Cordyceps brain infection – life cycle and pathogenesis



Widely known as Cordyceps brain infection, the fungal human pathogen Ophiocordyceps internicivus is a newly emerged species of “zombie fungus”, first described by Newman in 1970 as an endemic infection in Argentina and later, in 2003 by Ratna Pertiwi as the cause of a full-scale epidemy in Jaccarta. It is a highly aggressive species, first believed to be a mutated strain of O. unilateralis, but later found to be an entirely different species, initially restricted to small rodents in South America. In the current study, we summarized all known information on this significant pathogen, because of its significance for the current epidemiology.


Ophiocordyceps internicivus (Newm.) Pert. (2003) is a potent fungal pathogen, responsible for an apocalyptical pandemic on the Biblical scale, comparable to several viral pandemics (for reference: RECENT VIRAL OUTBREAKS OF BIBLICAL SCALE, Scientia Supernaturalis, February 2023). It drove the human species near extinction during the 2000s by transforming approximately 2/3 of the human population into aggressive mindless beings, eventually causing death. With time, when enough studies were done, it appeared that the life cycle of this parasite is much more complicated than previously thought, and the theory for a host jump from ants to humans of the known pathogen, O. unilateralis, is not plausible. Furthermore, the physiological differences between humans and ants are so significant, it was not hypothesized that such a pathogen could not overcome the species barrier. Later, it was found, that this fungal species is actually quite old in the evolutionary sense, but a previously unknown parasite on several species of rodents in South America, that incidentally infected the zero patient and then burst into the human population.


Unlike O. unilateralis and other fungi, the Cordyceps brain infection cannot spread airborne. It does form spores, but they do not contain the necessary adaptations to penetrate through the skin, and when inhaled, they cause the much less significant Cordyceps lung infection, similar to pneumonia and still deadly, but not transformative for the individual. It must be stated here, that unlike viruses and bacterial pathogens, the spores of the human Cordyceps do not travel by the bloodstream. Usually, when occurring inside a blood vessel, they attach and start to grow rapidly, forming mycelia with clear taxis toward the brain tissue. Therefore, the main mean of dispersal is through bites. Accordingly, the fruiting bodies of the human Cordyceps are formed inside the mouth, protruding from the sphenoid sinus through the soft palate. In approximately 5% of the cases, some spores travel through the veins to the heart, where they cause Cordyceps heart infection, characterized by sudden cardiac arrest and death. In the rest, the fast-growing mycelia reach the central neural system and form a fungal body around the main brain. According to a leaflet, distributed by FEDRA (Federal Disaster Response Administration), the complete infection occurs between 5 minutes (if the initial penetration into the bloodstream was near the neck) and 24 hours (when the bite from the infected person was on the leg). However, this was estimated based on the assumption, that the fungus reaches the brain by traveling through the bloodstream. Actually, the mycelia grow much slower, by several cm per day and full infection may be expected within 12 hours of minimum.


As well known, people, infected with Cordyceps brain infection undergo a slow transformation, starting with behavioral changes due to manipulation of the hormonal secretion from the hypothalamus and neuronal transmitters like a dopamine analog, secreted by the fungus itself. The infected person turns more aggressive and uncoordinated, gradually losing memory and consciousness, mainly because of the fungus selectively destroying the neurons of the temporal (responsible for memory), frontal (responsible for voluntary actions), and parietal (responsible for pain perception) lobes.

Fruiting bodies, or sporocarps, of the fungus, are formed within the next 5-6 hours and remain constantly active during the entire transformation process. Within them are the first known inter-Kingdom hybrid cells, formed by the fusion of fungal and human muscle cells, thus capable of limited active movements. First thought to be a composite, similar to lichens, now is established they are actually hybrid cells with multiple nuclei of both fungal and human origin. Such transformed individuals tend to aggressively attack and bite uninfected persons but for some reason do not attack other transformed individuals.

Finally, within several weeks when the storage compounds (fats and glycogen) of the infected person are depleted, the final stage of transformation occurs, when the mycelia protrude from the body of the infected and induce a stage of stasis. In fact, during the early stages of infection and transformation, the fungus feeds on the body of the host, while in later stages the mycelia decompose nutrients from the environment, feeding from the soil and providing nutrients to the host. By secreting a plethora of antibiotics, it also prevents the decomposition of the already dead, but still functioning body.

Long-distance communication

Probably the most puzzling feature of O. internicivus is its ability to communicate over long distances, observed by the ability of an infected person in stasis to “call for help” other transformants. The first theory was that the mycelia from many infected hosts in the late stage of transformation do form underground connections and secrete signaling molecules to communicate. However, although true, such a form of communication is not sufficient for the sophisticated behavior observed. Just recently, it was found that the underground connections are actually established by the second type of hybrid fungal-human cells, formed by fusion between mycelia and human neurons and functioning pretty much like an enormous collective brain. Such links are easily disrupted and formed again.

Species specificity

Very much like other fungal (and non-fungal) pathogens, O. internicivus is strictly specific to humans and apes. However, it should not be forgotten that it originated in a rodent species and it is very possible it could jump again to another mammalian species, which in turn could cause a species extinction on a much larger scale.

Immunity and Perspectives for a Cure

Since now, it is known, that if for some reason the initial infection does not develop into the transformative stage, the resident fungus releases substances, which prevent further infection from another spore. Such substance is also released from the first spore to develop. However, the isolation and production of this compound proved difficult, if not impossible, till now.

The current perspective for successful treatment of Cordyceps brain infection is focused on the identification of a possible hyper (or epi) parasite, a fungus, which is parasitic on the Cordyceps, as such is known to exist in O. unilateralis and is actually very effective in restricting the devastating potential of this pathogen in ants.


  • Naughty Dog, LLC (2013) The Last of Us. Sony Computer Entertainment.
  • Craig Mazin, Neil Druckmann (2023) The Last of Us. HBO.

Leave a Reply

Your email address will not be published. Required fields are marked *