A Recombinant CVA6 Infection Aggravates Left Ventricular Dysfunction and Myocardial Injury in a Child With Cardiomyopathy

To the Editors: The patients diagnosed with cardiomyopathy have a higher risk of ventricular arrhythmias earlier in life, and often develop atrial fibrillation and heart failure in adulthood. The development of left ventricular systolic dysfunction in childhood cardiomyopathy is associated with a poor prognosis in adults.1 Here, we reported a recombinant CVA6 infection exacerbated left ventricular dysfunction and myocardial injury in children with cardiomyopathy, which might lead to a poorer prognosis in future. A 5-year-old and 7-month-old girl presented with fever and rash for 2 days. Her parents gave her cold granules, ibuprofen, cefixime granules and Pudilan anti-inflammatory oral solution. However, the child still had a high fever and was hospitalized on June 20, 2023. Physical examination showed red rashes on her face, oropharyngeal congestion and red herpes in the oral mucosa. Red rashes on her hands and feet (Fig. 1A, B), atypical transparent bullae on the limbs and armpits were captured, and some of the bullae were ruptured (Fig. 1C, D). In addition, the child has cardiomyopathy and has a history of oral coenzyme Q10, levocanidin and vitamin B2 medications. Targeted sequencing of multiple pathogens in the respiratory tract indicated CVA6. The patient was given static vitamin B6, vitamin C nutritional support and symptomatic treatment such as antipyretic. Compared to preinfection (June 9, 2023), the levels of lactate dehydrogenase and creatine kinase MB were elevated after infection, which often indicates myocardial injury. The levels of urea, NA and creatinine in the urine were abnormal, and immunoglobulin E, procalcitonin, C-reactive protein and IL-6 were significantly higher than normal. Several observational studies found that the levels of urea, creatinine and Na+ in the urine of severe cases were decreased, which might be related to a certain impact on renal function. The patient's electrocardiogram showed sinus rhythm, left ventricular hypertension and ST-T changes (Fig. 1E). Further echocardiographic showed that the patient had left ventricular outflow tract obstruction and mild +; increased left ventricular myofibrils with honeycomb changes; foramen ovale not yet closed; and bicuspid and tricuspid regurgitation. Compared with the preinfection period, the patient had further thickened of the interventricular septum and an increase in the flow velocity in the left ventricular outflow tract (Fig. 1F–K). The cardiologist recommended that the child's propranolol tablets be increased to 5 mg/times 3 times a day in addition to the original medication, avoiding strenuous activity. After 6 days of hospitalization, the patient was cured and discharged from the hospital with herpes crusting all over the body, and perioral herpes exfoliation.FIGURE 1.: A, B: Obvious red rashes on the hands and feet. C, D: Atypical transparent bullae could be seen on the limbs and armpits, some of which had ruptured. E: The patient's electrocardiogram. F: The patient's preinfection interventricular septum measurement, 1.21 centimeters. G: The patient's postinfection septal measurement, 1.61 centimeters. H: Myocardial trabeculae of the patient before infection within the red dashed circle. I: Short-axis view of the left ventricle in the patient's postinfected hypertrophied myocardium. Myocardial trabeculae are shown within the red dashed circle. J: The patient's preinfection left ventricular outflow tract flow velocity was 247 cm/s. K: The patient's infection increased left ventricular outflow tract flow rate. The flow rate is 281 cm/s. L: MEGA 7.0 software was applied to analyze the evolutionary characteristics of isolated CVA6 strains. The prototype strain of Enterovirus A71 marked with red star. The prototype strain of CVA6 was marked with green triangle. The blue circle represented the strain isolated in this study. M: The Bootscan analysis of ZYX/China/2023 based on the region. Possible recombination region was marked by the red dashed line. N: Nucleotide sequence comparison and homology analysis of the VP1 region of CVA6 strain. O: Amino acid sequence comparison and homology analysis of the VP1 region of strain CVA6. P: Amino acid mutation sites in the VP1 region of strain CVA6.Considering the clinical presentation of the patient, we performed full-length sequencing and phylogenetic and evolutionary analyses of the strain. Our results revealed that this CVA6 strain was classified in subgroup D3 (Fig. 1L). There is recombination with CVA14 was detected in the nonstructured region of the strain (Fig. 1M). The 305 amino acid sites encoded in the VP1 region of the isolated strain were no deletions and insertions compared with Gdula (AY421764.1). All of these were substitution mutations. The VP1 nucleotide similarity between ZYX/China/2023 and Gdula (AY421764.1) was 95.4%, with a difference rate of 4.4% (Fig. 1N, O). A total of 13 loci (5, 8, 10, 14, 32, 98, 137, 160, 174, 194, 261, 279, 305) were mutated in the strain isolated in this study compared with the Gulda (AY421764.1) (Fig. 1P). The isolated strain (ZYX/China/2023) had amino acid mutations at multiple sites within the VP1 region, and mutations in VP1 region substitutions were significant for changing virulence.2 Except for the genetic evolution and recombination of viruses that have altered their pathogenicity, environmental and host factors such as age, nutrition and receipt of immunization may also lead to different clinical presentations.3 Notably, our findings suggest that this recombinant strain exacerbates left ventricular dysfunction and myocardial damage in children with cardiomyopathy which provide a reference about clinical diagnosis and management of CVA6-infected patients with cardiomyopathy.