key: cord-1040748-7qt0pgox
authors: FINSTERER, JOSEF; SCORZA, FULVIO
title: SARS-CoV-2 associated rhabdomyolysis in 32 patients
date: 2021-06-28
journal: Turk J Med Sci
DOI: 10.3906/sag-2012-327
sha: 90ba458974cbdf445f79a3ffa44bcc39e0f1e33b
doc_id: 1040748
cord_uid: 7qt0pgox

BACKGROUND/AIM: This mini-review aims at summarising and discussing previous and recent findings concerning the clinical manifestations, therapeutic management, and outcome of SARS-CoV-2 associated rhabdomyolysis. MATERIALS AND METHODS: Literature search in the PubMed database by applying appropriate search terms. RESULTS: A total of 26 articles reporting SARS-CoV-2 associated rhabdomyolysis in 32 patients were identified. Age ranged from 16 to 80 years. Four patients were female and 25 were male. Onset of rhabdomyolysis was prior to onset of COVID-19 in 7 patients, and after onset of COVID-19 in the remaining patients. Exposure to myotoxic medication was identified in 18 patients. Myotoxic drugs these patients were taking at the time rhabdomyolysis included azithromycin, hydroxy-chloroquine, placitaxel, propofol, imastinib, piperacillin and meropenem, hydrochlorothiazide, and acetaminophen. Peak creatine-kinase values ranged from 328 to >427656 U/l. The outcome was unreported in 8 cases, favourable in 15 partial, incomplete in 3 cases, and lethal in 6 cases. CONCLUSION: SARS-CoV-2 associated rhabdomyolysis is rare, may be most frequently due to the side effects of myotoxic anti-COVID-19 drugs, and only rarely due to virus myositis, and may have a favourable outcome in most patients.

= 3), alkalisation (n = 7), steroids (n = 3), antibiotics (n = 1, and hemodialysis (n = 4) (Table) . The outcome was unreported in 8 cases, favourable in 15 cases, incomplete in 3 cases, and lethal in 6 cases (Table) .

Rhabdomyolysis is an acute condition due to damage of myocytes in a single muscle, a group of muscles, or all striated muscles. The three cardinal manifestations of rhabdomyolysis are black tea coloured (dark) urine, myalgia, and fever. More rare clinical manifestations are muscle weakness, vomiting, and confusion. Rhabdomyolysis is diagnosed upon the clinical presentation and laboratory tests, showing marked elevation of creatine-kinase, transaminases, or myoglobin, electrolyte disturbances, and renal insufficiency. Importantly, after resolution of rhabdomyolysis, patients should undergo a neurological exam, needle electromyography, and eventually muscle biopsy or genetic tests. Rhabdomyolysis may result from direct myocyte injury or failure of energy production, leading to an unregulated increase in intracellular calcium and cellular lysis. Accordingly, there are multiple causes of rhabdomyolysis but the most frequent include crush injury, strenuous exercise, medication, drug abuse, infections, and sepsis. More rarely, rhabdomyolysis is due to endocrine abnormalities, electrical injury, heat stroke, prolonged immobilisation, arterial occlusion, snake bites, or inherited muscle disease. There are indications that rhabdomyolysis secondary to an infectious aetiology may be due to direct damage by the pathogen or due to an exaggerated inflammatory response. Similar theories have been proposed for SARS-CoV-2-associated rhabdomyolysis [7] . Viruses which may potentially cause rhabdomyolysis include influenza, HIV, enteroviruses, Epstein-Barr virus, cytomegalovirus, adenovirus, herpes simplex, varicella virus, Zika, Dengue, Coxsackie-B, Herpes-6, Chikungunya, arboviruses, parainfluenza, and metapneumovirus. Among the eight patients in whom rhabdomyolysis occurred prior to clinical manifestations of COVID-19, no exposure to myotoxic drugs has been identified in seven patients (Table) . Whether SARS-CoV-2 in these seven patients was truly the trigger of rhabdomyolysis remains speculative. Subclinical hereditary myopathy has not been excluded in any of them. The case reported by Beydon et al. is the only one in which rhabdomyolysis was due to myositis as confirmed by muscle MRI of lower legs [8] .

In the three patients reported by Su et al. creatine-kinase increase was only mild why the diagnosis rhabdomyolysis is questionable. Overall, the frequency of rhabdomyolysis in COVID-19 patients is lower than in patients with MERS-CoV of whom 14.4% experienced rhabdomyolysis.

In conclusion, SARS-CoV-2 associated rhabdomyolysis is rare, may be most frequently due to side effects of myotoxic compounds given to treat the infection and only rarely due to virus myositis, and may have a favourable outcome in most patients. COVID-19 patients should not receive myotoxic compounds. COVID-19 associated rhabdomyolysis requires further work-up for differentials of rhabdomyolysis after recovery. Not to miss muscle damage associated with COVID-19 high clinical suspicion must be held for any patient with COVID-19 demonstrating signs or symptoms of rhabdomyolysis.

Myopathy associated with serious SARS-CoV-2 infection

SARS-CoV-2 myopathy

Rhabdomyolysis as the initial presentation of SARS-CoV-2 in an adolescent

Rhabdomyolysis in COVID-19: report of four cases

A case of corticosteroid-responsive SARS-CoV-2 related massive rhabdomyolysis

Rhabdomyolysis and acute kidney injury in severe COVID-19 infection

SARS-CoV-2 Infection with associated rhabdomyolysis and probable myocarditis

Myositis as a manifestation of SARS-CoV-2

Severe rhabdomyolysis in a 35-yearold woman with COVID-19 due to SARS-CoV-2 infection: a case report

The authors declare no conflicts of interest.

No funding was received.Author contribution JF: design, literature search, discussion, first draft, critical comments.

Informed consent was obtained.

The study was approved by the institutional review board (board decision number?)