The Coronavirus is officially called SARS-CoV-2.
Covid-19 is the disease caused by SARS-CoV-2.
SARS is the disease caused by SARS-CoV-1 (also called SARS-CoV)
The following papers support the conclusion that the virus which causes Covid-19 has the capability, and in fact often exercises that capability, to invade brains in the central nervous system, including the brain itself and cranial nerves.
0. Moldofsky H., Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011;11:1–7. — Shows that SARS-CoV-2 can cross BBB into brain.
1. Huang, Jianhan, et al. “Potential of SARS-CoV-2 to cause CNS infection: biologic fundamental and clinical experience.” Frontiers in Neurology 11 (2020): 659.
* “In this review, we have summarized the possible mechanism for SARS-CoV-2 induced CNS infection, and conduct analysis on the potential of SARS-CoV-2 to cause CNS infection.”
2. Jakhmola, Shweta, et al. “SARS-CoV-2, an Underestimated Pathogen of the Nervous System.” SN Comprehensive Clinical Medicine (2020): 1-10.
* “Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts…. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Additionally, transmembrane serine protease 2 (TMPRSS2) and furin facilitate virus entry into the host.”
3. Lima, Maria, et al. “Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System.” Current Treatment Options in Neurology 22.11 (2020): 1-15.
* “SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. ?he olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS.”
4. Machado, Calixto, and Phillip A. DeFina. “Can SARS-CoV-2 invade the brain through an ocular route?.” Researchgate.net
*”The presence of the ACE2 receptors and TMPRSS2 protein on the corneal limbal stem cells may theoretically allow the SARS-CoV-2 to cross the ocular surface, and then entering the nervous system via the ophthalmic branch of trigeminal nerve…. ”
*”Astheeye surface is mainly exposed for virus contamination,2theoretically SARS-CoV-2 may invade the brain using synapse-connected routes from the cornea, retina, optic nerve.5Moreover, as the optic nerve subarachnoid space is filled by cerebral spinal fluid (CSF),4this might be other route for the virus to reach the CSF, widely spreading its infection.”
5. Ansari, Ahmed, And Sadaf Riyaz. “Letter to the Editor: Transneural transmission in COVID-19 without a positive nasopharyngeal swab.” Surgical Neurology International 11.284 (2020): 1.
* “Brain infection in COVID-19 patients is being seriously considered recently, owing to multiple reports of stroke, epilepsy, and encephalitis. ACE-2 expression in glia and neurons of brain is low, but well documented. SARS-CoV-2 invading high ACE-2 expressing non-neuronal olfactory epithelial cells is one such possibility and then passing to low ACE-2 expressing mature olfactory receptor neurons to be finally transported along olfactory axons to the brain. ?e lateral stria of olfactory tract carries axons to the primary olfactory cortex, located in the uncus of the temporal lobe. ?is can be argued as an important reason for the inflammation in medial temporal cortex and hippocampus in such patients.”
6. Wang, Lei, et al. “Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis.” Journal of Neurology (2020): 1-13.
* “Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses.
7. Uversky, Vladimir N., et al. “SARS-CoV-2 infection reaches the human nervous system: How?.” (2020).
* SARS-CoV-2 “can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARSCoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.”
8. Li, Zhengqian, et al. “Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain.” Frontiers of Medicine (2020): 1-9.
* “In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature andperipheral nerves.”
9. Orrù, Graziella, et al. “Neurological Complications of COVID-19 and Possible Neuroinvasion Pathways: A Systematic Review.” International Journal of Environmental Research and Public Health 17.18 (2020): 6688.
* “Given the rapid evolution of the pandemic emergency and in the light of the increasing amount ofclinical data reporting neurologic involvement in COVID-19, further investigations are required to betterunderstand the underlying pathogenic mechanisms of SARS-CoV-2 neuro-invasion.”
10. Song, Eric, et al. “Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model.” BioRxiv (2020).
* “These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV2.”
11. De Felice, Fernanda G., et al. “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System.” Trends in neurosciences (2020).
“Human neurodegenerative diseases often involve a gradual process that evolves, in some cases, over several decades. Large numbers of young adults worldwide are now infected, or will be infected in the near future, by SARS-CoV-2. For some, the severity of the disease will require hospitalization, opening up the possibility of detailed medical examination which could be leveraged for longitudinal studies, as discussed later. Literature on previously studied viruses raises the possibility that SARS-CoV-2 may affect the CNS.”
12. Liu, Jia‐Mei, et al. “Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement in the lethality of SARS‐CoV‐2 infection.” Journal of Medical Virology. 01 October 2020.
* “Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in 9 studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2.”
* “SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory and trigeminal pathways, especially at the early stage of infection.”
13. Cheng, Qi, Yue Yang, and Jianqun Gao. “Infectivity of human coronavirus in the brain.” EBioMedicine 56 (2020): 102799.
* “At present, it remains unclear the extent to which SARS-CoV-2 is present in the brain, and if so, its pathogenic role in the central nervous system (CNS). Evidence for neuroinvasion and neurovirulence of hCoVs has been recognised in animal and human studies. Given that SARS-CoV-2 belongs to the same family and shares characteristics in terms of receptor binding properties, it is worthwhile exploring its potential CNS manifestations. ”
14. Zubair, Adeel S., et al. “Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review.” JAMA Neurology (2020).
* “ACE2 expression has been identified in the motor cortex, cytoplasm of neurons, glial cells, and sympathetic pathways in the brainstem. In neuronal cell cultures, ACE2 is expressed both on the surface membrane and in the cytoplasm. Widespread ACE2 expression in the brain raises the concern that SARS-CoV-2, similarly to SARS-CoV-1, has the potential to infect neurons and glial cells throughout the CNS.”
15. DosSantos, Marcos F., et al. “Neuromechanisms of SARS-CoV-2: a review.” Frontiers in neuroanatomy 14 (2020): 37.
* “Some studies have demonstrated that synapse-connected routes may enable coronaviruses to access the central nervous system (CNS). However, evidence related to the presence of SARS-CoV-2 in the CNS, its direct impact on the CNS, and the contribution to symptoms suffered, remain sparse. Here, we review the current literature that indicates that SARS-CoV-2 can invade the nervous system. We also describe the neural circuits that are potentially affected by the virus and their possible role in the progress of COVID-19.”
Covid-19 mainly affects the respiratory system. Alternately, some cases affect the GI tract, with little involvement of the lungs. However, LongCovid is primarily a neurological disorder. If you subtract the neurological symptoms, and then treat the patient with ivermectin or steroids (not both at the same time!!), there is nothing left of the disease.
What Causes LongCovid? I independently arrived at the same answer to this question as William Petri, M.D. Ph.D., that the SARS-CoV-2 virus, which causes Covid-19, has become established in Immune Privileged Sites, especially the CNS. The usual treatments that work on Covid-19, work only partially on LongCovid. Ivermectin is highly effective against Covid-19, but it only reduces symptoms temporarily in LongCovid. Steroids have a similar effect on Covid-19 and LongCovid.
The above articles provide ample evidence that LongCovid is caused by a neuro-invasion of the CNS by SARS-CoV-2. The virus becomes established, in relative safety from the immune system, behind the BBB. Treatments for LongCovid must meet certain criteria.
1. The treatment must address the usual infection of the virus outside of Immune Privileged Sites, as these appear to be infected in a cyclic manner in LongCovid.
2. The treatments must cross the BBB and effectively inhibit the virus within neurons and other cells in the CNS.
3. Multiple inhibitors of SARS-CoV-2 which cross the BBB will be needed for effective inhibition, therefore the set of inhibitors must target all of the main viral proteins: Spike, N-protein, Mpro, PLpro, RdRp, as well as Nsp9, 14, 15, 16.
Which combination of medications and supplements will meet these criteria? I’m working on it.
Ronald L. Conte Jr.
an author, not a doctor