How SARS-CoV-2 might affect potassium balance via impairing epithelial sodium channels?

Maryam Noori, Seyed Aria Nejadghaderi, Mark J.M. Sullman, Kristin Carson-Chahhoud, Mohammadreza Ardalan, Ali Asghar Kolahi, Saeid Safiri

Research output: Contribution to journalReview articlepeer-review


Severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) is the causative agent of current coronavirus disease 2019 (COVID-19) pandemic. Electrolyte disorders particularly potassium abnormalities have been repeatedly reported as common clinical manifestations of COVID-19. Here, we discuss how SARS-CoV-2 may affect potassium balance by impairing the activity of epithelial sodium channels (ENaC). The first hypothesis could justify the incidence of hypokalemia. SARS-CoV-2 cell entry through angiotensin-converting enzyme 2 (ACE2) may enhance the activity of renin–angiotensin–aldosterone system (RAAS) classical axis and further leading to over production of aldosterone. Aldosterone is capable of enhancing the activity of ENaC and resulting in potassium loss from epithelial cells. However, type II transmembrane serine protease (TMPRSS2) is able to inhibit the ENaC, but it is utilized in the case of SARS-CoV-2 cell entry, therefore the ENaC remains activated. The second hypothesis describe the incidence of hyperkalemia based on the key role of furin. Furin is necessary for cleaving both SARS-CoV-2 spike protein and ENaC subunits. While the furin is hijacked by the virus, the decreased activity of ENaC would be expected, which causes retention of potassium ions and hyperkalemia. Given that the occurrence of hypokalemia is higher than hyperkalemia in COVID-19 patients, the first hypothesis may have greater impact on potassium levels. Further investigations are warranted to determine the exact role of ENaC in SARS-CoV-2 pathogenesis.

Original languageEnglish
JournalMolecular Biology Reports
Publication statusAccepted/In press - 2021


  • 2019-nCoV
  • COVID-19
  • Electrolytes
  • ENaC
  • Epithelial sodium channels
  • Hyperkalemia
  • Hypokalemia
  • SARS-CoV-2
  • Serum potassium


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