ABSTRACT
OBJECTIVES: Myalgia is a widely publicised feature of Covid-19, but severe muscle injury can occur. This systematic review summarises relevant evidence for skeletal muscle involvement in Covid-19. METHODS: A systematic search of OVID and Medline databases was conducted on 16/3/2021 and updated on 28/10/2021 to identify case reports or observational studies relating to skeletal muscle manifestations of Covid-19 (PROSPERO: CRD42020198637). Data from rhabdomyolysis case reports were combined and summary descriptive statistics calculated. Data relating to other manifestations were analysed for narrative review. RESULTS: 1920 articles were identified. From these, 61 case reports/series met inclusion criteria, covering 86 rhabdomyolysis cases. Median age of rhabdomyolysis patients was 50 years, (range 6-89). 49% had either hypertension, diabetes mellitus or obesity. 77% were male. Symptoms included myalgia (74%), fever (69%), cough (59%), dyspnoea (68%). Median peak CK was 15,783U/L. 28% required intravenous haemofiltration and 36% underwent mechanical ventilation. 62% recovered to discharge and 30% died. Dyspnoea, elevated CRP and need for intravenous haemofiltration increased risk of fatal outcome. Additional articles relating to skeletal muscular pathologies include 6 possible concomitant diagnoses or relapses of idiopathic inflammatory myopathies and 10 reports of viral-induced muscle injuries without rhabdomyolysis. Localised myositis and rhabdomyolysis with SARS-CoV-2 vaccination have been reported. CONCLUSIONS: Rhabdomyolysis is an infrequent but important complication of Covid-19. Increased mortality was associated with a high CRP, renal replacement therapy and dyspnoea. The idiopathic inflammatory myopathies (IIM) may have viral environmental triggers. However, to date the limited number of case reports do not confirm an association with Covid-19.
ABSTRACT
Background/AimsIt is increasingly understood that COVID-19 has a very broad range ofmulti-system manifestations. Myalgia is a widely publicised feature ofSARS-CoV-2 infection, however, more severe muscle injury can occur.There are several case reports of rhabdomyolysis with markedelevation in creatine kinase (CK) and myoglobinuria, leading to acuterenal failure, but also reports of myositis characterised by weakness, mildly raised CK and muscle oedema on MRI. We present a systematicliterature search to evaluate the clinical characteristics of skeletalmuscle involvement.MethodsA systematic search for terms related to "SARS-CoV-2" and "myalgia", "myositis", "rhabdomyolysis" or "muscle" was performed across foursearch engines (Web of Science, Pubmed, Mednar and Medrxiv) on10/09/2020. Only original research published or translated in Englishwas included. Information relating to skeletal muscle injury inconfirmed SARS-CoV-2 infection was summarised.ResultsThe search protocol identified 980 articles of which 200 wereappropriate for abstract review. 21 case reports covering 22 patientswith rhabdomyolysis were found. Other muscular pathology notdefined as rhabdomyolysis by authors, included 1 case of acutemyositis leading to compartment syndrome, 2 cases of myositis withclassical proximal weakness, elevated creatine kinase and proximalmuscle oedema on imaging, and one series of 7 patients withparaspinal myositis on MRI imaging. A histopathological study foundevidence of incidental myositis in 2 cases. Critical care myopathy andpolyneuropathy are described, along with many other neurologicalmanifestations. While 91 cohort studies were identified, none looked indetail at skeletal muscle involvement. There are 8 meta-analyses whichfind the prevalence of myalgia between 19-33%. The age ofrhabdomyolysis patients appears lower than expected for covid-19admissions at 46.7 years, but ranged from 16 to 88. Baselinecharacteristics mirror those at higher risk of severe covid-19: halfhad either hypertension, type 2 diabetes or obesity and 86.4% weremale. Common accompanying symptoms were myalgia (81.8%), fever(68.2%), cough (59.1%), dyspnoea (40.9%). Median peak CK was22, 511IU/L. 68.2% had changes consistent with covid-19 on chestimaging. Intravenous haemofiltration or mechanical ventilation wereeach required by 4 patients. Short term prognosis showed 18 (81.8%)being discharged, 2 deaths (9.1%) and 2 unknown outcomes. ConclusionSevere skeletal manifestations such rhabdomyolysis occur in covid-19. More research is needed to discover if this is through direct viralinvasion of the tissues, or indirectly via systemic cytokine release, hyperlactataemia and hypo-oxygenation. CK should be routinelychecked in those critically unwell or with severe myalgia or weaknessto identify treatable rhabdomyolysis early. Chronic autoimmuneconditions such as the idiopathic inflammatory myopathies may haveviral environmental triggers, and one case tested positive for a myositisspecific antibody. Whether patients with acute covid-19 relatedmyositis experience ongoing long-term muscle inflammation has notyet been reported.