Abstract
Introduction
Coronavirus disease 2019 (COVID-19) is a pandemic affecting millions. While it can lead to severe acute respiratory distress syndrome and death, it typically presents with clinical manifestations of acute respiratory illness, such as fever, cough, sore throat and rhinorrhoea. 1 Symptoms of myalgia and fatigue have also been noted. Here, we present a case of COVID-19 with rhabdomyolysis in addition to acute respiratory illness.
Case presentation
A 32-year-old Bangladeshi male presented to the National Centre for Infectious Diseases, Singapore, with a five-day history of dry cough, rhinorrhoea and fever. He also complained of a three-day history of bilateral upper chest pain and bilateral thigh pain, causing him difficulty in ambulating in the first two days of illness. His COVID-19 polymerase chain reaction test was positive, and he was admitted for inpatient care.
His past medical history included bilateral L5 nerve root radiculopathy seen on a magnetic resonance imaging scan of the lumbar spine in 2015. He was not on long-term medication. He denied any alcohol or recreational drug use and any traditional or herbal medication use. In particular, he denied any statin use.
He was originally from Bangladesh and was working as a construction worker in Singapore. He had reported his last day of work due to quarantine measures instituted at his dormitory to curb the spread of COVID-19 to be 18 days prior to his first day of illness, with no history of trauma at his work site or body aches after stopping work. He had not undertaken any strenuous physical activity during this period and had remained under quarantine in his place of residence.
On examination, he appeared comfortable and was able to ambulate independently in his room. His chest was clear on auscultation. Bilateral lateral aspects of his quadriceps were mildly tender.
His chest x-ray revealed no consolidation or lung lesions. His blood investigations were significant for unexplained raised serum lactate dehydrogenase levels (LDH) of 1016 IU/L. His electrolytes were normal, except for a mild hypokalaemia of K (3.4 mmol/L). Aspartate aminotransferase (AST) was elevated at 81 IU/L. Elevated LDH is a common feature in COVID 19 infection, with higher levels suggestive of severe infection requiring ICU care. In the case series from Huang et al., the highest LDH level recorded in ICU cases was 578 U/L 1 . In our patient, the degree of elevation was discordant with the patient’s mild respiratory symptoms, normal chest x-ray, and stable clinical condition. In view of the clinical presentation of bilateral thigh pain, and discordantly elevated LDH, creatine kinase (CK) was added to the investigations to evaluate for rhabdomyolysis. An elevated CK of 9205 U/L was recorded. Serum creatine kinase-MB (CK-MB) was 3.4 ug/L and creatinine was 66 umol/L, which was normal. Troponin-I was normal at 4 ng/L and electrocardiogram (ECG) showed normal sinus rhythm. Thyroid function and disseminated intravascular coagulopathy screening was unremarkable. Peripheral blood film did not show any haemolysed cells. Serum myoglobin was raised at 208 µg/L, suggestive of rhabdomyolysis. Urine microscopy and urine dipstick were normal, with no proteinuria or haematuria. Raised serum myoglobin (urine myoglobin was normal) and markedly elevated CK with normal CK-MB are consistent with a laboratory diagnosis of rhabdomyolysis.
He was started on hydration of 3.5 L of normal saline administered intravenously over 24 hours in addition to oral intake. His CK levels increased on the second day of admission to 11,071 IU/L despite hydration, but then decreased subsequently (Table 1). His renal function remained normal throughout the admission.
Trend of creatine kinase and lactate dehydrogenase levels during admission.
Intravenous fluid hydration was stopped on day 6 of admission. CK levels continued to decrease, and the patient remained clinically asymptomatic. He was discharged to a community isolation facility after nine days of inpatient care.
Discussion
Rhabdomyolysis is characterised by elevation of CK levels. The clinical presentation classically consists of myalgia, transient muscle weakness and pigmenturia. Common causes of rhabdomyolysis include physical exertion, metabolic or electrolyte disturbance, drugs (e.g. statins, steroids), prolonged immobilisation and trauma. 2 Infective causes, notably of viral aetiology, have been reported. For example, 62% of patients in a case series with influenza A presented with elevated CK levels on admission. 3 Other viral causes include human immunodeficiency virus, Epstein–Barr virus and cytomegalovirus. 4
We wish to share the following learning points from this case:
(1) Raised LDH in COVID-19 is non-specific, but is commonly performed as a prognostic marker of pneumonitis/lung inflammation in patients who may later require care in the intensive care unit (ICU). Cases with normal chest X-ray findings but raised LDH should be pursued with evaluation of liver and cardiac enzymes, the exclusion of haemolytic anaemia and the exclusion of rhabdomyolysis by checking CK levels.
(2) Clinicians should have a high index of suspicion for rhabdomyolysis if patients with COVID-19 present with antalgic gait, difficulty walking or muscle pain described over large muscle groups such as the quadriceps and calf muscles.
(3) Rhabdomyolysis may cause acute kidney injury (AKI), necessitating renal replacement therapy in severe cases. Hence, early detection and aggressive hydration are key to the prevention of AKI.
(4) Rhabdomyolysis may also present early in disease and in stable non-ICU patients. A literature review revealed two case reports associated with COVID-19. One was a late presentation of rhabdomyolysis in the ICU, 5 and another was in an 88-year-old male on statins. 6 In the original case series of COVID-19 from Wuhan, China, 33% of patients had elevated CK levels >185 IU/L, and 44% of patients presented with myalgia and fatigue. 1
We recognise that musculoskeletal aches are a common presenting complaint in the COVID-19 patient population, but CK levels are not routinely screened. We suggest that patients should be screened for rhabdomyolysis with CK levels if they complain of severe muscle aches or if the raised LDH is unexplained. If elevated, other causes of rhabdomyolysis should be excluded on history taking and with targeted investigations. If confirmed, fluid hydration should be initiated and renal function should be monitored closely for AKI, a common complication of rhabdomyolysis.
Conclusion
Rhabdomyolysis has been well described in other viral infections, including severe acute respiratory syndrome in 2003, 7 and it appears that for COVID-19, this is also not an exception. It is clinically relevant due to the risk of AKI, disseminated intravascular coagulation and electrolyte imbalance that it poses to patients with COVID-19. We propose that CK levels should be considered routinely in any patients who present with muscle pain or weakness, especially if LDH levels are significantly raised. Prompt recognition and initiation of appropriate treatment can help prevent complications from renal impairment.
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