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.