Case Report

A previously healthy 15-year-old female of West African descent presented with cough, fever, myalgia and poor oral intake on the eighth day of SARS-CoV-2 infection (NSW Delta variant outbreak, 2021). Her body mass index was on the 75th percentile.

On presentation, she was tachycardic, tachypnoeic, normotensive and afebrile. She was not hypoxic; however, she reported marked myalgia in all four limbs. She was commenced on maintenance intravenous fluid and received several fluid boluses due to concerns regarding hydration state. Initial blood tests demonstrated a significant acute kidney injury (AKI) (creatinine of 382 μmol/L, urea of 23 mmol/L) with nephrotic range proteinuria. This was associated with a markedly raised creatinine kinase (CK) (746 352 U/L) and myoglobinuria consistent with rhabdomyolysis. Cardiac enzymes were unremarkable and liver function tests deranged (Aspartate transaminase 3079 U/L, Alanine transaminase 539 U/L, Gamma-glutamyltransferase 59 U/L). She was mildly anaemic with lymphopaenia (0.8 × 109/L) consistent with her viral infection.

Given her severely deranged biochemistry, her care was escalated to the paediatric intensive care unit. Fluid rate was increased to 250 mL/h with additional bicarbonate for 3 days to correct her associated acidosis. Diuresis was successfully driven by frusemide at 1 mg/kg four times a day. Due to concerns regarding an inflammatory component to her severe presentation, she was commenced on intravenous dexamethasone. Remdesivir was considered but not prescribed given the duration of her COVID-19 illness.

Her creatinine peaked at 518 μmol/L and urea at 33.4 mmol/L on day 8 of admission. Despite this, her urine output remained adequate and renal replacement therapy (RRT) was not required (Fig. 1).

Creatinine () and creatinine kinase () progress throughout admission.

A screen for underlying susceptibility to rhabdomyolysis was unremarkable including investigation for fatty acid oxidation disorders, mitochondrial disorders and thyroid dysfunction. She was incidentally found to have sickle cell trait but no other haematological abnormalities.

On day 6 of admission (day 14 of her COVID-19 illness), she was discharged from the paediatric intensive care unit and following intensive rehabilitation was discharged home after 14 days. A week later her creatinine was back to the normal range.

Discussion

We present this case of a 15-year-old female with sickle cell trait and COVID-19-associated rhabdomyolysis with a significant AKI and markedly elevated CK.

COVID-19 initially tended to spare the paediatric population; however, as the pandemic has progressed increased numbers of children have been affected. The majority of children, however, continue to show mild illness.1

Our patient presented with fever and cough, two of the most commonly reported symptoms in children with COVID-19.1 Severe myalgias were an important differentiating feature in this case. Myalgia has been reported in up to 12% of COVID-19-affected children and in this case was initially thought to be just a symptom of the primary disease.1 The increasing severity of the myalgia however triggered further investigation and the identification of a significant AKI. AKI is one of the most common complications of COVID-19 and is estimated to occur in up to 30% of paediatric patients.2 The aetiology is probably multifactorial but includes cytokine storm, macrophage and complement activation; endothelial dysfunction; and direct viral infection of podocytes and tubular cells. There are very few reports, however, of children with COVID-19 developing AKI secondary to rhabdomyolysis.1

Rhabdomyolysis is characterised by breakdown of skeletal muscle with subsequent release of muscle enzymes and systemic complications including AKI.3 It is most commonly acquired in the context of trauma, viral infections or toxins, and presents with myalgia, elevated CK and dark urine secondary to myoglobinuria.3 Interestingly, despite significantly elevated CK, our patient did not have any visible discolouration of her urine, although it was subsequently positive for myoglobin. Known risk factors for developing rhabdomyolysis include male sex, increased body mass index and African descent, only the latter of which is relevant to our patient.3

The few case reports of COVID-19-associated rhabdomyolysis in children have been in adolescents, with significantly elevated CK (although the highest previously reported was 400 000 U/L, substantially less than this case).4, 5 All were febrile and had myalgia, a majority had cough and/or dyspnoea and one, a 16-year-old male with no co-morbidities, died. Management for all was supportive with fluids, diuresis and correction of electrolyte anomalies. None of the previously reported cases were prescribed antivirals, steroids or required RRT.4 At least two of the four children reported were of African background.

Sickle cell trait was previously unknown in this patient and diagnosed when screening tests were performed due to the ethnic background. Sickle cell trait is very common with at least 300 million affected world-wide and largely considered a benign condition. Some health impacts have been reported in sickle carriers, but direct causality is usually hard to prove. Exertional rhabdomyolysis appeared to occur at an increased risk in American soldiers with sickle cell trait following extreme exercise6 and a report linked sickle cell trait and CK rise during viral infection.7 Whether sickle cell trait contributed to the development of rhabdomyolysis or aggravated its severity in our patient remains uncertain.

This case highlights the importance of investigating rhabdomyolysis in individuals with COVID-19 who present with myalgia or AKI. It highlights the effectiveness of fluid, diuretics and steroid therapy in managing, even severe rhabdomyolysis and avoiding RRT. Finally, this case supports the possibility that sickle cell trait may predispose patients to rhabdomyolysis in the setting of a viral illness.

Institutional ethics approval for a case report has been obtained. Written and verbal consent has been obtained from the family and patient involved in this case report.