Cited by 1,237Renin-Angiotensin System StudiesSARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studies

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The pivotal link between ACE2 deficiency and SARS-CoV-2 infection

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Verdecchia, Paolo, Cavallini, Claudio, Spanevello, Antonio, Angeli, Fabio·2020·European Journal of Internal Medicine

DOI 10.1016/j.ejim.2020.04.037PMC PMC7167588

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Abstract

Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin 1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin 1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the 'adverse' ACE→Angiotensin II→AT1 receptor axis and the 'protective' ACE2→Angiotensin 1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin 1-7. In this setting, recombinant ACE2, angiotensin 1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.

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RETRACTED ARTICLE: Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways
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“[29, [31] [32] [33] ACE2 is expressed on the luminal side of the bronchial ciliated epithelia, where it removes a single amino acid residue also from the polypeptide des-Arg [9] bradykinin (DABK), [6] thereby preventing the binding of DABK on the bradykinin receptor B1 receptor.”
Background
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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
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“The present review discusses the role of angiotensin converting enzyme 2 (ACE2) receptors which are not only the door through which the virus enters into cells, [2,3] but also the conductor of several pathophysiological reactions associated with the clinical features of the disease, with potential therapeutic implicat…”
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“[69,70] In this context, administration of soluble recombinant ACE2 [12] or angiotensin1-7 [71] could be promising therapeutic approaches, requiring urgent evaluation in clinical trials.”
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“The present review discusses the role of angiotensin converting enzyme 2 (ACE2) receptors which are not only the door through which the virus enters into cells, [2,3] but also the conductor of several pathophysiological reactions associated with the clinical features of the disease, with potential therapeutic implicat…”
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“AngII acts in a pro-inflammatory and a pro-oxidant manner inducing vasoconstriction, enhanced inflammation, thrombosis, and increased collagen synthesis in lung fibroblasts [41,74] causing acute lung injury, alveolar edema, and increased incidence of secondary lung fibrosis [42 – 45].”
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Background
Dietary fish intake increased the concentration of soluble ACE2 in rats: can fish consumption reduce the risk of COVID-19 infection through interception of SARS-CoV-2 by soluble ACE2?
O’Keeffe, M., Oterhals, Å., Vikøren, L. A. S., Drotningsvik, A., Mellgren, G., Halstensen, A. I., & Gudbrandsen, O. A. (2023) · British Journal Of Nutrition · doi:10.1017/s0007114523000776 · Cited by 3
“ACE2 catalyses the removal of the carboxyterminal amino acid from angiotensin II to produce the vasodilator angiotensin-(1 – 7), and, with less affinity, removes the carboxyterminal leucyl residue from angiotensin I to produce angiotensin (1 – 9) (7) .”
BackgroundInfluential
Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective analysis
Yang, Y. W., You, Y., Liu, Y., Geng, L., Huang, L., Zhou, H., Piao, X. L., Liu, X., Wu, M., Wang, Y., et al. (2023) · BMC Infectious Diseases · doi:10.1186/s12879-023-08223-x · Cited by 3
Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi
Wadhwa, B., Malhotra, V., Kerai, S., Husain, F., Pandey, N. B., Saxena, K. N., Singh, V., Quinn, T. M., Li, F., Gaughan, E. E., et al. (2023) · BMC Infectious Diseases · doi:10.1186/s12879-023-08286-w · Cited by 3
“Down regulation of the ACE2 receptor as a consequence of viral infection may result in the loss of angiotensin II conversion to angiotensin [7].”
Background
Bioinformatics Approach to Identify the Influences of COVID-19 on Ischemic Stroke
Zhu, J., Li, X., Lv, F., & Zhou, W. (2023) · Biochemical Genetics · doi:10.1007/s10528-023-10366-0 · Cited by 3
“…system (RAS), is expressed in airway epithelium, lung parenchyma, renal cells, heart, testis, vascular endothelial cells, intestinal epithelial cells and brain, and has significant antithrombotic effects by reducing platelet aggregation and nitric oxide release (Verdecchia et al. 2020).”
Design of a Multi-epitope Vaccine against Covid-19: An In silico Approach
Mishra, K. K., Mishra, A. K., Anand, V., Pandey, A., Budhwar, S., & Sharma, D. C. (2023) · Current Biotechnology · doi:10.2174/2211550112666230612153430 · Cited by 3
A cell-based assay for rapid assessment of ACE2 catalytic function
Meyers, W. M., Hong, R. J., Sin, W. C., Kim, C. S., & Haas, K. Z. (2023) · Scientific Reports · doi:10.1038/s41598-023-41389-7 · Cited by 3
“ACE2 has been linked to multiple disease states, including obesity 12 , diabetes 13,14 , and cardiovascular diseases 15–17 , COVID-19 infection 18,19 , comorbidities associated with poor COVID-19 outcomes 20–23 , as well as long-haul COVID-19 pathophysiology 4 .”
Background
Development and validation of a predicted nomogram for mortality of COVID-19: a multicenter retrospective cohort study of 4,711 cases in multiethnic
Shi, Y., Zheng, Z., Wang, P., Wu, Y., Liu, Y., & Liu, J. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1136129 · Cited by 3
“However, SARSCoV-2 can markedly downregulate ACE2 by entering into cells, which might be extra detrimental in the old population via age-related baseline ACE2 deficiency (20).”
Background
Reported long-term effects of COVID-19 patients after hospital discharge in Jordan
Karasneh, R. A., Sharie, S. A., Al-Azzam, S. I., Altawalbeh, S. M., Khassawneh, B. Y., Talafha, M., Nusair, M. B., Al-Mistarehi, A.-H. W., Yonis, O. B., Al-Omary, M. A., et al. (2023) · Medicine · doi:10.1097/md.0000000000034633 · Cited by 3
Alteration in innate immune cues assessed by analyzing peripheral blood immune system in post-covid patients
Dobrynina, M. A., Zurochka, A. V., Komelkova, M. V., Александрович, З. В., Praskurnichiy, E. A., Ryabova, L. V., & Sarapultsev, A. (2023) · Russian Journal of Infection and Immunity · doi:10.15789/2220-7619-aii-9641 · Cited by 3
Comparative immunohistochemical evaluation of variable expression of ACE2 and TMPRSS2 in different age groups
Kanthaswamy, V., Kumar, V. V., Annasamy, R., Ramadoss, R., & Krishnan, R. (2023) · Asia-Pacific Journal of Molecular Biology and Biotechnology · doi:10.35118/apjmbb.2023.031.4.07 · Cited by 3
Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post‐COVID‐19 pulmonary fibrosis
Mohamed, R. H., hay, N. H. A., Fawzy, N. M., Tamim, Y. M., Karem, M., Yehia, D. A. Y., Abdel-Maksoud, O. M., & Abdelrahim, D. S. (2024) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12994 · Cited by 3
“Therefore, downregulation of ACE2 upon virus binding disturbs downstream activities of the renin-angiotensin system (RAS) resulting in increased inflammation and development of PF [5, 6].”
Background
Effective expression and characterization of the receptor binding domains in SARS-CoV-2 Spike proteins from original strain and variants of concern using Bombyx mori nucleopolyhedrovirus in silkworm
Tsukamoto, A., Man, L. J., Oyama, K., Masuda, A., Mon, H., Ueda, T., & Kusakabe, T. (2024) · Protein Expression and Purification · doi:10.1016/j.pep.2024.106450 · Cited by 3
Bibliometric and visual analysis of ACE2/Ang 1–7/MasR axis in diabetes and its microvascular complications from 2000 to 2023
Hu, W., Tan, J., Lin, Y.-T., Tao, Y., & Zhou, Q. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e31405 · Cited by 3
Healing through herbs: everaging herbal remedies against COVID-19
Beladiya, U., Chaliha, J., Mevada, V. A., Gandhi, H. R., & Patel, R. K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15383-9.00015-9 · Cited by 3
Quercetin may reduce the risk of developing the symptoms of COVID-19.
Ajami, M., Sotoudeheian, M., Houshiarrad, A., Esmaili, M., Naeini, F., Mohammadi‐Nasrabadi, F., Doaei, S., & Milani-Bonab, A. (2024) · PubMed Central · doi:10.22038/ajp.2023.22920 · Cited by 3
“SARS-CoV-2-infected cells produce excessive levels of angiotensin II leading to the down-regulation of ACE-2 expression (Verdecchia et al., 2020).”
Background
Severe COVID-19 infection: An institutional review and literature overview
Akpoviroro, O., Sauers, N. K., Queeneth, U., Castagne, M., Akpoviroro, O. P., Humayun, S., Mirza, W., & Woodard, J. (2024) · PLoS ONE · doi:10.1371/journal.pone.0304960 · Cited by 4
T-cell immunobiology and cytokine storm of COVID-19
Eltayeb, A., & Redwan, E. M. M. M. (2025) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2024.10.003 · Cited by 4
Sex-specific impact of the COVID-19 outbreak on the incidence of metabolic syndrome: a comparative study of 2018–2019 and 2020–2021
Chun, K., Kim, H., Kang, D. R., Kim, J., Kim, W., Jeong, Y. W., Han, S. H., Koh, K. K., & on behalf of the Taskforce Team of the Metabolic Syndrome Fact Sheet of the Korean Society of Cardiometabolic Syndrome (2025) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2024.288 · Cited by 3
“A significant association between metabolic syndrome and COVID-19 exacerbates the severity of COVID-19 outcomes in individuals with underlying metabolic conditions such as obesity, hypertension, diabetes, and dyslipidemia [15,16].”
The differential expression of the ACE2 receptor across ages and gender explains the differential lethality of SARS-Cov-2 and suggests possible therapy
Bastolla, U. (2020) · DIGITAL.CSIC (Spanish National Research Council (CSIC)) · Cited by 3
How a COVID-19 positive patient can present to an otolaryngologist, a variable presentation: what not to miss?
Maqbool, T., Mehta, K. S., & Mustafa, H. (2020) · International Journal of Otorhinolaryngology and Head and Neck Surgery · doi:10.18203/issn.2454-5929.ijohns20203207 · Cited by 3
“So the virus can affect the organs where this enzyme is highest in concentration like lungs.(2,3) Real time polymerase chain reaction is used for the diagnosis.”
Method
Tratamiento de COVID-19 en receptores de trasplante renal
Morales-Buenrostro, L. E., & Villca-Gonzales, R. (2020) · Revista Mexicana de Trasplantes · doi:10.35366/94507 · Cited by 3
Atopic endotypes as a modulating factor for SARS-CoV-2 infection: mechanisms and implications
Huntley, K. S., Fine, L. M., & Bernstein, J. A. (2021) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000724 · Cited by 3
“Dysregulation of the ACE/ACE2 balance may have deleterious effects such as increasing ARDS susceptibility and has been implicated in cardiometabolic disorders [34,75].”
Background
"Iron-Based Nanoparticles, an Accurate and Powerful Sniper Targeting SARS- Cov-2"
Mohamed, N. A. (2020) · Advancements in Cardiovascular Research · doi:10.32474/acr.2020.03.000162 · Cited by 3
“Also, it has been shown that other ethnic groups have some structural variations of the ACE2, that confirmed its protective effects due to its low binding affinity to the viral S protein [11].”
BackgroundInfluential
Continuous positive air pressure (CPAP) should be used in all COVID-19 patients when the first and mild respiratory symptoms commence
Machado, C., DeFina, P. A., Machado, Y., Chinchilla, M., Bravo, E. C., & Machado, Y. (2020) · Journal of Respiratory Diseases and Medicine · doi:10.15761/jrdm.1000124 · Cited by 3
“Subsequently, both hypoxemia and related ACE-2 upregulation may deteriorate clinical outcomes in COVID-19 [11,36-45].”
Background
Neuropsychiatrische Aspekte von COVID-19 – Eine narrative Übersicht
Rittmannsberger, H., Barth, M., Malik, P., & Yazdi, K. (2021) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/a-1523-3850 · Cited by 3
“Die teilweise sehr heftige Immunreaktion auf die Infektion („Cytokinsturm“) könnte durch diese Prozesse begünstigt werden [6, 7].”
Background
COVID-19 Masquerading as Postoperative Surgical Complications after Cancer Surgery
Sharma, R. K., Chaudhary, D., Goel, P., Khandelwal, S., Singh, V., & Kapoor, R. K. (2021) · Indian Journal of Surgical Oncology · doi:10.1007/s13193-021-01452-z · Cited by 3
A Review and CFD Case Study: The Effect of Temperature, Humidity, Aerodynamics on Corona Virus Transmission, Mitigation in Open and Enclosed Environments
Hamad, F. (2021) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2021.33.005444 · Cited by 3
Incidence of dystonia related to COVID-19 infection
Thiel, M. F., & Jost, W. H. (2023) · Neurologia i Neurochirurgia Polska · doi:10.5603/pjnns.a2023.0007 · Cited by 3
“The pathophysiological correlation can possibly be explained by the binding of the viral spike protein to angiotensin converting enzyme 2 (ACE2), which is expressed in many tissues, as well as in the brain [6].”
Background
The Effect of Omega-3 Supplements on The Serum Levels Of ACE/ACE2 Ratio As A Potential Key in Cardiovascular Disease: A Randomized Clinical Trial in Participants with Vitamin D Deficiency
Daboul, S. M., Abusamak, M., Mohammad, B. A., Alsayed, A. R., Habash, M., Mosleh, I. M., Al-Shakhshir, S., Issa, R. A., & Abu‐Samak, M. (2023) · Pharmacy Practice · doi:10.18549/pharmpract.2023.1.2761 · Cited by 3
Angiotensin-Converting Enzyme 2, Feedback Systems, and COVID-19
Salgo, M. (2020) · Consultant · doi:10.25270/con.2020.10.00006 · Cited by 3
“ACE2 AND VIRUS ENTRY INTO EPITHELIAL CELLS “Surreptitiously,” SARS-CoV-2 also utilizes ACE2 as a cellular entry receptor.(6) It is not known why this key enzyme of the RAS serves as the entry point for SARS viruses; the answer may lie in the distant phylogenetic past.”
Influential
The Effect of Chronic and Inhospital Exposure to Renin‐Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients
Gaspar, P., Parreira, I., Meireles, P. A., Bessa, F., Silva, V. D., Abrantes, A. M., de Lacerda, A. P., & Mota, C. (2021) · International Journal of Hypertension · doi:10.1155/2021/5517441 · Cited by 3
Sudden Cardiac Death Caused by Cardiac Small Vessel Vasculitis after COVID-19 Vaccination (BNT162b2 nCov-19): A Case Report
Park, S., Kim, M. K., & Baek, K. (2021) · Korean Journal of Legal Medicine · doi:10.7580/kjlm.2021.45.4.133 · Cited by 3
Thrombosis and Fibrosis: Mutually Inclusive Targets to Combat in COVID-19
Ağırbaşlı, M. A. (2021) · Future Science OA · doi:10.2144/fsoa-2021-0127 · Cited by 3
“However, ACE2 is downregulated in COVID-19, as another potential reason for hypercoagulable state in COVID-19 [5,6,15].”
Background
Mecanismos del COVID-19 en el cuerpo humano: Lo que sabemos hasta ahora
Kumar, A., Narayan, R. K., Prasoon, P., Kumari, C., Kaur, G., Kumar, S., Kulandhasamy, M., Sesham, K., Pareek, V., Faiq, M. A., et al. (2022) · Kompass Neumología · doi:10.1159/000521507 · Cited by 6
Impact of the withdrawal of renin-angiotensin-aldosterone inhibitors on mortality in COVID-19 patients
Caro‐Codón, J., Rey, J. R., Iniesta, Á. M., Rosillo, S. O., Castrejón‐Castrejón, S., Rodríguez‐Sotelo, L., García‐Veas, J. M., Clement, I. M., Martinez, L. A., Martín‐Polo, L., et al. (2022) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2021.06.021 · Cited by 3
Neurological Complications of SARS-CoV-2 Infection and COVID-19 Vaccines: From Molecular Mechanisms to Clinical Manifestations
Yepes, M. (2022) · Current Drug Targets · doi:10.2174/1389450123666220919123029 · Cited by 4
Angiotensin converting enzyme 2 activation improves allergic rhinitis and suppresses Th2 cytokine release
Sun, X., Xu, Y. M., & Zhou, J. (2023) · Immunity Inflammation and Disease · doi:10.1002/iid3.763 · Cited by 3
“Following the viral invasion, additional ACE2 deficit may amplify dysregulation of the ACE2 regulatory axis.(31) Nevertheless, this study is limited to the focus on ACE2, and its upstream and downstream are still unknown.”
Background
COVID-19;-The origin, genetics,and management of the infection of mothers and babies
El‐Sayyad, H. I., & Abdalhafid, Y. K. A. (2020) · Egyptian Journal of Basic and Applied Sciences · doi:10.1080/2314808x.2020.1843119 · Cited by 3
In Silico Modeling of Virus Particle Propagation and Infectivity along the Respiratory Tract: A Case Study for SARS-COV-2Preprint
Vimalajeewa, D., Balasubramaniam, S., Berry, D. P., & Barry, G. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.20.259242 · Cited by 3
“This replication rate is compromised as the immune system starts to attack the virus based on the innate immune response first line of defence [21].”
Background
RAAS Blockers and Region-Specific Variations in COVID-19 Outcomes: Findings from a Systematic Review and Meta-AnalysisPreprint
Kaur, U., Chakrabarti, S. S., & Patel, T. K. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3684465 · Cited by 3
Renin-Angiotensin System, SARS-CoV-2 and Hypotheses about Some Adverse Effects Following VaccinationPreprint
Bellavite, P. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3781903 · Cited by 3
“Recent reviews highlighted a possible beneficial effect of recombinant ACE2 [2,25] and reported clinical improvements after treatments with recombinant ACE2 in SARS-CoV-2, associated with reduction of inflammatory markers [26].”
Background
ACE2 polymorphisms interplay with the apelinergic peptide system: potential tools for COVID-19 diagnosis and treatmentPreprint
Kelleni, M. T. (2021) · doi:10.31219/osf.io/enjxt · Cited by 3
ACE2, TMPRSS2, TYK2, SLC6A20, and IFNAR2 human genes variants influence SARS‑CoV‑2 infection susceptibilityPreprint
Aghamirli, S. S., & Saleh-Gohari, N. (2023) · doi:10.22541/au.169035663.39913026/v1 · Cited by 3
In silico evaluation of S -adenosyl-L-homocysteine analogs as inhibitors of nsp14-viral cap N7 methyltranferase and PLpro of SARS-CoV-2: synthesis, molecular docking, physicochemical data, ADMET and molecular dynamics simulations studies
Srivastava, R., Panda, S. K., Gupta, P. S. S., Chaudhary, A., Naaz, F., Yadav, A. K., Ram, N. K., Rana, M. K., Singh, R. K., & Srivastava, R. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2297005 · Cited by 3
“The binding of the receptor-binding domain (RBD) in the S1 sub-unit of the spike protein of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE 2) receptors of the human cells facilitates the viral entry into human cells (Verdecchia et al., 2020; Wan et al., 2020; Zhou et al., 2020).”
Modulation of the renin-angiotensin system against COVID-19: A path forward?
Camelo, S., Dioh, W., Teixeira, J. P., Busse, L. W., NAIR, G. B., Plantefève, G., Morélot‐Panzini, C., Lobo, S. M., Self, W. H., Collins, S. P., et al. (2025) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2025.107867 · Cited by 3
“We and others have hypothesized that COVID-19 severity was directly correlated to RAS imbalance linked to an “ACE2 deﬁciency” due to viral occupancy [ 3 ].”
Design and Evaluation of ATN-161 Analogues as Fusion Inhibitors Targeting Integrins in SARS-CoV-2
Munawar, M., Khan, N., Jabeen, S., Taj, S., Bashir, R., Abbas, W., Rauf, W., & Iqbal, M. (2025) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-025-10734-x · Cited by 2
“The RBD contains an Arg-Gly-Asp (RGD) motif recognized by α5β1, facilitating viral attachment, cell-cell fusion, and inflamma - tory signaling (Verdecchia et al. 2020; Robles et al. 2022; Zhang et al. 2023 ).”
Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: An In Silico and In Vitro Study
Wang, X., He, J., Hosseini-Gerami, L., Thomas, M. C., Thompson, S., Ford, J., Ortalli, S., Chen, Z., Destro, G., Bender, A., et al. (2025) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.5c00918 · Cited by 2
"Prevention and Treatment of Acute Respiratory Distress Syndrome by COVID-19: Role of Vitamin D on Immunomodulation and Renin-Angiotensin- Aldosterone System Regulation"
Jahangiria, M. (2021) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2021.39.006314 · Cited by 2
“In this sense, the mechanisms described could represent potential immunomodulatory pathways against the SARS-CoV-2 virus induced by VD, outlined in Figure 1.”
BackgroundInfluential
Angiotensin-converting enzyme 1 and voltage-gated potassium channel-interacting protein 4 gene polymorphisms in COVID-19 patients from east of Iran
Abbaszadeh, H., Mohammadi, F., Rajabi-Moghaddam, M., Kabiri-rad, H., Ghafari, S., Abedi, F., & Miri-Moghaddam, E. (2022) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/j.cca.2022.09.006 · Cited by 2
“Viral adsorption to susceptible target cells defined as a prerequisite for membrane fusion and host cell entry process, is predominantly mediated by ACE2 interaction with the virus S protein in COVID-19 infection [14].”
Background
ACUTE CEREBROVASCULAR ACCIDENT IN COVID-19
Щербак, С. Г., Вологжанин, Д. А., Камилова, Т. А., & Голота, А. С. (2023) · University therapeutic journal · doi:10.56871/utj.2023.57.78.001 · Cited by 2
The ACE 2 G8790A and IL-22 Gene Polymorphisms and their Association with Susceptibility to COVID-19 in Yaounde, Cameroon
Tah, C. F., Nji, A. M., Chedjou, J. P. K., Ngum, L. N., Tchinda, C. N. N., Laban, R. B., Mbu’u, C. M., Eric, M. B., Netongo, P. M., Wami, T. T., et al. (2023) · Biochemistry and Molecular Biology · doi:10.11648/j.bmb.20230802.12 · Cited by 2
Interaktion von körperlichen Veränderungen und psychischen Störungen bei COVID-19. Ein Scoping Review
Rittmannsberger, H., Barth, M., Lamprecht, B., Malík, P., & Yazdi‐Zorn, K. (2023) · Neuropsychiatrie · doi:10.1007/s40211-023-00487-8 · Cited by 2
Nasopharyngeal angiotensin converting enzyme 2 (ACE2) expression as a risk-factor for SARS-CoV-2 transmission in concurrent hospital associated outbreaks
Nikiforuk, A. M., Kuchinski, K. S., Short, K., Roman, S., Irvine, M. A., Prystajecky, N., Jassem, A. N., Patrick, D. M., & Sekirov, I. (2024) · BMC Infectious Diseases · doi:10.1186/s12879-024-09067-9 · Cited by 3
“In the later stages of replication, SARS-CoV-2 downregulates ACE2 , preventing any benefits to the host mediated by interferon stimulated upregulation [20, 21].”
Background
Chloroquine: Rapidly withdrawing from first-line treatment of COVID-19
Jia, Y., Tian, W., Li, Y., Teng, Y., Liu, X., Li, Z., & Zhao, M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37098 · Cited by 2
Molecular targets in SARS-CoV-2 infection: An update on repurposed drug candidates
Rahmani, D., Jafari, A., Kesharwani, P., & Sahebkar, A. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155589 · Cited by 4
Outcomes of cerebral venous thrombosis with and without COVID-19 infection
Arora, R., Srinivasan, P., Omprakash, O., Reddy, V. B. N., & Nagaraja, N. (2025) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2025.123529 · Cited by 2

Authors: Verdecchia, P., Cavallini, C., Spanevello, A., & Angeli, F.
Affiliations: University of Insubria (IT)
Corresponding author: Verdecchia, Paolo
ORCID: Verdecchia, Paolo
Cavallini, Claudio
Spanevello, Antonio
Angeli, Fabio
Venue: European Journal of Internal Medicine
Publisher: Elsevier BV
Published: 2020-06
Volume: 76
Pages: 14-20
ISSN: 0953-6205 (ISSN-L)
DOI: 10.1016/j.ejim.2020.04.037
PMC: PMC7167588
OpenAlex: W3017331996
Cited by: 1,237
References: 85
Citations by year: 2026: 22 · 2025: 50 · 2024: 84 · 2023: 156 · 2022: 245 · 2021: 384 · 2020: 295
FWCI: 45.93
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: European Journal of Internal Medicine (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
IrInSubria (University of Insubria) (submittedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: ACE2 receptor, COVID-19 pandemic, angiotensin II, angiotensin-(1-7), Mas receptor, angiotensin II type 1 receptor, lung inflammation, thrombosis, hypertension, diabetes mellitus, cardiovascular disease, angiotensin receptor blockers, COVID-19 severity
MeSH terms: Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Angiotensins, Diabetes Mellitus, Heart Failure, Humans, Hypertension, Peptidyl-Dipeptidase A, Pneumonia, Viral, Receptors, Virus, Recombinant Proteins, Risk Factors, Coronavirus Infections, Angiotensin II Type 1 Receptor Blockers, Drug Discovery, Pandemics

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