New insights into how coronavirus affects the brain

Injecting spike protein into mouse skulls causes brain inflammation

Prolonged COVID-19 is a condition characterized by multiple persistent symptoms that sometimes occur even after a mild infection. Among these, memory loss, brain fog, and sleep disturbances indicate brain involvement. MRI scans taken before and after COVID-19 show shrinkage in certain areas of the brain, suggesting tissue loss. This raises important questions: How do respiratory viruses affect the brain? And what causes brain inflammation in these patients? Two recent papers provides insight into how it indirectly affects the brain.

Research published in Cell hosts and microorganisms We conclude that the continued presence of the viral spike protein can lead to inflammation and neurodegenerative changes in the brain. Spikes also activate inflammatory pathways. When researchers injected the spike protein into the skulls of mice, they observed brain inflammation along with behavioral changes.

The authors found that spike protein-based vaccines did not have similar efficacy. They found that spike protein levels were lower in vaccinated mice infected with the virus. Additionally, long-term coronavirus symptoms are rarely associated with vaccination. This suggests that the immune response to the virus, rather than vaccination, is responsible for the spike protein's widespread presence in the body.

In human studies, researchers identified the spike protein in the skulls of people who died from causes other than the coronavirus. This indicates that the spike protein remains in the body long after the initial infection, which may have occurred several months ago. Long-term coronavirus patients with persistent spike protein also had elevated levels of biomarkers such as tau protein in their cerebrospinal fluid. These biomarkers are released when brain cells are damaged.

What's so special about the spike protein found inside the skull? The hollow center of the skull houses a unique type of bone marrow that's different from what's found inside other bones. The cranial marrow is directly connected to the covering of the brain through blood vessels and plays a role in brain health and disease. Immune activity within the bone marrow of the skull can influence both the progression and recovery of various brain diseases.

The next question is how exactly these immune changes cause brain damage. Paper published in Brain, Behavior and Immunity – Health We will investigate the interaction between viruses and microglia, which are brain-resident immune cells. These cells function similarly to macrophages in the rest of the body, removing debris, eliminating viruses, and coordinating immune responses. Just as a gardener shapes a hedge, microglia cut away unnecessary connections between brain cells. This is an essential process for early brain development and neuroplasticity. However, dysregulation of this pruning can contribute to a variety of brain disorders. Under normal conditions, microglia remain quiescent. However, when activated, such as after a coronavirus infection, it can cause long-term brain inflammation, leading to memory loss and other symptoms.

Other routes also need to be studied. Early in the pandemic, loss of smell lasting months or years suggested the virus could enter the brain via the olfactory nerve, a direct shortcut from the nose. Alternatively, the coronavirus could breach the brain's protective shield, the blood-brain barrier, allowing harmful particles to enter.

Therefore, this virus appears to leave a footprint in the body long after it has disappeared, resulting in persistent health problems in a small number of people. There is currently no definitive treatment for long coronavirus, but some people do improve over time. The lack of specific treatments reflects an incomplete understanding of the mechanisms involved and the challenge of effectively targeting these complex pathways without harming the body. Understanding these pathways could pave the way to treatments that prevent or reduce symptoms and restore quality of life for people living with long-term COVID-19 infection.

(Rajeev Jayadevan is co-chairman of the National IMA Coronavirus Task Force)