Abstract
Chagas and COVID-19 are diseases caused by Trypanosoma cruzi and SARS-CoV-2, respectively. These diseases present very different etiological agents despite showing similarities such as susceptibility/risk factors, pathogen-associated molecular patterns (PAMPs), recognition of glycosaminoglycans, inflammation, vascular leakage hypercoagulability, microthrombosis, and endotheliopathy; all of which suggest, in part, treatments with similar principles. Here, both diseases are compared, focusing mainly on the characteristics related to dysregulated immunothrombosis. Given the in-depth investigation of molecules and mechanisms related to microthrombosis in COVID-19, it is necessary to reconsider a prompt treatment of Chagas disease with oral anticoagulants.
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Introduction
Chagas disease (CD) and COVID-19 caused by Trypanosoma cruzi and SARS-CoV-2, respectively, have the common characteristic of dysregulated immunothrombosis. Here, we have integrated the reported evidence of both, which leads us to consider that the possibility of anticoagulant treatment in Chagas disease can prevent the immunothrombosis stage.
Although the prevalence of immunothrombotic dysregulation in Chagas disease and COVID-19 is not yet known, the proportion depends on the method of detection and the group studied. As an example, the chronic cardiac form of CD was inferred through echocardiography in a study of ischemic cerebrovascular events (ICE); the authors found cardioembolism as a factor associated with 20% of CD cases [1], however, could reach 44% [2]. Even though the reported evidence is extremely diverse, it currently indicates that the incidence of deep vein thrombosis (DVT) in COVID-19 patients ranges between 6 and 66% [3]. In mild/moderate COVID-19, deep venous thrombosis (DVT) was found in the lower extremities by duplex ultrasound, with a rate of around 25% [4], but it could reach as much as 82% by computed tomography venography (CTV) and doppler ultrasound [5]. In pulmonary vessels, it is 46% [6], while in arterial thromboses, it is 9.6% [7].
Immunothrombosis has been reported in COVID-19 [8] and Chagas disease [9, 10]. Immune-driven thrombosis, immunothrombosis, or thrombo-inflammation [11] has the characteristics of upregulation of monocytes/macrophages and vessel wall-exposing podoplanin, activating C-type lectin-like receptor-2 (CLEC-2) in platelets on the microvasculature [12], which causes endotheliopathy and microthrombi [13]. The expression of podoplanin, known as gp38, T1α, D2-40, or Aggrus, is also upregulated during inflammation by cytokines and other compounds in different cells, such as T helper cells, fibroblasts, epithelial cells, and in fibroblastic reticular cells in secondary lymphoid organs [14].
In viral diseases such as dengue and H5N1 influenza, CLEC-2 binds fucoidans in a similar way to a ligand [15, 16]. These glycans interact with viruses, such as the dengue virus, which binds to CLEC-2 on platelets [16]. In the dengue virus, interaction with CLEC-2 on platelets releases exosomes and microvesicles that trigger the activation of CLEC5A and TLR2, and promote the release of neutrophil-derived extracellular traps (NETs) in addition to the release of proinflammatory cytokines in neutrophils and macrophages [12]. NETs, due to the content of DNA-histone complexes and high mobility group box 1 proteins (HMGB1), are cytotoxic and procoagulant [17, 18].
In SARS-CoV-2 infection, the spike protein induces platelet activation [19]. This is explained by the fact that platelets have ACE2-TMPRSS2 receptor-protease axis [20], and also, platelets favour increases in fibrinogen, von Willebrand factor, and factor XII [21], this favours the prothrombotic state [22].
In COVID-19, activation of the complement through mannose-binding lectin (MBL) has been reported [23]. In SARS-CoV, MBL initiates the complement activation in a calcium-dependent and a mannan-inhibitable manner [24]. MBL circulates in a complex with mannose-associated serine protease (MASP)-1 and MASP-2. MASP-1 can activate coagulation through factor XIII (FXIII) and thrombin-activatable fibrinolysis inhibitor (TAFI) [25]. That is, MBL acts from a different route to that of heparin (thrombin and factor Xa), which could explain thromboembolic events in patients with thromboprophylaxis.
In the severe form of Chagas disease, a greater binding capacity of MBL was observed, which could facilitate the internalization of T. cruzi in cardiomyocytes [26] Furthermore, MASP-2 deficiency does not represent an important mechanism against T. cruzi infection [27].
A disparity is assumed since the etiological agent is different, added to the large inter-individual and inter-population differences between Chagas disease and COVID-19. Nevertheless, when these illnesses are compared regarding susceptibility/risk, ethnicity, age, sex, and other co-morbidities, there are similarities in both diseases. For example, there are genetic polymorphisms associated with the protection or greater risk of damage, as in Chagas disease in which the genetic variant of CCL5 and CCR1 + confers protection, while CCR5 deficiency is associated with cardiac damage [28]. On the other hand, depending on the population studied, a higher or lower risk may be related to variants CCL2, MBL, CCL5, AHSG, and IL4 in COVID-19 [29]. We compare and show a series of different factors in both infections (Table 1).
Chagas disease
Chagas disease (CD) is a neglected tropical disease, with an estimated 6 to 7 million people infected with T. cruzi worldwide [30]. In 2006, the number of cases recorded in Latin America was 7,544,500 [31]. Migration, blood transfusion, and organ transplantation have caused the spread of CD not only in Latin America but also in many other places around the world, e.g. the prevalence per in some European countries is 2.7–4.8 in Spain; 2.0–4.8 in Switzerland; 1.3–1.7 in France; and 1.3–2.4 in The United Kingdom [32].
In a post-mortem study in Sao Paulo Brazil with 1,345 studied cases of Chagas heart disease, a thromboembolic phenomenon was found in 44% of patients, and this included infarction at different phases of evolution and cardiac thrombosis in 27% of cases [2]. The protocol for treatment recommends just benznidazole and nifurtimox [33]; however, anticoagulants or antiplatelet agents should be considered in addition.
Hypercoagulability and endotheliopathy in Chagas disease
In Chagas disease, hypercoagulability is characterized by an increase in the prothrombin fragment 1 + 2 (F1 + 2), endogenous thrombin potential (ETP), D-dimer, and plasmin-antiplasmin complexes (PAP), before or after treatment [13, 34]. Thrombin activation causes a procoagulant and fibrinolysis pathway. Furthermore, platelet hyperactivity and endothelial damage occur, which are correlated with increases in circulating microparticles from endothelial cells, macrophages, and CD8 + T cells [35], PAC-1 (GPIIb/IIIa), and CD62P (P-selectin) [36].
In the initial host-trypanosome interaction, the infective trypomastigote recognizes 2,3-sialyl residues [37] and releases neuraminidase, which can desialylate myocardial or human vascular endothelial cells, and mediate the development of Chagas heart disease [38]. Different mechanisms affect the invasion process of trypomastigote forms in cardiomyocytes by T. cruzi. One of the known mechanisms is through glycosaminoglycan-binding or heparin-binding proteins in the amastigote and trypomastigote forms of T. cruzi, which bind to cardiomyocyte heparan sulphate proteoglycans (HSPG) [39, 40].
T. cruzi infection also causes generalized vasculitis with peculiar characteristics in the myocardium, such as vasospasm, myocardial ischaemia, myonecrosis, and platelet hyperaggregation. Therefore, activation of the extracellular signal-regulated kinase, activator-protein-1, endothelin-1, and cyclins release thromboxane (TX2) from T. cruzi [41, 42].
COVID-19, immunothrombosis and endotheliopathy
The COVID-19 pandemic caused by SARS-CoV-2 has resulted in more than 169 million confirmed infections and 3.5 million deaths worldwide as of May 29, 2021 [43].
SARS-CoV-2 entry depends on the ACE2 receptor and the serine protease TMPRSS2 for S protein priming [44], as well as other proteins such as endosomal cysteine proteases cathepsins B/L (CTSB, CTSL) [45]. These molecules are primarily co-expressed in the respiratory tract, kidneys, heart, and gastrointestinal system [34] and show higher levels of ACE2 gene expression in the testes, thyroid, and adipose tissue [46], as well as in arterial and venous endothelial cells, and arterial smooth muscle cells [47, 48].
The concept of dysregulation of immunothrombosis defines a vicious cycle of immune activation and formation of microthrombi [11]. Microthrombi have been reported in different tissues, in alveolar capillaries, kidneys, and glomerular capillaries; furthermore, they are accompanied by signs of disseminated intravascular coagulation despite anticoagulation [49] in pulmonary, hepatic, renal, and cardiac microvasculature [50], in addition to pulmonary arterial thrombi [51]. Microthrombosis is assumed to be found in larger series in different extrapulmonary tissues, depending on the expression of ACE2 and TMPRSS2 [52].
In COVID-19 immunothrombosis, monocytes and neutrophils activate platelets and coagulation through ACE2 receptors and TMPRSS2 protease from the entry of the virus into the body [53], particularly in pneumocytes and the endothelial cells. Microvascular dysfunction, apoptosis of endothelial cells, and mononuclear cells have been observed [54], which may explain endothelial damage and the elevation of circulating endothelial cells in the presence of SARS-CoV-2 infection [55].
Regarding endothelial damage in non-critical patients in the non-intensive care unit (non-ICU), pro-angiogenic factors such as VEGF-A, PDGF-AA, and PDGF-AB/BB increase significantly, while critical patients in the ICU have significantly increased levels of biomarkers related to endotheliopathy such as angiopoietin-2, FLT-3L, and PAI-1 [56]. This is consistent with the pathological findings of severe endothelial injury associated with the intracellular SARS-CoV-2 virus and alveolar-capillary microthrombi [57].
Hypercoagulability in COVID-19
COVID-19 is associated with hypercoagulability and thrombosis due to damaged endothelial cells through ACE2 receptors. Subsequently or simultaneously, when SARS-CoV-2 enters, its pathogen-associated molecular pattern (PAMP) can be recognized. This activates the innate and adaptive immune response, platelet activation, the release of neutrophil extracellular traps (NETs), the tissue factor release and contact pathway activation, the activation of the coagulation system and thrombin generation, complement activation, and the activation of the fibrinolytic and anticoagulant systems [58]. All these activation mechanisms are expressed to different degrees but integrate dysregulated immunothrombosis [59] and then thrombosis.
In COVID-19 infection, hypercoagulability mimics disseminated intravascular coagulopathy and are characterized by thrombocytopenia and platelet hyperreactivity [19, 60]. Results are heterogeneous, depending on the severity of the patient, e.g. in initial presentations, abnormalities in prothrombin time, partial thromboplastin time, and platelet counts show little change [61]. Nevertheless, in patients with severe pneumonia and a poor prognosis, an elevated D-dimer and higher prothrombin time (PT) are observed [62] in up to 50% of patients [63]. A state of hypercoagulation and aberrant hyperfibrinolysis [64] is characterized by an increase in the activated partial thromboplastin time (APTT) and fibrinogen, with lower platelet count [65] and an increase in fibrin degradation products (FDP) [66].
Anticoagulants in COVID-19 and Chagas disease
The use of low molecular weight heparin (LMWH) is preferred over unfractionated heparin (UFH) for the treatment or reduction of an increased risk of venous thromboembolism (VTE) [67]; however, direct oral anticoagulants (DOAC) (dabigatran, apixaban and rivaroxaban) and viral medications (lopinavir, ritonavir, or darunavir) are commonly used in COVID-19 patients, although DOAC plasma levels increase significantly, as observed in the Cremona study. Therefore, they suggest the use of parenteral anticoagulants [68].
In general, prophylactic anticoagulation (including oral, subcutaneous, or intravenous forms) in COVID-19 patients results in lower mortality [69]. Moreover, derivatives of heparin have been proposed. Heparinoids constituted of heparan, dermatan, and chondroitin sulphate, are found in plants and animals, and are also of synthetic origin [70]. In the production of low molecular weight heparin, two waste heparinoids are obtained: Danaparoid and Sulodexide. Danaparoid is 84% heparan sulphate [71]; it inhibits activated factor X (Factor Xa) and activates factor II (Factor IIa) and has low cross-reactivity with antibodies associated with heparin-induced thrombocytopenia [72]. Sulodexide constituted of 80% heparan sulphate [73], increases the effect of antithrombin III and heparin cofactor II [74], and releases an inhibitor of the endothelial tissue factor pathway [75].
Another sub-group of heparinoids are Fucoidans, which have 30–60% sulphated polysaccharides [55]. These also increase the interaction of thrombin with Antithrombin III (AT-III) and heparin cofactor II (HC-II) [76].
Heparan sulphate is a heparinoid constituted of repeating units of disaccharide N-acetylglucosamine and glucuronic acid (1 → 4 linked) with alternatively sulphated domain structures [77]. Heparan sulphate and heparin are related to cell adhesion, recognition, migration, modulation of enzymatic activities, and anticoagulant activity [55].
A ubiquitous molecular component on the cell surface is heparan sulphate proteoglycans (HSPG) which are constituted of heparan sulphate (HS) polysaccharides attached to core protein by the global negative charge from HSPG. This facilitates interaction with viral molecules such as the herpes simplex virus, dengue virus, and coronaviruses [78].
SARS-CoV-2 recognizes 9-O-acetyl-sialic acid [79] and sulphated polysaccharides [80]. Various studies have reported the participation of heparin or heparan sulphate in initial virus adherence [81], and heparin and enoxaparin also bind to the spike (S1) protein receptor-binding domain (S1 RBD) [82]. Low-molecular weight heparin is the best treatment for inhibiting microthrombosis in SARS-CoV-2 infections. In addition, heparin or its derivatives could be used to compete with the virus and reduce its entry into the organism, as has been shown [83].
It should be noted that in Chagas disease with hypercoagulability, with or without associated COVID-19, the incorporation of anticoagulants is important. Considering that heparan sulphate proteoglycans participate in Chagas cardiomyopathy, the initial proposal may favour the use of heparin, heparinoids, or HS mimetics substituted carboxymethyl dextran sulphates or RGTA [84] in treatment. However, there are two important reasons not to use unfractionated heparin (UFH) or heparinoids: the first is the activation of bradykinin receptors through a papain-like enzyme called cruzipain, derived from infective forms of T. Cruzi (Tripomastigotes), this enzyme enhances cell invasion; in addition, heparan sulphate enhances the interaction of molecules of the kinin system, such as high molecular weight kininogen (HK) and cruzipain, which would potentiate cell invasion [85]. Something similar has been reported in COVID-19, a critical imbalance in the renin-angiotensin system (RAS) in combination with decreased ACE expression, increases in ACE2, renin, and angiotensin, which causes the bradykinin cascade to accelerate [86]. The second reason for not using unfractionated heparin or heparinoids is that these molecules would be blocked in all patients with chronic Chagas disease because anti-sulphatide antibodies have been found. These antibodies are inhibited and compete with heparin, dextran sulphate, and chondroitin sulphate [87].
Therefore, it is necessary to consider whether thromboprophylaxis using DOAC is required in patients with Chagas disease and understand the mechanisms of activation and regulation of microthrombosis in COVID-19. More clinical trials are certainly required in these fields.
Conclusion
We have reviewed the mechanisms and found some similarities between SARS-CoV-2 and T. cruzi infections. In particular, both clinical entities present microthrombosis and endotheliopathy. Low-molecular weight heparin (LMWH) is commonly used in moderate to severe COVID-19, although some cases do not respond to this, which suggests MBL-MASP-2 pathway activation. On the other hand, in Chagas disease, it is important to carry out further clinical trials and consider thromboprophylaxis using DOAC.
References
Nunes MC, Kreuser LJ, Ribeiro AL, Sousa GR, Costa HS, Botoni FA, de Souza AC, Gomes Marques VE, Fernandez AB, Teixeira AL, da Costa Rocha MO (2015) Prevalence and risk factors of embolic cerebrovascular events associated with Chagas heart disease. Glob Heart 10:151–157. https://doi.org/10.1016/j.gheart.2015.07.006
Samuel J, Oliveira M, Correa De Araujo RR, Navarro MA, Muccillo G (1983) Cardiac thrombosis and thromboembolism in chronic Chagas’ heart disease. Am J Cardiol 52:147–151. https://doi.org/10.1016/0002-9149(83)90085-1
Porfidia A, Valeriani E, Pola R, Porreca E, Rutjes A, Di Nisio M (2020) Venous thromboembolism in patients with COVID-19: systematic review and meta-analysis. Thromb Res 196:67–74. https://doi.org/10.1016/j.thromres.2020.08.020
Ierardi AM, Gaibazzi N, Tuttolomondo D, Fusco S, La Mura V, Peyvandi F, Aliberti S, Blasi F, Cozzi D, Carrafiello G, De Filippo M (2021) Deep vein thrombosis in COVID-19 patients in general wards: prevalence and association with clinical and laboratory variables. Radiol Med 126(5):722–728. https://doi.org/10.1007/s11547-020-01312-w
Chen B, Jiang C, Han B, Guan C, Fang G, Yan S, Wang K, Liu L, Conlon CP, **e R, Song R (2021) High prevalence of occult thrombosis in cases of mild/moderate COVID-19. Int J Infect Dis 104:77–82. https://doi.org/10.1016/j.ijid.2020.12.042
Vlachou M, Drebes A, Candilio L, Weeraman D, Mir N, Murch N, Davies N, Coghlan JG (2021) Pulmonary thrombosis in Covid-19: before, during and after hospital admission. J Thromb Thrombolysis 51(4):978–984. https://doi.org/10.1007/s11239-020-02370-7
de Roquetaillade C, Chousterman BG, Tomasoni D, Zeitouni M, Houdart E, Guedon A, Reiner P, Bordier R, Gayat E, Montalescot G, Metra M, Mebazaa A (2021) Unusual arterial thrombotic events in Covid-19 patients. Int J Cardiol 323:281–284. https://doi.org/10.1016/j.ijcard.2020.08.103
Jayarangaiah A, Kariyanna PT, Chen X, Jayarangaiah A, Kumar A (2020) COVID-19-associated coagulopathy: an exacerbated immunothrombosis response. Clin Appl Thromb Hemost 26:1076029620943293. https://doi.org/10.1177/1076029620943293
Pinazo MJ, Posada Ede J, Izquierdo L, Tassies D, Marques AF, de Lazzari E, Aldasoro E, Muñoz J, Abras A, Tebar S, Gallego M, de Almeida IC, Reverter JC, Gascon J (2016) Altered hypercoagulability factors in patients with chronic chagas disease: potential biomarkers of therapeutic response. PLoS Negl Trop Dis 10(1):e0004269. https://doi.org/10.1371/journal.pntd.0004269
Alonso-Padilla J, Tassies D, Cortes-Serra N, Gascon J, Reverter JC, Pinazo MJ (2019) Host-derived molecules as novel chagas disease biomarkers: hypercoagulability markers in plasma. Methods Mol Biol 955:275–286. https://doi.org/10.1007/978-1-4939-9148-8_21
Beristain-Covarrubias N, Perez-Toledo M, Thomas MR, Henderson IR, Watson SP, Cunningham AF (2019) Understanding infection-induced thrombosis: lessons learned from animal models. Front Immunol 10:2569. https://doi.org/10.3389/fimmu.2019.02569
Beristain-Covarrubias N, Perez-Toledo M, Flores-Langarica A, Zuidscherwoude M, Hitchcock JR, Channell WM, King LDW, Thomas MR, Henderson IR, Rayes J, Watson SP (2019) Cunningham AF (2019) Salmonella-induced thrombi in mice develop asynchronously in the spleen and liver and are not effective bacterial traps. Blood 133(6):600–604. https://doi.org/10.1182/blood-2018-08-867267
Chang JC (2017) Thrombocytopenia in critically ill patients due to vascular microthrombotic disease: pathogenesis based on “two activation theory of the endothelium.” Vascul Dis Ther 2(5):1–7. https://doi.org/10.15761/VDT.1000132
Quintanilla M, Montero-Montero L, Renart J, Martín-Villar E (2019) Podoplanin in inflammation and cancer. Int J Mol Sci 20(3):707. https://doi.org/10.3390/ijms20030707
Manne BK, Getz TM, Hughes CE, Alshehri O, Dangelmaier C, Naik UP, Watson SP, Kunapuli SP (2013) Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2). J Biol Chem 288(11):7717–7726. https://doi.org/10.1074/jbc.M112.424473
Sung PS, Hsieh SL (2019) CLEC2 and CLEC5A: pathogenic host factors in acute viral infections. Front Immunol 10:2867. https://doi.org/10.3389/fimmu.2019.02867
Liaw PC, Ito T, Iba T, Thachil J, Zeerleder S (2016) DAMP and DIC: the role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC. Blood Rev 30(4):257–261. https://doi.org/10.1016/j.blre.2015.12.004
Kim JE, Lee N, Gu JY, Yoo HJ, Kim HK (2015) Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation. Thromb Res 135(6):1064–1069. https://doi.org/10.1016/j.thromres.2015.03.014
Zhang S, Liu Y, Wang X, Yang L, Li H, Wang Y, Liu M, Zhao X, **e Y, Yang Y, Zhang S, Fan Z, Dong J, Yuan Z, Ding Z, Zhang Y, Hu L (2020) SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol 13(1):120. https://doi.org/10.1186/s13045-020-00954-7
Sahai A, Bhandari R, Koupenova M, Freedman J, Godwin M, McIntyre T, Chung M, Iskandar JP, Kamran H, Aggarwal A, Kalra A, Bartholomew J, McCrae K, Elbadawi A, Svensson L, Kapadia S, Hariri E, Cameron S 2020 SARS-CoV-2 Receptors are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 Patients. Res Sq [Preprint] 23:rs.3.rs-119031 Doi: https://doi.org/10.21203/rs.3.rs-119031/v1
Taus F, Salvagno G, Canè S, Fava C, Mazzaferri F, Carrara E, Petrova V, Barouni RM, Dima F, Dalbeni A, Romano S, Poli G, Benati M, De Nitto S, Mansueto G, Iezzi M, Tacconelli E, Lippi G, Bronte V, Minuz P (2020) Platelets promote thromboinflammation in SARS-CoV-2 pneumonia. Arterioscler Thromb Vasc Biol 40(12):2975–2989. https://doi.org/10.1161/ATVBAHA.120.315175
Ladikou EE, Sivaloganathan H, Milne KM, Arter WE, Ramasamy R, Saad R, Stoneham SM, Philips B, Eziefula AC, Chevassut T (2020) Von Willebrand factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19? Clin Med (Lond) 20(5):e178–e182. https://doi.org/10.7861/clinmed.2020-0346
Eriksson O, Hultström M, Persson B, Lipcsey M, Ekdahl KN, Nilsson B, Frithiof R (2020) Mannose-binding lectin is associated with thrombosis and coagulopathy in critically Ill COVID-19 patients. Thromb Haemost 120(12):1720–1724. https://doi.org/10.1055/s-0040-1715835
Ip WK, Chan KH, Law HK, Tso GH, Kong EK, Wong WH, To YF, Yung RW, Chow EY, Au KL, Chan EY, Lim W, Jensenius JC, Turner MW, Peiris JS, Lau YL (2005) Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection. J Infect Dis 191(10):1697–1704. https://doi.org/10.1086/429631
Hess K, Ajjan R, Phoenix F, Dobó J, Gál P, Schroeder V (2012) Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. PLoS ONE 7(4):e35690. https://doi.org/10.1371/journal.pone.0035690
Azevedo EAN, Barreto S, de Lima RE, Teixeira RH, Diniz G, Oliveira W Jr, Cavalcanti MDGAM, Gomes YM, Moura PMMF, Morais CNL (2028) Binding capacity of mannose-binding lectin (MBL) is associated with the severity of chronic Chagas cardiomyopathy. Parasitol Int 67(5):593–596. https://doi.org/10.1016/j.parint.2018.05.009
Ribeiro CH, Lynch NJ, Stover CM, Ali YM, Valck C, Noya-Leal F, Schwaeble WJ, Ferreira A (2015) Deficiency in mannose-binding lectin-associated serine protease-2 does not increase susceptibility to Trypanosoma cruzi infection. Am J Trop Med Hyg 92(2):320–324. https://doi.org/10.4269/ajtmh.14-0236
Batista AM, Alvarado-Arnez LE, Alves SM, Melo G, Pereira IR, Ruivo LAS, da Silva AA, Gibaldi D, da Silva TDESP, de Lorena VMB, de Melo AS, de Araújo Soares AK, Barros MDS, Costa VMA, Cardoso CC, Pacheco AG, Carrazzone C, Oliveira W Jr, Moraes MO, Lannes-Vieira J (2018) Genetic Polymorphism at CCL5 Is associated with protection in Chagas’ heart disease: antagonistic participation of CCR1+ and CCR5+ cells in chronic chagasic cardiomyopathy. Front Immunol 11(9):615. https://doi.org/10.3389/fimmu.2018.00615
Smatti MK, Al-Sarraj YA, Albagha O, Yassine HM (2020) Host genetic variants potentially associated with SARS-CoV-2: a multi-population analysis. Front Genet 11:e578523. https://doi.org/10.3389/fgene.2020.578523
WHO (2020) Chagas disease (also known as American trypanosomiasis). https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis.
Amieva C 2014 Chagas en la actualidad de Latinoamérica: viejos y nuevos problemas, grandes desafíos Chagas in Latin America today: old and new problems, great challenges. Aposta: Revista de Ciencias Sociales 62:1–19
Conners EE, Vinetz JM, Weeks JR, Brouwer KC (2016) A global systematic review of Chagas disease prevalence among migrants. Acta Trop 156:68–78. https://doi.org/10.1016/j.actatropica.2016.01.002
Pérez-Molina JA, Molina I (2018) Chagas disease. Lancet 391(10115):82–94. https://doi.org/10.1016/S0140-6736(17)31612-4
Pinazo MJ, Tàssies D, Muñoz J, Fisa R, Posada Ede J, Monteagudo J, Ayala E, Gállego M, Reverter JC, Gascon J (2011) Hypercoagulability biomarkers in Trypanosoma cruzi -infected patients. Thromb Haemost 106(4):617–623. https://doi.org/10.1160/TH11-04-0251
Chowdhury IH, Koo SJ, Gupta S, Liang LY, Bahar B, Silla L, Nuñez-Burgos J, Barrientos N, Zago MP, Garg NJ (2017) gene expression profiling and functional characterization of macrophages in response to circulatory microparticles produced during Trypanosoma cruzi infection and Chagas disease. J Innate Immun 9(2):203–216. https://doi.org/10.1159/000451055
Castillejos FR, Mayoral LP, Andrade GM, Hernandez-Huerta MT, Pina-Canseco S, Cruz RM, Colmenares EH, Mayoral EP, Salazar PM, Torres MB, Bravo MC, Cruz MM, Cervantes CM, Albarraz RD, Matias JL, Rios Arias GI, Bernardino GH, Matus EP, Trujillo RM, Navarro LMS, Perez Santiago AD, Campos EP (2018) A preliminary study of platelet hyperactivity in the chronic indeterminate phase of Chagas’ disease. Trop Biomed 35(3):678–683
Ming M, Chuenkova M, Ortega-Barria E, Pereira ME (1993) Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome. Mol Biochem Parasitol 59(2):243–252. https://doi.org/10.1016/0166-6851(93)90222-j
Libby P, Alroy J, Pereira ME (1986) A neuraminidase from Trypanosoma cruzi removes sialic acid from the surface of mammalian myocardial and endothelial cells. J Clin Invest 77(1):127–135. https://doi.org/10.1172/JCI112266
Bambino-Medeiros R, Oliveira FO, Calvet CM, Vicente D, Toma L, Krieger MA, Meirelles MN, Pereira MC (2011) Involvement of host cell heparan sulfate proteoglycan in Trypanosoma cruzi amastigote attachment and invasion. Parasitology 138(5):593–601. https://doi.org/10.1017/S0031182010001678
Oliveira FO Jr, Alves CR, Calvet CM, Toma L, Bouças RI, Nader HB, Castro Côrtes LM, Krieger MA, Meirelles Mde N, Souza Pereira MC (2008) Trypanosoma cruzi heparin-binding proteins and the nature of the host cell heparan sulfate-binding domain. Microb Pathog 44(4):329–338. https://doi.org/10.1016/j.micpath.2007.10.003
Petkova SB, Huang H, Factor SM, Pestell RG, Bouzahzah B, Jelicks LA, Weiss LM, Douglas SA, Wittner M, Tanowitz HB (2001) The role of endothelin in the pathogenesis of Chagas’ disease. Int J Parasitol 31(5–6):499–511. https://doi.org/10.1016/s0020-7519(01)00168-0
Scharfstein J, Andrade D (2011) Infection-associated vasculopathy in experimental chagas disease pathogenic roles of endothelin and kinin pathways. Adv Parasitol 76:101–127. https://doi.org/10.1016/B978-0-12-385895-5.00005-0
Dong E, Du H, Gardner L (2020) An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 20(5):533–534. https://doi.org/10.1016/S1473-3099(20)30120-1
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2):271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052
Gkogkou E, Barnasas G, Vougas K, Trougakos IP (2020) Expression profiling meta-analysis of ACE2 and TMPRSS2, the putative anti-inflammatory receptor and priming protease of SARS-CoV-2 in human cells, and identification of putative modulators. Redox Biol 36:e101615. https://doi.org/10.1016/j.redox.2020.101615
Li MY, Li L, Zhang Y, Wang XS (2020) Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 9(1):45. https://doi.org/10.1186/s40249-020-00662-x
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203(2):631–637. https://doi.org/10.1002/path.1570
Vaarala MH, Porvari KS, Kellokumpu S, Kyllönen AP, Vihko PT (2001) Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues. J Pathol 193(1):134–140. https://doi.org/10.1002/1096-9896(2000)9999:9999%3c::AID-PATH743%3e3.0.CO;2-T
Menter T, Haslbauer JD, Nienhold R, Savic S, Hopfer H, Deigendesch N, Frank S, Turek D, Willi N, Pargger H, Bassetti S, Leuppi JD, Cathomas G, Tolnay M, Mertz KD, Tzankov A (2020) Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 77(2):198–209. https://doi.org/10.1111/his.14134
Rapkiewicz AV, Mai X, Carsons SE, Pittaluga S, Kleiner DE, Berger JS, Thomas S, Adler NM, Charytan DM, Gasmi B, Hochman JS, Reynolds HR (2020) Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. EClinicalMedicine 24:e100434. https://doi.org/10.1016/j.eclinm.2020.100434
Bradley BT, Maioli H, Johnston R, Chaudhry I, Fink SL, Xu H, Najafian B, Deutsch G, Lacy JM, Williams T, Yarid N, Marshall DA (2020) Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. Lancet 396(10247):320–332. https://doi.org/10.1016/S0140-6736(20)31305-2
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW (2020) Extrapulmonary manifestations of COVID-19. Nat Med 26(7):1017–1032. https://doi.org/10.1038/s41591-020-0968-3
Song J, Li Y, Huang X, Chen Z, Li Y, Liu C, Chen Z, Duan X (2020) Systematic analysis of ACE2 and TMPRSS2 expression in salivary glands reveals underlying transmission mechanism caused by SARS-CoV-2. J Med Virol 92(11):2556–2566. https://doi.org/10.1002/jmv.26045
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 2395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5
Nizzoli ME, Merati G, Tenore A, Picone C, Consensi E, Perotti L, Ferretti VV, Sambo M, Di Sabatino A, Iotti GA, Arcaini L, Bruno R, Belliato M (2020) Circulating endothelial cells in COVID-19. Am J Hematol 95(8):E187–E188. https://doi.org/10.1002/ajh.25881
Pine AB, Meizlish ML, Goshua G, Chang CH, Zhang H, Bishai J, Bahel P, Patel A, Gbyli R, Kwan JM, Won CH, Price C, Dela Cruz CS, Halene S, van Dijk D, Hwa J, Lee AI, Chun HJ (2020) Circulating markers of angiogenesis and endotheliopathy in COVID-19. Pulm Circ 10(4):2045894020966547. https://doi.org/10.1177/2045894020966547
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D (2020) Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med 383(2):120–128. https://doi.org/10.1056/NEJMoa2015432
Becker RC (2020) COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis 50(1):54–67. https://doi.org/10.1007/s11239-020-02134-3
Gaertner F, Massberg S (2016) Blood coagulation in immunothrombosis-At the frontline of intravascular immunity. Semin Immunol 28(6):561–569. https://doi.org/10.1016/j.smim.2016.10.010
Manne BK, Denorme F, Middleton EA, Portier I, Rowley JW, Stubben C, Petrey AC, Tolley ND, Guo L, Cody M, Weyrich AS, Yost CC, Rondina MT, Campbell RA (2020) Platelet gene expression and function in patients with COVID-19. Blood 136(11):1317–1329. https://doi.org/10.1182/blood.2020007214
Connors JM, Levy JH (2020) COVID-19 and its implications for thrombosis and anticoagulation. Blood 135(23):2033–2040. https://doi.org/10.1182/blood.2020006000
Long H, Nie L, **ang X, Li H, Zhang X, Fu X, Ren H, Liu W, Wang Q, Wu Q (2020) D-Dimer and prothrombin time are the significant indicators of severe COVID-19 and poor prognosis. Biomed Res Int 2020:6159720. https://doi.org/10.1155/2020/6159720
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, **ang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395(10229):1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3
Ji HJ, Su Z, Zhao R, Komissarov AA, Yi G, Liu SL, Idell S, Matthay MA (2020) Insufficient hyperfibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression. medRxiv [Preprint] 2020.09.07.20190165 Doi: https://doi.org/10.1101/2020.09.07.20190165.
Di Minno MND, Calcaterra I, Lupoli R, Storino A, Spedicato GA, Maniscalco M, Di Minno A, Ambrosino P (2020) Hemostatic changes in patients with COVID-19: a meta-analysis with meta-regressions. J Clin Med 9(7):2244. https://doi.org/10.3390/jcm9072244
Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, Psaltopoulou T, Gerotziafas G, Dimopoulos MA (2020) Hematological findings and complications of COVID-19. Am J Hematol 95(7):834–847. https://doi.org/10.1002/ajh.25829
Barnes GD, Burnett A, Allen A, Blumenstein M, Clark NP, Cuker A, Dager WE, Deitelzweig SB, Ellsworth S, Garcia D, Kaatz S, Minichiello T (2020) Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 50(1):72–81. https://doi.org/10.1007/s11239-020-02138-z
Esta S, Prandoni P, Paoletti O, Morandini R, Tala M, Dellanoce C, Giorgi-Pierfranceschi M, Betti M, Danzi GB, Pan A, Palareti G (2020) Direct oral anticoagulant plasma levels’ striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents: the Cremona experience. J Thromb Haemost 18(6):1320–1323. https://doi.org/10.1111/jth.14871
Paranjpe I, Fuster V, Lala A, Russak AJ, Glicksberg BS, Levin MA, Charney AW, Narula J, Fayad ZA, Bagiella E, Zhao S, Nadkarni GN (2020) Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 76(1):122–124. https://doi.org/10.1016/j.jacc.2020.05.001
Ishihara M, Nakamura S, Sato Y, Takayama T, Fukuda K, Fujita M, Murakami K, Yokoe H (2019) Heparinoid complex-based heparin-binding cytokines and cell delivery carriers. Molecules 24(24):4630. https://doi.org/10.3390/molecules24244630
Thiagarajan P, Wu KK (1999) Mechanisms of antithrombotic drugs. Adv Pharmacol 46:297–324. https://doi.org/10.1016/s1054-3589(08)60474-3
Wilde MI, Markham A (1997) Danaparoid a review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia. Drugs 54(6):903–924. https://doi.org/10.2165/00003495-199754060-00008
Carroll BJ, Piazza G, Goldhaber SZ (2019) Sulodexide in venous disease. J Thromb Haemost 17(1):31–38. https://doi.org/10.1111/jth.14324
Cosmi B, Cini M, Legnani C, Pancani C, Calanni F, Coccheri S (2003) Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res 109(5–6):333–339. https://doi.org/10.1016/s0049-3848(03)00246-9
Borawski J, Gozdzikiewicz J, Dubowski M, Pawlak K, Mysliwiec M (2009) Tissue factor pathway inhibitor release and depletion by sulodexide in humans. Adv Med Sci 54(1):32–36. https://doi.org/10.2478/v10039-009-0009-4
Minix R, Doctor VM (1997) Interaction of fucoidan with proteases and inhibitors of coagulation and fibrinolysis. Thromb Res 87(5):419–429. https://doi.org/10.1016/s0049-3848(97)00158-8
Dou H, Song A, Jia S, Zhang L (2019) Heparinoids Danaparoid and Sulodexide as clinically used drugs. Prog Mol Biol Transl Sci 163:55–74. https://doi.org/10.1016/bs.pmbts.2019.02.005
Cagno V, Tseligka ED, Jones ST, Tapparel C (2019) Heparan sulfate proteoglycans and viral attachment: true receptors or adaptation bias? Viruses 11(7):596. https://doi.org/10.3390/v11070596
Kim CH (2020) SARS-CoV-2 evolutionary adaptation toward host entry and recognition of receptor o-acetyl sialylation in virus-host interaction. Int J Mol Sci 21(12):4549. https://doi.org/10.3390/ijms21124549
Tandon R, Sharp JS, Zhang F, Pomin VH, Ashpole NM, Mitra D, McCandless MG, ** W, Liu H, Sharma P, Linhardt RJ (2021) Effective inhibition of SARS-CoV-2 entry by heparin and enoxaparin derivatives. J Virol 95(3):e01987-e2020. https://doi.org/10.1128/JVI.01987-20
Tiwari V, Beer JC, Sankaranarayanan NV, Swanson-Mungerson M, Desai UR (2020) Discovering small-molecule therapeutics against SARS-CoV-2. Drug Discov Today 25(8):1535–1544. https://doi.org/10.1016/j.drudis.2020.06.017
Mycroft-West CJ, Su D, Pagani I, Rudd TR, Elli S, Gandhi NS, Guimond SE, Miller GJ, Meneghetti MCZ, Nader HB, Li Y, Nunes QM, Procter P, Mancini N, Clementi M, Bisio A, Forsyth NR, Ferro V, Turnbull JE, Guerrini M, Fernig DG, Vicenzi E, Yates EA, Lima MA, Skidmore MA (2020) Heparin Inhibits cellular Invasion by SARS-CoV-2: structural dependence of the interaction of the spike s1 receptor-binding domain with heparin. Thromb Haemost 120(12):1700–1715. https://doi.org/10.1055/s-0040-1721319
van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B (2020) Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care 24(1):454. https://doi.org/10.1186/s13054-020-03148-2
Barritault D, Gilbert-Sirieix M, Rice KL, Siñeriz F, Papy-Garcia D, Baudouin C, Desgranges P, Zakine G, Saffar JL, van Neck J (2017) Glycoconj J 34(3):325–338. https://doi.org/10.1007/s10719-016-9744-5
Lima AP, Almeida PC, Tersariol IL, Schmitz V, Schmaier AH, Juliano L, Hirata IY, Müller-Esterl W, Chagas JR, Scharfstein J (2002) Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain. J Biol Chem 277(8):5875–5881. https://doi.org/10.1074/jbc.M108518200
Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, Mast AE, Justice A, Aronow B, Jacobson D (2020) A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. Elife 9:e59177. https://doi.org/10.7554/eLife.59177
Avila JL, Rojas M, Carrasco H (1993) Elevated levels of antibodies against sulphatide are present in all chronic chagasic and dilated cardiomyopathy sera. Clin Exp Immunol 92(3):460–465. https://doi.org/10.1111/j.1365-2249.1993.tb03421.x
Souza DH, Vaz Mda G, Fonseca CR, Luquetti A, Rezende Filho J, Oliveira EC (2013) Current epidemiological profile of Chagasic megaesophagus in Central Brazil. Rev Soc Bras Med Trop 46(3):316–321. https://doi.org/10.1590/0037-8682-0065-2013
Puigbó JJ, Nava Rhode JR, Carcía Barrios H, Gil Yépez C (1968) A 4-year follow-up study of a rural community with endemic Chagas’ disease. Bull World Health Organ 39(3):341–348
Nimgaonkar I, Valeri L, Susser E, Hussain S, Sunderram J, Aviv A (2021) The age pattern of the male-to-female ratio in mortality from COVID-19 mirrors that of cardiovascular disease in the general population. Aging (Albany NY) 13(3):3190–3201. https://doi.org/10.18632/aging.202639
Ahrenfeldt LJ, Otavova M, Christensen K, Lindahl-Jacobsen R (2020) Sex and age differences in COVID-19 mortality in Europe. Wien Klin Wochenschr 133(7–8):393–398. https://doi.org/10.1007/s00508-020-01793-9
Jacot D, Greub G, Jaton K, Opota O (2020) Viral load of SARS-CoV-2 across patients and compared to other respiratory viruses. Microbes Infect 22(10):617–621. https://doi.org/10.1016/j.micinf.2020.08.004
Mahallawi WH, Alsamiri AD, Dabbour AF, Alsaeedi H, Al-Zalabani AH (2021) Association of Viral Load in SARS-CoV-2 Patients With Age and Gender. Front Med (Lausanne) 8:e608215. https://doi.org/10.3389/fmed.2021.608215
Alves RM, Thomaz RP, Almeida EA, Wanderley Jda S, Guariento ME (2009) Chagas’ disease and ageing: the coexistence of other chronic diseases with Chagas’ disease in elderly patients. Rev Soc Bras Med Trop 42(6):622–628. https://doi.org/10.1590/s0037-86822009000600002
Yin T, Li Y, Ying Y, Luo Z (2021) Prevalence of comorbidity in Chinese patients with COVID-19: systematic review and meta-analysis of risk factors. BMC Infect Dis 21(1):200. https://doi.org/10.1186/s12879-021-05915-0
Ballinas-Verdugo MA, Mejía-Domínguez AM, Sánchez-Guerrero SA, Lerma C, Martínez-Cruz M, Álvarez-Manilla-Toquero E, Jiménez-Díaz X, Barrera-Trujillo F, Ticante-Cruz MD, Estevez-Garcia IO, Amezcua-Guerra LM, Reyes-Lopez PA (2016) The Type of Trypanosoma Cruzi Strain (Native or Non-Native) used as substrate for immunoassays influences the ability of screening asymptomatic blood donors. Rev Invest Clin 68(6):286–291
Marques DS, Canesin MF, Barutta Júnior F, Fuganti CJ, Barretto AC (2006) Evaluation of asymptomatic patients with chronic Chagas disease through ambulatory electrocardiogram, echocardiogram and B-Type natriuretic peptide analyses. Arq Bras Cardiol 87(3):336–343. https://doi.org/10.1590/s0066-782x2006001600017
Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, Ma K (2021) A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect 54(1):12–16. https://doi.org/10.1016/j.jmii.2020.05.001
Ayo CM, Dalalio MM, Visentainer JE, Reis PG, Sippert EÂ, Jarduli LR, Alves HV, Sell AM (2013) Genetic susceptibility to Chagas disease: an overview about the infection and about the association between disease and the immune response genes. Biomed Res Int 2013:e284729. https://doi.org/10.1155/2013/284729
Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, Thompson RF (2020) Human leukocyte antigen susceptibility map for severe acute respiratory syndrome coronavirus 2. J Virol 94(13):e00510-e520. https://doi.org/10.1128/JVI.00510-20
Moreno M, Silva EL, Ramírez LE, Palacio LG, Rivera D, Arcos-Burgos M (2004) Chagas’ disease susceptibility/resistance: linkage disequilibrium analysis suggests epistasis between major histocompatibility complex and interleukin-10. Tissue Antigens 64(1):18–24. https://doi.org/10.1111/j.1399-0039.2004.00260.x
Zhu J, Liu C, Teng X, Yin J, Zheng L, Wang L, Tang W, Gu H, Gu B, Chen L (2016) Chen L (2016) association of the interleukin-18 receptor 1 and interleukin-18 receptor accessory protein polymorphisms with the risk of esophageal cancer. Biomed Rep 4:227–235
Strauss M, Acosta-Herrera M, Alcaraz A, Casares-Marfil D, Bosch-Nicolau P, Lo Presti MS, Molina I, González CI, Chagas Genetics CYTED, Network MJ (2019) Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations. PLoS Negl Trop Dis 13(11):e0007859. https://doi.org/10.1371/journal.pntd.0007859
Rolandelli A, Hernández Del Pino RE, Pellegrini JM, Tateosian NL, Amiano NO, de la Barrera S, Casco N, Gutiérrez M, Palmero DJ, García VE (2017) The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina. Sci Rep 7:40666. https://doi.org/10.1038/srep40666
Strauss M, Palma-Vega M, Casares-Marfil D, Bosch-Nicolau P, Lo Presti MS, Molina I, González CI, Chagas Genetics CYTED, Network MJ, Acosta-Herrera M (2020) Genetic polymorphisms of IL17A associated with Chagas disease: results from a meta-analysis in Latin American populations. Sci Rep 10(1):5015. https://doi.org/10.1038/s41598-020-61965-5
Reis PG, Ayo CM, de Mattos LC, Brandão de Mattos CC, Sakita KM, de Moraes AG, Muller LP, Aquino JS, Conci Macedo L, Mazini PS, Sell AM, Marques DSO, Bestetti RB, Visentainer JEL (2017) Genetic polymorphisms of IL17 and chagas disease in the South and Southeast of Brazil. J Immunol Res 2017:1017621. https://doi.org/10.1155/2017/1017621
Hou Y, Zhao J, Martin W, Kallianpur A, Chung MK, Jehi L, Sharifi N, Erzurum S, Eng C, Cheng F (2020) New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Med 18(1):216. https://doi.org/10.1186/s12916-020-01673-z
Severe Covid-19 GWAS Group Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P et al 2020 Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med 383(16): 1522–1534 Doi: https://doi.org/10.1056/NEJMoa2020283
Frade-Barros AF, Ianni BM, Cabantous S, Pissetti CW, Saba B, Lin-Wang HT, Buck P, Marin-Neto JA, Schmidt A, Dias F, Hirata MH, Sampaio M, Fragata A, Pereira AC, Donadi E, Rodrigues V, Kalil J, Chevillard C, Cunha-Neto E (2020) Polymorphisms in genes affecting interferon-γ production and Th1 t cell differentiation are associated with progression to chagas disease cardiomyopathy. Front Immunol 11:1386. https://doi.org/10.3389/fimmu.2020.01386.Erratum.In:FrontImmunol2020;11:593759
Torres OA, Calzada JE, Beraún Y, Morillo CA, González A, González CI, Martín J (2010) Role of the IFNG +874T/A polymorphism in Chagas disease in a Colombian population. Infect Genet Evol 10(5):682–685. https://doi.org/10.1016/j.meegid.2010.03.009
Kim YC, Jeong BH (2020) Strong Correlation between the Case Fatality Rate of COVID-19 and the rs6598045 Single Nucleotide Polymorphism (SNP) of the interferon-induced transmembrane protein 3 (IFITM3) gene at the population-level. Genes (Basel) 12(1):42. https://doi.org/10.3390/genes12010042
Maiti AK (2020) The African-American population with a low allele frequency of SNP rs1990760 (T allele) in IFIH1 predicts less IFN-beta expression and potential vulnerability to COVID-19 infection. Immunogenetics 72(6–7):387–391. https://doi.org/10.1007/s00251-020-01174-6
Teixeira Vde P, Martins E, Almeida Hde O, Soares S, de Souza HM, de Morais CA (1987) Sistema ABO e formas anatomoclínicas da doença de Chagas crônica [The ABO system and anatomoclinical forms of chronic Chagas disease]. Rev Soc Bras Med Trop 20(3):163–167
Bernardo CR, Camargo AVS, Ronchi LS, de Oliveira AP, de Campos JE, Borim AA, Brandão de Mattos CC, Bestetti RB, de Mattos LC (2016) ABO, Secretor and Lewis histo-blood group systems influence the digestive form of Chagas disease. Infect Genet Evol 45:170–175. https://doi.org/10.1016/j.meegid.2016.08.027
Szymanski J, Mohrmann L, Carter J, Nelson R, Chekuri S, Assa A, Spund B, Reyes-Gil M, Uehlinger J, Baron S, Paroder M (2021) ABO blood type association with SARS-CoV-2 infection mortality: a single-center population in New York City. Transfusion 61(4):1064–1070. https://doi.org/10.1111/trf.16339
Lopes GP, Ferreira-Silva MM, Ramos AA, Moraes-Souza H, Prata A, Correia D (2013) Length and caliber of the rectosigmoid colon among patients with Chagas disease and controls from areas at different altitudes. Rev Soc Bras Med Trop 46(6):746–751. https://doi.org/10.1590/0037-8682-0247-2013
Sze S, Pan D, Nevill CR, Gray LJ, Martin CA, Nazareth J, Minhas JS, Divall P, Khunti K, Abrams KR, Nellums LB, Pareek M (2020) Ethnicity and clinical outcomes in COVID-19: a systematic review and meta-analysis. EClinicalMedicine 29:e100630. https://doi.org/10.1016/j.eclinm.2020.100630
Ibarra-Nava I, Flores-Rodriguez KG, Ruiz-Herrera V, Ochoa-Bayona HC, Salinas-Zertuche A, Padilla-Orozco M, Salazar-Montalvo RG (2021) Ethnic disparities in COVID-19 mortality in Mexico: a cross-sectional study based on national data. PLoS ONE 16(3):e0239168. https://doi.org/10.1371/journal.pone.0239168
Del Nery E, Juliano MA, Lima AP, Scharfstein J, Juliano L (1997) Kininogenase activity by the major cysteinyl proteinase (cruzipain) from Trypanosoma cruzi. J Biol Chem 272(41):25713–25718
Oehmcke-Hecht S, Köhler J (2018) Interaction of the human contact system with pathogens-an update. Front Immunol 9:312. https://doi.org/10.3389/fimmu.2018.00312
Herrera RN, Díaz de Amaya EI, Pérez Aguilar RC, Joo Turoni C, Marañón R, Berman SG, Luciardi HL, Coviello A, Peral de Bruno M (2011) Inflammatory and prothrombotic activation with conserved endothelial function in patients with chronic, asymptomatic Chagas disease. Clin Appl Thromb Hemost 17(5):502–507. https://doi.org/10.1177/1076029610375814
Venter C, Bezuidenhout JA, Laubscher GJ, Lourens PJ, Steenkamp J, Kell DB, Pretorius E (2020) Erythrocyte, platelet, serum ferritin, and p-selectin pathophysiology implicated in severe hypercoagulation and vascular complications in COVID-19. Int J Mol Sci 21(21):8234. https://doi.org/10.3390/ijms21218234
Venturelli S, Benatti SV, Casati M, Binda F, Zuglian G, Imeri G, Conti C, Biffi AM, Spada MS, Bondi E, Camera G, Severgnini R, Giammarresi A, Marinaro C, Rossini A, Bonaffini PA, Guerra G, Bellasi A, Cesa S, Rizzi M (2021) Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation. Epidemiol Infect 149:e32. https://doi.org/10.1017/S0950268821000145
Modin D, Claggett B, Sindet-Pedersen C, Lassen MCH, Skaarup KG, Jensen JUS, Fralick M, Schou M, Lamberts M, Gerds T, Fosbøl EL, Phelps M, Kragholm KH, Andersen MP, Køber L, Torp-Pedersen C, Solomon SD, Gislason G, Biering-Sørensen T (2020) Acute COVID-19 and the incidence of ischemic stroke and acute myocardial infarction. Circulation 142(21):2080–2082. https://doi.org/10.1161/CIRCULATIONAHA.120.050809
Weckbach LT, Curta A, Bieber S, Kraechan A, Brado J, Hellmuth JC, Muenchhoff M, Scherer C, Schroeder I, Irlbeck M, Maurus S, Ricke J, Klingel K, Kääb S, Orban M, Massberg S, Hausleiter J, Grabmaier U (2021) Myocardial inflammation and dysfunction in COVID-19-associated myocardial injury. Circ Cardiovasc Imaging 14(1):e012220. https://doi.org/10.1161/CIRCIMAGING.120.011713
Scharfstein J (2018) Subverting bradykinin-evoked inflammation by co-opting the contact system: lessons from survival strategies of Trypanosoma cruzi. Curr Opin Hematol 25(5):347–357. https://doi.org/10.1097/MOH.0000000000000444
Schmitz V, Almeida LN, Svensjö E, Monteiro AC, Köhl J, Scharfstein J (2014) C5a and bradykinin receptor cross-talk regulates innate and adaptive immunity in Trypanosoma cruzi infection. J Immunol 193(7):3613–3623. https://doi.org/10.4049/jimmunol.1302417
Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D (2021) Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation 44(1):13–34. https://doi.org/10.1007/s10753-020-01337-3
Spoto S, Agrò FE, Sambuco F, Travaglino F, Valeriani E, Fogolari M, Mangiacapra F, Costantino S, Ciccozzi M, Angeletti S (2021) High value of mid-regional proadrenomedullin in COVID-19: a marker of widespread endothelial damage, disease severity, and mortality. J Med Virol 93(5):2820–2827. https://doi.org/10.1002/jmv.26676
van de Veerdonk FL, Netea MG, van Deuren M, van der Meer JW, de Mast Q, Brüggemann RJ, van der Hoeven H (2020) Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome. Elife 9:e57555. https://doi.org/10.7554/eLife.57555
Acknowledgements
The authors thank Charlotte Grundy, Maricela Morales Hernández, and Eli Cruz Parada for their technical assistance. We also thank the National Technology of Mexico (TecNM, project 8703.20-P) and the Faculty of Medicine and Surgery, "Benito Juárez" Autonomous University of Oaxaca.
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Conceptualization EPC. Writing—original draft preparation: LPCM, MTHH, DPG, DB, EZ, and EPC. Manuscript revision: LPCM, MTHH, LMSN, EPCM, CAMC, MMC, GMA, MLC, GVM, CLS, SPC, RMC, and EPC. All authors have read and agreed to the printed version of the manuscript.
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Pérez-Campos Mayoral, L., Hernández-Huerta, M.T., Papy-García, D. et al. Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation. Mol Cell Biochem 476, 3815–3825 (2021). https://doi.org/10.1007/s11010-021-04204-3
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DOI: https://doi.org/10.1007/s11010-021-04204-3