Bacterial and fungal cultures were negative. A 22-year-old previously healthy male presented to our neurology clinic for chronic bilateral retroauricular tension headaches described as a 3/10 nonradiating squeezing pain with bilateral masseter muscle tightness and difficulty opening his jaw. This began shortly after a COVID-19 infection, diagnosed by PCR, 4 Amifampridine months prior to presentation. At the time, Omicron was the dominant strain, Amifampridine and he was unvaccinated. He initially also experienced severe malaise and myalgia for 4 days, which gradually resolved and did not require hospitalization. However, his headaches persisted. The patient reported no neurologic or systemic abnormalities. Physical exam and laboratory evaluation were unremarkable. Previous evaluations by a local emergency room and oral surgeon were negative for temporomandibular joint (TMJ) dysfunction and meningitis. Magnetic resonance imaging (MRI) revealed rim-enhancing fluid collections in the bilateral masticator spaces, measuring approximately 3.5 cm on the left and 1 cm on the right (Fig.?1). Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps demonstrated facilitated diffusion in the center of the lesions (Figs.?1C and D). Due to concern for possible infection, CT guided aspiration of the left fluid collection was performed. Bacterial and fungal cultures were negative. On cytopathology, numerous CD68 and PU.1 positive macrophages were present without malignant cells. The patient was diagnosed with myositis/myonecrosis of the bilateral masticator muscles secondary to COVID-19 and was given a 6-week prednisone course. The patient’s condition has greatly improved since beginning treatment with only mild residual left sided headache. Open in a separate window Fig. 1 (A) T2-weighted fat-suppressed and (B) contrast-enhanced T1-weighted DIXON fat-suppressed images show rim-enhancing fluid collections (arrows) involving the anterior aspect of the bilateral masticator spaces. (C) Diffusion-weighted and corresponding (D) apparent diffusion coefficient (ADC) map shows facilitated diffusion in the center of the fluid collections. Discussion Myositis specifically due to COVID-19 was not formally reported until September 2020 [3]. Since then, many additional case reports have been published demonstrating various musculoskeletal manifestations including myasthenia, dermatomyositis, rhabdomyolysis, paraspinal myositis, and asymptomatic rises in creatinine kinase [2]. However, despite an increasing understanding in literature, there has not yet been a case of COVID-19-related myositis or myonecrosis presenting in the head and neck region to the best of our knowledge. The precise mechanisms involved in the development of COVID-19-related myositis and myonecrosis is unknown. In general, there Timp1 is strong evidence suggesting that autoimmune sequela of COVID-19 is due to a massive pro-inflammatory cytokine reaction, termed a cytokine storm, with additional contributions from hyperactivated T-cells, monocytes, macrophages, and neutrophils [4]. While these mechanisms are perhaps most associated with acute respiratory distress syndrome and multiorgan dysfunction syndrome, it’s plausible that they may also underlie myositis. Specific damage to muscle tissue can occur due to abnormal activation of the adaptive immune system. SARS-CoV-2 proteins show 3 immunogenic linear epitopes that are highly similar in sequence to ones found in autoimmune dermatomyositis, suggesting similar pathophysiology through T-cell antigen presentation [5]. Stimulation of humoral immunity, cross-reactivity due to molecular mimicry, and direct-intake of viral antigens by myocytes through the ACE2 receptor are additional proposed mechanisms of muscle inflammation [2]. Lastly, a subset of myonecrosis cases may be a consequence of COVID-19s thrombotic and vasculitic milieu, possibly augmented by compartment-syndrome [6]. Diagnosis of head and neck myositis secondary to COVID-19 can be difficult given the lack of previous reports and the broad differential diagnosis for head and neck myalgia. Physicians should first rule out common or life-threatening etiologies, such as TMJ dysfunction, cluster headaches, or meningoencephalitis. After this, clinical and laboratory evaluation can provide important clues. In general, COVID-19-related myositis presents in males aged 33-88 years old [2]. While elevations Amifampridine in muscle enzymes are often present, they are not a reliable indicator of diagnosis or prognosis [2]. Radiographic evaluation is equally as important. In cases of COVID-19-associated rhabdomyolysis, computed tomography (CT) imaging can demonstrate Amifampridine hypoattenuation with or without rim-enhancement on postcontrast images [7]. When possible, MRI is the imaging modality of choice [8]. Two patterns of imaging findings are a.