Lack of Evidence for a Role of ACE-2 Polymorphisms as a Bedside Clinical Prognostic Marker of COVID-19

Viruses. 2023 Jun 27;15(7):1448. doi: 10.3390/v15071448.


The novel SARS-CoV-2 coronavirus causes a severe respiratory syndrome referred to as coronavirus disease (COVID-19). The angiotensin-converting enzyme 2 (ACE-2) plays an important role as a cellular receptor for SARS-CoV-2 and is largely expressed in lungs, kidneys, heart and the gastrointestinal tract along with being shed in plasma. The ACE-2 gene and protein show a high level of genetic polymorphism, including simple nucleotide variation, transcriptional variation, post-transcriptional changes, and putative protein mutations that could interfere with the binding or entry of SARS-CoV-2 and affect tissue damage in lungs or other organs. Genetic polymorphisms can impact SARS-CoV-2 viral entry and COVID-19 severity. This single-center study evaluated the possible role of the main ACE-2 polymorphisms (rs143936283, rs2285666, rs41303171, rs35803318, and rs2106809) as potential prognostic markers in SARS-CoV-2-infected individuals. Frozen whole blood was used for DNA isolation and genomic DNA samples were sheared using the Covaris LE220 Focused-ultrasonicator for targeting a peak size of 410 bp. Whole-genome sequencing libraries were generated from fragmented DNA using the Illumina TruSeq DNA PCR-Free HT Library Preparation Kit and sequenced on an Illumina NovaSeq 6000. We did not identify any correlation between ACE-2 polymorphisms and COVID-19 prognosis, suggesting that the interpretation and clinical use of ACE-2 genetic polymorphisms in real-world clinical settings requires further experimental and clinical validation.

Keywords: angiotensin-converting enzyme 2 (ACE-2); respiratory distress syndrome (ARDS); severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); single nucleotide polymorphism (SNP).

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Biomarkers
  • COVID-19* / diagnosis
  • COVID-19* / genetics
  • Humans
  • Polymorphism, Genetic
  • Prognosis
  • SARS-CoV-2* / genetics


  • Angiotensin-Converting Enzyme 2
  • Biomarkers
  • ACE2 protein, human

Grants and funding

This study was supported in part by the Intramural Research Program of NIAID/NIH. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.