The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

doi:10.1016/j.ejim.2021.09.007

Review

. 2021 Nov:93:28-34.

doi: 10.1016/j.ejim.2021.09.007. Epub 2021 Sep 20.

The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

Fabio Angeli¹, Martina Zappa², Gianpaolo Reboldi³, Monica Trapasso⁴, Claudio Cavallini⁵, Antonio Spanevello¹, Paolo Verdecchia⁶

Affiliations

¹ Department of Medicine and Surgery, University of Insubria, Varese, Italy; Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, Italy.
² Department of Medicine and Surgery, University of Insubria, Varese, Italy.
³ Department of Medicine, and Centro di Ricerca Clinica e Traslazionale (CERICLET), University of Perugia, Perugia, Italy.
⁴ Dipartimento di Igiene e Prevenzione Sanitaria, PSAL, Sede Territoriale di Varese, ATS Insubria, Varese, Italy.
⁵ Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.
⁶ Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy; Fondazione Umbra Cuore e Ipertensione-ONLUS, Perugia, Italy. Electronic address: verdecchiapaolo@gmail.com.

PMID: 34588140
PMCID: PMC8450306
DOI: 10.1016/j.ejim.2021.09.007

Free PMC article

Review

The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

Fabio Angeli et al. Eur J Intern Med. 2021 Nov.

Free PMC article

. 2021 Nov:93:28-34.

doi: 10.1016/j.ejim.2021.09.007. Epub 2021 Sep 20.

Authors

Fabio Angeli¹, Martina Zappa², Gianpaolo Reboldi³, Monica Trapasso⁴, Claudio Cavallini⁵, Antonio Spanevello¹, Paolo Verdecchia⁶

Affiliations

¹ Department of Medicine and Surgery, University of Insubria, Varese, Italy; Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, Italy.
² Department of Medicine and Surgery, University of Insubria, Varese, Italy.
³ Department of Medicine, and Centro di Ricerca Clinica e Traslazionale (CERICLET), University of Perugia, Perugia, Italy.
⁴ Dipartimento di Igiene e Prevenzione Sanitaria, PSAL, Sede Territoriale di Varese, ATS Insubria, Varese, Italy.
⁵ Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy.
⁶ Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy; Fondazione Umbra Cuore e Ipertensione-ONLUS, Perugia, Italy. Electronic address: verdecchiapaolo@gmail.com.

PMID: 34588140
PMCID: PMC8450306
DOI: 10.1016/j.ejim.2021.09.007

No abstract available

Keywords: ACE2; COVID-19; Renin-angiotensin-aldosterone system; SARS-CoV-2; Therapy; Vaccines.

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Figures

Fig 1 — **Fig. 1**
Mechanisms implicated in the development of Angiotensin II storm during the SARS-CoV-2 infection. The deleterious effects of this phenomenon are also depicted. See text for details. Legend: A_I=angiotensin I; A_II=angiotensin II; A_1,7=angiotensin_1,7; A_1,9=angiotensin_1,9; ACE2=angiotensin coverting enzyme 2; ADAM17= disintegrin and metalloproteinase domain-containing protein 17; AT₁R=angiotensin II type 1 receptor; BKB-₁R=bradykinin B1 receptor; DABK= des-Arg₉ bradykinin; MasR=Mas receptor; NF-kB= nuclear factor kappa-light-chain-enhancer of activated B cells; PRRs=pattern recognition receptors; SARS-CoV-2= severe acute respiratory syndrome coronavirus-2.

Fig 2 — **Fig. 2**
Pre-existing ACE2 deficiency (as documented for elderly patients, diabetes mellitus, COPD, hypertension, and chronic disease) contributes to an unfavourable outcome in SARS-CoV-2 infection. See text for details. Legend: A_II=angiotensin II; A_1,7=angiotensin_1,7; ACE2=angiotensin coverting enzyme 2; RAAS=renin-angiotensin-aldosterone system; SARS-CoV-2= severe acute respiratory syndrome coronavirus-2.

Fig 3 — **Fig. 3**
Potential therapeutic approaches of restoring the ACE2/Angiotensin_1-7 pathway or to trap the virus and to stimulate the renin-angiotensin-aldosterone system protective pathway. See text for details. Legend: A_II=angiotensin II; A_1,7=angiotensin_1,7; ACE2=angiotensin coverting enzyme 2; ACE-Is=ACE inhibitors; ARBs=angiotensin receptor blockers; AT₁R=angiotensin II type 1 receptor; DRIs=direct renin inhibitors; RAAS=renin-angiotensin-aldosterone system; SARS-CoV-2= severe acute respiratory syndrome coronavirus-2.

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References

1. Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8:475–481. doi: 10.1016/S2213-2600(20)30079-5. - DOI - PMC - PubMed
1. Verdecchia P., Cavallini C., Spanevello A., Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14–20. doi: 10.1016/j.ejim.2020.04.037. - DOI - PMC - PubMed
1. Verdecchia, P., C. Cavallini, A. Spanevello, and F. Angeli, COVID-19: ACE2centric Infective Disease? Hypertension, 2020. 76: p. 294-299. 10.1161/HYPERTENSIONAHA.120.15353. - PubMed
1. Verdecchia P., Reboldi G., Cavallini C., Mazzotta G., Angeli F. [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus] G Ital Cardiol (Rome) 2020;21:321–327. doi: 10.1714/3343.33127. - DOI - PubMed
1. Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586–590. doi: 10.1007/s00134-020-05985-9. - DOI - PMC - PubMed

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[1] Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8:475–481. doi: 10.1016/S2213-2600(20)30079-5. - DOI - PMC - PubMed

[2] Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8:475–481. doi: 10.1016/S2213-2600(20)30079-5. - DOI - PMC - PubMed

[3] Verdecchia P., Cavallini C., Spanevello A., Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14–20. doi: 10.1016/j.ejim.2020.04.037. - DOI - PMC - PubMed

[4] Verdecchia P., Cavallini C., Spanevello A., Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14–20. doi: 10.1016/j.ejim.2020.04.037. - DOI - PMC - PubMed

[5] Verdecchia, P., C. Cavallini, A. Spanevello, and F. Angeli, COVID-19: ACE2centric Infective Disease? Hypertension, 2020. 76: p. 294-299. 10.1161/HYPERTENSIONAHA.120.15353. - PubMed

[6] Verdecchia, P., C. Cavallini, A. Spanevello, and F. Angeli, COVID-19: ACE2centric Infective Disease? Hypertension, 2020. 76: p. 294-299. 10.1161/HYPERTENSIONAHA.120.15353. - PubMed

[7] Verdecchia P., Reboldi G., Cavallini C., Mazzotta G., Angeli F. [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus] G Ital Cardiol (Rome) 2020;21:321–327. doi: 10.1714/3343.33127. - DOI - PubMed

[8] Verdecchia P., Reboldi G., Cavallini C., Mazzotta G., Angeli F. [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus] G Ital Cardiol (Rome) 2020;21:321–327. doi: 10.1714/3343.33127. - DOI - PubMed

[9] Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586–590. doi: 10.1007/s00134-020-05985-9. - DOI - PMC - PubMed

[10] Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586–590. doi: 10.1007/s00134-020-05985-9. - DOI - PMC - PubMed

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The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

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The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

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