What’s the connection between Covid-19 and hypokalemia?

The association of hypokalemia with hospitalized Covid-19 patients has been recognized since the early days of the pandemic, with more severe cases associated with lower concentration of serum potassium.1-4

A study involving 175 hospitalized patients with Covid-19 found low serum potassium in 54% of patients with 18% having severe hypokalemia (<3.0 mmol/L) and 37% having serum potassium 3.-3.5 mmol/L.  Compared to patients with mild to moderate Covid-19, those with severe or critical disease were more likely to have low serum potassium (3.5 mmol/L or less) (85% vs 45%).1

Another study involving 306 hospitalized patients with Covid-19, nearly a third (31%) had hypokalemia (3.5 mmol/L or less). Hypokalemia was associated with invasive mechanical ventilation, longer hospital and ICU stays.2 In contrast, a non-peer-reviewed MedRxive study found no association between hypokalemia and ICU admission or in-hospital mortality, possibly related to milder hypokalemia in the patients studied.3

Although various mechanisms may be invoked to explain hypokalemia in hospitalized Covid-19 patients (eg, poor intake, diuretics, corticosteroids, diarrhea, etc…), the most fascinating explanation may revolve around the direct impact of SARS-CoV-2 on the renin-angiotensin system.5  Because this virus uses the enzymatic receptor of ACE2 to penetrate the host cell, it can lead to downregulation of ACE2. Since ACE2 serves as a counterbalance to ACE by transforming a part of angiotensin I and II before they attach to angiotensin II type 1 receptor (AT1R), aldosterone effect is enhanced with resultant hypokalemia. High urinary excretion of potassium in many patients with Covid-19 seem to support the latter hypothesis.1,3  

Who would have predicted the versatility of this virus in causing hypokalemia in addition to all the other physiologic derangements it causes?  

Bonus Pearl: Did you know that there may be an association between lower prevalence of dry cough in patients with Covid-19 and hypokalemia, possibly related to low ACE2—therefore bradykinin— activity mediated by SARS-CoV-2? 2

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References

  1. Chen D, Li X, Song Q, et al. Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China. JAMA Network Open 2020;3(6):e2011122. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767008
  2. Moreno-Perez O, Leon-Ramirez JM, Fuertes-Kenneally L, et al. 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. International J Infect Dis 2020;100:449-54. https://www.ijidonline.com/article/S1201-9712(20)30749-9/pdf
  3. Gaetano A, Annachiara F, Francesco F, et al. Hypokalemia in patients with COVID-19. MedRxive preprint. Doi:https://doi.org/10.1101/2020.0614.20131169. https://www.medrxiv.org/content/10.1101/2020.06.14.20131169v2.full.pdf
  4. Lippi G, South Am, Henry BM. Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19). Ann Clin Biochem 2020;57:262-65. https://pubmed.ncbi.nlm.nih.gov/32266828/
  5. Silhol F, Sarlon G, Deharo JC, et al. Downregulation of ACE2 induces overstimulation of renin-angiotensin system in COVID-19: Should we block the renin-angiotensin system? Hypertension Research 2020;43:854-856. https://www.nature.com/articles/s41440-020-0476-3

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the connection between Covid-19 and hypokalemia?