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  • Writer's pictureP.K. Peterson

Fever vs Hyperthermia: Life-Saving vs Life-Threatening

“Not all records are meant to be broken. … We ignore science at our own peril.”

- Inger Andersen, director, United Nations Environment Programme


“It ain’t the heat, it’s the humility.”

- Yogi Berra, American professional baseball catcher, manager, and coach




Recently, a study published in Nature Communications revealed an elegant mechanism whereby elevated body temperature (fever) promotes increased resistance to influenza A virus and SARS-CoV-2, the virus that causes COVID-19. About the same time, two alarming heat-related events occurred: (1) July 3, 2023 was the hottest day ever recorded globally (Information from the U.S. National Centers for Environmental Prediction); and (2) during the last week of June, at least 13 people in Texas died from heat-related illnesses.


Elevated body temperature can either be good news or bad news. Fever is a good thing because it serves as an important host defense mechanism against invasive pathogens. But elevated body temperature due to extreme heat is not; it may signal a life-threatening condition called hyperthermia. In this Germ Gems post, I explain both.

Fever is your friend. Up until 1975, many scientists and clinicians (including me) believed fever to be detrimental. That year, the journal Science published “Fever and survival.” This study revolutionized the thinking of many of us about the crucial role fever played as a host defense mechanism. (See January 4, 2023 Germ Gems post, “Fever Is Your Friend.”)


Using cleverly designed boxes that allowed control of ambient (surrounding) temperature, University of Michigan physiologists demonstrated that when iguanas were challenged with a gram-negative bacterium they all died if they were prohibited access to an area in the box where the temperature was set at the level of a fever. But if the iguanas were allowed access to the heated area, they all survived. (Iguanas are cold-blooded animals, so the main way they elevate their body temperature is to find an area where the ambient temperature is elevated. You may have seen one sitting on a rock sunning itself.)


In the experiment recently described in Nature Communications, “High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection,” a group of Japanese scientists showed that exposure of mice to high ambient temperature (in the fever range) increased their resistance to these viral pathogens.


More interesting, however, was the discovery of the mechanism which involved the gut microbiota. The bacteria residing in the gut of high heat-exposed mice produced more bile acids that in turn increased host resistance (reduced viral replication) and suppressed tissue damage. The Japanese scientists concluded, “These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.”


Adding these recent findings to previous research supports the concept that “fever is your friend,” or, as stated in a 2021 publication in Evolution, Medicine, and Public Health, “Let fever do its job: The meaning of fever in the pandemic era.”

It’s all about homeostasis. Taken together with the alarming death toll due to heat exposure, the burgeoning evidence supporting the benefit of fever underscores the complexity of life. More important, it also underscores the validity of an organizing principal of physiology called homeostasis –“the self-regulating process by which an organism maintains internal stability while adjusting to changing external conditions.” Body temperature control in humans is one of the most familiar (and elegant) examples of homeostasis.


In response to invading pathogens, the body has several mechanisms for raising the body’s internal temperature including a resetting of the body’s temperature set point in the brain (and, presumably, calling on the gut microbiome). If you’re an adult and your temperature is 100 F (37.8 C) or higher you have a fever. Nature appears, however, to have put a lid on how high your temperature can go when you have a fever. To preserve homeostasis, fever is rarely, if ever, associated with a body temperature exceeding 106 F (41 C).


During exposure to extreme ambient temperatures (during a heat wave or a period of abnormally hot weather), homeostatic mechanisms are thrown out the window. Body temperature becomes elevated very quickly, despite there being no change of the set point in the thermoregulatory center of the brain. This condition of uncontrolled increased body temperature is referred to as hyperthermia. It is commonly held that the maximum temperature at which humans can survive is 108 F (42 C). At this temperature proteins may denature and cause irreparable brain damage.


Treatment of elevated body temperature. Now that you know that fever is generally a good thing, whereas hyperthermia is potentially life-threatening, you can understand why the remedy for the two conditions is so vastly different. In the case of fever, thank Mother Nature for providing humans with this homeostatic mechanism for fighting infection. The use of antipyretics, like aspirin or Tylenol, is of little or no value (except to the manufacturer). If, however, the fever is caused by a bacterial infection, an antibiotic is likely indicated.


Elevated body temperature due to extreme ambient temperature (hyperthermia), on the other hand, can be fatal. The urgent use of a cooling blanket or immersion in cold water can be life-saving. The Centers for Disease Control and Prevention’s (CDC) website, “Frequently Asked Questions (FAQ) About Extreme Heat” is an excellent resource on the epidemiology, clinical signs, and treatments of heat-related illnesses, such as, heat stroke, heat exhaustion, heat cramps, and heat rash. The same can be said for Cleveland Clinic’s website on “Heat Illness,” which includes advice about when to call your doctor.

Heat-related deaths and illnesses worldwide. According to the World Health Organization, from 1998-2017, more than 166,000 people died due to heatwaves, including more than 70,000 who died during a 2003 heatwave in Europe. In the U.S., the CDC reports that extreme heat kills more than 600 people every year. And globally because of climate change, extreme temperature events are increasing in their frequency, duration, and magnitude. (A “super El Nino” is brewing in the Pacific Ocean this year fostering heat-related emergencies.)


What about humidity? Nobody knows for sure what Yogi Berra, one of the greatest baseball catchers in history, had in mind by fracturing the word “humidity” in the above cited quote. But it prompted me to look into the role of humidity in fighting infection.


I was surprised to find that since the beginning of the COVID-19 pandemic a considerable amount of scientific evidence suggests that high humidity reduces the transmission of SARS-CoV-2 and other viruses. (See, for example, “Keeping indoor humidity levels at a “sweet spot” may reduce spread of Covid-19,” in MIT News by senior writer Jennifer Chu.) To me, Yogi’s use of the word humility had a purpose; it showed me there is always something new to learn.


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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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