Association between electrolyte supplementation and cardiac injury in long COVID-19

Abstract

Background

Cardiac injury is a common complication of long coronavirus disease 2019 (COVID-19), affecting heart function and quality of life. This study aimed to investigate the association between electrolyte supplementation and cardiac injury in long COVID-19.

Methods

This retrospective study was conducted at Guangdong Provincial People’s Hospital Zhuhai Hospital (Zhuhai Golden Bay Hospital), utilizing data from patients with cardiac injury related to long COVID-19 who were admitted and managed between January 2021 and January 2023. The patients were grouped according to electrolyte supplementation (supplementation group) or no supplementation (control group). The outcomes included heart rate variability (HRV) parameters, the Minnesota Heart Failure Quality of Life questionnaire, and numerical rating scale (NRS) assessments of quality of life.

Results

A total of 144 patients with cardiac injury related to long COVID-19 were included in the analysis (supplementation group, n=72; control group, n=72). After adjusting for age, sex, creatinine, total cholesterol, and low-density lipoprotein, multivariable linear regression analysis indicated a significant association between supplementation and increased levels of potassium [β=1.3, 95% confidence interval (CI): 1.1–1.5, P=0.001] and magnesium (β=0.18, 95% CI: 0.07–0.29, P=0.001), as well as improvements in HRV parameters, including standard deviation of normal-to-normal RR intervals over 24 hours, root mean square of successive differences, and high-frequency domain indices/low-frequency domain indices (all P<0.05). Additionally, supplementation correlated with a reduced frequency of premature contractions (β=−5.61, 95% CI: −7.50 to −3.72, P=0.01), lower Minnesota scores (β=−6.7, 95% CI: −9.1 to −4.3, P=0.001), and decreased NRS scores (β=−7.2, 95% CI: −6.5 to −7.9, P=0.02).

Conclusions

Electrolyte supplementation may be beneficial in managing cardiac injury associated with long COVID-19. Further research is needed to clarify the role of electrolytes in cardiac injury related to long COVID-19 and to explore management strategies that incorporate electrolyte supplementation.

Highlight box.

Key findings

• Electrolyte supplementation is significantly associated with potassium and magnesium levels improvement and cardiac function metrics enhancement in long coronavirus disease 2019 (COVID-19) patients with cardiac injury.

What is known and what is new?

• Cardiac injury is a common complication of long COVID-19, affecting heart function and quality of life.

• The study provides evidence that electrolyte supplementation may help improve heart rate variability and may reduce symptoms of cardiac injury in long COVID-19 patients.

What is the implication, and what should change now?

• Further research is necessary to establish guidelines on electrolyte management in long COVID-19 patients with cardiac complications and to implement supplementation strategies in clinical practice.

Introduction

Coronavirus disease 2019 (COVID-19) is predominantly recognized for its respiratory manifestations; however, accumulating evidence underscores its significant cardiovascular ramifications (1,2). Myocardial injury has been identified in patients with COVID-19, including individuals without pre-existing heart disease (3,4). This COVID-19-related myocardial injury has been linked to an elevated risk of mortality (5), with notably high mortality rates observed in patients with cardiovascular diseases (CVDs) concomitant with COVID-19 (6). A substantial cohort study utilizing data from the U.S. Department of Veterans Affairs (VA) in 2022 indicated a markedly higher incidence of cardiovascular disorders, arrhythmia, ischemic heart disease, and heart failure in the period ranging from 30 days to 12 months following COVID-19 infection (7). Emerging literature suggests that COVID-19 may induce enduring cardiovascular effects even post-recovery, a phenomenon often referred to as cardiac injury in long COVID-19 (8-10). Magnetic resonance imaging (MRI) studies have revealed persistent myocardial inflammation and endothelial dysfunction in certain recovered patients (11-13). Nonetheless, the detection of positive organic cardiac findings in individuals with cardiac injury in long COVID-19 can prove challenging (14,15). It has been posited that the symptoms associated with cardiac injury in long COVID-19 may be linked to autonomic nervous system (ANS) dysfunction and autonomic instability (16). Consequently, addressing ANS dysfunction may represent a viable therapeutic strategy for managing long COVID-19 (17,18).

Electrolyte imbalances have been identified as prognostic factors associated with adverse outcomes in patients afflicted with COVID-19 (19,20). Although COVID-19 can induce acute electrolyte disturbances through various pathophysiological mechanisms, the delayed or exacerbated effects of these abnormalities remain inadequately understood (21). Electrolytes, such as potassium and magnesium, play critical roles in electrical conduction and myocardial contraction; variations in these electrolyte levels can influence cardiac autonomic function in both healthy individuals and patients with diverse clinical conditions (22). Maintaining appropriate electrolyte levels is recognized as a method to enhance cardiac autonomic function (23,24).

However, the relationships between cardiac autonomic function and cardiac injury in long COVID-19 are complex (25). The implications of electrolyte imbalance in the context of cardiac injury in long COVID-19, along with the potential advantages of sustaining electrolyte balance through supplementation, warrant further investigation (26).

Thus, the objective of this study was to investigate the association between electrolyte supplementation and cardiac injury in long COVID-19. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-689/rc).

Methods

Study design and patients

This retrospective study was conducted at Guangdong Provincial People’s Hospital Zhuhai Hospital (Zhuhai Golden Bay Hospital), utilizing data from patients admitted and managed between January 2021 and January 2023. According to the World Health Organization (WHO)-led Delphi consensus, long COVID is defined as a complex cluster of symptoms that emerges at least three months after COVID-19 onset, persists for over two months, and cannot be attributed to an alternative diagnosis (27). Cardiac injury related to COVID-19 is characterized by chest discomfort, including chest pain, shortness of breath, chest pressure, and other unexplained sensations, occurring three months after the onset of COVID-19 and lasting for more than two months. We also referenced the COLHEART-19 study investigating COVID-19-related cardiac injury and further refined the manifestations of cardiac involvement, including elevation in troponin, ventricular arrhythmias, ischemic electrocardiogram (ECG) changes, elevation in BNP or N-terminal (NT)-pro-BNP, decrease in EF based on echocardiography, to enhance the identification of patients with organic cardiac injury requiring targeted therapy (28). This approach improves the representativeness of the study population and increases the statistical power of the research.

The inclusion criteria for the study were as follows: (I) with chest discomfort (chest pain, shortness of breath, chest pressure, and other unexplained sensations) occurring three months after the onset of COVID-19 and lasting for more than two months; (II) aged 18 or older; and (III) having complete medical records available before and 14 days after treatment, which included heart rate variability (HRV) parameters, the Minnesota Heart Failure Quality of Life questionnaire, and numerical rating scale (NRS) assessments of quality of life.

The exclusion criteria included: (I) evidence of cardiac injury or heart failure [elevation in troponin, ventricular arrhythmias, ischemic ECG changes, elevation in BNP or NT-pro-BNP, decrease in EF based on echocardiography or New York Heart Association (NYHA) stage II–IV]; (II) renal insufficiency [glomerular filtration rate (GFR) <90 mL/min]; (III) hyperlipidemia, hyperglycemia, hyperuricemia, ongoing lung inflammation, ischemic heart disease (acute coronary syndrome within 30 days before the index admission or a positive treadmill exercise test during screening), anemia (hemoglobin <90 g/L), hypotension (blood pressure <90/60 mmHg), or hypertension (blood pressure >140/90 mmHg); or (IV) incomplete clinical data.

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, standard practice, and internationally recognized standards for research practice and reporting. The study was approved by the Ethics Committee of Guangdong Provincial People’s Hospital Zhuhai Hospital (Zhuhai Golden Bay Hospital) (No. 2024101H). All participants were informed about the study protocol and provided written informed consent to participate in the study.

In this retrospective study, the patients who received both lifestyle advice and potassium and magnesium supplementation during the study period were included in the supplementation group. The patients who received only lifestyle advice were included as controls. The patients received supplementation based on their attending physician’s clinical judgment.

Data collection

The following data were obtained from the electronic medical record system: Holter electrocardiogram, treadmill exercise test, echocardiogram, chest computed tomography (CT), and blood tests encompassing routine blood examination, fasting blood glucose (FBG), lipid profile, BNP or NT-pro-BNP, liver function, and renal function analysis, Hamilton Anxiety Scale (HAS), Hamilton Depression Scale (HDS), Minnesota Heart Failure Score, and NRS for symptoms. The syndrome and quality of life were assessed using the Minnesota Heart Failure Quality of Life questionnaire (29). All data were collected from the evaluations conducted at admission and 14 days later.

The data from Holter electrocardiogram and electrolyte measurements before and after treatment were extracted from the patient charts. All HRV parameters were calculated a posteriori using the Holter data in the patient charts: RR intervals, standard deviation of normal-to-normal RR intervals over 24 hours (SDNN), mean standard deviation of RR intervals over 5-minute periods (SDNN index), root mean square of successive differences (rMSSD), percentage of differences between adjacent normal RR intervals exceeding 50 milliseconds (pNN50), low-frequency (LF) band, high-frequency (HF) band, and the LF/HF ratio. Arrhythmias, including premature contractions, atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, and second-degree or higher atrioventricular block were also identified. Frequent premature contractions were defined as constituting 10% of total contractions.

Outcomes

Primary outcomes assessed included HRV parameters and scores from the Minnesota Heart Failure Quality of Life Questionnaire. Secondary outcomes comprised evaluations using the NRS and serum electrolyte levels (potassium and magnesium).

Statistical analysis

Statistical analysis was performed using SPSS 23 (IBM Corp, Armonk, NY, USA). The continuous variables were tested for normal distribution. Normally distributed variables were presented as mean ± standard deviation (SD) and analyzed using Student’s t-test (intergroup comparison) and the paired t-test (before/after intragroup comparisons). Non-normally distributed variables were presented as medians (P25–P75) and analyzed using the Mann-Whitney U-test (intergroup comparison) and the paired samples Wilcoxon test (before/after intragroup comparisons). The categorical variables were presented using n (%) and analyzed using the chi-squared test.

A multivariable linear regression analysis was conducted to evaluate the effects of electrolyte supplementation on cardiac injury, while adjusting for variables including age, sex, creatinine levels, total cholesterol, and low-density lipoprotein. To further evaluate the potential impact of electrolyte supplementation treatment under the interference of additional confounding factors, an additional factorial analysis incorporating more confounding variables (ethnicity, education level, smoking status, alcohol consumption, C-reactive protein, baseline nutritional status including body mass index (BMI), waist circumference, body fat percentage, albumin levels, and homocysteine) was conducted. Two-sided P values <0.05 were considered statistically significant.

Results

Characteristics of the patients

The study included 144 patients experiencing cardiac injury in long COVID-19 (Figure S1). Continuous quantitative data are expressed as mean ± standard deviation (SD), while categorical data are presented as percentages. The admission data showed no significant differences between the two groups (all P>0.05) (Table 1). The time from COVID-19 diagnosis to the onset of cardiac long COVID-19 symptoms, the duration of cardiac injury in long COVID-19, and the time from COVID-19 diagnosis to electrolyte treatment also showed no significant differences between the two groups (Table 1, Figure 1) (all P>0.05).

Table 1. Characteristics of the patients.

Characteristics	All (n=144)	Supplementation (n=72)	Control (n=72)	P
Age (years)	52.6±8.2	51.3±7.9	53.9±8.6	0.23
Sex (male)	58 (40.3)	27 (37.5)	31 (43.1)	0.61
Heart rate (bpm)	85±23	82±16	86±24	0.17
SBP (mmHg)	109±27	110±21	105±24	0.34
DBP (mmHg)	68±15	71±17	67±16	0.32
BMI (kg/m2)	24.6±3.4	24.3±2.8	25.0±4.1	0.11
Current smoker	17 (11.8)	10 (13.9)	7 (9.7)	0.61
Cr (µmol/L)	83.9±16.2	78.1±12.9	84.8±13.4	0.15
LDL-C (mmol/L)	2.80±0.7	3.11±0.9	2.73±1.1	0.25
Uric acid (µmol/L)	292±58	315±81	279±67	0.08
Hemoglobin (g/L)	137±17	132±22	141±13	0.56
FBG (mmol/L)	5.1±0.8	4.8±1.4	5.2±0.9	0.92
TC (mmol/L)	4.52±0.6	4.71±0.7	4.42±1.3	0.14
EF (%)	62±13	64±15	58±9	0.25
COVID-19 to long COVID-19 (months)	3.6±0.2	3.5±0.4	3.8±0.3	0.74
Duration of long COVID-19 (months)	2.8±0.1	2.9±0.2	2.7±0.1	0.85

Continuous variables are expressed as mean ± standard deviation, and categorical data are presented as n (%). BMI, body mass index; COVID-19, coronavirus disease 2019; Cr, creatinine; DBP, diastolic blood pressure; EF, ejection fraction; FBG, fasting blood glucose; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TC, total cholesterol.

Figure 1.

The time from COVID-19 infection to the onset of long COVID-19 syndrome, and the duration of long COVID-19 between two groups. COVID-19, coronavirus disease 2019.

Electrolyte characteristics are detailed in Table 2. The initial levels of potassium and magnesium and the rate of electrolyte imbalances were comparable between the two groups. At 14 days after admission, the potassium levels (4.86±0.23 vs. 3.73±0.27 mmol/L, P=0.001) and magnesium (0.92±0.09 vs. 0.83±0.10 mmol/L, P=0.04) levels were higher in the supplementation group compared with the control group, though the rates of electrolyte imbalances remained similar. No patients with hyperkalemia or hypermagnesemia were observed. The initial Minnesota questionnaire and NRS scores showed no significant differences between the two groups (all P>0.05). At 14 days after admission, the Minnesota questionnaire scores (24±15 vs. 72±9, P<0.001) and NRS scores (2.65±1.54 vs. 7.82±1.32, P<0.001) were significantly lower in the supplementation group than in the control group (Table 2).

Table 2. Electrolyte and syndrome evaluation characteristics.

Variables	All (n=144)	Supplementation (n=72)	Control (n=72)	P
Initial potassium (mmol/L)	3.62±0.25	3.58±0.31	3.65±0.72	0.30
Initial hypokalemia	33 (22.9)	18 (25.0)	15 (20.8)	0.69
Final potassium (mmol/L)	4.15±0.14	4.86±0.23	3.73±0.27	0.001
Final hypokalemia	7 (4.9)	0 (0.0)	7 (9.7)	0.007
Initial magnesium (mmol/L)	0.73±0.08	0.71±0.10	0.77±0.12	0.25
Initial hypomagnesemia	5 (3.5)	3 (4.2)	2 (2.8)	>0.99
Final magnesium (mmol/L)	0.86±0.08	0.92±0.09	0.83±0.10	0.04
Final hypomagnesemia	0 (0.0)	0 (0.0)	0 (0.0)	>0.99
Initial Minnesota questionnaire	90±7	91±9	89±6	0.36
Final Minnesota questionnaire	60±28	24±15	72±9	<0.001
Initial NRS	10	10	10	>0.99
Final NRS	6.13±2.97	2.65±1.54	7.82±1.32	<0.001

Continuous variables are expressed as mean ± standard deviation, and categorical data are presented as n (%). NRS, numerical rating scale.

HRV characteristics

The initial HRV parameters were comparable between the two groups (all P>0.05). At 14 days after admission, the SDNN (154±21 vs. 117±45 ms, P=0.02), rMSSD (52±9 vs. 39±13 ms, P=0.01), and LF/HF (3.38±1.09 vs. 2.25±1.43, P=0.01) were higher in the supplementation group than in the control group, while premature contraction (152±87 vs. 861±298, P=0.001) and HF (206±131 vs. 314±159 ms², P=0.01) were lower (Table S1). In the supplementation group, after 14 days and compared with the admission values, SDNN was higher (113±39 vs. 154±21 ms, P=0.01), premature contraction number was lower (1,145±139 vs. 152±87, P=0.02), and LF/HF was higher (2.04±1.10 vs. 3.38±1.09, P=0.03) (Table S2).

Regression analysis

The univariable and multivariable linear regression analysis results are presented in Table 3. Electrolyte supplementation was independently associated with higher potassium [β=1.3, 95% confidence interval (CI): 1.1 to 1.5, P=0.001], magnesium (β=0.18, 95% CI: 0.07 to 0.29, P=0.001), SDNN (β=36, 95% CI: 31 to 41, P=0.02), rMSSD (β=10, 95% CI: 8 to 12, P=0.03), and LF/HF (β=1.07, 95% CI: 0.83 to 1.29, P=0.04), lower HF (β=−97, 95% CI: −132 to −76, P=0.01) and premature contractions (β=−5.61, 95% CI: −7.50 to −3.72, P=0.01), and improved Minnesota Heart Failure questionnaire (β=−6.7, 95% CI: −9.1 to −4.3, P=0.001) and NRS (β=−7.2, 95% CI: −6.5 to −7.9, P=0.02) scores. Factorial analysis is presented in Table S3. Electrolyte supplementation was still associated with improvement of HRV and syndrome indicators whereas none of the confounding factors (ethnicity, education level, smoking status, alcohol consumption, C-reactive protein, baseline nutritional status including BMI, waist circumference, body fat percentage, albumin levels, and homocysteine) exerted a statistically significant influence.

Table 3. Regression analysis of electrolyte replacement therapy.

Variables	Univariable analysis				Multivariable analysis
	β	95% CI	P		β	95% CI	P
Final serum potassium (mmol/L)	1.4	1.1 to 1.7	0.001		1.3	1.1 to 1.5	0.001
Final serum magnesium (mmol/L)	0.19	0.14 to 0.23	0.02		0.18	0.07 to 0.29	0.001
Final SDNN (ms)	23	12 to 29	0.04		36	31 to 41	0.02
Final rMSSD (ms)	17	−16 to 28	0.14		10	8 to 12	0.03
Final pNN50 (%)	13	−7 to 21	0.56		5	−7 to 11	0.09
Final LF (ms2)	−175	−213 to −132	0.04		−89	−105 to 34	0.46
Final HF (ms2)	−86	−115 to −54	0.02		−97	−132 to −76	0.01
Final LF/HF	0.61	0.32 to 0.94	0.02		1.07	0.83 to 1.29	0.04
Final premature contraction (per 100 contractions)	−321	−392 to −213	0.02		−5.61	−7.50 to −3.72	0.01
Final Minnesota questionnaire (per 10 points)	−42	−71 to −28	0.03		−6.7	−9.1 to −4.3	0.001
Final NRS (per point)	−4.8	−5.9 to −2.6	0.03		−7.2	−6.5 to −7.9	0.02

Multivariable linear regression analysis adjusted for age, sex, creatinine, total cholesterol, and low-density lipoprotein. CI, confidence interval; HF, high-frequency domain indices of HRV; HRV, heart rate variability; LF, low-frequency domain indices of HRV; NRS, numerical rating scale; pNN50, percentage of differences between adjacent normal RR intervals exceeding 50 milliseconds; rMSSD, root mean square of successive differences; SDNN, standard deviation of normal-to-normal RR intervals over 24 hours.

Discussion

The results showed that after 14 days of supplementation, the supplementation group showed higher serum potassium and magnesium levels, improved HRV parameters, fewer premature beats, lower Minnesota questionnaire scores, and lower NRS than the control group. The multivariable linear regression analysis supported the changes observed with electrolyte supplementation. These results provide clues for improving the management of patients with cardiac injury related to long COVID-19.

The present study showed that potassium and magnesium supplementation were associated with more beneficial cardiac parameters in patients with cardiac injury in long COVID-19. Although the exact mechanisms for the benefits could not be determined in the present study due to its retrospective design, some working hypotheses could be formulated for later mechanistic studies. Indeed, potassium and magnesium are vital electrolytes involved in the heart’s electrical conduction and muscle contraction. Adequate potassium intake may help regulate blood pressure, particularly in high-risk cardiac patients (30), and hypokalemia can elevate the risk of fatal arrhythmias and worsen heart failure (31). Magnesium is essential for maintaining electrolyte balance, cardiac rhythm, and vascular tone. Hypomagnesemia is associated with hypertension, arrhythmias, and endothelial dysfunction (32). Magnesium supplementation can reduce inflammatory markers (33). A meta-analysis revealed that higher magnesium intake reduces the risk of stroke, coronary artery disease, and arrhythmias, with a recommended daily intake of 310–420 mg, and that higher intake may benefit patients with CVDs (34). Hence, potassium and magnesium are vital for maintaining normal cardiac electrophysiology and contractility and supplementing potassium and magnesium in patients with cardiac injury in long-COVID-19 could explain, at least in part, the more optimal HRV parameters observed in the supplementation group. COVID-19 is associated with significant electrolyte imbalances that correlate with prognosis (19,20,35). In the present study, potassium and magnesium supplementation resulted in higher serum potassium and magnesium levels than controls, but without significant differences in the rates of hypokalemia and hypomagnesemia. Whether the electrolyte imbalance is associated or has a causality relationship with cardiac injury in long COVID-19 remains to be determined. Although evidence suggests that confounding factors such as nutritional status may influence COVID-19 patient outcomes (36,37), the factorial analysis still indicates that these confounding factors exhibit no significant impact on HRV parameters, while the efficacy of electrolyte supplement remains unaffected. This phenomenon may be attributed to the stringent exclusion criteria, whereby high-risk patients with cardiac injury or pathophysiological conditions (e.g., hyperlipidemia, hypertension, anemia, renal disease) were systematically excluded. The analyzed cohort exclusively comprised patients whose conditions could not be definitively diagnosed through conventional modalities which represents a focal point in long COVID-19 management. By specifically screening patients, we aimed to identify effective therapy. This factorial analysis further substantiates the clinical feasibility and potential value of electrolyte supplement for long COVID-19.

It has been suggested that cardiac injury in long COVID-19 could be associated with autonomic dysfunction (16,38). The alterations in HRV parameters observed in patients with long COVID-19 could help identify autonomic function abnormalities. HRV is a noninvasive, objective, and validated measure for evaluating cardiovascular ANS function (8). HRV is also considered an index for clinical conditions related to ANS dysfunction (9,10). A lower HRV is associated with autonomic dysfunction, increasing the risk of cardiovascular events, including arrhythmias, in patients with long COVID (39). One cohort study analyzed the HRV parameters in patients with previous COVID and found that SDNN and rMSSD were significantly lower in the study group than in the control group, indicating impaired resting parasympathetic activity (40). Another study also found significant decreases in most HRV parameters, including SDNN, rMSSD, LF, and HF, after COVID-19 (41). Still, some conflicting conclusions can be observed. Asarcikli et al. (38) found that patients with long COVID had significantly higher SDNN and rMSSD than age- and sex-matched healthy controls, possibly explaining unresolved orthostatic symptoms. Heterogeneity in study populations, timing of HRV assessments, and methodologies probably explain the discrepancies among studies.

HF reflects parasympathetic activity, while LF reflects sympathetic activity. The LF/HF ratio indicates the balance between the sympathetic and parasympathetic systems (38). This present study strongly suggests that electrolyte supplementation might be associated with HRV parameters improvement (higher SDNN, lower HF, and higher LF/HF ratio), fewer premature beats, and fewer syndrome complaints, supported by the multivariable linear regression analysis. Nevertheless, the association of electrolyte levels with HRV is inconsistent in the literature. Indeed, an experimental study of induced hypokalemia in healthy adults observed reduced HRV parameters, such as SDNN and rMSSD, but no correlations were observed between serum potassium levels and HRV (42). Similarly, another study found that hypomagnesemia in diabetic patients decreased the HRV parameters, but no direct correlations with serum magnesium were observed (43). A study in patients with cardiomyopathy found that those with hypomagnesemia had significantly lower HRV than those with normal magnesium levels (44). Although the link between electrolyte depletion and HRV is not fully understood, it underscores the importance of electrolyte homeostasis in modulating cardiac autonomic function and electrophysiological stability. Further research must clarify the relationship between electrolytes and cardiac autonomic function.

Elevated urinary potassium excretion is reported as the primary cause of hypokalemia in COVID-19 (45). Angiotensin-converting enzyme 2 (ACE2) inhibits the function of ACE in transforming angiotensin I into angiotensin II, stimulating aldosterone release and enhancing urinary potassium excretion (46). In patients with COVID-19, the downregulation of ACE2 due to coronavirus binding leads to over-activated ACE, resulting in increased aldosterone production and subsequent potassium wasting via urine. Approximately half of the hypokalemic patients also exhibit magnesium deficiency (47). Depleted magnesium levels can exacerbate hypokalemia by impairing Na-K ATPase pump function and increasing urinary potassium loss through ROMK channels (48). Additional contributing factors include diarrhea, vomiting, anorexia, alkalosis, acidosis, corticosteroids, and antiviral drugs. Consequently, the pathophysiology of COVID-19-induced electrolyte disturbances supports the present study. Data on the final impact of electrolyte and autonomic disturbances manifesting as syndromes are worthy of study and remain contentious. Patients with chronic fatigue syndrome (CFS) exhibit increased LF, lower HF, higher LF/HF, and lower SDNN (49), supporting the present study.

Patients with COVID-19 display dynamic changes in T wave morphology, suggesting altered potassium channel function during infection and demonstrating COVID-19-induced electrical instability (50). In addition, COVID-19 directly inhibits human ether-a-go-go-related gene (hERG) channels in cell models expressing hERG channels, with viral proteins potentially interfering with channel trafficking or function through direct binding, contributing to COVID-19-induced QT prolongation (51). Electrolyte supplement therapy directly increases serum electrolyte levels and gradually raises intracellular electrolyte levels (52), improving HRV and syndrome parameters observed in the present study.

The current study exhibited several limitations that could influence the results. First, this study represents a single-center experience with a limited population. Zhuhai City presents complex demographics because of the large proportion of immigrants from all over China, potentially introducing bias due to differences in genetics and lifestyle habits. The generalizability of the findings requires further validation. Second, the study was retrospective and observational. The variables were limited to the data available in the patient charts. The exact lifestyle habits and whether the supplementation led to changes in lifestyle habits could not be assessed from the available data. Future prospective studies are necessary to confirm the results observed here.

Conclusions

The present retrospective analysis, grounded in HRV assessment and syndrome questionnaires, indicates that electrolyte supplementation may be a viable intervention for managing cardiac injury in long COVID-19. Disturbances in intracellular electrolyte levels could represent a potential mechanism contributing to the manifestations of cardiac injury in long COVID-19. Further confirmatory research involving larger patient cohorts is essential to assess the role of electrolytes in cardiac injury related to long COVID-19 and to facilitate the development of novel therapeutic approaches for this condition.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Research Ethics Committee of Guangdong Provincial People’s Hospital Zhuhai Hospital (Zhuhai Golden Bay Hospital) (No. 2024101H). All participants were informed about the study protocol and provided written informed consent to participate in the study.

Data Sharing Statement

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DOI: 10.21037/jtd-2025-689