Discussion
We describe the case of a 47-year-old man positive for severe acute
respiratory syndrome coronavirus 2 who presented with a 4-day history of
fever and dyspnea. His chest computed tomography findings were
consistent with those of COVID-19 pneumonia; laboratory test results and
clinical findings revealed multiorgan failure and extremely elevated
creatine kinase (CK) levels. The proportion of CK-MB was not high; thus,
we did not suggest heart diseases. However, several other differential
diagnoses, such as malignant hyperthermia, malignant syndrome, and
rhabdomyolysis, were thought of causing severe CK elevation. As the
patient was not taking any volatile anesthetic (for example,
halothane, isoflurane, sevoflurane, desflurane), succinylcholine,
or antipsychotic drugs, malignant hyperthermia and malignant syndrome
were ruled out. However, the CK elevation was later thought to be a
symptom of rhabdomyolysis. Moreover, his initially remittent fever later
developed into the sustained type, a sequela that has not yet been
associated with previous COVID-19 cases.
Furthermore, altered consciousness, multiorgan failure, and extreme
hyperthermia with a temperature > 40.5°C are symptoms
consistent with heatstroke. 3 In addition, the patient
had a 5-year history of untreated diabetes mellitus that could have had
a role in the disease course and outcome of the patient, which should be
investigated in subsequent similar reports.
In addition to these findings, the symptoms of multiorgan failure began
to show signs of improvement upon regulation of the body temperature
using VA-ECMO. This suggests that the patient’s symptoms may have been
caused by heat stress. In the case of heatstroke, oxidative
phosphorylation becomes uncoupled because of extreme hyperthermia and a
variety of enzymes cease to function. A cytokine-mediated systemic
inflammatory response develops, and the production of heat-shock
proteins is increased. Blood is shunted from the splanchnic circulation
to the skin and muscles, resulting in gastrointestinal ischemia and an
increased permeability of the intestinal mucosa. Hepatocytes, vascular
endothelium, and neural tissue are most sensitive to increased core
temperatures, but all organs may ultimately be involved. Typical
symptoms of heatstroke are a rectal core temperature of 105°F (40.6℃) or
greater, multiorgan damage, and central nervous dysfunction,4 and in severe cases, circulation failure and
disseminated intravascular coagulation are found. 5His clinical symptoms are consistent with heatstroke, but the absence of
environmental factors that could have caused this condition makes
proving an association between this case and heatstroke difficult. We
thought that the heat dissipation mechanism could be disrupted by
COVID-19, which caused prolonged hyperthermia and acute physiological
alterations such as circulatory failure, hypoxemia, and increased
metabolic demands, and direct heat-related cytotoxic effects could
escalate, causing multiorgan failure. Despite all this, it must be noted
that fever has beneficial effects, such as strengthening the immune
response.6 Proactive core body temperature regulation
such as using extracorporeal apparatus is usually not conducted for
hyperthermia but should be considered in cases of COVID-19.