All Variants of SARS-CoV-2 Virus Can Infect the Brain's Olfactory Area

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Research Finds All Variants of the SARS-CoV-2 Virus Can Infect the Brain’s Olfactory Area

Research Finds All Variants of the SARS-CoV-2 Virus Can Infect the Brain’s Olfactory Area

Years after the emergence of the SARS-CoV-2 virus, which causes COVID-19, many mysteries still surround it.

One such mystery is whether cognitive issues associated with COVID-19 are a result of direct viral infection of brain cells or solely due to a broader systemic inflammatory response.

Research Finds All Variants of the SARS-CoV-2 Virus Can Infect the Brain's Olfactory Area

Coculture of human neurons and epithelial cells. Cells infected with SARS-CoV-2 are stained green. Multiple infected neurons are seen. Cell nuclei are shown in blue. Picture/Pasteur Institute-Guilherme Dias de Melo

Studies conducted on human brain tissue have yielded conflicting results. Some studies have found direct traces of SARS-CoV-2, while others have reported only inflammation-related damage.

Animal models undeniably demonstrate the potential of the virus to infect the brain, but human tissue samples are typically collected post-mortem, leaving researchers to speculate about what happens during the acute infection phase.

In a new study led by scientists at the Pasteur Institute and the University of Paris, several unanswered questions were explored using an animal model.

The study aimed to understand how SARS-CoV-2 enters the brain through the olfactory system, the likelihood of different SARS-CoV-2 variants entering the brain, and the relationship between the loss of the sense of smell and the virus’s direct entry into the brain.

Using a hamster model, researchers compared the original SARS-CoV-2 virus from 2020 to subsequent variants, including Gamma, Delta, and Omicron/BA.1 variants. Interestingly, the study confirmed epidemiological observations that the severity of acute illness during Omicron infections is reduced. However, all variants exhibited similar neuroinvasive capabilities. Most notably, regardless of whether individuals experienced anosmia (loss of smell), all variants infected the brain’s olfactory area.

Guilherme Dias de Melo, the study’s first author, stated, “This suggests that anosmia and neuronal infection are two unrelated phenomena. According to this line of reasoning, even asymptomatic—thus clinically benign—infections are likely to manifest as viral spread in the nervous system.”

To precisely study how SARS-CoV-2 infects brain cells, researchers used a modeling system called microfluidic cell culture. This system allowed them to observe how the virus moved between neurons at close range. The results indicated that the virus could effectively utilize the physiological mechanisms of neurons for bidirectional movement. The SARS-CoV-2 variants studied—Wuhan ancestral, Gamma, Delta, and Omicron/BA.1—infected neurons in vitro and could move along axons.

The researchers concluded that all SARS-CoV-2 variants have the ability to infect the brain via the olfactory route, regardless of clinical disease presentation. This implies that even mild infections may lead to viral entry into the brain.

Hervé Bourhy, another author of the study, emphasized the need for future research to explore the relationship between acute SARS-CoV-2 brain infections and the persistent symptoms seen in Long COVID cases.

Bourhy said, “The next step for us will be to understand whether the virus can persist in the brain after the acute infection phase and whether the presence of the virus can induce persistent inflammation and symptoms described in long-term COVID cases, such as anxiety, depression, and brain fog.”

This new research was published in Nature Communications.