I. (2021). parasite (Krl\Turmiska & Olender, 2017; Varikuti et?al.,?2018; Xiao et?al.,?2018). 1.2. BI 2536 Protozoan parasite infections and other protozoan parasites have achieved intracellular infections in over a billion people (Krl\Turmiska & Olender, 2017; Varikuti et?al.,?2018; Xiao et?al.,?2018). protozoan parasites typically infect people after food or water ingestion (Krl\Turmiska & Olender, 2017). experiences three life stages: tachyzoites during active infections, bradyzoite tissue cysts during latent infections, and sporozoites to infect new hosts from contaminated food or water (Xiao et?al.,?2018). Besides infections by congenital transmission from mother to fetus, or sporadic\infected organ or tissue transplants, a new host is acquired by ingestion of sporozoites that release activated protozoa to breach the gastrointestinal epithelium, particularly in the small intestine, and enter the host’s circulatory system (Xiao et?al.,?2018). and other protozoan parasites can create latent infections of the brain and central nervous system (CNS), through tissue cysts in hosts and cause immune system dysfunctions (Xiao et?al.,?2018). has documented links to several neuropathologies, especially recent onset psychiatric illnesses in some individuals, including schizophrenia, bipolar disorders, obsessive\compulsive disorders, autism, and general anxiety disorders (Xiao et?al.,?2018). 2.?DISCUSSION bradyzoites have been observed in muscles, brain neurons, and the CNS including eye retinas (Xiao BI 2536 et?al.,?2018). Individuals having infections exhibit brain neuroinflammation, activated microglia and astrocytes in the brain, and complement factor C1q, which can ultimately initiate the classical complement pathway (Xiao et?al.,?2018). In addition, cysts in the brain can induce major disruptions in the levels of the metabolite kynurenine and neurotransmitters including glutamate, gamma\aminobutyric acid, and dopamine (Xiao et?al.,?2018). These neurotransmitter disruptions could also explain some cases of schizophrenia (Xiao et?al.,?2018). Long duration latent infections can also result in CD8 T\cell exhaustion, which is capable of ultimately inducing reactivations and localized tissue inflammations (Xiao et?al.,?2018). It is interesting that T\cell exhaustion, such as CD8 T\cell exhaustion, and a weaker antiviral response have also been documented in COVID\19 patients who have more severe infections and outcomes (H. Y. Zheng et?al.,?2020; M. Zheng et?al.,?2020). 2.1. Evidence of microglial activation and microglial nodules in brain autopsies of COVID\19 fatalities It has been recently reported that 41 patients, with ages ranging from 38 to 97?years, who died from COVID\19, had brain autopsies in 2020 at the Columbia University Irving Medical Center (Thakur et?al.,?2021). The patients tested BI 2536 before death showed elevated inflammatory cytokines, including elevated interleukin\6 (IL\6) in 26 (96%) of the 27 patients tested (Thakur et?al.,?2021). The neuropathological examination of 20 and up to 30 areas from each mind found microglial activation in 34 of the 41 brains (81%) (Thakur et?al.,?2021). Microglial clusters (microglial BI 2536 nodules) were found in 26 of the brains (63%), becoming most common in the brainstem, and neurons were found in some of the microglial nodules, which were interpreted as neuronophagia (Thakur et?al.,?2021). However, viral RNA and viral proteins were not significantly recognized in the brain cells or the microglial nodules, while acute and subacute hypoxic damage was reported for each and every mind; therefore the formation of the microglial nodules was attributed to hypoxia, instead of BI 2536 the RNA disease SARS\CoV\2 (Thakur et?al.,?2021). It is well recorded that mind hypoxia disrupts the bloodCbrain barrier (BBB), causing leakage of pro\inflammatory plasma proteins, including immunoglobulins, fibrinogen, and match (Lana et?al.,?2020). It is also well recorded that microglial activation and perivascular microglial clusters can be caused by fibrin deposition from perivascular leakage of plasma protein fibrinogen into areas of BBB disruption (Devalos et?al., 2012). In Layn addition, the formation of apoptotic neuronCastrocyteCmicroglia triads and considerable damage to the myelin sheath (demyelination) from oxidative stress and inflammatory stress has been well recorded for mind hypoxia/ischemia (Lana et?al.,?2020). But while neurons were found in some microglial nodules, no apoptotic neuronCastrocyteCmicroglia triads were reported, and there was no evidence of any demyelination seen in any of the brains autopsied (Thakur et?al.,?2021). If.