trx1 expression in the ASD group. Further, TrxR enzymatic activity was also elevated in T cells of the ASD group. Furthermore, T cells of the ASD group had a decreased Bcl2 expression and an increased % of annexin V immunostaining. Treatment of T cells with LPS caused greater apoptosis in the ASD group than the TDC group, with same treatment. These data reveal that the redox couple TrxR1/Trx1 is dysregulated in T cells of ASD subjects, which is associated with decreased Bcl2 expression and increased apoptosis. This may lead to decreased survival of T cells in ASD subjects during chronic inflammation. Future studies should investigate environmental factors, such as gut dysbiosis and pollutants, that may cause abnormal immune responses in the T cells of ASD subjects due to chronic inflammation. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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16 pages, 3123 KiB

Open AccessArticle

Activation of Granulocytes in Response to a High Protein Diet Leads to the Formation of Necrotic Lesions in the Liver

by Ante Benić, Sanja Mikašinović, Felix M. Wensveen and Bojan Polić

Metabolites 2023, 13(2), 153; https://doi.org/10.3390/metabo13020153 - 19 Jan 2023

Viewed by 1602

Abstract

In their aspiration to become healthy, people are known to follow extreme diets. However, the acute impact on organs regulating systemic metabolism is not well characterized. Here, we investigated the acute impact of six extreme diets on the liver in mice. Most diets [...] Read more.

In their aspiration to become healthy, people are known to follow extreme diets. However, the acute impact on organs regulating systemic metabolism is not well characterized. Here, we investigated the acute impact of six extreme diets on the liver in mice. Most diets did not lead to clear pathology after short-term feeding. However, two weeks of feeding with a high protein diet (HPD) resulted in an acute increase of liver enzymes in the blood, indicative of liver damage. Histology revealed the formation of necrotic lesions in this organ which persisted for several weeks. Flow cytometric analysis of hepatic immune cell populations showed that HPD feeding induced activation of macrophages and neutrophils. Neutralization of the pro-inflammatory cytokine IL-1β or depletion of macrophages with clodronate-loaded liposomes or with genetic models did not ameliorate liver necrosis. In contrast, the depletion of neutrophils prevented HPD-induced hepatic inflammation. After prolonged feeding, HPD-feeding was associated with a strong increase of the cytokines IL-10 and IL-27, suggesting that anti-inflammatory mediators are activated to prevent nutrient-overload-induced damage to the liver. In summary, whereas our data indicates that most extreme diets do not have a major impact on the liver within two weeks, diets with a very high protein content may lead to severe, acute hepatic damage and should therefore be avoided. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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15 pages, 3862 KiB

Open AccessArticle

Blockade of Tyrosine Kinase, LCK Leads to Reduction in Airway Inflammation through Regulation of Pulmonary Th2/Treg Balance and Oxidative Stress in Cockroach Extract-Induced Mouse Model of Allergic Asthma

by Saleh A. Alqarni, Abdulwahab Bineid, Sheikh F. Ahmad, Naif O. Al-Harbi, Faleh Alqahtani, Khalid E. Ibrahim, Nemat Ali and Ahmed Nadeem

Metabolites 2022, 12(9), 793; https://doi.org/10.3390/metabo12090793 - 25 Aug 2022

Cited by 7 | Viewed by 1672

Abstract

Asthma is one of the most common inflammatory diseases affecting the airways. Approximately 300 million individuals suffer from asthma around the world. Allergic immune responses in the asthmatic airways are predominantly driven by Th2 cells and eosinophils. Lymphocyte-specific protein tyrosine kinase (LCK) is [...] Read more.

Asthma is one of the most common inflammatory diseases affecting the airways. Approximately 300 million individuals suffer from asthma around the world. Allergic immune responses in the asthmatic airways are predominantly driven by Th2 cells and eosinophils. Lymphocyte-specific protein tyrosine kinase (LCK) is a non-receptor tyrosine kinase which regulates several key intracellular events through phosphorylation of its substrates. Some of the intracellular signaling pathways activated by LCK phosphorylation help in differentiation of Th2 cells which secrete allergic cytokines that amplify airway inflammation. Therefore, this investigative study was designed to determine the role of LCK in a cockroach extract (CE)-induced airway inflammation murine model of allergic asthma. Further, the effect of a pharmacological LCK inhibitor, A-770041, on allergic airway inflammation and key intracellular pathways in CD4+ T cells was assessed. Our data exhibit that there is an activation of LCK during allergic airway inflammation as depicted by increased p-LCK levels in CD4+ T cells. Activated LCK is involved in the activation of ITK, PLC-γ, GATA3, NFkB, and NFATc1. Activated LCK is also involved in the upregulation of Th2 related cytokines, such as IL-4/IL-5/IL-13 and oxidative stress, and the downregulation of Treg cells. Furthermore, utilization of LCK inhibitor causes the reduction in p-LCK, PLC-γ, GATA3, and NFATc1 as well as Th2 cytokines and oxidative stress. LCK inhibitor causes upregulation of Treg cells in allergic mice. LCK inhibitor also caused a reduction in CE-induced airway inflammation and mucus secretion. Therefore, the inhibition of LCK signaling could be a fruitful approach to adjust allergic airway inflammation through the attuning of Th2/Treg immune responses. This study could lead to the design of newer treatment options for better management of allergic inflammation in asthma. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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16 pages, 5288 KiB

Open AccessArticle

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

by Jinzi Zeng, Ning Zhao, Jiajia Yang, Weiyang Kuang, Xuewei Xia, Xiaodan Chen, Zhiyuan Liu and Riming Huang

Metabolites 2022, 12(7), 653; https://doi.org/10.3390/metabo12070653 - 15 Jul 2022

Cited by 7 | Viewed by 3264

Abstract

Puerarin is a natural flavonoid with significant anti-inflammatory effects. Recent studies have suggested that ferroptosis may involve puerarin countering inflammation. However, the mechanism of ferroptosis mediated by the anti-inflammatory process of puerarin has not been widely explored. Herein, puerarin at a concentration of [...] Read more.

Puerarin is a natural flavonoid with significant anti-inflammatory effects. Recent studies have suggested that ferroptosis may involve puerarin countering inflammation. However, the mechanism of ferroptosis mediated by the anti-inflammatory process of puerarin has not been widely explored. Herein, puerarin at a concentration of 40 μM showed an anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophages RAW264.7. The analysis of network pharmacology indicated that 51 common targets were enriched in 136 pathways, and most of the pathways were associated with ferroptosis. Subsequently, the analysis of metabolomics obtained 61 differential metabolites that were enriched in 30 metabolic pathways. Furthermore, integrated network pharmacology and metabolomics revealed that puerarin exerted an excellent effect on anti-inflammatory in RAW264.7 via regulating ferroptosis-related arachidonic acid metabolism, tryptophan metabolism, and glutathione metabolism pathways, and metabolites such as 20-hydroxyeicosatetraenoic acid (20-HETE), serotonin, kynurenine, oxidized glutathione (GSSG), gamma-glutamylcysteine and cysteinylglycine were involved. In addition, the possible active binding sites of the potential targeted proteins such as acyl-CoA synthetase long-chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 15-lipoxygenase (ALOX15) and glutathione peroxidase 4 (GPX4) with puerarin were further revealed by molecular docking. Thus, we suggested that ferroptosis mediated the anti-inflammatory effects of puerarin in macrophages RAW264.7 induced by LPS. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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0 pages, 2038 KiB

Open AccessArticle

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

by Naama Karu, Alida Kindt, Lieke Lamont, Adriaan J. van Gammeren, Anton A. M. Ermens, Amy C. Harms, Lutzen Portengen, Roel C. H. Vermeulen, Willem A. Dik, Anton W. Langerak, Vincent H. J. van der Velden and Thomas Hankemeier

Metabolites 2022, 12(7), 619; https://doi.org/10.3390/metabo12070619 - 04 Jul 2022

Cited by 14 | Viewed by 2633

Abstract

COVID-19 is characterised by a dysregulated immune response, that involves signalling lipids acting as mediators of the inflammatory process along the innate and adaptive phases. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS [...] Read more.

COVID-19 is characterised by a dysregulated immune response, that involves signalling lipids acting as mediators of the inflammatory process along the innate and adaptive phases. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The second publication in a series reports the results of quantitative LC-MS/MS profiling of 63 small lipids including oxylipins, free fatty acids, and endocannabinoids. Compared to samples taken from ward patients, intensive care unit (ICU) patients had 2–4-fold lower levels of arachidonic acid (AA) and its cyclooxygenase-derived prostanoids, as well as lipoxygenase derivatives, exhibiting negative correlations with inflammation markers. The same derivatives showed 2–5-fold increases in recovering ward patients, in paired comparison to early hospitalisation. In contrast, ICU patients showed elevated levels of oxylipins derived from poly-unsaturated fatty acids (PUFA) by non-enzymatic peroxidation or activity of soluble epoxide hydrolase (sEH), and these oxylipins positively correlated with markers of macrophage activation. The deficiency in AA enzymatic products and the lack of elevated intermediates of pro-resolving mediating lipids may result from the preference of alternative metabolic conversions rather than diminished stores of PUFA precursors. Supporting this, ICU patients showed 2-to-11-fold higher levels of linoleic acid (LA) and the corresponding fatty acyl glycerols of AA and LA, all strongly correlated with multiple markers of excessive immune response. Our results suggest that the altered oxylipin metabolism disrupts the expected shift from innate immune response to resolution of inflammation. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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10 pages, 2809 KiB

Open AccessArticle

Low-Concentrations of Fatty Acids Induce an Early Increase in IL-8 Levels in Normal Human Astrocytes

by Ana-Maria Dobri, Elena Codrici, Ionela-Daniela Popescu, Lucian Albulescu, Emanuel Tudor Fertig, Ana-Maria Enciu, Cristiana Tanase and Mihail E. Hinescu

Metabolites 2022, 12(4), 329; https://doi.org/10.3390/metabo12040329 - 06 Apr 2022

Viewed by 1791

Abstract

Fatty acids (FAs) have been shown to exhibit a pro-inflammatory response in various cell types, but astrocytes have been mostly overlooked. FAs, both saturated and unsaturated, have previously been shown to induce pro-inflammatory responses in astrocytes at high concentrations of hundreds of µg/mL. [...] Read more.

Fatty acids (FAs) have been shown to exhibit a pro-inflammatory response in various cell types, but astrocytes have been mostly overlooked. FAs, both saturated and unsaturated, have previously been shown to induce pro-inflammatory responses in astrocytes at high concentrations of hundreds of µg/mL. SSO (Sulfo-N-succinimidyl Oleate sodium), an inhibitor of FA translocase CD36, has been shown to prevent inflammation in the mouse brain by acting on local microglia and infiltrating monocytes. Our hypothesis was that SSO treatment would also impact astrocyte pro-inflammatory response to FA. In order to verify our assumption, we evaluated the expression of pro- and anti-inflammatory cytokines in normal human astrocyte cell culture pre-treated (or not) with SSO, and then exposed to low concentrations of both saturated (palmitic acid) and unsaturated (oleic acid) FAs. As a positive control for astrocyte inflammation, we used fibrillary amyloid. Neither Aβ 1–42 nor FAs induced CD36 protein expression in human astrocytes in cell culture At low concentrations, both types of FAs induced IL-8 protein secretion, and this effect was specifically inhibited by SSO pre-treatment. In conclusion, low concentrations of oleic acid are able to induce an early increase in IL-8 expression in normal human astrocytes, which is specifically downregulated by SSO. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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Review

Jump to: Research, Other

15 pages, 371 KiB

Open AccessReview

Copper/Zinc Ratio in Childhood and Adolescence: A Review

by Marlene Fabiola Escobedo-Monge, Enrique Barrado, Joaquín Parodi-Román, María Antonieta Escobedo-Monge, María Carmen Torres-Hinojal and José Manuel Marugán-Miguelsanz

Metabolites 2023, 13(1), 82; https://doi.org/10.3390/metabo13010082 - 03 Jan 2023

Cited by 4 | Viewed by 2827

Abstract

Both copper (Cu) and zinc (Zn) are crucial micronutrients for human growth and development. This literature review covered the last five years of available evidence on the Cu/Zn ratio in children and adolescents. We searched PubMed, Web of Science, Google Scholar, Cochrane Library, [...] Read more.

Both copper (Cu) and zinc (Zn) are crucial micronutrients for human growth and development. This literature review covered the last five years of available evidence on the Cu/Zn ratio in children and adolescents. We searched PubMed, Web of Science, Google Scholar, Cochrane Library, and Science Direct for publications between 2017 and 2022, especially in English, although publications in other languages with abstracts in English were included. The main terms used were “copper”, “zinc”, “copper-zinc”, and “zinc-copper” ratios. Cu and Zn determinations made in blood, plasma, or serum were included. This review comprises several cross-sectional and case–control studies with substantial results. The bibliographic search generated a compilation of 19 articles, in which 63.2% of the studies mostly reported a significantly higher Cu/Zn ratio, and 57.9% of them informed significantly lower levels of Zn. We conclude that children and adolescents with acute and chronic conditions are at greater risk of developing elevated Cu/Zn ratios, related to altered nutritional, infectious, and inflammatory status. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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35 pages, 14336 KiB

Open AccessReview

Infective Endocarditis in High-Income Countries

by Francesco Nappi, Giorgia Martuscelli, Francesca Bellomo, Sanjeet Singh Avtaar Singh and Marc R. Moon

Metabolites 2022, 12(8), 682; https://doi.org/10.3390/metabo12080682 - 25 Jul 2022

Cited by 18 | Viewed by 2727

Abstract

Infective endocarditis remains an illness that carries a significant burden to healthcare resources. In recent times, there has been a shift from Streptococcus sp. to Staphylococcus sp. as the primary organism of interest. This has significant consequences, given the virulence of Staphylococcus and [...] Read more.

Infective endocarditis remains an illness that carries a significant burden to healthcare resources. In recent times, there has been a shift from Streptococcus sp. to Staphylococcus sp. as the primary organism of interest. This has significant consequences, given the virulence of Staphylococcus and its propensity to form a biofilm, rendering non-surgical therapy ineffective. In addition, antibiotic resistance has affected treatment of this organism. The cohorts at most risk for Staphylococcal endocarditis are elderly patients with multiple comorbidities. The innovation of transcatheter technologies alongside other cardiac interventions such as implantable devices has contributed to the increased risk attributable to this cohort. We examined the pathophysiology of infective endocarditis carefully. Inter alia, the determinants of Staphylococcus aureus virulence, interaction with host immunity, as well as the discovery and emergence of a potential vaccine, were investigated. Furthermore, the potential role of prophylactic antibiotics during dental procedures was also evaluated. As rates of transcatheter device implantation increase, endocarditis is expected to increase, especially in this high-risk group. A high level of suspicion is needed alongside early initiation of therapy and referral to the heart team to improve outcomes. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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Other

Jump to: Research, Review

12 pages, 1454 KiB

Open AccessViewpoint

Inflammation Control and Immunotherapeutic Strategies in Comprehensive Cancer Treatment

by Victor Ivanovich Seledtsov, Adas Darinskas, Alexei Von Delwig and Galina Victorovna Seledtsova

Metabolites 2023, 13(1), 123; https://doi.org/10.3390/metabo13010123 - 13 Jan 2023

Viewed by 1573

Abstract

Tumor growth and expansion are determined by the immunological tumor microenvironment (TME). Typically, early tumorigenic stages are characterized by the immune system not responding or weakly responding to the tumor. However, subsequent tumorigenic stages witness the tumor promoting its growth and metastasis by [...] Read more.

Tumor growth and expansion are determined by the immunological tumor microenvironment (TME). Typically, early tumorigenic stages are characterized by the immune system not responding or weakly responding to the tumor. However, subsequent tumorigenic stages witness the tumor promoting its growth and metastasis by stimulating tumor-protective (pro-tumor) inflammation to suppress anti-tumor immune responses. Here, we propose the pivotal role of inflammation control in a successful anti-cancer immunotherapy strategy, implying that available and novel immunotherapeutic modalities such as inflammation modulation, antibody (Ab)-based immunostimulation, drug-mediated immunomodulation, cancer vaccination as well as adoptive cell immunotherapy and donor leucocyte transfusion could be applied in cancer patients in a synergistic manner to amplify each other’s clinical effects and achieve robust anti-tumor immune reactivity. In addition, the anti-tumor effects of immunotherapy could be enhanced by thermal and/or oxygen therapy. Herein, combined immune-based therapy could prove to be beneficial for patients with advanced cancers, as aiming to provide long-term tumor cell/mass dormancy by restraining compensatory proliferation of surviving cancer cells observed after traditional anti-cancer interventions such as surgery, radiotherapy, and metronomic (low-dose) chemotherapy. We propose the Inflammatory Prognostic Score based on the blood levels of C-reactive protein and lactate dehydrogenase as well as the neutrophil-to-lymphocyte ratio to effectively monitor the effectiveness of comprehensive anti-cancer treatment. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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31 pages, 3471 KiB

Open AccessSystematic Review

Thromboembolic Disease and Cardiac Thrombotic Complication in COVID-19: A Systematic Review

by Francesco Nappi, Pierluigi Nappi, Ivancarmine Gambardella and Sanjeet Singh Avtaar Singh

Metabolites 2022, 12(10), 889; https://doi.org/10.3390/metabo12100889 - 22 Sep 2022

Cited by 7 | Viewed by 2483

Abstract

The coronavirus 2019 pandemic has affected many healthcare systems worldwide. While acute respiratory distress syndrome (ARDS) has been well-documented in COVID-19, there are several cardiovascular complications, such as myocardial infarction, ischaemic stroke, and pulmonary embolism, leading to disability and death. The link between [...] Read more.

The coronavirus 2019 pandemic has affected many healthcare systems worldwide. While acute respiratory distress syndrome (ARDS) has been well-documented in COVID-19, there are several cardiovascular complications, such as myocardial infarction, ischaemic stroke, and pulmonary embolism, leading to disability and death. The link between COVID-19 and increasing thrombogenicity potentially occurs due to numerous different metabolic mechanisms, ranging from endothelial damage for direct virus infection, associated excessive formation of neutrophil extracellular traps (NETs), pathogenic activation of the renin-angiotensin-aldosterone system (RAAS), direct myocardial injury, and ischemia induced by respiratory failure, all of which have measurable biomarkers. A search was performed by interrogating three databases (MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations, and EMBASE). Evidence from randomized controlled trials (RCT), prospective series, meta-analyses, and unmatched observational studies were evaluated for the processing of the algorithm and treatment of thromboembolic disease and cardiac thrombotic complications related to COVID-19 during SARS-CoV-2 infection. Studies out with the SARS-Cov-2 infection period and case reports were excluded. A total of 58 studies were included in this analysis. The role of the acute inflammatory response in the propagation of the systemic inflammatory sequelae of the disease plays a major part in determining thromboembolic disease and cardiac thrombotic complication in COVID-19. Some of the mechanisms of activation of these pathways, alongside the involved biomarkers noted in previous studies, are highlighted. Inflammatory response led to thromboembolic disease and cardiac thrombotic complications in COVID-19. NETs play a pivotal role in the pathogenesis of the inflammatory response. Despite moving into the endemic phase of the disease in most countries, thromboembolic complications in COVID-19 remain an entity that substantially impacts the health care system, with long-term effects that remain uncertain. Continuous monitoring and research are required. Full article

(This article belongs to the Special Issue Metabolism of Immune System in Inflammatory and Infectious Diseases)

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