Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness

Abstract

BACKGROUND: While electrolyte abnormalities are common among patients with COVID-19, very little has been reported on magnesium homeostasis in these patients. Here we report the incidence of hypermagnesemia and its association with outcomes among patients admitted with COVID-19. METHODS: We retrospectively identified all patients with a positive test result for SARS-CoV-2 who were admitted to a large quaternary care center in New York City in spring 2020. Details of the patients' demographics and hospital course were obtained retrospectively from the medical record. Patients were defined as having hypermagnesemia if their median magnesium over the course of their hospitalization was >2.4 mg/dL. RESULTS: A total of 1685 patients hospitalized with COVID-19 had magnesium levels checked during their hospitalization and were included in the final study cohort, among whom 355 (21%) had hypermagnesemia. Hypermagnesemic patients had a higher incidence of shock requiring pressors (35 vs 27%, p<0.01), respiratory failure requiring mechanical ventilation (28 vs 21%, p=0.01), acute kidney injury (65 vs 50%, p<0.001), and acute kidney injury severe enough to require renal replacement therapy (18 vs. 5%, p<0.001). In an adjusted multivariable model, hypermagnesemia was observed more commonly with increasing age, male sex, AKI requiring RRT, hyperkalemia, and higher CPK. Survival probability at 30 days was 34% for the patients with hypermagnesemia compared to 65% for patients without hypermagnesemia. An adjusted multivariable time to event analysis identified an increased risk of mortality with older age, need for vasopressors, higher C-reactive protein levels, and hypermagnesemia (HR 2.03, 95% CI 1.63-2.54, p<0.001). CONCLUSIONS: In conclusion, we identified an association between hypermagnesemia among patients hospitalized with COVID-19 and increased mortality. While the exact mechanism of this relationship remains unclear, hypermagnesemia potentially represents increased cell turnover and higher severity of illness which is frequently associated with more severe forms of AKI.

Pathophysiological metabolic changes associated with disease modify the proarrhythmic risk profile of drugs with potential to prolong repolarisation

“…T A B L E 2 Frequency of observed cessation of beating/loss of capture on MEA in response to either 10-μM hydroxychloroquine alone or in combination with 5-μM azithromycin The potency of compounds that block hERG is sensitive to a variety of pathophysiological states including temperature, electrolyte concentrations and pH (Barrows et al, 2009;Du et al, 2011;Po et al, 1999;Windley et al, 2016). Of relevance to COVID-19, febrile temperature is reported in >90% of hospitalised cases (Pan et al, 2020;Zhou et al, 2020), hypokalaemia in $40% of patients (Lippi et al, 2020), hypermagnesaemia in 21% (Stevens et al, 2021) and acidosis in 9% of cases and 30% of non-survivors (Zhou et al, 2020). There is also evidence that COVID-19 patients treated with hydroxychloroquine/chloroquine show more severe QTc prolongation than healthy individuals (Chorin et al, 2020), and those patients with acute renal failure exhibited the most extreme effects.…”

Metabolic and electrolyte abnormalities as risk factors in drug-induced long QT syndrome

“…The importance of such considerations has been highlighted recently in relation to repurposing of drugs for treatment of COVID-19. Specifically, various combinations of drugs that are known to carry some degree of proarrhythmic risk, including chloroquine, hydroxychloroquine, azithromycin, erythromycin and lopinavir/ritanavir, have been proposed as potential therapies (Delaunois et al 2021 ; Zequn et al 2021 ) in COVID-19 patients where fever (Aslam et al 2021 ; Pan et al 2020 ; Zhou et al 2020 ), acidosis (Zhou et al 2020 ) and electrolyte disturbances (Alfano et al 2021 ; Lippi et al 2020 ; Stevens et al 2021 ) were also reported. Here, we will review both the clinical occurrence of diLQTS in the context of fever, hypokalaemia, hypomagnesemia and other electrolyte disturbances and the mechanisms by which these factors contribute to altered potency of hERG block and proarrhythmic risk.…”

The Impact of COVID-19 in Bone Metabolism: Basic and Clinical Aspects

“…In contrast, in a cohort of 280 patients with renal failure hospitalized for COVID-19, hypophosphatemia was associated with lower mortality [36]. Both hyper-and hypo-magnesemia have been reported in patients suffering from COVID-19, and both disorders have been associated with adverse outcomes [37,38]. 4…”