Severe rhabdomyolysis following COVID-19 infection

The patient

A 29-year-old man presented to the hospital with four days of upper respiratory tract infection symptoms and two days of dark urine and myalgias. His medical history was significant for childhood asthma and two episodes of postviral rhabdomyolysis (in 2014 and 2015). The night before admission he developed myalgias; he woke up in the morning with dark urine and bilateral flank pain.

On admission, his physical exam was remarkable for diffuse tenderness to palpation in all extremities and his abdomen, with pain most severe in the right upper quadrant. Viral polymerase chain reaction studies were positive for COVID-19 and negative for all other viruses in the panel. Urinalysis showed a urine protein level of 100 mg/dL (reference range, negative), a urine protein-to-creatinine ratio of 635 mg/g (reference range, <150 mg/g), and large urine blood (reference range, negative) with no red or white blood cells appreciated. Additional urine studies included a urine protein electrophoresis that consisted of polyclonal immunoglobulins without paraproteins identified, which likely demonstrated myoglobin in the urine.

The patient's initial creatine phosphokinase (CPK) level was greater than 45,000 U/L (reference range, 55 to 170 U/L), and it peaked at 2,130,400 U/L on day 4 after manual dilution. Initial aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels were 143 U/L (reference range, 8 to 48 U/L) and 651 U/L (reference range, 7 to 55 U/L), respectively. His transaminitis reached a peak at the same time as his CPK level, with an AST of 1,058 U/L and an ALT of 4,854 U/L. The patient's elevated aminotransferase levels reflected a hepatocellular pattern, with an alkaline phosphatase level of 37 U/L (reference range, 34 to 104 U/L).

The patient's initial blood urea nitrogen (BUN) level was 16 mg/dL (reference range, 7 to 25 mg/dL) from a baseline of 15 mg/dL; serum creatinine level was 1.15 mg/dL (reference range, 0.70 to 1.30 mg/dL) from a baseline of 1.0 mg/dL. For 11 consecutive days, the patient received aggressive fluid resuscitation (normal saline, 250 cc/h). Kidney function was closely monitored during hospitalization, and creatinine level remained below 1.15 mg/dL. ALT and AST levels also trended down, to 85 U/L and 46 U/L at follow-up a week after discharge. CPK level had decreased to 12,843 U/L at the time of discharge. With such aggressive fluid resuscitation, he developed edema in all extremities near the end of his treatment course. Discontinuation of IV fluid and adherence to diuretics at home fully resolved his edema.

The diagnosis

The diagnosis is postviral rhabdomyolysis. Rhabdomyolysis, a condition characterized by the breakdown of skeletal muscle, can result in the release of cell contents, including CPK, myoglobin, urate, potassium, and phosphate, into the bloodstream. This damage to muscle tissues classically presents with myalgias, weakness, and dark urine. It most commonly occurs in the settings of trauma or infections. The most common viral infections implicated in rhabdomyolysis include influenza (33%), Coxsackievirus (17%), Epstein-Barr (10%), parainfluenza (10%), adenovirus (7%), echovirus (7%), and herpes (7%). Postviral cases make up about 5% of all cases of rhabdomyolysis in adults. Risk factors for postviral rhabdomyolysis are not fully understood, but recent reports have indicated that there might be a genetic component, with a number of gene variants identified as contributors. Inpatient management of rhabdomyolysis consists of early identification through serum CPK monitoring, followed by pain management and aggressive fluid resuscitation to prevent acute kidney injury secondary to myoglobin accumulation.

Rhabdomyolysis is an uncommon sequela of COVID-19. A review published in 2023 identified 117 reported cases of COVID-19-associated rhabdomyolysis. No association has been shown between severity of COVID-19 infection and risk of postviral rhabdomyolysis, although studies have indicated that patients with COVID-19-associated rhabdomyolysis have elevated risk of ICU admission and mortality compared to other patients with rhabdomyolysis, so clinicians should consider COVID-19 as a potential etiology.

Typically, rhabdomyolysis presents with a CPK level ranging from about 5,000 U/L to higher than 100,000 U/L. Acute renal failure occurs in about 15% of patients with rhabdomyolysis and risk is increased with a CPK above 16,000 U/L, making early fluid resuscitation even more important in these cases. There is no CPK level that is universally accepted as safe for discharge. Typically, CPK levels below 5,000 U/L are unlikely to cause kidney injury. It may be safe to discharge patients before they reach that threshold if their levels are clearly trending down and they will continue adequate hydration.

Pearls

• Although rhabdomyolysis is not a common finding associated with COVID-19 infection, clinicians should consider checking CPK levels when treating a patient who is COVID-19-positive and presents with symptoms of rhabdomyolysis.
• Early and aggressive fluid resuscitation is efficacious in preventing acute kidney injury in severe cases of rhabdomyolysis.

*Ms. Cole and Dr. Sterling are co-first authors.