Discussion
In this study we evaluated the CK levels of a large cohort of COVID-19 patients focusing on muscle symptoms and clinical outcome.
To our knowledge, few studies analysed the correlation between CK levels and muscle injury 5,9,10.
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Mao et al. studied the neurological manifestations of 214 patients with Coronavirus disease showing that patients with muscle injury (i.e. those with skeletal muscle pain and serum CK greater than 200 U/L) had significantly higher levels of CK (median: 400 U/L [range 203.0-12216.0] vs median: 58.5 U/L [range 8.8-212.0]; p < .001) compared with other subjects. Therefore, they speculated that muscle symptoms were owing to skeletal muscle injury and significantly elevated proinflammatory cytokines in serum may cause skeletal muscle damage 5. Conversely, Vacchiano et al. analyzed 108 COVID-19 patients finding that muscle pain was not associated with CK high levels, supporting the notion that this symptom was not directly accounted for by muscle injury and making a direct viral mechanism unlikely 9. As the Italian colleagues, we did not find significant correlation among muscle symptomatology and CK levels. Instead, we found that patients with history of falls (i.e. patients admitted to hospital after falling at home) had CK levels higher than others (p < 0.002) even if there was no clinical evidence of muscle trauma on ER reports.
Regarding the clinical aspects, in literature the rate of cases presenting muscular symptoms varies from 63% 7 to 26% 8. In our population only 2.8% patients presented myalgia and/or arthralgia. This percentage rises to 15.9% if we include fatigue in the muscular manifestations.
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Fatigue is a highly non-specific symptom, and it is hard to assess retrospectively if this figure was related to the infection itself or to a hidden muscle injury.
The low percentage of muscular symptoms observed could be due to the extreme hospital circumstances at the peak of this pandemic for which ER clinicians reported only the prevalent symptoms of the patients. Moreover, a proportion of subjects were unconscious at the time of arrival in the hospital or suffered of previous severe cognitive impairment so it was hard to access if neuromuscular symptoms were present or not. Furthermore, electrophysiological studies that could have been done to evaluate myopathy were infeasible during the COVID-19 epidemic.
In our cohort the mortality rate was 16.6% in line with previous studies 16. Interestingly, we found that elevated CK levels were related with respiratory failure rather than with SARS pneumonia, in accordance with literature data 5. Although it is impossible to establish a time-dependent relationship between respiratory failure and hyperckemia because of the retrospective nature of the study, we found that CK levels were significantly correlated to fatal outcome. Previous studies conducted during SARS-CoV outbreak found that CK is an important predictor of oxygenation failure and death in patients with Severe Acute Respiratory Syndrome 17,18. In 2007 Chan et al. made a retrospective analysis of 1312 patients affected with SARS showing that CK is one of the predictive elements of oxygenation failure and poor outcome in these patients 19. The most recent literature regarding SARS-CoV-2 infection reported raised serum CK levels in 33% of patients, reaching 46% for Intensive care unit patients 6. A Chinese retrospective study confirmed that median CK levels (normal values < 190) were higher in deceased patients (189 U/L) than in the other patients (84 U/L) 20. Recently, Bonetti et al. found that CK represents one of the laboratory predictors of death from Covid-19 21 while Pitscheider et al. showed a strong correlation among CK levels, disease severity and markers of inflammation 10. There are currently also a few published case reports of rhabdomyolysis with myalgia and fatigue associated with severe SARS-CoV-2 infection 22 with potential implications on renal function 23. Considered all together the above considerations, we thus can conclude that CK levels are correlated with the severity of COVID infection, more likely as an expression of myopathic involvement of skeletal and respiratory muscles during COVID-19 infection, rather than of a distress condition due to the strenuous respiratory muscle effort secondary to SARS interstitial pneumonia.
