This study was a retrospective analysis of RSV-positive patients aged <12 months who were admitted with respiratory symptoms within 7 days of onset at Jeonbuk National University Children’s Hospital (JNUH) over 4 years (January 2016 to December 2019). This study was approved by the Institutional Review Board of JNUH (IRB No. 2020-03-043). All the patients were confirmed to have RSV infection on the basis of a nasopharyngeal swab using a respiratory polymerase chain reaction (PCR) panel, which included RSV, influenza virus, parainfluenza virus, coronavirus, rhinovirus, adenovirus, human metapneumovirus, bocavirus, and enterovirus. Any patients who tested positive for a virus other than RSV were excluded from the study. Patients whose laboratory results were missing or showed hemolysis were also excluded. Patients who had taken any form of diuretics or steroids that could affect the serum sodium level or had underlying diseases such as brain damage, heart anomaly, renal disease, or thyroid disease were also excluded from the study.

Each patient’s demographic factors, clinical findings, and laboratory results were collected by reviewing admission and progression notes through the electronic medical record system. The demographic factors included age, sex, gestational age, and birth weight. The complete blood count, liver function test results, and levels of serum electrolytes, blood urea nitrogen (BUN), creatinine, glucose, and C-reactive protein (CRP) at admission were reviewed. Hyponatremia was defined as a serum sodium concentration of <136 mmol/L, and each patient was categorized as having RSV infection either with or without hyponatremia [6]. In addition, patients with serum sodium concentrations between 125 and 129 mmol/L were classified as having moderate hyponatremia, and those with concentrations <125 mmol/L were classified as having severe hyponatremia according to the United States guidelines [7]. Dehydration was defined as a fluid deficit of ≥10% of body weight. Clinical findings included vital signs and PRS on the day of admission. The PRS is comprised of four elements, namely respiratory rate, chest retraction, dyspnea, and auscultation findings. Each element was given 0 to 3 points [5]. Infants aged <2 months with respiratory rates of ≤60, 61 to 69, ≥70 breaths per minute were given 1, 2, and 3 points, respectively. Meanwhile, infants aged 2 to 12 months with respiratory rates of ≤50, 51 to 59, and ≥60 breaths per minute were given 1, 2, and 3 points, respectively. For chest retraction, 1 point was given for subcostal or intercostal retraction; 2 points, if two of subcostal, intercostal, substernal retraction, and nasal flaring were present; and 3 points, if 3 or more of subcostal, intercostal, substernal, suprasternal, supraclavicular retraction, nasal flaring, and head bobbing were present. Scores given for dyspnea were based on the patient’s feeding and activity as follows: 1 point, if any feeding intolerance or agitation was present; 2 points, if two of these symptoms were present; and 3 points, if feeding was impossible or the patient was lethargic. Auscultation points were assigned according to the patient’s breath sounds as follows: 1 point, if wheezing was heard only at the end of expiration; and 2 points, if wheezing was heard throughout the whole expiration. If both inspiratory and expiratory wheezing were heard or if the breath sounds were decreased, 3 points were given. The total points for these four elements were categorized into severity groups as follows: normal (0 to 3 points), mild (4 to 6 points), moderate (7 to 9 points), and severe (10 to 12 points).

The patients’ demographic characteristics, laboratory findings, and PRS at admission were compared between the infants with and without hyponatremia. For continuous variables, the Mann-Whitney U-test or t-test was performed for two groups according to the distribution or homogeneity of the variables. For categorical variables, the chi-square or Fisher exact test was performed. Logistic regression analysis, with stepwise backward elimination, was performed to confirm the risk factor of hyponatremia at admission in patients with RSV infection. All statistical analyses were performed using SPSS version 25.0 (IBM Co., Armonk, NY, USA). Statistical significance was considered as a P-value of <0.05.

Of the 334 RSV-positive patients aged <12 months who were admitted at JNUH between January 2016 and December 2019, 143 were excluded from this study because they had coinfections based on the respiratory PCR panel. Another 65 patients were excluded because they had inappropriate laboratory results due to missing laboratory or hemolysis data. One patient was excluded because of diuretic medication. None of the patients had brain damage, cardiac anomaly, renal disease, or thyroid disease. The 125 patients included in the study had a mean±SD age of 2.7±3.3 months, of whom 16 (12.8%) were born at <37 weeks of gestational age, while 30 (24.0%) were born at <1 month (<28 days) of gestational age. The mean±SD serum sodium concentration was 138.4±2.8 mmol/L (range, 131 to 147), and 20 (16.0 %) patients had hyponatremia on admission (Table 1, Figure 1).

The patients were first categorized into those with or without hyponatremia, and the demographics and clinical characteristics of each group were compared. The patients with RSV infection and hyponatremia had lower birth weights and longer hospital stays. Other factors such as age at admission, gestational age, sex ratio, RSV type, palivizumab vaccination, and dehydration showed no significant differences between the two groups (Table 1). Besides the serum sodium level, serum chloride level was lower and BUN and CRP levels were significantly higher in the patients with hyponatremia. Complete blood count, serum potassium level, liver function tests, and blood glucose level showed no significant differences between the two groups (Table 2). This study did not include any infants with moderate to severe hyponatremia or small for gestational age in both groups.

To compare the clinical symptoms of RSV infection between the two groups, vital signs and PRSs at admission were compared. At the time of admission, the vital signs were similar, but the PRS was significantly higher in the patients with hyponatremia. The independent elements of dyspnea within the PRS was significantly higher in those with hyponatremia. The non-hyponatremia group had more normal PRSs than the hyponatremia group (35.2% vs. 10.0%, P<0.05), which had more severe PRSs than the nonhyponatremia group (10.0% vs. 0.0%, P<0.05). The patients with and without hyponatremia showed no significant differences in mild and moderate PRSs (Table 3).

In the univariate logistic regression analysis, birth weight, BUN level, CRP level, and PRS grade were significantly associated with hyponatremia in the patients with RSV infection. After adjusting for age at admission, birth weight (kg; odds ratio [OR], 0.357; 95% confidence interval [CI], 0.145 to 0.881; P<0.05), BUN level (OR, 1.218; 95% CI, 1.023 to 1.451; P<0.05), and PRS grade (OR, 2.885; 95% CI, 1.158 to 7.187; P<0.05) were identified as independent risk factors of hyponatremia in infants with RSV infection (Table 4).