What's Driving ‘Brain Fog’in People With COVID-19? 

Last Updated 5 March, 2021. Cellspect Co., Ltd.

The novel coronavirus is a respiratory virus, and therefore, some symptoms like chest pains and coughing are reasonably to be expected. However, more and more evidences show that various neurological manifestations have also been associated with COVID-19. One of the unusual symptoms that have emerged in COVID-19 patients is a condition that's called "brain fog" or "COVID brain." It's characterized by confusion, headaches, difficulty thinking, cognitive impairment and loss of short-term memory. In severe cases, it can lead to psychosis and even seizures. It usually emerges weeks after someone first becomes sick with COVID-19 and may last even after the patients recovered.


In the February 8, a study published in journal Cancer Cell reports a possible underlying cause of COVID brain: the presence of inflammatory molecules in the liquid surrounding the brain and spinal cord (called the cerebrospinal fluid). Researchers in this study found that the COVID-19 patients developed neurologic sequelae due to leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. This prolonged, systemic cytokine release syndrome led to long-term neurocognitive dysfunction. Cytokines are a broad category of proteins that are involved with signaling in the immune system. In some cases of COVID-19, an over-production of these molecules results in what's known as a cytokine storm, which can cause excessive inflammation and is potentially deadly. These findings suggest an important role for anti-inflammatory treatment in the management of neurologic complications of COVID-19 infection and anti-inflammatory drugs, such as steroids, may be useful for treating the condition. [1]     

Early in last Dec, A study in Nature Neuroscience has shown that SARS-CoV-2, the virus responsible for COVID-19, is capable of crossing the blood-brain barrier, likely contributing to symptoms of brain fog and other cognitive effects reported by people infected with the virus. The spike protein of the coronavirus, which is usually referred to as the S1 protein, is the key driver that helps the virus cross the blood-brain barrier. According to the lead author William A. Banks, binding proteins like S1 typically cause damage by themselves as they sometimes detach from the virus and cause causes the brain to release cytokines and inflammatory products. [2]   


At the same time, a study from pathologists at Johns Hopkins Medicine have suggested that megakaryocytes may migrate to the brain in a journey precipitated by the destructive activity of coronavirus.  The researchers autopsied brains of COVID victims and discovered megakaryocytes that shouldn't have been there.  These out-of-place megakaryocytes may take up precious space, reducing or completely block blood flow through individual capillaries in the cerebral cortex where the majority of information processing takes place. This phenomenon may be responsible for COVID-19 induced brain fog. The researchers don’t yet know if the megakaryocytes they found in the brain are just the result of blood flow carrying them there or if a specific change occurs in the brain vessels that trap them. Because standard brain autopsy sections represent only a minute portion of the cerebral cortex, the actual numbers of these cells in the brain could be considerable — as could their potentially negative neurological impacts on those who survive. [3]     


In conclusion, coronavirus is undoubtably able to invade the brain and nearby nerves and induces inflammation of the brain, causing the brain to not function normally. It had been already known that the virus can induce a large-scale immune response and that immune response can cause a cytokine storm. Such kind of excessive mobilization of the immune system destroys cells and causes damage to other organs like the brain, liver, kidneys and heart. Therefore, in the treatment of patients and the relief of sequelae, there are still many challenges waiting for doctors and scientists.


  1. Jan Remsik et al. 08 Feb 2021"nflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients" Cancer Cell

  2. Rhea EM et al., 16 Dec 2020. “The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice” Nat Neurosci. 

  3. David W et al. 12 Feb 2021 “Assessing Brain Capillaries in Coronavirus Disease 2019” JAMA Neurol.

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