Autopsy and Case Reports
https://app.periodikos.com.br/journal/autopsy/article/doi/10.4322/acr.2021.262
Autopsy and Case Reports
Autopsy Case Report

COVID-19: a closer look at the pathology in two autopsied cases. Is the pericyte at the center of the pathological process in COVID-19?

Hubert Daisley Jr; Arlene Rampersad; Martina Daisley; Amit Ramdin; Oneka Acco; Farhaana Narinesingh; Ornella Humphrey

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Abstract

We performed autopsies on two cases of COVID-19. The microcirculations of all organs were the site of the pathological findings. Thrombotic microangiopathy was found in the brain and also the kidneys. Vasculitis was also a feature of the autopsy findings, together with portal triaditis of the liver. The major pathological findings in both cases were fibrin deposits. Within the lung, the fibrin deposits were observed in the alveolar microcirculation in sub-endothelial locations of capillaries, arterioles, post capillary venules, and the adventitia of larger vessels. These fibrin deposits in the lungs occurred at the sites where pericytes are located in these vessels. The pericyte with its high concentration of ACE-2 receptors and its procoagulant state may represent one of the primary sites of action of SARS-CoV-2. A review of pericytes in health and disease is undertaken. COVID-19 is a disease of the microcirculation.

Keywords

Microcirculation, Pericytes, Fibrin, SARS virus

References

1 Worldometer. Coronavirus. 2020 [cited 2020 Oct 18]. Available from: www.worldometers.info

2 Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020;69(12):1181-9. http://dx.doi.org/10.1007/s00011-020-01401-6. PMid:32918567.

3 Kaur S, Tripathi DM, Yadav A. The enigma of endothelium in COVID-19. Front Physiol. 2020;11:989. http://dx.doi.org/10.3389/fphys.2020.00989. PMid:32848893.

4 Kasal DA, De Lorenzo A, Tibiriçá E. COVID-19 and microvascular disease: pathophysiology of sars-cov-2 infection with focus on the renin-angiotensin system. Heart Lung Circ. 2020;29(11):1596-602. http://dx.doi.org/10.1016/j.hlc.2020.08.010. PMid:32972810.

5 Jiang L, Tang K, Levin M, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020;20(11):e276-88. http://dx.doi.org/10.1016/S1473-3099(20)30651-4. PMid:32818434.

6 National Institutes of Health. Immune-based therapy under evaluation for treatment of COVID-19. 2020 [cited 2020 Oct 18]. Available from: www.covid19treatmentguidlines.nih.gov

7 National Institutes of Health. Antiviral drugs that are under evaluation for the treatment of COVID-19. 2020 [cited 2020 Oct 18]. Available from: www.covid19treatmentguidlines.nih.gov

8 Connolly A, Finkbeiner W, Ursell P, Davis R. Autopsy pathology: a manual and atlas. 3rd ed. Philadelphia: Elsevier; 2016.

9 McFadyen JD, Stevens H, Peter K. The emerging threat of (micro)thrombosis in COVID-19 and its therapeutic implications. Circ Res. 2020;127(4):571-87. http://dx.doi.org/10.1161/CIRCRESAHA.120.317447. PMid:32586214.

10 Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97(6):512-23. http://dx.doi.org/10.1161/01.RES.0000182903.16652.d7. PMid:16166562.

11 Cuevas P, Gutierrez-Diaz JA, Reimers D, Dujovny M, Diaz FG, Ausman JI. Pericyte endothelial gap junctions in human cerebral capillaries. Anat Embryol. 1984;170(2):155-9. http://dx.doi.org/10.1007/BF00319000. PMid:6517350.

12 Winkler EA, Bell RD, Zlokovic BV. Central nervous system pericytes in health and disease. Nat Neurosci. 2011;14(11):1398-405. http://dx.doi.org/10.1038/nn.2946. PMid:22030551.

13 Zhao H, Chappell JC. Microvascular bioengineering: a focus on pericytes. J Biol Eng. 2019;13(1):26. http://dx.doi.org/10.1186/s13036-019-0158-3. PMid:30984287.

14 Bonkowski D, Katyshev V, Balabanov RD, Borisov A, Dore-Duffy P. The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival. Fluids Barriers CNS. 2011;8(1):8. http://dx.doi.org/10.1186/2045-8118-8-8. PMid:21349156.

15 Corselli M, Chen CW, Sun B, Yap S, Rubin JP, Péault B. The tunica adventitia of human arteries and veins as a source of mesenchymal stem cells. Stem Cells Dev. 2012;21(8):1299-308. http://dx.doi.org/10.1089/scd.2011.0200. PMid:21861688.

16 Ferland-McCollough D, Slater S, Richard J, Reni C, Mangialardi G. Pericytes, an overlooked player in vascular pathobiology. Pharmacol Ther. 2017;171:30-42. http://dx.doi.org/10.1016/j.pharmthera.2016.11.008. PMid:27916653.

17 Zhang ZS, Zhou HN, He SS, Xue MY, Li T, Liu LM. Research advances in pericyte function and their roles in diseases. Chin J Traumatol. 2020;23(2):89-95. http://dx.doi.org/10.1016/j.cjtee.2020.02.006. PMid:32192909.

18 Davis GE, Norden PR, Bowers SL. Molecular control of capillary morphogenesis and maturation by recognition and remodeling of the extracellular matrix: functional roles of endothelial cells and pericytes in health and disease. Connect Tissue Res. 2015;56(5):392-402. http://dx.doi.org/10.3109/03008207.2015.1066781. PMid:26305158.

19 Ahmed S, Zimba O, Gasparyan AY. Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad. Clin Rheumatol. 2020;39(9):2529-43. http://dx.doi.org/10.1007/s10067-020-05275-1. PMid:32654082.

20 Kwaan HC. Microvascular thrombosis: a serious and deadly pathologic process in multiple diseases. Semin Thromb Hemost. 2011;37(8):961-78. http://dx.doi.org/10.1055/s-0031-1297375. PMid:22198861.

21 Wolberg AS, Aleman MM, Leiderman K, Machlus KR. Procoagulant activity in hemostasis and thrombosis: virchow’s triad revisited. Anesth Analg. 2012;114(2):275-85. http://dx.doi.org/10.1213/ANE.0b013e31823a088c. PMid:22104070.

22 Rudziak P, Ellis CG, Kowalewska PM. Role and molecular mechanisms of pericytes in regulation of leukocyte diapedesis in inflamed tissues. Mediators Inflamm. 2019;2019:4123605. http://dx.doi.org/10.1155/2019/4123605. PMid:31205449.

23 Proebstl D, Voisin MB, Woodfin A, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med. 2012;209(6):1219-34. http://dx.doi.org/10.1084/jem.20111622. PMid:22615129.

24 Gane J, Stockley R. Mechanisms of neutrophil transmigration across the vascular endothelium in COPD. Thorax. 2012;67(6):553-61. http://dx.doi.org/10.1136/thoraxjnl-2011-200088. PMid:21543441.

25 Kutcher ME, Herman IM. The pericyte: cellular regulator of microvascular blood flow. Microvasc Res. 2009;77(3):235-46. http://dx.doi.org/10.1016/j.mvr.2009.01.007. PMid:19323975.

26 Walpole J, Mac Gabhann F, Peirce SM, Chappell JC. Agent-based computational model of retinal angiogenesis simulates microvascular network morphology as a function of pericyte coverage. Microcirculation. 2017;24(8):e12393. http://dx.doi.org/10.1111/micc.12393. PMid:28791758.

27 Chang WG, Andrejecsk JW, Kluger MS, Saltzman WM, Pober JS. Pericytes modulate endothelial sprouting. Cardiovasc Res. 2013;100(3):492-500. http://dx.doi.org/10.1093/cvr/cvt215. PMid:24042014.

28 Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus: afirst step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-7. http://dx.doi.org/10.1002/path.1570. PMid:15141377.

29 Huertas A, Montani D, Savale L, et al. Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Eur Respir J. 2020;56(1):2001634. http://dx.doi.org/10.1183/13993003.01634-2020. PMid:32554538.

30 Jaunmuktane Z, Mahadeva U, Green A, et al. Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19. Acta Neuropathol. 2020;140(3):397-400. http://dx.doi.org/10.1007/s00401-020-02190-2. PMid:32638079.

31 Tavazzi G, Pellegrini C, Maurelli M, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911-5. http://dx.doi.org/10.1002/ejhf.1828. PMid:32275347.

32 Mehra MR, Ruschitzka F. COVID-19 illness and heart failure: a missing link? JACC Heart Fail. 2020;8(6):512-4. http://dx.doi.org/10.1016/j.jchf.2020.03.004. PMid:32360242.

33 Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116(6):1097-100. http://dx.doi.org/10.1093/cvr/cvaa078. PMid:32227090.

34 Stone E, Kiat H, McLachlan CS. Atrial fibrillation in COVID-19: a review of possible mechanisms. FASEB J. 2020;34(9):11347-54. http://dx.doi.org/10.1096/fj.202001613. PMid:33078484.

35 Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-32. http://dx.doi.org/10.1038/s41591-020-0968-3. PMid:32651579.

36 Feng G, Zheng KI, Yan QQ, et al. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. J Clin Transl Hepatol. 2020;8(1):18-24. http://dx.doi.org/10.14218/JCTH.2020.00018. PMid:32274342.

37 Robba C, Battaglini D, Pelosi P, Rocco RMP. Multiple organ dysfunction in SARS-CoV-2: MODS-CoV-2. Expert Rev Respir Med. 2020;14(9):865-8. http://dx.doi.org/10.1080/17476348.2020.1778470. PMid:32567404.

38 Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med. 2020;383(2):120-8. http://dx.doi.org/10.1056/NEJMoa2015432. PMid:32437596.

39 Bouchard BA, Shatos MA, Tracy PB. Human brain pericytes differentially regulate expression of procoagulant enzyme complexes comprising the extrinsic pathway of bloodcoagulation. Arterioscler Thromb Vasc Biol. 1997;17(1):1-9. http://dx.doi.org/10.1161/01.ATV.17.1.1. PMid:9012630.

40 Frantzeskaki F, Armaganidis A, Orfanos S. Immunothrombosis in acute respiratory distress syndrome: cross talks between inflammation and coagulation. Respiration. 2017;93(3):212-25. http://dx.doi.org/10.1159/000453002. PMid:27997925.

41 Colantuoni A, Martini R, Caprari P, et al. COVID-19 sepsis and microcirculation dysfunction. Front Physiol. 2020;11:747. http://dx.doi.org/10.3389/fphys.2020.00747. PMid:32676039.

42 Martini R. The compelling arguments for the need of microvascular investigation in COVID-19 critical patients. Clin Hemorheol Microcirc. 2020;75(1):27-34. http://dx.doi.org/10.3233/CH-200895. PMid:32568186.
 


Submitted date:
10/18/2020

Accepted date:
02/09/2021

Publication date:
05/06/2021

609443e1a9539515d52f9eb6 autopsy Articles
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