Introduction

Rhabdomyolysis is the breakdown of skeletal muscles following an insult or injury, with common causes that include trauma, excessive exercise, immobility, drug or alcohol use, medications, or neuroleptic malignant syndrome [1]. Further, rhabdomyolysis has been established as a complication of SARS-CoV-2 infection [2]. Despite being highly effective in preventing COVID-19-related morbidity and mortality [3], several cases of COVID-19 mRNA vaccination-induced rhabdomyolysis were identified on a comprehensive MEDLINE and Embase literature review [4,5,6,7,8,9,10,11,12]. These previously reported cases have exhibited a wide range of clinical features with little consistency between patients, although the prognoses have generally been favorable [4,5,6,7,8,9,10,11,12]. There has been one previously reported case in the pediatric population [12]. We describe a rare presentation of a patient with severe rhabdomyolysis secondary to COVID-19 mRNA vaccination, and the second case reported in a pediatric patient.

Case presentation

A 16-year-old male presented to the emergency department with a 2-day history of severe bilateral upper extremity myalgia and a 1-day history of dark urine. Several hours prior to the onset of symptoms, he received his first dose of COVID-19 mRNA vaccine (Pfizer-BioNtech). The initial symptoms appeared overnight, presenting with severe bilateral upper extremity myalgia causing nocturnal wakening. Over the next day, his upper body muscle pain worsened, limiting his ability to perform normal daily activities such as carrying a school bag. He also noticed progressive darkening of his urine, prompting his presentation to the emergency department.

In the emergency department, he was afebrile, hemodynamically stable, and reported 10/10 muscle pain in both upper extremities. He appeared well and was cooperative. On exam, he had a limited range of motion of his upper extremities secondary to muscle pain. There was no visible rash, no sign of injury, and the neurological exam was within normal limits. The remainder of his physical exam was unremarkable. The initial blood work revealed an elevated creatinine kinase (CK) of 141,300 U/L and a creatinine of 69 umol/L. The cardiovascular screening, including electrocardiogram and serum troponin, yielded no abnormal results, and myocarditis was ruled out. Similarly, ultrasound of the abdomen and pelvis was performed and was within normal limits; specifically, the right kidney measured 10.5 cm, and the left kidney measured 10.2 cm, with normal parenchyma, good cortico-medullary differentiation, and no hydronephrosis. The urinalysis was positive for blood on dipstick with the absence of red blood cells on microscopy, suggestive of myoglobinuria. He was diagnosed with rhabdomyolysis and was admitted for intravenous hydration, sodium bicarbonate infusion, and monitoring of kidney function.

His medical history included long-standing asthma treated with inhaled salbutamol and seasonal allergies treated with over-the-counter cetirizine; he was taking no other medications. There was no recent history of trauma, crush injury, new medications, or previous adverse reactions to vaccines or other medications. He denied recent exercise, weightlifting, fever, or any other infectious symptoms. Notably, the patient had been infected with SARS-CoV-2 four months prior to the vaccination, which resolved following mild symptoms. The patient had no contributory family history.

The patient was admitted for a total of 5 days, and his symptoms resolved rapidly. His CK peaked at 147,600 U/L within 16 h of admission and returned to normal levels within 13 days, his kidney function remained normal, and no electrolyte abnormalities developed. On the 14-day follow-up, he remained asymptomatic and creatinine remained at a baseline of 78 umol/L. His physical exam was unremarkable, he reported no upper extremity myalgia, and his urine appeared normal. A medical genetics consult was initiated to investigate potential metabolic causes of acute-onset rhabdomyolysis. All subsequent investigations, including fatty acid oxidation defects (i.e., carnitine palmitoyltransferase II deficiency), glycogen storage diseases (i.e., type V and type IX), purine metabolism disorders, and mitochondrial disorders of the respiratory chain, had unremarkable findings. On the 3-month follow-up, it was noted that his creatinine was slightly elevated at 80 umol/L. Glomerular filtration rate was 139 ml/m (per 1.73 m2). His bloodwork and urinalysis were normal; he had a normal blood pressure and was back to all normal activities with no muscle pain.

Discussion

We describe a case of rhabdomyolysis following COVID-19 vaccination in a previously healthy 16-year-old male that resolved with no lasting sequelae after supportive care. There have been a small number of case reports of rhabdomyolysis secondary to COVID-19 mRNA vaccination, with this being the second description in a pediatric patient. The previous pediatric case was that of a 16-year-old girl who presented with myalgia and weakness [12]. She had presented previously with similar symptoms following other immunologic stimuli such as the Gardasil vaccine [12]. Her symptoms also resolved following IV hydration and alkaline diuresis [12]. As global vaccination efforts against COVID-19 continue, it is important to document potential adverse events associated with vaccination, particularly in patients with preexisting COVID-19 infection, as these patients were excluded from early vaccine trials.

Mack et al. (2021) were the first team to report rhabdomyolysis that was presumed to be secondary to mRNA vaccination [4]. They described an 80-year-old diabetic man who presented with myalgia, nausea, and vomiting 2 days after his second Moderna COVID-19 vaccination [4]. His symptoms resolved following a 1-day course of supportive care. A similar case was later described by Elias et al. [7]. The case most analogous to ours was reported by Nassar et al. (2021), in which a healthy 21-year-old man with asthma presented with muscle pain and swelling in his lower back 1 day after vaccination with the Pfizer mRNA vaccine [9]. After the diagnosis of rhabdomyolysis was made, he was admitted for 5 days and made a full recovery with IV fluids and supportive care [9]. Faissner et al. described a case of rhabdomyolysis in a healthy 28-year-old female with a 4-week course that required IV methylprednisolone [5]. Rhabdomyolysis secondary to vaccination has also been described in a patient with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis [8] and in a patient with a ryanodine receptor 1 (RYR1) gene mutation [10]. One complex case presented with myocarditis, pulmonary hemorrhage, myositis, and rhabdomyolysis [11]. Finally, one fatal case of rhabdomyolysis following vaccination was reported, with the patient having many preexisting comorbidities [6]. The patient’s preexisting heart failure with preserved ejection fraction prevented aggressive fluid therapy, leading to disease progression and death [6]. The previously reported cases of rhabdomyolysis secondary to COVID-19 mRNA vaccination are summarized in Table 1. The true rate of rhabdomyolysis secondary to COVID-19 mRNA vaccination could be much higher than these limited case reports would suggest, as it has been reported 228 times with 16 deaths, as per a query in the Vaccine Adverse Event Reporting System (VAERS) on June 22, 2022.

Table 1 Comparison of our case presentation with the other nine published case reports about rhabdomyolysis secondary to COVID-19 mRNA vaccination
Full size table

The mechanism of a rhabdomyolysis event after mRNA COVID-19 vaccination is not known. There have been previous reports of rhabdomyolysis following viral vector COVID-19 vaccinations [13, 14] and influenza vaccinations [15]. It is thus plausible that this is a rare nonspecific reaction to any vaccination and not unique to mRNA or COVID-19 vaccines. Previous reports have speculated that the mechanism of some instances of rhabdomyolysis could be viral invasion of myocytes or exaggerated immunological reactions, analogous to cytokine storm [4]. The latter could be supported by the significantly more potent immune response following mRNA vaccination when compared to traditional vaccines [4]. However, as there are very few similarities in the patient characteristics of the reported cases, it is challenging to suggest risk factors without a further study. Notably, myalgia near the injection site is among the most common side effects following mRNA vaccination [16]. While the underlying pathophysiology of this muscle pain has not been identified, nonspecific inflammatory response and trauma have been speculated to be possible mechanisms [16]. It is plausible that rhabdomyolysis represents the extreme end of the spectrum of muscle injury following vaccination.

Conclusion

We provide the second description of a pediatric case of rhabdomyolysis presenting after COVID-19 mRNA vaccination. Vaccination is the safest and most effective way to prevent morbidity from COVID-19. Clinicians should be aware that rhabdomyolysis could be a rare but treatable adverse event of COVID-19 mRNA vaccination. With early recognition and diagnosis and supportive management, rhabdomyolysis has an excellent prognosis, as is demonstrated in the majority of reported cases.