DISCUSSION:
ChAdOx1 nCoV-19 is a recombinant, replication-deficient chimpanzee adenovirus vector which encodes the SARS-CoV-2 Spike (S) glycoprotein. When administered, it causes the genetic material of part of the coronavirus to be expressed, thereby stimulating an immune response. Direct inoculation of vaccine via an intramuscular route exposes the muscle to these modified contaminant agents and elicits an immune response to the antigen injected [7].
Autoimmunity associated with vaccines can be attributed to the cross-reactivity between antigens or to the effect of adjuvants [8]. ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants) is a complex entity referring to the autoimmune manifestations that appear to be caused by adjuvants and may be related to specific HLA phenotypes, the development of autoantibodies, or even evolve into a rheumatological disorder [9]. ASIA is characterised by inflammatory musculoskeletal, neurocognitive, and/or constitutional symptoms on exposure to an external stimulus and improves when the stimulus is withdrawn[9]. Recently, Das et al.[10] have reported a case of ASIA syndrome following the first dose of the ChAdOx1 nCoV-19 vaccine in a 47-year-old patient, manifesting as subacute thyroiditis.
It is known that COVID-19 can lead to myositis and rhabdomyolysis due to immune hyperactivation and excessive cytokine release[11]. The antibodies against SARS-CoV-2 spike glycoproteins cross-reacting with structurally similar host proteins (molecular mimicry) have been suggested as a possible cause for this acute autoimmune response. Other proposed mechanisms include cytokine-mediated autoinflammation, CD8 T-cell overactivation, formation of antigen-antibody complexes, and structural deformity of myocytes caused by intake of viral antigen[11]. It has been suggested that the COVID-19 vaccination could also trigger such a response[12]. However, the exact mechanism remains unclear. The clinical features suggestive of COVID-19-induced myositis include proximal muscle weakness, myalgia, features of muscle inflammation in MRI, dermatomyositis, and rhabdomyolysis evidenced by elevated CK and myoglobinuria[11].
Theodorou et al.[7] have reported a case similar to ours, with a 56-year-old woman presenting with myalgia and progressive muscle weakness that started 8 days after the second dose of COVID-19 vaccination. As opposed to our case, the symptoms were limited to the left upper arm, where the vaccination was given. Myositis was diagnosed based on elevated CK and typical MRI findings. Maramattom et al.[1] have recently reported three similar cases, all of which showed features of inflammatory myositis on MRI, while one patient showed features of vasculitis in addition to myositis on biopsy.
CK levels in myositis are variable. Though CK levels are raised in most cases of inflammatory myopathy, they may be minimally elevated or even normal in some cases like inclusion myositis. Although injection site myositis has been reported following various vaccinations, it is usually associated with elevated CK. Our case showed myositis in the injection site and in other muscles following the COVID-19 vaccine, though CK was only mildly raised, with radiologic evidence of myositis and considerable patient symptoms and activity limitation. This merited medical attention since ChAdOx 1 nCoV 19 is a newly developed vaccine that is under Emergency Use Authorization.
Although muscle biopsy was not performed in our patient, the temporal link between the vaccination procedure and the patient’s symptoms, imaging features, the reversible nature of symptoms, and lack of alternative cause suggests a diagnosis of COVID-19 vaccine-associated myositis as the cause. In addition, the other possible causes of muscle edema, like trauma, infection, neoplastic infiltration, and infarction (as in microvascular disease like diabetes mellitus), were not present in this case. Though the symptoms were mild, they incapacitated the patient for some time, resulting in a loss of work days, which was relieved with rest and NSAIDs, not requiring treatment with steroids. Hence, we are reporting this case, which might lead to the formulation of newer studies to look into the mechanistic pathways of COVID-19 vaccine associated myositis.