The currently spreading COVID-19 pandemic has been found to present in various ways, often with respiratory symptoms, but also with significant gut symptoms, skin symptoms, and in critical illness, multi-organ dysfunction may occur. Now a new study by an Italian team of researchers published in June 2020 on the preprint server medRxiv* reports that potassium levels are often low in COVID-19 disease, mostly due to the urinary loss of potassium.
The incidence of severe or critical COVID-19 is known to be higher among older patients and those with underlying medical conditions, including diabetes, cardiovascular disease, and obesity. These patients often need to remain in hospital for supportive medical care for weeks, with various needs ranging from mechanical ventilation to cytokine inhibitors to reduce hyperactive inflammation.
Hypokalemia is Common in COVID-19
Both the protean manifestations of sickness, as well as the side effects of the medications used can cause electrolyte imbalance. Accordingly, the current study shows that hypokalemia, or low potassium levels in the blood, occurs quite commonly. This is a concerning issue since, below a certain threshold, low potassium levels can lead to abnormalities of the heart rhythm, sometimes fatal.
The exact reasons for the development of hypokalemia are not clear, but several have been proposed. These include activation of the renin-angiotensin system, loss of potassium through the gut, loss of appetite and poor diet due to the infection, and kidney damage, perhaps due to direct viral cytotoxicity on tubular cells.
The current study focused on describing the incidence, impact, and mechanism of causation of hypokalemia on hospitalized COVID-19 patients. There were 1,671 blood samples, collected from 290 patients. Among these, 171 had normal potassium levels and were selected to be a control group.
Low potassium was present in 119 patients, accounting for 41% of the sample. The serum potassium levels ranged from 2.4 mEq/l to 3.5 mEq/l with a mean of 3.1 mEq/l. Most patients in this group had mild hypokalemia (about 91%), occurring along with hypocalcemia, and lower average magnesium levels.
Clinical Characteristics of Hypokalemic Patients
This group of patients also required a more extended period of follow-up, probably because the disease took a more severe form. In less than 40%, the urine potassium-to-creatinine ratio was measured and found to be over 1.5 mEq/mmol in over 95% of them. This indicates a high potassium excretion in urine.
Half of these 45 patients were on diuretics, and a quarter on steroids when potassium in serum was measured. Of the remaining quarter, 90% had low sodium excretion, while all of them had normal serum magnesium levels. Most of them were in metabolic alkalosis, with the remaining 30% equally distributed among respiratory alkalosis, respiratory acidosis, and normal acid-base balance.
Treatment of Hypokalemia
Hypokalemia was corrected using potassium salts orally in a quarter of patients and intravenously in 6%, with both being used in one patient. Magnesium deficiency was corrected with intravenous magnesium sulfate. Notably, frusemide was in use among 38% of patients at the time of hypokalemia, perhaps because of hypertension, cardiovascular disease, and/or poor renal function.
Risk Factors for Hypokalemia
The three factors most closely related to the occurrence of hypokalemia were the female sex, the use of diuretics, and corticosteroid therapy. Being female increased the risk by 244%, while diuretics were correlated with a 194% increase. Females are known to have less interchangeable potassium stores in their bodies, especially as they age, which puts them at higher risk for hypokalemia following diuretic use.
Explanations and Implications of Hypokalemia
However, hypokalemia was not associated with either severe disease or death during hospitalization. This may be explained by the mostly mild level of hypokalemia, induced by factors such as reduced intake of food, medication-induced diarrhea, viral injury to the gut, and the use of diuretics and corticosteroids.
Despite the very low incidence of moderate or severe hypokalemia, which can cause cardiac rhythm abnormalities, paralysis, and rhabdomyolysis, the study indicates the need to monitor this group of patients for arrhythmias, especially when drugs like hydroxychloroquine and azithromycin are used off-label to treat COVID-19. These medications are known to reduce the rate of cardiac conduction.
Does COVID-19 by itself cause urinary potassium loss? The viral has been found in urine samples from patients with severe COVID-19 and may possibly cause acute kidney injury, causing abnormal potassium handling. Another explanation is that the renin-angiotensin system is abnormally activated by the loss of ACE2 function in disrupted cells. However, more data on the levels of renin and aldosterone are required to support this hypothesis, despite the findings of metabolic alkalosis and low sodium excretion.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.