Rare case of respiratory syncytial virus induced myocarditis in a neonate: A case report

Abstract

BACKGROUND

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in neonates. While typically associated with bronchiolitis and pneumonia, RSV can rarely cause extrapulmonary complications such as myocarditis, which may present with life-threatening symptoms if not promptly recognized.

CASE SUMMARY

We describe the case of a 26-day-old male neonate who presented with respiratory distress, poor feeding, and irritability. Initial evaluation revealed an RSV infection confirmed via nasopharyngeal swab. As the clinical course progressed, the infant developed cardiac arrhythmias, elevated cardiac enzymes, and echocardiographic findings consistent with myocarditis. Management included mechanical ventilation, corticosteroid therapy, L-carnitine, and vitamin D supplementation. The patient responded well to treatment and was successfully extubated and discharged in stable condition after nine days of hospitalization.

CONCLUSION

This case highlights the importance of early recognition and multidisciplinary management of RSV-associated myocarditis in neonates.

Key Words: Respiratory syncytial virus; Respiratory syncytial virus; Myocarditis; Neonatal myocarditis; L-carnitine; Bronchiolitis; Respiratory syncytial virus induced cardiomyopathy; Case report

Core Tip: We report a rare case of respiratory syncytial virus (RSV)-induced myocarditis in a 26-day-old neonate initially diagnosed with bronchiolitis. Early cardiac evaluation revealed elevated t troponin levels, a reduced ejection fraction, and mitral regurgitation. Multimodal management, including corticosteroids, L-carnitine, vitamin D, and conventional cardiac therapies, led to full recovery. This case highlights the diagnostic challenges of RSV myocarditis in neonates and emphasizes the potential value of adjunctive therapies targeting immune modulation and mitochondrial support. Early recognition and a personalized approach may improve outcomes in this under-diagnosed complication of RSV infection.

INTRODUCTION

Respiratory syncytial virus (RSV) is most recognized for infecting the lower respiratory tract, resulting in bronchiolitis and pneumonia in newborns and young children. However, aside from respiratory symptoms, RSV has been reported to generate a wide range of extra-pulmonary problems in pediatric patients. These include neurological (seizures, central apnea, and focal neurologic abnormalities), hepatic (hepatitis), metabolic (hyponatremia, metabolic acidosis), and, most importantly, cardiovascular symptoms such as myocarditis and arrhythmias[1]. Studies that reveal significant multi-system involvement as well as respiratory distress highlight the systemic aspect of RSV infection, requiring extensive care measures[1,2].

Cardiac problems from RSV infection, while rare, have been observed in multiple cases. These include arrhythmias, cardiac failure, and myocarditis. RSV-induced myocarditis is particularly concerning since it can cause severe hemodynamic compromise and, in rare cases, sudden cardiac death[2].

The first clinically symptomatic cardiac involvement associated with RSV was reported in 1972 as a fatal case of interstitial myocarditis[3]. Gavotto et al[4] described the sudden death of a nearly four-year-old healthy boy caused by RSV myopericarditis, which was likely associated with arrhythmias. Reports of RSV-induced neonatal myocarditis are uncommon. As a result, each case provides valuable insights into the clinical presentation, management, and outcomes.

CASE PRESENTATION

Chief complaints

A 26-day-old male infant born via normal vaginal delivery at 40 weeks of gestation with an unremarkable antenatal and neonatal history was referred to our hospital as a case of bronchiolitis in severe respiratory distress for intensive care management.

History of present illness

The neonate had experienced fever, cough, rhinorrhea, and progressive respiratory distress for several days before admission.

Upon arrival, the infant seemed lethargic and had a weak, hoarse cry, suggesting possible vocal cord involvement or prolonged distress; he had signs of respiratory distress in the form of subcostal and intercostal retractions, tachypnea, and low O₂ sat of 86% while on O₂ nasal cannula 3 L/minute.

History of past illness

Unremarkable antenatal and neonatal history.

Personal and family history

He had a free personal and family history.

Physical examination

Chest examination revealed decreased air entry on the right with diffuse wheezing and harsh breath sounds. The heart exam revealed a regular heart rate without any murmurs. There were no signs of cyanosis, rash, or pallor. Abdominal and neurological examinations were normal.

Vital signs assessment at admission showed a heart rate of 165, a respiratory rate of 68, a rectal temperature of 37.8 °C, an O₂ saturation of 86%-88% on nasal cannula, and normal blood pressure readings. Arterial blood gases revealed hypoxia and an elevated CO₂ level. The baby was intubated and admitted to the neonatal intensive care unit (NICU), connected to mechanical ventilation on sedation.

Laboratory examinations

Laboratory investigations indicated leukocytosis (white blood cell 15.39 × 10⁹/L) with lymphocytic predominance, anemia (hemoglobin 9.1 g/dL), thrombocytosis (platelet 553 × 10⁹/L) likely reactive to inflammation, and an elevated C-reactive protein (CRP) level of 32.6 mg/L. A chest radiograph showed bilateral diffuse interstitial opacities with patchy atelectasis more pronounced on the right. A nasopharyngeal swab and Blood culture were taken, and the baby was started on the appropriate empirical antibiotics. Follow-up ABGs showed improvement, allowing the FiO₂ to be de-escalated. However, the baby remained on mechanical ventilation due to multiple failed extubation attempts caused by persistent respiratory distress. The result of the nasopharyngeal swab was later reported as positive for RSV and negative for enterovirus, adenovirus, SARS-CoV-2, Influenza, cytomegalovirus, Epstein–Barr virus, herpes simplex virus, varicella zoster virus, human herpesvirus 6, and serology was negative for Parvovirus B19.

Clinical assessment by day three of admission documented tachycardia and fever. Comprehensive septic evaluation yielded negative results, including cerebrospinal fluid analysis and urine culture. CRP levels were rising, along with increased infiltration and air bronchograms on radiographs, suggesting the possibility of bacterial superinfection. This prompted the addition of vancomycin (20 mg/kg/dose every 6 hours) to the treatment regimen. The cardiac shadow was mildly enlarged, with a cardiothoracic ratio exceeding 70%. An electrocardiogram (ECG) was performed and showed sinus tachycardia with nonspecific ST changes, including ST depression and an inverted T wave. Myocarditis was suspected based on radiological and ECG findings. Hence, cardiac enzyme testing was done, and elevated troponin levels (0.17 ng/mL) and creatine kinase-MB levels (60.5 U/L) were found. Liver enzymes exhibited elevated aspartate aminotransferase.

Imaging examinations

Increased infiltration and air bronchograms on radiographs, the cardiac shadow was mildly enlarged, with a cardiothoracic ratio exceeding 70%.

Echocardiography revealed mild left atrial and ventricular dilation with decreased ejection fraction (45%-50%) and mild to moderate mitral regurgitation, which supports the diagnosis of myocarditis.

FINAL DIAGNOSIS

RSV-induced myocarditis.

TREATMENT

Management included furosemide (3 mg/dose q 12 hours) and captopril (0.2 mg/dose q 8 hours), as recommended by pediatric cardiology. Additionally, L-carnitine, a course of methylprednisolone, and vitamin D were administered.

OUTCOME AND FOLLOW-UP

These interventions resulted in significant clinical improvement over the following week, enabling successful extubation to nasal CPAP. The settings were gradually reduced until the baby no longer required oxygen support, showing no respiratory distress and stable oxygen saturation. Laboratory investigations on discharge were normal, including CBC, CRP, and troponin. Follow-up troponin levels decreased from 0.17 to 0.02. A week later, an echocardiogram revealed moderate concentric left ventricular hypertrophy, showing that the heart had begun to respond to increased demand. There was good systolic function and a trace of tricuspid regurgitation, with no mitral regurgitation or effusion. The baby was discharged home in good condition, with clear instructions and follow-up arrangements in place. The clinical timeline, relevant investigations, and management details are summarized in Table 1.

Table 1 Clinical course, key investigations, and management of the neonate with respiratory syncytial virus-associated myocarditis.

Timeline	Clinical findings	Key investigations	Management
Day 1 (Admission)	Respiratory distress, O2 sat 86%, hypoactive, hoarse cry	ABG: Hypoxia/hypercapnia; CBC: Leukocytosis, anemia, thrombocytosis; CRP: 32.6 mg/L; CXR: Bilateral infiltrates	Mechanical ventilation, empirical antibiotics
Day 2–3	Persistent respiratory failure	RSV PCR positive, cultures pending	Continued supportive care
Day 3	Tachycardia, fever, cardiomegaly, increased infiltrates	ECG: ST/T changes; Troponin: 0.17 ng/mL; CK-MB: 60.5 U/L; Echo: ↓LVEF, LA/LV dilation, MR	Initiated furosemide, captopril, corticosteroids, L-carnitine, vitamin D
Day 4–12	Clinical improvement	Improved ABGs, FiO2 reduced	Extubated to CPAP, weaned off oxygen
Discharge	Hemodynamically stable, no respiratory distress	Normalized labs; Troponin: 0.02 ng/mL	Discharged with outpatient follow-up
1-week follow-up	Clinically stable, good systolic function	Echo: Moderate concentric LVH, no MR, trace TR	Continued outpatient care and serial follow-up

ABG: Arterial blood gas; CBC: Complete blood count; CK-MB: Creatine kinase-MB; CRP: C-reactive protein; CXR: Chest X-ray; ECG: Electrocardiogram; FiO₂: Fraction of inspired oxygen; LA: Left atrium; LV: Left ventricle; LVH: Left ventricular hypertrophy; CPAP: Continuous positive airway pressure; LVEF: Left ventricular ejection fraction; MR: Mitral regurgitation; PCR: Polymerase chain reaction; RSV: Respiratory syncytial virus; TR: Tricuspid regurgitation.

DISCUSSION

Myocarditis is a known complication of viral infections in children, yet RSV is rarely identified as a primary cause of cardiac inflammation. Bowles et al[5] documented cases of RSV myocarditis; RSV is rarely diagnosed as the primary cause of myocarditis in young patients[5]. This under-diagnosis may be because of RSV's primary pulmonary involvement, with cardiac complications reported in only a small number of infants. A retrospective analysis found that the most common presenting symptoms in children with myocarditis were respiratory in origin. This led to initial misdiagnoses with pneumonia or asthma in half of the cases before myocarditis was identified[6]. Nonspecific symptoms, including gastrointestinal manifestations such as vomiting, may further delay early recognition. These cases highlight the difficulties in distinguishing myocarditis from other pediatric conditions affecting multiple organ systems[7]. Eisenhut et al[1] suggests that clinicians should consider RSV in the differential diagnosis of myocarditis, even though it remains a rare cause of myocardial inflammation. This highlights the need for increased clinical suspicion in infants with severe RSV infections presenting with persistent tachycardia or hemodynamic instability[1].

Diagnosing RSV-induced myocarditis in newborns and young children poses several challenges. First, symptoms overlap with other common pediatric conditions. Infants cannot verbalize symptoms such as chest pain, making reliance on objective findings crucial for diagnosis. Second, conventional diagnostic tools have limitations. Chest radiographs may reveal cardiomegaly or pulmonary venous congestion, but abnormalities were present in only 50% of radiographs in a case series[6]. Similarly, nonspecific ECG findings, such as ST/T wave changes and low-voltage QRS complexes, are present in most cases, which can aid in clinically correlating with radiographs to help physicians make a more accurate diagnosis[6]. While cardiac enzymes and other biomarkers are essential for diagnosing myocardial damage, they may also be elevated in various conditions[7,8].

The diagnosis of RSV-induced myocarditis in our patient was based on the complexity of the clinical course, laboratory findings of elevated inflammatory markers and high cardiac biomarkers, chest radiograph, Changes in ECG, and echocardiographic evidence of systolic dysfunction, all in the absence of other identified causes. While Endomyocardial biopsy was not pursued due to its invasiveness. The combination of these findings strongly indicates a diagnosis of myocarditis. However, the lack of direct confirmation from the heart tissue limits the certainty of the diagnosis. Other potential etiologies, such as enterovirus, adenovirus, or influenza virus, were considered but not confirmed, as the respiratory viral panel yielded negative results.

Endomyocardial biopsy is considered the gold standard for diagnosing myocarditis; however, it is rarely performed because of its invasive nature and limited sensitivity in detecting viral pathogens[9]. While polymerase chain reaction (PCR) testing can be useful, it may not always effectively detect RSV directly in myocardial tissue, making it difficult to confirm a direct viral cause[5]. Due to these limitations, it is crucial to maintain a high level of clinical suspicion and employ a multimodal diagnostic approach. This should include serial echocardiography, cardiac biomarkers, and clinical correlation to enable early detection and management. Recognizing myocarditis early and providing supportive care is essential to improve patient outcomes, as delays in diagnosis can lead to irreversible myocardial damage and poor prognosis, including the need for heart transplantation in severe cases[10]. Additionally, in rare situations, as noted by Huang et al[2], ventricular tachycardia—an uncommon arrhythmic complication of RSV—may occur due to myocardial inflammation or pericarditis. These clinical considerations underscore the importance of regular monitoring for newborns with RSV, especially in severe or refractory cases where cardiac involvement might be underestimated[11].

The pathogenesis of viral myocarditis occurs in three stages: Viral replication, autoimmune injury, and cardiac dilation. The autoimmune phase is critical to progression, leading to chamber dilation that increases cardiac demand and stimulates hypertrophy[12,13]. This phase has prompted the investigation of immunosuppressive drugs as a potential treatment for pediatric myocarditis. However, the pathogenesis and treatment responses in children significantly differ from those in adults, leading to ongoing debates regarding the efficacy of immunosuppressive medications in pediatric cases. He et al[14] conducted a comprehensive review and meta-analysis on the effects of immunosuppressive medication for pediatric myocarditis, revealing notable benefits. In four studies, receiving immunosuppressive therapy showed a significant improvement in left ventricular ejection fraction (LVEF) compared to those receiving conventional treatment. Additionally, three studies indicated a substantial reduction in left ventricular end-diastolic dimension with immunosuppressive therapy. Most importantly, the meta-analysis by He et al[14]. demonstrated that the immunosuppressive treatment group had a lower overall rate of death or the need for heart transplantation compared to the conventional therapy group. Management of RSV-induced myocarditis is primarily supportive, with goals including respiratory stabilization, hemodynamic support, and myocardial recovery. In our case, the patient required mechanical ventilation, diuretics (furosemide), and after-load reduction with captopril, consistent with standard care for neonatal cardiac dysfunction. Supportive therapy, oxygen supplementation, fluid balance, and rest are central in mild cases, while severe presentations may necessitate intensive care with inotropes. The role of immunosuppressive therapy remains a topic of debate. While the Myocarditis Treatment Trial in adults showed no clear benefit, some pediatric studies have suggested improved LVEF with corticosteroids or intravenous immunoglobulin, especially in virus-associated cases. In our case, in addition to standard supportive measures, our management included corticosteroids, L-carnitine, and vitamin D.

Although these adjunct therapies were selected based on their underlying mechanisms and some supportive literature, their effectiveness in treating viral myocarditis remains uncertain. For example, given the immune-mediated phase of myocarditis, corticosteroids may help reduce immune-mediated cardiac damage due to their anti-inflammatory effects. Although evidence linking steroid use to viral myocarditis in pediatric patients is limited, some individual cases have indicated that corticosteroids may be associated with improved LVEF. This finding is based on eight randomized controlled trials involving a total of 719 patients[15]. Additionally, a systematic review of six studies involving 604 children demonstrated significant improvements in left ventricular function, as measured by ejection fraction, in those with acute myocarditis who received corticosteroids[16]. In our patient, corticosteroid use correlated with clinical and echocardiographic improvement, supporting a possible role in the inflammatory mechanism of myocarditis[13].

Likewise, vitamin D and L-carnitine were included for their respective immunomodulatory and metabolic advantages. Vitamin D plays a crucial role in regulating the immune system and preventing infections. It enhances the production of antimicrobial proteins, such as cathelicidin, which helps monocytes defend against infections. Furthermore, vitamin D interacts with Toll-like receptors (TLR1/2) and mTOR signaling to enhance macrophage antimicrobial activity and reduce airway inflammation[17]. The pathophysiology of heart failure and myocarditis increasingly points toward a significant inflammatory component involving cytokines, reactive oxygen species, and immune dysregulation. Vitamin D, known for its anti-inflammatory and immune-modulating properties, may, therefore, play a supportive role in myocardial recovery. Vitamin D receptors are widely expressed in the cardiovascular system, and their absence has been linked to adverse cardiac remodeling in experimental models. Clinically, vitamin D deficiency has been associated with reduced LVEF and increased mortality in heart failure patients. In a recent meta-analysis, Rodriguez et al[18] demonstrated that vitamin D supplementation significantly improved LVFF and reversed structural remodeling in patients with heart failure. These benefits are hypothesized to occur via modulation of inflammatory pathways[17,18]. While evidence in neonatal myocarditis is limited, our patient's clinical and echocardiographic improvement following vitamin D administration aligns with these findings, suggesting potential therapeutic value. Further pediatric research, particularly randomized trials, is warranted to explore the role of vitamin D as an adjunctive therapy in RSV-induced myocarditis.

Mitochondrial dysfunction plays a significant role in myocardial injury associated with myocarditis. Research has shown that L-carnitine supplementation can improve cardiac function, as the heart primarily relies on fatty acid oxidation for energy. Carnitine is crucial for transporting long-chain fatty acids into the mitochondria, where they are metabolized to produce energy in the form of ATP. During myocarditis, myocardial cells suffer from energy depletion. Supplementing with carnitine enables cardiomyocytes to restore efficient energy production, resulting in enhanced contractility and improved overall heart function. A study conducted by Kothari and Sharma demonstrated that L-carnitine supplementation improved heart function in adolescents with idiopathic dilated cardiomyopathy, as evidenced by an increase in LVEF from 36.9% to 46.9%[19]. Additionally, another study found that L-carnitine administration also enhanced LVEF in pediatric patients experiencing systolic dysfunction[20]. Although robust clinical trials do not yet support the use of L-carnitine in neonatal viral myocarditis, its inclusion in our case was based on its potential to improve myocardial energetics. Given the observed improvement in our patients’ cardiac function following supplementation, L-carnitine may represent a promising adjunctive therapy in similar cases and warrants further studies.

The treatment modalities employed in this case resulted in significant clinical improvement. Troponin levels returned to normal, and systolic function showed improvement on the follow-up echocardiogram. Overall, the patient achieved stability. This case highlights the effectiveness of a personalized, multimodal approach to treating pediatric myocarditis. The prognosis of RSV myocarditis varies based on disease severity and timely intervention. While many cases resolve with supportive care, severe cases may progress to chronic cardiomyopathy, necessitating long-term follow-up. The three-phase model of myocarditis pathogenesis suggests that early inflammation triggers myocardial dilation and hypertrophy as compensatory mechanisms, underscoring the importance of prompt diagnosis and management to prevent irreversible damage. In some cases, RSV myocarditis is associated with arrhythmia, warranting continuous monitoring in high-risk patients[14]. Despite earlier reports of fulminant myocarditis requiring inotropic support and ECMO, our patient experienced a milder course and gradually improved with conservative therapy. Serial follow-up confirmed the resolution of myocardial dysfunction.

However, this case report is subject to inherent limitations. As a single-patient observation, its findings are not generalizable to the broader neonatal population. The absence of long-term follow-up restricts the assessment of delayed complications, such as the development of chronic cardiomyopathy or arrhythmias. Furthermore, the diagnostic process was limited by the inability to perform confirmatory investigations such as endomyocardial biopsy or PCR-based viral detection in myocardial tissue, which, while considered gold standards, are often impractical in neonates due to their invasive nature and limited sensitivity. Despite these constraints, the diagnosis was supported by a consistent clinical presentation, elevated cardiac biomarkers, echocardiographic evidence of systolic dysfunction, and a positive RSV PCR in the absence of other viral etiologies, underscoring the value of a multimodal, clinically integrated diagnostic approach.

Additionally, while the therapeutic interventions used in this case, namely corticosteroids, L-carnitine, and vitamin D, were selected based on a plausible mechanistic rationale and supportive findings from related contexts, current evidence remains limited, particularly in the neonatal population. The clinical response observed in this case may indicate a potential adjunctive benefit of these agents in comparable settings; however, their therapeutic efficacy remains unsubstantiated, pending validation through rigorous, controlled clinical studies.

CONCLUSION

RSV myocarditis, although uncommon, should be considered in infants with severe RSV bronchiolitis and persistent tachycardia or hemodynamic instability. Early recognition, supported by serial cardiac monitoring, biomarkers, and echocardiography, is critical to improving outcomes. This case also highlights the potential role of adjunctive therapies, such as vitamin D, corticosteroids, and L-carnitine, in modulating inflammation and supporting cardiac function, warranting further investigation in future studies.

ACKNOWLEDGEMENTS

The authors would like to thank the NICU medical and nursing staff for their support in caring for the patient. We also acknowledge the patient's family for their cooperation and consent to share this case for academic purposes.