Long COVID and its Effects on the Central Nervous System

March 31, 2023

Post-acute COVID-19 syndrome, known as long COVID, affects many COVID-19 patients. Symptoms that characterize long COVID include loss of sense of smell and taste, cognitive impairments, depression, anxiety, Chronic Fatigue Syndrome (ME/ CFS), and so-called “brain fog,” an umbrella term for a collection of symptoms like impaired attention, concentration, memory, speed of information processing, and executive function.

Studies have shown that two months after initial infection, more than 70% of people experience at least one long COVID symptom, with many symptoms lasting for months after the infection. While long COVID symptoms can affect people who experienced mild COVID-19 symptoms, the risk is higher for those with severe illness. 

A recent paper published in Cell collected different hypotheses regarding the central nervous system and the mechanisms driving long COVID. 

The central nervous system can be affected by COVID-19 in several ways. One of them is the immune system’s response, which can lead to neuro-inflammation. Increased production of cytokines, chemokines, and immune cells can result in the dysregulation of immune cell function in the brain and brain borders. 

SARS-CoV-2 can also induce an autoimmune response against the immune system. Studies analyzing antibodies of COVID-19 patients found autoantibodies against numerous organs, including the central nervous system. Additionally, rare cases of autoimmune disease, namely, Acute Disseminated Encephalomyelitis (ADEM), have been reported following a COVID-19 infection. Scientists advise long-term studies, as the autoimmune disease may take time to exhibit symptoms.

Another mechanism can involve the reactivation of dormant herpes viruses. Most humans are infected with viruses, which reside in a dormant state. These viruses can be reactivated by another viral infection, such as SARS-CoV-2. One such virus is the Epstein-Barr virus (EBV). EBV reactivation can contribute to neuroinflammation through the production of viral proteins and the immune system’s response. Studies show that more than 60% of patients with long COVID are positive for EBV reactivation, compared to only 10% of controls. 

SARS-CoV-2 can also, although rarely, directly infect the nervous system. There are also hypotheses that multi-organ dysfunction during severe COVID-19 can lead to low oxygen levels in the blood, very low blood pressure, and metabolic perturbations that negatively affect neural cells. COVID-19 infection increases the risk of ischemic stroke, a condition that prevents the brain from getting enough oxygen due to interruptions in the brain’s blood supply. Disruptions in blood flow or blood-brain barrier function can also play a role in neuroinflammation.

While there are many possibilities of how COVID-19 influences the central nervous system and causes long COVID, they are not exclusive and can occur in combination; understanding them will offer better treatment options for patients with long COVID.