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.