Even mild Covid-19 can cause permanent brain fog (part 1)

This is part 2 of a series focused on cognitive impairment and inflammation.read the first article hereFor more articles on inflammation and Covid-19, visit my website. www. williamhaseltine.com

Inflammation is a common feature of viruses and many other infectious diseases, but SARS-CoV-2 causes a particularly intense inflammatory response. The exact reason remains unknown.what teeth On the other hand, it is becoming increasingly clear that much of the damage associated with Covid-19 is due to this hyperinflammation. It is also true long-term during the acute sequelae of AD (PASC). Cognitive deficits such as ‘brain fog’, difficulty concentrating and poor short-term memory constitute some of the more worrying long Covid symptoms. , has a significant impact on quality of life.

and Joint research, researchers at Yale and Stanford Universities have identified one plausible cause: inflammation. activation and may lead to dysregulation of cells required for healthy cognitive function, such as oligodendrocytes and neurons. Surprisingly, Fernández-Castañeda et al. It turns out that even mild cases of Covid-19 cause enough inflammation to cause impairment in cognition and brain health.

Here, we review the first part of their findings, microglial reactivity, and in a follow-up article, discuss how this affects brain health.

Microglial cells are a type of macrophage found in the brain and spinal cord, where they are organized. 10-15% of total cellsTheir role as macrophages is to actively devour and destroy invading microbes. In addition, they produce various signaling proteins known as cytokines and chemokines, stimulate inflammatory responses, and attract other immune cells to areas in need of protection. Despite being there to protect us, microglial cell reactivity is also associated with cognitive issues. Inflammation is important for helping us clear infections, but too much of it can have devastating consequences, especially in a sensitive environment like the brain.

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Cancer treatment-related cognitive impairment is an example of, hippocampal microglial reactivity causes neuronal dysfunction. The overlap in Long’s symptoms with Covid, including the continued presence of “chemo his fog,” has led Fernández, his Castañeda and his colleagues to suspect a similar mechanism at work. I was.

To test this theory, experts turned to mouse models. They exposed a group of mice with human angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2’s main entry route, to mild SARS-CoV-2 infections that did not last longer than a week. Mice had no observable symptoms and no weight loss.

Importantly, mice are engineered to carry only ACE2 receptors in their respiratory tract, strictly limiting infection to the nose, throat and lungs. I can no longer. That is, cognitive impairment should have been the result of knock-on effects instead.

Despite mild and essentially asymptomatic infection, all mice showed elevated levels of pro-inflammatory cytokines and chemokines both in blood and cerebrospinal fluid. These include IFN-γ, IL6, TNF-α, CXCL10, CCL7, CCL2, CCL11, GMCSF, and BAFF. Certain cytokines remained elevated up to 7 weeks after the initial respiratory infection.

as I touched on last time paper, IL-6 is involved in cognitive impairment after cranial radiotherapy. Second, the chemokine CCL11 is implicated in age-related cognitive decline.Of note, her CCL11 levels in blood normalized seven weeks after the first infection, whereas in cerebrospinal fluid taller than 7 weeks after infection than 7 days after infection.

Scientists then set out to see if long-term surges in cytokine levels in the cerebrospinal fluid correlated with marked changes in the brain.

Compared with pseudovirus-infected control mice, which also harbor human ACE2 in the respiratory tract, SARS-CoV-2-exposed mice showed increased microglial reactivity in subcortical white matter. White matter makes up the deeper tissues of the brain and is responsible for connecting and enabling communication between different parts of the central nervous system, especially the spinal cord and the gray matter areas that make up the surface of the brain. Think of it as a kind of superhighway. White matter is important for healthy cognitive function, and changes in white matter can affect the efficiency and speed of sending ‘messages’ throughout the central nervous system.

Although the total number of microglia remained the same in both Covid-19 and control mice, Activate Microglia were significantly higher in the diseased group. Similar to cytokine levels, reactive microglial cells persisted up to 7 weeks post-infection.

Fernández-Castañeda and colleagues also had the rare opportunity to study microglial cell reactivity in human samples. The researchers analyzed the subcortical white matter of nine individuals who were SARS-CoV-2 positive at death and confirmed by nasal PCR testing. Although not necessarily mild cases, he was the only two who required admission to the ICU, as none died during hospitalization, as all nine died from infection-related complications. Their lungs also showed no or only moderate signs of damage. Nonetheless, all nine patients had elevated levels of microglial activation when compared to the control cohort, mirroring what was seen in the mouse model (Fig. 1).

To better understand the state of microglial cells after Covid-19, scientists performed single-cell RNA sequencing. Fine-grained technology. Fernández-Castañeda et al. analyzed data from approximately 6000 individual microglial cells. noted upregulation of genes associated with inflammation, including cytokine production and cytotoxicity. This was accompanied by downregulation of genes associated with normal homeostatic function. maintaining proper connections between neurons, pruning rarely used synapses, and nurturing critical synapses. Basically, genes that help keep things in balance and support cognitive health.

After Covid-19 run-in, the genetic profiles of reactive microglial cells are very similar to those of Alzheimer’s disease-associated and senescence-associated microglial cells. Both are closely associated with cognitive decline.

So mild Covid-19 can trigger an inflammatory response that can enter the brain and activate microglial cells. These cells stimulate additional inflammatory molecules and general cytotoxicity that can persist for up to 7 weeks post-infection.

The next article in this series will focus on the consequences of such sustained microglial responses, particularly in white matter regions of the brain.