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European Journal of Clinical Microbiology & Infectious Diseases
Published in: European Journal of Clinical Microbiology & Infectious Diseases 5/2021

01-05-2021 | SARS-CoV-2 | Review

COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection

Authors: Stephany Beyerstedt, Expedito Barbosa Casaro, Érika Bevilaqua Rangel

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 5/2021

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Abstract

COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin–angiotensin–aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
Literature
1.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270–273PubMedPubMedCentralCrossRef
2.
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454PubMedPubMedCentralCrossRef
3.
Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L (2020) Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & Molecular Immunology 17:613–620CrossRef
4.
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O, Graham BS, McLellan JS (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:1260PubMedPubMedCentralCrossRef
5.
Xu J, Xu X, Jiang L, Dua K, Hansbro PM, Liu G (2020) SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis. Respiratory Research 21:182PubMedPubMedCentralCrossRef
6.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, 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 181:271–280.e8PubMedPubMedCentralCrossRef
7.
8.
Iwai M, Horiuchi M (2009) Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis. Hypertension Research: Official Journal of the Japanese Society of Hypertension 32:533–536CrossRef
9.
Silhol F, Sarlon G, Deharo JC, Vaïsse B (2020) Downregulation of ACE2 induces overstimulation of the renin–angiotensin system in COVID-19: should we block the renin–angiotensin system? Hypertension Research 43:854–856PubMedPubMedCentralCrossRef
10.
Murray E, Tomaszewski M, Guzik TJ (2020) Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications. Cardiovascular Research 116:e87–e89PubMedCrossRef
11.
Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensin-converting enzyme. Journal of Biological Chemistry 275:33238–33243CrossRef
12.
Tikellis C, Bernardi S, Burns WC (2011) Angiotensin-converting enzyme 2 is a key modulator of the renin–angiotensin system in cardiovascular and renal disease. Current Opinion in Nephrology and Hypertension 20:62–68PubMedCrossRef
13.
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD (2020) Renin–angiotensin–aldosterone system inhibitors in patients with COVID-19. New England Journal of Medicine 382:1653–1659CrossRef
14.
Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, Simmons G, Hofmann H, Kuri T, Weber F, Eichler J, Drosten C, Pöhlmann S (2010) Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. Journal of Virology 84:1198PubMedCrossRef
15.
Madeddu P, Emanueli C, El-Dahr S (2007) Mechanisms of disease: the tissue kallikrein–kinin system in hypertension and vascular remodeling. Nat Clin Pract Nephrol 3(4):208–221PubMedCrossRef
16.
Rhaleb N-E, Yang X-P, Carretero OA (2011) The kallikrein-kinin system as a regulator of cardiovascular and renal function. Compr Physiol 1(2):971–993PubMedPubMedCentralCrossRef
17.
Karmouty-Quintana H, Thandavarayan RA, Keller SP, Sahay S, Pandit LM, Akkanti B (2020) Emerging mechanisms of pulmonary vasoconstriction in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) and potential therapeutic targets. Int J Mol Sci 21(21):E8081PubMedCrossRef
18.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 323:1061–1069PubMedPubMedCentralCrossRef
19.
Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G, Merson L, Lee J, Plotkin D, Sigfrid L, Halpin S, Jackson C, Gamble C, Horby PW, Nguyen-Van-Tam JS, Ho A, Russell CD, Dunning J, Openshaw PJ, Baillie JK, Semple MG (2020) Features of 20133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 369:m1985PubMedPubMedCentralCrossRef
20.
Lin L, Jiang X, Zhang Z, Huang S, Zhang Z, Fang Z, Gu Z, Gao L, Shi H, Mai L, Liu Y, Lin X, Lai R, Yan Z, Li X, Shan H (2020) Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut 69:997PubMedCrossRef
21.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B (2020) Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurology 77:683–690PubMedCrossRef
22.
Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of Medicine 14:185–192PubMedCrossRef
23.
Qi F, Qian S, Zhang S, Zhang Z (2020) Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochemical and Biophysical Research Communications 526:135–140PubMedPubMedCentralCrossRef
24.
Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, Li Z, Cui X, Xiao J, Zhan J, Meng T, Zhou W, Liu J, Xu H (2020) Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process. Gut 69:1010–1018CrossRef
25.
Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W (2020) Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2. American Journal of Respiratory and Critical Care Medicine 202:756–759PubMedPubMedCentralCrossRef
26.
Zhang J, Wu Y, Wang R, Lu K, Tu M, Guo H, Xie W, Qin Z, Li S, Zhu P, Wang X (2020) Bioinformatic analysis reveals that the reproductive system is potentially at risk from SARS-CoV-2. Preprints
27.
Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, Winter H, Meister M, Veith C, Boots AW, Hennig BP, Kreuter M, Conrad C, Eils R (2020) SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. The EMBO Journal 39:e105114–e105114PubMedPubMedCentralCrossRef
28.
29.
Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, Li T, Chen Q (2020) High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. International Journal of Oral Science 12:8PubMedPubMedCentralCrossRef
30.
Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, Zhou J, Shi G, Fang N, Fan J, Cai J, Fan J, Lan F (2020) Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv
31.
Chen J, Jiang Q, Xia X, Liu K, Yu Z, Tao W, Gong W, Han J-DJ (2020) Individual variation of the SARS-CoV2 receptor ACE2 gene expression and regulation. Aging Cell 19:e13168PubMedCentralCrossRef
32.
Liu F, Long X, Zou W, Fang M, Wu W, Li W, Zhang B, Zhang W, Chen X, Zhang Z (2020) Highly ace2 expression in pancreas may cause pancreas damage after SARS-CoV-2 infection. Clin Gastroenterol Hepatol 18(9):2128–2130.e2PubMedPubMedCentralCrossRef
33.
Su H, Yang M, Wan C, Yi L-X, Tang F, Zhu H-Y, Yi F, Yang H-C, Fogo AB, Nie X, Zhang C (2020) Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney International 98:219–227PubMedPubMedCentralCrossRef
34.
Pan XW, Xu D, Zhang H, Zhou W, Wang LH, Cui XG (2020) Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Medicine 46:1114–1116PubMedPubMedCentralCrossRef
35.
Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB (2020) Multiorgan and renal tropism of SARS-CoV-2. New England Journal of Medicine 383:590–592CrossRef
36.
Douglas GC, O’Bryan MK, Hedger MP, Lee DKL, Yarski MA, Smith AI, Lew RA (2004) The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology 145:4703–4711PubMedCrossRef
37.
Wang Z, Xu X (2020) scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia, Leydig and Sertoli cells. Cells 9:920PubMedCentralCrossRef
38.
Li M, Chen L, Zhang J, Xiong C, Li X (2020) The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLOS ONE 15:e0230295PubMedPubMedCentralCrossRef
39.
40.
Saheb Sharif-Askari N, Saheb Sharif-Askari F, Alabed M, Temsah M-H, al Heialy S, Hamid Q, Halwani R (2020) Airways expression of SARS-CoV-2 receptor, ACE2, and TMPRSS2 is lower in children than adults and increases with smoking and COPD. Molecular Therapy. Methods & Clinical Development 18:1–6CrossRef
41.
Vaarala MH, Porvari KS, Kellokumpu S, Kyllönen AP, Vihko PT (2001) Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues. The Journal of Pathology 193:134–140PubMedCrossRef
42.
Glowacka I, Bertram S, Müller MA, Allen P, Soilleux E, Pfefferle S, Steffen I, Tsegaye TS, He Y, Gnirss K, Niemeyer D, Schneider H, Drosten C, Pöhlmann S (2011) Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. Journal of Virology 85:4122PubMedPubMedCentralCrossRef
43.
Lechien JR, Chiesa-Estomba CM, de Siati DR, Horoi M, le Bon SD, Rodriguez A, Dequanter D, Blecic S, el Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, de Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S (2020) Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European Archives of Oto-Rhino-Laryngology 277:2251–2261PubMedPubMedCentralCrossRef
44.
Vaira LA, Salzano G, Deiana G, de Riu G (2020) Anosmia and ageusia: common findings in COVID-19 patients. The Laryngoscope 130:1787PubMedCrossRef
45.
Brann DH, Tsukahara T, Weinreb C, Lipovsek M, van den Berge K, Gong B, Chance R, Macaulay IC, Chou H, Fletcher R, Das D, Street K, de Bezieux HR, Choi Y-G, Risso D, Dudoit S, Purdom E, Mill JS, Hachem RA, Matsunami H, Logan DW, Goldstein BJ, Grubb MS, Ngai J, Datta SR (2020) Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science Advances 6:eabc5801PubMedCrossRef
46.
Galougahi MK, Ghorbani J, Bakhshayeshkaram M, Naeini AS, Haseli S (2020) Olfactory bulb magnetic resonance imaging in SARS-CoV-2-induced anosmia: the first report. Academic Radiology 27:892–893PubMedPubMedCentralCrossRef
47.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, Fafi-Kremer S, Ohana M, Anheim M, Meziani F (2020) Neurologic features in severe SARS-CoV-2 infection. New England Journal of Medicine 382:2268–2270CrossRef
48.
Baig AM, Khaleeq A, Ali U, Syeda H (2020) Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chemical Neuroscience 11:995–998PubMedCrossRef
49.
Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M (2020) Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Journal of Medical Virology 92:699–702PubMedCrossRef
50.
Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, Ueno M, Sakata H, Kondo K, Myose N, Nakao A, Takeda M, Haro H, Inoue O, Suzuki-Inoue K, Kubokawa K, Ogihara S, Sasaki T, Kinouchi H, Kojin H, Ito M, Onishi H, Shimizu T, Sasaki Y, Enomoto N, Ishihara H, Furuya S, Yamamoto T, Shimada S (2020) A first case of meningitis/encephalitis associated with SARS-coronavirus-2, International Journal of Infectious Diseases: IJID : Official Publication of the International Society for Infectious Diseases. 94:55–58
51.
Amirian ES (2020) Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health. International Journal of Infectious Diseases 95:363–370PubMedPubMedCentralCrossRef
52.
Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brünink S, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C (2020) Virological assessment of hospitalized patients with COVID-2019. Nature 581:465–469PubMedCrossRef
53.
Smyk W, Janik MK, Portincasa P, Milkiewicz P, Lammert F, Krawczyk M (2020) COVID-19: focus on the lungs but do not forget the gastrointestinal tract. European Journal of Clinical Investigation e13276
54.
Argenziano MG, Bruce SL, Slater CL, Tiao JR, Baldwin MR, Barr RG, Chang BP, Chau KH, Choi JJ, Gavin N, Goyal P, Mills AM, Patel AA, Romney M-LS, Safford MM, Schluger NW, Sengupta S, Sobieszczyk ME, Zucker JE, Asadourian PA, Bell FM, Boyd R, Cohen MF, Colquhoun MI, Colville LA, de Jonge JH, Dershowitz LB, Dey SA, Eiseman KA, Girvin ZP, Goni DT, Harb AA, Herzik N, Householder S, Karaaslan LE, Lee H, Lieberman E, Ling A, Lu R, Shou AY, Sisti AC, Snow ZE, Sperring CP, Xiong Y, Zhou HW, Natarajan K, Hripcsak G, Chen R (2020) Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. BMJ 369:m1996PubMedPubMedCentralCrossRef
55.
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. New England Journal of Medicine 383:120–128CrossRef
56.
Li Y, Xu Q, Ma L, Wu D, Gao J, Chen G, Li H (2020) Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID-19/SARS-CoV-2. Journal of Cellular and Molecular Medicine 24:9478–9482PubMedPubMedCentralCrossRef
57.
Li L, Qin L, Xu Z, Yin Y, Wang X, Kong B, Bai J, Lu Y, Fang Z, Song Q, Cao K, Liu D, Wang G, Xu Q, Fang X, Zhang S, Xia J, Xia J (2020) Artificial intelligence distinguishes COVID-19 from community acquired pneumonia on chest CT. Radiology 296:E65–E71PubMedCrossRef
58.
Stelzig KE, Canepa-Escaro F, Schiliro M, Berdnikovs S, Prakash YS, Chiarella SE (2020) Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology 318:L1280–L1281PubMedPubMedCentralCrossRef
59.
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. Journal of Medical Virology 92:2556–2566PubMedCrossRef
60.
Bradding P, Richardson M, Hinks TSC, Howarth PH, Choy DF, Arron JR, Wenzel SE, Siddiqui S (2020) ACE2, TMPRSS2, and furin gene expression in the airways of people with asthma-implications for COVID-19. The Journal of Allergy and Clinical Immunology 146:208–211PubMedPubMedCentralCrossRef
61.
62.
Pinto BGG, Oliveira AER, Singh Y, Jimenez L, Goncalves ANA, Ogava RLT, Creighton R, Peron JPS, Nakaya HI (2020) ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. The Journal of Infectious Diseases 222:556–563PubMedCrossRef
63.
Leung JM, Yang CX, Tam A, Shaipanich T, Hackett T-L, Singhera GK, Dorscheid DR, Sin DD (2020) ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. The European Respiratory Journal 55:2000688PubMedPubMedCentralCrossRef
64.
Brake SJ, Barnsley K, Lu W, McAlinden KD, Eapen MS, Sohal SS (2020) Smoking upregulates angiotensin-converting enzyme-2 receptor: a potential adhesion site for novel coronavirus SARS-CoV-2 (COVID-19). Journal of Clinical Medicine 9:841PubMedCentralCrossRef
65.
Higham A, Singh D (2020) Increased ACE2 expression in the bronchial epithelium of COPD patients who are overweight. Obesity 28:1586–1589PubMedCrossRef
66.
Song C, Wang Y, Li W, Hu B, Chen G, Xia P, Wang W, Li C, Diao F, Hu Z, Yang X, Yao B, Liu Y (2020) Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients. Biology of Reproduction 103:4–6PubMedCrossRef
67.
Yu Y, Xu D, Fu S, Zhang J, Yang X, Xu L, Xu J, Wu Y, Huang C, Ouyang Y, Yang L, Fang M, Xiao H, Ma J, Zhu W, Hu S, Hu Q, Ding D, Hu M, Zhu G, Xu W, Guo J, Xu J, Yuan H, Zhang B, Yu Z, Chen D, Yuan S, Shang Y (2020) Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study. Critical Care 24:129CrossRef
68.
Levy A, Yagil Y, Bursztyn M, Barkalifa R, Scharf S, Yagil C (2008) ACE2 expression and activity are enhanced during pregnancy. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 295:R1953–R1961PubMedCrossRef
69.
Bharadwaj MS, Strawn WB, Groban L, Yamaleyeva LM, Chappell MC, Horta C, Atkins K, Firmes L, Gurley SB, Brosnihan KB (2011) Angiotensin-converting enzyme 2 deficiency is associated with impaired gestational weight gain and fetal growth restriction. Hypertension 58:852–858PubMedCrossRef
70.
Brosnihan KB, Neves LAA, Anton L, Joyner J, Valdes G, Merrill DC (2004) Enhanced expression of Ang-(1-7) during pregnancy. Brazilian Journal of Medical and Biological Research 37:1255–1262PubMedCrossRef
71.
Baergen RN, Heller DS (2020) Placental pathology in COVID-19 positive mothers: preliminary findings. Pediatric and Developmental Pathology 23:177–180PubMedPubMedCentralCrossRef
72.
Sutton D, Fuchs K, D’Alton M, Goffman D (2020) Universal screening for SARS-CoV-2 in women admitted for delivery. New England Journal of Medicine 382:2163–2164CrossRef
73.
Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, Li J, Zhao D, Xu D, Gong Q, Liao J, Yang H, Hou W, Zhang Y (2020) Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet 395:809–815CrossRef
74.
Cosma S, Carosso AR, Cusato J, Borella F, Carosso M, Bovetti M, Filippini C, D’Avolio A, Ghisetti V, Di Perri G, Benedetto C (2020) Coronavirus disease 2019 and first-trimester spontaneous abortion: a case-control study of 225 pregnant patients. Am J Obstet Gynecol S0002-9378(20):31177–31177
75.
Marín Gabriel MA, Reyne Vergeli M, Caserío Carbonero S, Sole L, Carrizosa Molina T, Rivero Calle I, Cuadrado Pérez I, Álvarez Fernández B, Forti Buratti A, Fernández-Cañadas Morillo A, Neo-COVID-19 Research Group (2020) Maternal, perinatal and neonatal outcomes with COVID-19: a multicenter study of 242 pregnancies and their 248 infant newborns during their first month of life. Pediatr Infect Dis J
76.
Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, Ji R, Wang H, Wang Y, Zhou Y (2020) Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases 94:91–95CrossRef
77.
Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, Consortium and the NC-19 R (2020) Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 323:2052–2059PubMedPubMedCentralCrossRef
78.
Pranata R, Lim MA, Huang I, Raharjo SB, Lukito AA (2020) Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: a systematic review, meta-analysis and meta-regression. JRAAS 21:1470320320926899–1470320320926899PubMedPubMedCentral
79.
Huang I, Lim MA, Pranata R (2020) Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – a systematic review, meta-analysis, and meta-regression. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14:395–403CrossRef
80.
Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, Khare S, Srivastava A (2020) Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14:535–545CrossRef
81.
Santoso A, Pranata R, Wibowo A, Al-Farabi MJ, Huang I, Antariksa B (2020) Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: a meta-analysis. The American Journal of Emergency Medicine S0735-6757(20):30280–30281
82.
Pranata R, Huang I, Lim MA, Wahjoepramono EJ, July J (2020) Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19–systematic review, meta-analysis, and meta-regression. Journal of Stroke and Cerebrovascular Diseases 29:104949PubMedPubMedCentralCrossRef
83.
Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois F, Stachel A (2020) Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission. Clinical Infectious Diseases 71:896–897PubMedCrossRef
84.
Klang E, Kassim G, Soffer S, Freeman R, Levin MA, Reich DL (2020) Morbid obesity as an independent risk factor for COVID-19 mortality in hospitalized patients younger than 50. Obesity 28:1595–1599PubMedCrossRef
85.
Henry BM, Lippi G (2020) Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. International Urology and Nephrology 52:1193–1194PubMedPubMedCentralCrossRef
86.
Patanavanich R, Glantz SA (2020) Smoking is associated with COVID-19 progression: a meta-analysis. Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco 22:1653–1656CrossRef
87.
Alqahtani JS, Oyelade T, Aldhahir AM, Alghamdi SM, Almehmadi M, Alqahtani AS, Quaderi S, Mandal S, Hurst JR (2020) Prevalence, severity and mortality associated with COPD and smoking in patients with COVID-19: a rapid systematic review and meta-analysis. PLOS ONE 15:e0233147PubMedPubMedCentralCrossRef
88.
Collaborative Covids (2020) Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet 396:27–38CrossRef
89.
Gómez J, Albaiceta GM, García-Clemente M, López-Larrea C, Amado-Rodríguez L, Lopez-Alonso I (2020) Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome. Gene 762:145102PubMedPubMedCentralCrossRef
90.
Yang CW, Lu LC, Chang CC, Cho CC, Hsieh WY, Tsai CH, Lin YC, Lin CS (2017) Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session. Ren Fail 39(1):719–728PubMedPubMedCentralCrossRef
91.
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 395:1417–1418PubMedPubMedCentralCrossRef
92.
Konopka KE, Nguyen T, Jentzen JM, Rayes O, Schmidt CJ, Wilson AM, Farver CF, Myers JL (2020) Diffuse alveolar damage (DAD) from coronavirus disease 2019 infection is morphologically indistinguishable from other causes of DAD. Histopathology 77:570–578PubMedCrossRef
93.
Edler C, Schröder AS, Aepfelbacher M, Fitzek A, Heinemann A, Heinrich F, Klein A, Langenwalder F, Lütgehetmann M, Meißner K, Püschel K, Schädler J, Steurer S, Mushumba H, Sperhake J-P (2020) Dying with SARS-CoV-2 infection—an autopsy study of the first consecutive 80 cases in Hamburg, Germany. International Journal of Legal Medicine 134:1275–1284PubMedPubMedCentralCrossRef
94.
Schaefer IM, Padera RF, Solomon IH, Kanjilal S, Hammer MM, Hornick JL, Sholl LM (2020) In situ detection of SARS-CoV-2 in lungs and airways of patients with COVID-19. Mod Pathol 33(11):2104–2114PubMedPubMedCentralCrossRef
95.
Mitchell JM, Rakheja D, Gopal P (2020) SARS-CoV-2-related hypercoagulable state leading to ischemic enteritis secondary to superior mesenteric artery thrombosis. Clinical Gastroenterology and Hepatology 17:S1542-3565(20)30835-1
96.
Cugno M, Meroni PL, Gualtierotti R, Griffini S, Grovetti E, Torri A, Panigada M, Aliberti S, Blasi F, Tedesco F, Peyvandi F (2020) Complement activation in patients with COVID-19: a novel therapeutic target. The Journal of Allergy and Clinical Immunology 146:215–217PubMedPubMedCentralCrossRef
97.
Ren Y, Shu T, Wu D, Mu J, Wang C, Huang M, Han Y, Zhang X-Y, Zhou W, Qiu Y, Zhou X (2020) The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cellular & Molecular Immunology 17:881–883CrossRef
98.
Nicklin SA (2016) A novel mechanism of action for angiotensin-(1–7) via the angiotensin type 1 receptor. Hypertension 68:1342–1343PubMedCrossRef
99.
Bao L, Deng W, Huang B, Gao H, Liu J, Ren L, Wei Q, Yu P, Xu Y, Qi F, Qu Y, Li F, Lv Q, Wang W, Xue J, Gong S, Liu M, Wang G, Wang S, Song Z, Zhao L, Liu P, Zhao L, Ye F, Wang H, Zhou W, Zhu N, Zhen W, Yu H, Zhang X, Guo L, Chen L, Wang C, Wang Y, Wang X, Xiao Y, Sun Q, Liu H, Zhu F, Ma C, Yan L, Yang M, Han J, Xu W, Tan W, Peng X, Jin Q, Wu G, Qin C (2020) The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 583:830–833PubMedCrossRef
100.
Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM (2018) Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease. PLOS ONE 13:e0198144PubMedPubMedCentralCrossRef
101.
Epelman S, Shrestha K, Troughton RW, Francis GS, Sen S, Klein AL, Wilson Tang WH (2009) Soluble angiotensin-converting enzyme 2 in human heart failure: relation with myocardial function and clinical outcomes. Journal of Cardiac Failure 15:565–571PubMedPubMedCentralCrossRef
102.
Walters TE, Kalman JM, Patel SK, Mearns M, Velkoska E, Burrell LM (2016) Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling. EP Europace 19:1280–1287
103.
Ramchand J, Patel SK, Kearney LG, Matalanis G, Farouque O, Srivastava PM, Burrell LM (2020) Plasma ACE2 activity predicts mortality in aortic stenosis and is associated with severe myocardial fibrosis. JACC: Cardiovascular Imaging 13:655–664PubMed
104.
105.
Kornilov SA, Lucas I, Jade K, Dai CL, Lovejoy JC, Magis AT (2020) Plasma levels of soluble ACE2are associated with sex, metabolic syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19. Critical care 24:452PubMedPubMedCentralCrossRef
106.
Sama IE, Ravera A, Santema BT, van Goor H, ter Maaten JM, Cleland JGF, Rienstra M, Friedrich AW, Samani NJ, Ng LL, Dickstein K, Lang CC, Filippatos G, Anker SD, Ponikowski P, Metra M, van Veldhuisen DJ, Voors AA (2020) Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors. European Heart Journal 41:1810–1817PubMedPubMedCentralCrossRef
107.
Nicin L, Abplanalp WT, Mellentin H, Kattih B, Tombor L, John D, Schmitto JD, Heineke J, Emrich F, Arsalan M, Holubec T, Walther T, Zeiher AM, Dimmeler S (2020) Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. European Heart Journal 41:1804–1806PubMedCrossRef
108.
109.
Dudoignon E, Moreno N, Deniau B, Coutrot M, Longer R, Amiot Q, Mebazaa A, Pirracchio R, Depret F, Legrand M (2020) Activation of the renin-angiotensin-aldosterone system is associated with acute kidney injury in COVID-19. Anaesth Crit Care Pain Med 39(4):453–455PubMedPubMedCentralCrossRef
110.
Villard O, Morquin D, Molinari N, Raingeard I, Nagot N, Cristol JP, Jung B, Roubille C, Foulongne V, Fesler P, Lamure S, Taourel P, Konate A, Maria ATJ, Makinson A, Bertchansky I, Larcher R, Klouche K, Le Moing V, Renard E, Guilpain P (2020) The plasmatic aldosterone and c-reactive protein levels, and the severity of COVID-19: the Dyhor-19 Study. J Clin Med 9(7):2315PubMedCentralCrossRef
111.
Moreno-P O, Leon-Ramirez JM, Fuertes-Kenneally L, Perdiguero M, Andres M, Garcia-Navarro M, Ruiz-Torregrosa P, Boix V, Gil J, Merino E, COVID19-ALC Research Group (2020) Hypokalemia as a sensitive biomarker of disease severity and the requirement for invasive mechanical ventilation requirement in COVID-19 pneumonia: a case series of 306 Mediterranean patients. Int J Infect Dis 100:449–454PubMedCrossRef
112.
Rieder M, Wirth L, Pollmeier L, Jeserich M, Goller I, Baldus N, Schmid B, Busch HJ, Hofmann M, Kern W, Bode C, Duerschmied D, Lother A (2020) Serum ACE-2, angiotensin II, and aldosterone levels are unchanged in patients with COVID-19. Am J Hypertens hpaa169
113.
Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G (2020) Renin–angiotensin–aldosterone system blockers and the risk of COVID-19. New England Journal of Medicine 382:2431–2440CrossRef
114.
Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, Hausvater A, Newman JD, Berger JS, Bangalore S, Katz SD, Fishman GI, Kunichoff D, Chen Y, Ogedegbe G, Hochman JS (2020) Renin–angiotensin–aldosterone system inhibitors and risk of COVID-19. New England Journal of Medicine 382:2441–2448CrossRef
115.
Fosbøl EL, Butt JH, Østergaard L, Andersson C, Selmer C, Kragholm K, Schou M, Phelps M, Gislason GH, Gerds TA, Torp-Pedersen C, Køber L (2020) Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA 324:168–177PubMedPubMedCentralCrossRef
116.
de Abajo FJ, Rodríguez-Martín S, Lerma V, Mejía-Abril G, Aguilar M, García-Luque A, Laredo L, Laosa O, Centeno-Soto GA, Gálvez MÁ, Puerro M, González-Rojano E, Pedraza L, de Pablo I, Abad-Santos F, Rodríguez-Mañas L, Gil M, Tobías A, Rodríguez-Miguel A, Rodríguez-Puyol D, Barreira-Hernandez D, Zubiaur P, Santos-Molina E, Pintos-Sánchez E, Navares-Gómez M, Aparicio RM, García-Rosado V, Gutiérrez-Ortega C, Pérez C, Ascaso A, Elvira C (2020) Use of renin–angiotensin–aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. The Lancet 395:1705–1714CrossRef
117.
Guo X, Zhu Y, Hong Y (2020) Decreased mortality of COVID-19 with renin-angiotensin-aldosterone system inhibitors therapy in patients with hypertension: a meta-analysis. Hypertension 76:e13–e14PubMedCrossRef
118.
Gao C, Cai Y, Zhang K, Zhou L, Zhang Y, Zhang X, Li Q, Li W, Yang S, Zhao X, Zhao Y, Wang H, Liu Y, Yin Z, Zhang R, Wang R, Yang M, Hui C, Wijns W, McEvoy JW, Soliman O, Onuma Y, Serruys PW, Tao L, Li F (2020) Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. European Heart Journal 41:2058–2066PubMedCrossRef
119.
Baral R, White M, Vassiliou VS (2020) Effect of renin-angiotensin-aldosterone system inhibitors in patients with COVID-19: a systematic review and meta-analysis of 28,872 patients. Curr Atheroscler Rep 22(10):61PubMedPubMedCentralCrossRef
120.
Milne S, Yang CX, Timens W, Bossé Y, Sin DD (2020) SARS-CoV-2 receptor ACE2 gene expression and RAAS inhibitors. The Lancet Respiratory Medicine 8:e50–e51PubMedCrossRef
121.
Wu J, Li W, Shi X, Chen Z, Jiang B, Liu J, Wang D, Liu C, Meng Y, Cui L, Yu J, Cao H, Li L (2020) Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19). Journal of Internal Medicine 288:128–138PubMedCrossRef
122.
Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, Labreuche J, Mathieu D, Pattou F, Jourdain M, group the L and the LC-19 and O study (2020) High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity 28:1195–1199PubMedCrossRef
123.
Zhang F, Xiong Y, Wei Y, Hu Y, Wang F, Li G, Liu K, Du R, Wang C-Y, Zhu W (2020) Obesity predisposes to the risk of higher mortality in young COVID-19 patients. Journal of Medical Virology 92:2536–2542PubMedCrossRef
124.
Moriconi D, Masi S, Rebelos E, Virdis A, Manca ML, de Marco S, Taddei S, Nannipieri M (2020) Obesity prolongs the hospital stay in patients affected by COVID-19, and may impact on SARS-COV-2 shedding. Obesity Research & Clinical Practice 14:205–209CrossRef
125.
Hajifathalian K, Kumar S, Newberry C, Shah S, Fortune B, Krisko T, Ortiz-Pujols S, Zhou XK, Dannenberg AJ, Kumar R, Sharaiha RZ (2020) Obesity is associated with worse outcomes in COVID-19: analysis of early data from New York City. Obesity 28:1606–1612PubMedCrossRef
126.
Ryan PM, Caplice NM (2020) Is adipose tissue a reservoir for viral spread, immune activation, and cytokine amplification in coronavirus disease 2019? Obesity 28:1191–1194PubMedCrossRef
127.
Zheng KI, Gao F, Wang X-B, Sun Q-F, Pan K-H, Wang T-Y, Ma H-L, Chen Y-P, Liu W-Y, George J, Zheng M-H (2020) Letter to the Editor: Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease. Metabolism: Clinical and Experimental 108:154244CrossRef
128.
Patel VB, Mori J, McLean BA, Basu R, Das SK, Ramprasath T, Parajuli N, Penninger JM, Grant MB, Lopaschuk GD, Oudit GY (2016) ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity. Diabetes 65:85–95PubMedCrossRef
129.
Mori J, Oudit GY, Lopaschuk GD (2020) SARS-CoV-2 perturbs the renin-angiotensin system and energy metabolism. American Journal of Physiology-Endocrinology and Metabolism 319:E43–E47PubMedPubMedCentralCrossRef
130.
Kruglikov IL, Scherer PE (2020) The role of adipocytes and adipocyte-like cells in the severity of COVID-19 infections. Obesity 28:1187–1190PubMedCrossRef
131.
Batlle D, Wysocki J, Satchell K (2020) Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clinical Science 134:543–545PubMedCrossRef
132.
Yi C, Sun X, Ye J, Ding L, Liu M, Yang Z, Lu X, Zhang Y, Ma L, Gu W, Qu A, Xu J, Shi Z, Ling Z, Sun B (2020) Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cellular & Molecular Immunology 17:621–630CrossRef
133.
Wysocki J, Ye M, Rodriguez E, González-Pacheco FR, Barrios C, Evora K, Schuster M, Loibner H, Brosnihan KB, Ferrario CM, Penninger JM, Batlle D (2010) Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II-dependent hypertension. Hypertension 55:90–98PubMedCrossRef
134.
Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X, Yu J, Shan S, Zhou B, Song S, Tang X, Yu J, Lan J, Yuan J, Wang H, Zhao J, Zhang S, Wang Y, Shi X, Liu L, Zhao J, Wang X, Zhang Z, Zhang L (2020) Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584:115–119PubMedCrossRef
135.
Hurlburt NK, Wan YH, Stuart AB, Feng J, McGuire AT, Stamatatos L, Pancera M (2020) Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation. Nat Commun 11:5413PubMedPubMedCentralCrossRef
136.
Wu Y, Wang F, Shen C, Peng W, Li D, Zhao C, Li Z, Li S, Bi Y, Yang Y, Gong Y, Xiao H, Fan Z, Tan S, Wu G, Tan W, Lu X, Fan C, Wang Q, Liu Y, Zhang C, Qi J, Gao GF, Gao F, Liu L (2020) A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science 368:1274–1278PubMedPubMedCentralCrossRef
137.
Shi R, Shan C, Duan X, Chen Z, Liu P, Song J, Song T, Bi X, Han C, Wu L, Gao G, Hu X, Zhang Y, Tong Z, Huang W, Liu WJ, Wu G, Zhang B, Wang L, Qi J, Feng H, Wang F, Wang Q, Gao GF, Yuan Z, Yan J (2020) A human neutralizing antibody targets the receptor binding site of SARS-CoV-2. Nature 584:120–124PubMedCrossRef
138.
Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr (2020) Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature 584(7821):443–449PubMedPubMedCentralCrossRef
139.
Rogers TF, Zhao F, Huang D, Beutler N, Burns A, He WT, Limbo O, Smith C, Song G, Woehl J, Yang L, Abbott RK, Callaghan S, Garcia E, Hurtado J, Parren M, Peng L, Ramirez S, Ricketts J, Ricciardi MJ, Rawlings SA, Wu NC, Yuan M, Smith DM, Nemazee D, Teijaro JR, Voss JE, Wilson IA, Andrabi R, Briney B, Landais E, Sok D, Jardine JG, Burton DR (2020) Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369(6506):956–963PubMedPubMedCentralCrossRef
140.
Baum A, Fulton BO, Wloga E, Copin R, Pascal KE, Russo V, Giordano S, Lanza K, Negron N, Ni M, Wei Y, Atwal GS, Murphy AJ, Stahl N, Yancopoulos GD, Kyratsous CA (2020) Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 369:1014–1018PubMedCrossRef
141.
Hassan AO, Case JB, Winkler ES, Thackray LB, Kafai NM, Bailey AL, McCune BT, Fox JM, Chen RE, Alsoussi WB, Turner JS, Schmitz AJ, Lei T, Shrihari S, Keeler SP, Fremont DH, Greco S, McCray PB Jr, Perlman S, Holtzman MJ, Ellebedy AH, Diamond MS (2020) A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies. Cell 182(3):744-753.e4
142.
Li W, Chen C, Drelich A, Martinez DR, Gralinski LE, Sun Z, Schäfer A, Kulkarni SS, Liu X, Leist SR, Zhelev DV, Zhang L, Kim YJ, Peterson EC, Conard A, Mellors JW, Tseng CK, Falzarano D, Baric RS, Dimitrov DS (2020) Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection. Proc Natl Acad Sci U S A 2:202010197
143.
Miao X, Luo Y, Huang X, Lee SMY, Yuan Z, Tang Y, Chen L, Wang C, Wu F, Xu Y, Jiang W, Gao W, Song X, Yan Y, Pang T, Chen C, Zou Y, Fu W, Wan L, Gilbert-Jaramillo J, Knight M, Tan TK, Rijal P, Townsend A, Sun J, Liu X, James W, Tsun A, Xu Y (2020) A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy. MAbs 12(1):1804241PubMedPubMedCentralCrossRef
144.
Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM, BLAZE-1 Investigators (2020) SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19. N Engl J Med
145.
Li Q, Cao Z, Rahman P (2020) Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations. Molecular Genetics & Genomic Medicine 8:e1344CrossRef
146.
Zheng H, Cao JJ (2020) Angiotensin-converting enzyme gene polymorphism and severe lung injury in patients with coronavirus disease 2019. The American journal of pathology 190:2013–2017PubMedCrossRef
147.
Pati A, Mahto H, Padhi S, Panda AK (2020) ACE deletion allele is associated with susceptibility to SARS-CoV-2 infection and mortality rate: An epidemiological study in the Asian population. Clinica Chimica Acta; International Journal of Clinical Chemistry 510:455–458PubMedPubMedCentralCrossRef
148.
Adamzik M, Frey U, Sixt S, Knemeyer L, Beiderlinden M, Peters J, Siffert W (2017) ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS. European Respiratory Journal 29:482CrossRef
149.
Yamamoto N, Ariumi Y, Nishida N, Yamamoto R, Bauer G, Gojobori T, Shimotohno K, Mizokami M (2020) SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype. Gene 758:144944PubMedPubMedCentralCrossRef
150.
Hatami N, Ahi S, Sadeghinikoo A, Foroughian M, Javdani F, Kalani N, Fereydoni M, Keshavarz P, Hosseini A (2020) Worldwide ACE (I/D) polymorphism may affect COVID-19 recovery rate: an ecological meta-regression. Endocrine 68:479–484PubMedPubMedCentralCrossRef
151.
Mathew J, Basheeruddin K, Prabhakar S (2001) Differences in frequency of the deletion polymorphism of the angiotensin-converting enzyme gene in different ethnic groups. Angiology 52(6):375–379PubMedCrossRef
Metadata
Title
COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection
Authors
Stephany Beyerstedt
Expedito Barbosa Casaro
Érika Bevilaqua Rangel
Publication date
01-05-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 5/2021
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-020-04138-6

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