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

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