Discussion
The acute symptoms of COVID-19 include headache, fever, cough, anosmia, dysgeusia, and myalgia, and, in severe cases, respiratory and multiple organ failure (2). In addition to these acute symptoms, several individuals develop longer-term COVID-19 sequelae, among these being ME/CFS. The combination of morbid fatigue, pain, and cognitive–affective symptoms associated with ME/CFS, all of which may worsen after exertion, can significantly reduce quality of life. As there is still no established treatment for ME/CFS, its impact on rehabilitation and nursing care as well as multiple medical fields is immeasurable (9). Given the difficulty in diagnosing ME/CFS, patients who have recovered from the acute phase of COVID-19 but who still present with symptoms often wait several years before receiving appropriate care for ME/CFS; this prolonged period without an effective diagnosis may contribute to the 30% of patients who develop depression and other psychiatric complications during long COVID (10).
In an attempt to facilitate timely diagnosis, the National Academy of Medicine proposed diagnostic criteria for ME/CFS in 2015 and, in the process, suggested a new term, systemic exertion intolerance disease, to replace the combined phrase of ME/CSF (7, 11). Of the proposed criteria (Table 3), two factors were especially salient for our patient and, therefore, were pivotal in directing our attention to the possibility of ME/CFS in the context of post-COVID recovery. The first factor is PEM, which is clearly stated in the diagnostic criteria. Often when a patient presents with concerns of muscle pain or weakness, the treating physician will advise exercise, which, in turn, may exacerbate rather than ameliorate the disease and prompt further psychological distress. In ME/CFS, any form of strenuous exercise should be avoided. In contrast, graded exercise therapy and cognitive behavioral therapy have been reported to be safe and effective (12). The second factor that led to an accurate diagnosis of ME/CFS for our patient is serum acylcarnitine. A literature search for “(”acylcarnitine”[tiab]) AND (”fatigue syndrome, chronic”[MeSH] OR ”chronic fatigue syndrome”[tiab] OR ”myalgic encephalomyelitis”[tiab] OR ”systemic exertion intolerance disease”[tiab])” in PubMed revealed 13 references, of which only 4 were from the last 20 years (5, 13-15). Despite varied opinion in these references about the precise role of l-carnitine in fatty acid oxidation, there is widespread agreement that ME/CFS is associated with changes in acylcarnitine and l-carnitine homeostasis (16). Viral infections are known to disrupt the mitochondrial fatty acid oxidation cascade (17), thus potentially contributing to a decrease in serum acylcarnitine. Consistent with this, research indicates that the rates of ME/CFS increase in conjunction with viral infections, including SARS-CoV-2. As we found in our case study, when ME/CFS is suspected, it may be useful to measure serum acylcarnitine level even if other laboratory tests are negative. We look forward to the development of effective laboratory tests and treatments with the accumulation of more cases in the future.