Can All Variants of COVID-19 Infect the Brain?

Highlights:

The primary variants of COVID-19 include the original SARS-CoV-2 (Wuhan)- Alpha, Beta, Gamma, Delta, Omicron, and recombinants
All variants of COVID-19 have the ability to enter the brain and spread to nerve tissue, primarily through the olfactory network
The Omicron variant is more virulent in impacting brain cells than all other variants

SARS-CoV-2 which causes COVID-19 infects upper and lower respiratory tract cells causing a wide range of respiratory and extra-respiratory symptoms, including neurological ones such as headache, dizziness, anosmia, and even stroke.

Although COVID is linked to a wide range of neurological symptoms, both acute and chronic, it is still unclear if the virus is actually causing brain cell infection or if the systemic inflammatory response is the primary cause of these cognitive problems.

Coronavirus
Coronaviruses infect animals, humans, and birds. Human coronaviruses, such as SARS, MERS, and 2019-nCoV cause respiratory distress and even death. The S protein is the infectious agent of the virus.

‘Did you know? COVID-19 and all of its variations affected the brain's olfactory regions regardless of whether anosmia was present or not. #covid19 #covidvariants #brainhealth #neuralnetwork #medindia’

Tweet it Now

What are all the Variants of COVID-19?

Several variants of concern (VoCs) based on their evolution include:

2019: original SARS-CoV-2 (Wuhan) - Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1.
2020: VoC Delta B1.617.2, AY
2021–2022: VoC Omicron and its lineages - BA.1, BA.2, and BA.5 and recombinants (XBB)

All of these COVID-19 variations have the ability to infect nerve tissue and enter the brain, primarily through the olfactory nerves. It was found that olfactory impairment is mostly induced by the SARS-CoV-2 ORF7 mutant ().

Test your Knowledge on Coronavirus (COVID-19)
Coronavirus is a large positive-strand RNA virus that is surrounded by a protein envelope. The virus obtains its name from the S protein spikes on its surface, which resemble a crown. The overall pattern of increasing coronavirus cases is shown to ...

The Respiratory-Brain Link in COVID-19 Infection

After comparing infection with the 2020 original SARS-CoV-2 virus to a number of later variants, including the Gamma, Delta, and Omicron/BA.1 variants, it was discovered that all of the variants had comparable neuroinvasive potential. Most remarkably, all variations infected the olfactory areas of the brain, independent of the presence or absence of anosmia (loss of smell) symptoms ().

SARS-CoV-2 is shown to enter the brain primarily through the olfactory pathway in vivo and to move both retrogradely and anterogradely down axons in microfluidic neuron-epithelial networks in vitro. It was proposed that axonal transport by cranial nerves (olfactory, vagus, and trigeminal) or the hematogeneous route might cause SARS-CoV-2 neuroinvasion.

There was a clear "variant-effect" in both the tissue-related inflammation and the clinical presentation, with the illness severity manifesting in the following order:

SARS-CoV-2 Wuhan > Gamma > Delta > OmicronBA.1.

This suggests that Omicron/BA.1 evolution has led to a tropism more limited to the upper respiratory tract, hence creating a less severe clinical illness.

Beyond identifying viral RNA and isolating the infectious virus from the olfactory bulbs, SARS-CoV-2's neuroinvasive capacity allowed researchers to see SARS-CoV-2-infected brain neurons with excellent clarity.

Even though clinical presentations evolved more similarly among COVID-19 variants, anosmia was less common in animals infected with SARS-CoV-2 Wuhan when compared to other variants. It may also be connected to the less severe initial aggression suffered by the olfactory epithelium due to lower viral doses. This may explain why other studies did not find olfaction failure despite detecting inflammatory alterations in the brain.

Omicron Variant of COVID-19
Omicron variant is a mutated strain of coronavirus (SARS-CoV-2) with faster transmissibility and enhanced virulence compared to the original COVID-19 virus.

Cell Specific Targets of Omicron Variants

Research indicates the following cytopathic changes- structural changes in host cells caused by COVID-19 infection:

The wild-type (Wuhan) virus was cytopathic to all cell types except astrocytes
Alpha and Beta variants were cytopathic for pericytes
Omicron variants were cytopathic to endothelial cells and pericytes

All virus variations, with the exception of Beta, modify the extracellular glutamate levels, which can cause excitotoxicity or change neurotransmission. The wild-type virus also increases the permeability of the blood-brain barrier.

Researchers are able to identify specific treatment strategies for each COVID-19 variant thanks to this cellular-level analysis of variants.

In conclusion, regardless of how the disease manifests clinically, SARS-CoV-2 variations have the ability to infect the brain through the olfactory route. This implies that a virus may be able to enter the brain through even minor infections.

References:

Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants - (https://www.nature.com/articles/s41467-023-40228-7)
Differential effects of SARS-CoV-2 variants on central nervous system cells and blood-brain barrier functions - (https://pubmed.ncbi.nlm.nih.gov/37537664/)

Source-Medindia

Post-COVID Syndrome
Post-COVID complications are the conditions that develop weeks after recovering from COVID-19