COVID-19 infection and severe rhabdomyolysis

Abstract

Although patients with COVID-19 can have mild nonspecific myalgia and mild elevation of creatinine kinase levels, severe myalgia along with elevation of creatinine kinase levels >10 times the upper normal limit and dark-colored urine indicate an underlying severe rhabdomyolysis. This report describes a 60-year-old morbidly obese man who was found to have severe rhabdomyolysis, along with acute kidney injury, dark-colored urine, and a positive COVID-19 test. He had a prolonged hospital course requiring continuous renal replacement therapy, mechanical ventilation, and multiple vasopressors and eventually died of multiorgan failure. The management of severe rhabdomyolysis and COVID-19 is challenging, and fluid resuscitation should be done cautiously, monitoring for early signs of fluid overload.

Although the respiratory system is the main target and cause of morbidity and mortality in COVID-19, the disease can affect other organ systems with devastating outcomes. To our knowledge, COVID-19 is rarely associated with severe rhabdomyolysis, and its incidence is not well reported.^1,2 In this report, we present a case of nonspecific myalgias that were found to be due to severe rhabdomyolysis in the setting of COVID-19 infection.

CASE PRESENTATION

A 60-year-old morbidly obese man (body mass index of 43 kg/m²) with known chronic kidney disease stage II and asthma presented to the emergency department with complaints of generalized fatigue, myalgia, decreased appetite, and mild nonproductive cough for 2 to 3 days. Before his emergency department visit, he had been seen by his primary care physician with similar complaints and was prescribed acetaminophen and a muscle relaxant. He was a nonsmoker, nonalcoholic, and denied any illicit substance abuse or herbal supplements. His family history was unknown for any neuromuscular disorders or myopathies. His home medications included mometasone-formoterol inhaler, cyclobenzaprine, and sildenafil as needed. His initial vital signs showed a blood pressure of 146/97 mm Hg, heart rate of 97 beats/minute, temperature of 37.2°C, respiratory rate of 20 breaths/minute, and oxygen saturation of 92% on room air. On physical examination, he appeared ill and had tenderness over major muscle groups, particularly in the arms and legs and paraspinal muscles of the back. His initial laboratory workup is summarized in Table 1.

Table 1.

Initial laboratory and diagnostic workup

Test	Result	Normal value
Sodium (mmol/L)	136	136–145
Chloride (mmol/L)	99	98–107
Potassium (mmol/L)	3.1	3.3–5.1
Creatinine (mg/dL)	1.96	0.5–1.18
Urea nitrogen (mg/dL)	28	6–21
Glucose (mg/dL)	97	67–99
Anion gap (mmol/L)	14	8–16
C-reactive protein (mg/L)	78	0–5
Troponin I (pg/mL)	99	<20
Brain natriuretic peptide (pg/mL)	39	<100
Hemoglobin (g/dL)	15.5	13–16.5
White blood cell count (/mm3)	5.4	4000–10,000
Platelets (/mm3)	183	150,000–450,000
Aldolase (U/L)	810	1.5–8.1
Creatine kinase (U/L)	>40,000	0–840
Lactate dehydrogenase (IU/L)	4000	135–235
Total protein (g/dL)	7.2	6.4–8.3
Aspartate aminotransferase (IU/L)	930	0–37
Alanine aminotransferase (IU/L)	117	0–50
Total bilirubin (mg/dL)	0.8	0–1
D-dimer (μg/mL)	2.18	<0.50
Ferritin (ng/dL)	717	24–336
Interleukin-6 (pg/mL)	18.5	<6
Thyroid-stimulating hormone (IU/L)	0.4	0.4–5
Urine toxicology	Negative
Respiratory viral panel	Negative
Urinalysis	+Myoglobin
Blood culture	No growth
HIV antigen/antibody	Negative
Acute/remote hepatitis panel	Negative
Lower extremity Doppler ultrasound, arterial and venous	Negative for thrombosis
Anti-nuclear antibodies	Negative
Anti-Jo1-antibody	Negative
Anti-Smith antibody	Negative
Myositis panel	Negative
Anti SS-A, SS-B antibody	Negative
Anti-ds-DNA antibody	Negative
Anti-RNP antibody	Negative

The patient was started on 2 L/min oxygen supplementation and intravenous fluid resuscitation with Ringer’s lactate solution at 200 mL/h. Over the next few hours, his oxygen requirement gradually increased, and he was subsequently placed on a nonrebreather mask with 100% oxygen supplementation. Computed tomography of the chest and abdomen with contrast showed diffuse ground-glass opacities in both lungs without any pulmonary embolism, consolidation, or lung masses (Figure 1). The patient’s oxygenation continued to worsen over the next 24 hours, and he was transferred to the intensive care unit.

Figure 1.

Chest radiograph on (a) day 1 and (b) day 20 showing progression of bilateral infiltrates.

In the intensive care unit, empiric broad-spectrum antibiotics were started, and fluid resuscitation was continued. Meanwhile, the patient’s COVID-19 polymerase chain reaction nasopharyngeal swab came back positive and intravenous dexamethasone (6 mg daily) was initiated. His hospital course was complicated by severe acute respiratory distress syndrome requiring mechanical ventilation; anuric renal failure and severe metabolic acidosis requiring continuous renal replacement therapy; and septic shock requiring multiple vasopressors. The patient ultimately had multiorgan failure and died from a cardiac arrest. An autopsy was offered and was declined by family members.

DISCUSSION

Rhabdomyolysis is a life-threatening condition caused by skeletal muscle damage from various etiologies such as trauma, autoimmune conditions, ischemia, and infectious.³ Viral-associated rhabdomyolysis is an uncommon presentation in adults and has been described with the influenza virus, human immunodeficiency virus, and Epstein-Barr virus.³ Mild elevations in creatine kinase (CK) and myalgias can be expected in COVID-19 infection; however, the diagnostic criteria for rhabdomyolysis require the presence of CK levels at least 10 times the upper limit of normal, along with myalgia, myoglobinuria, and acute kidney injury.⁴

The case presented here is important in multiple aspects. First, COVID-19 can often present with nonspecific symptoms and therefore a high degree of vigilance is required to identify such cases. The patient had minimal respiratory symptoms during his primary care physician’s visit, and the possibility of COVID-19 infection was overlooked. Second, the management of severe rhabdomyolysis and COVID-19 can be challenging. In general, patients with severe rhabdomyolysis should receive aggressive fluid resuscitation to prevent acute kidney injury or to prevent further damage to an already compromised kidney, such as in our case. However, liberal fluid resuscitation may result in volume overload and worsen oxygenation, especially in patients with acute respiratory distress syndrome, and underresuscitation may lead to worsening renal function. Therefore, we suggest cautious fluid resuscitation while being vigilant about the urine output and oxygen requirement, as well as frequent physical examination to detect early signs of fluid overload.

Our case was limited by the lack of histopathology results and our knowledge about any inherited disorders that might have predisposed or accelerated our patient’s viral-induced rhabdomyolysis. Although patients with COVID-19 can have clinical signs of dehydration, and hypovolemia may contribute to renal impairment and transiently elevated CK levels, our patient presented with extremely high levels of CK along with diffuse myalgias, whereas clinical signs of dehydration were not present (Figure 2). No other cause for rhabdomyolysis was found (Table 1).

Figure 2.

Creatine kinase and creatine trend during admission.

In conclusion, disproportionate muscle tenderness, muscle weakness, or dark urine should raise concerns of rhabdomyolysis and can sometimes be the initial presentation of COVID-19. Rhabdomyolysis, especially when associated with compromised renal function, carries high mortality and therefore warrants high clinical vigilance.