Long COVID is a complex condition that has confounded the medical community. Defined as coronavirus symptoms that last longer than four weeks after initial infection, it can cause continued breathing difficulties, brain fog, weakness and fatigue as well as other neurological issues. Far more serious than the common cold or flu, COVID-19 appears to have similar long-term health effects seen in other infectious diseases. A new study investigating the long-term effects of coronavirus offers clues into the impact of long COVID on the brain and links cognitive symptoms to an overreaction of the body’s immune system.

What is long COVID?

Coronavirus or COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Once infected, individuals can develop common symptoms including fever, a dry cough, fatigue, headache and temporary loss of taste or smell. These usually last around 1-2 weeks, with up to 80% of those who develop symptoms recovering without the need for treatment [1].

However, as well as placing the remaining 20% of those infected in hospital, coronavirus can have lasting consequences to health long after initial infection. Known as long COVID, this complex condition has perplexed the medical community with its wide variety of symptoms.

Defined as displaying coronavirus symptoms for longer than four weeks with no other explanation, long COVID causes typical coronavirus symptoms as well as more serious symptoms like breathing difficulties, brain fog, weakness and fatigue, joint pain, loss or change to sense of taste and/or smell and other neurological issues.

Similarly to coronavirus, older people and those with underlying health conditions are more likely to contract long COVID, as well as those who experienced more symptoms during initial infection.

Read more about long COVID HERE

Coronavirus and cognitive function

As the name suggests, ‘brain fog’ effects cognitive abilities and is characterised by loss of mental focus, confusion and forgetfulness. It is a common after-effect in long COVID.

A new study by UC San Francisco and Weill Cornell Medicine, published in Annals of Clinical and Translational Neurology, investigated the long-term impact of coronavirus and goes someway in explaining this common symptom. The small study analysed cerebrospinal fluid that surrounds the brain and spinal cord from adults who had previously been infected with coronavirus either with or without cognitive symptoms.

The researchers found that all of the samples from participants with cognitive symptoms displayed anomalies, while the samples from participants with no cognitive symptoms did not.

Further examination revealed that the anomalous cerebrospinal fluid contained elevated levels of protein, indicating inflammation, as well as antibodies found in an activated immune system. This is similar to abnormalities found in the cerebrospinal fluid of individuals with other infectious diseases. Indeed, cognitive symptoms can be produced by other viruses such as HIV, hepatitis C, Epstein-Barr virus and coronaviruses SARS and MERS [2].

Participants with cognitive symptoms were found to have on average 2.5 cognitive risk factors, compared with the average of less than one risk factor in participants without such symptoms. Risk factors included diabetes and hypertension, mild cognitive impairment and vascular dementia, a history of ADHD, disorders like anxiety and depression, learning disabilities as well as heavy use of alcohol or other stimulants.

Participants with cognitive symptoms had difficulty in everyday functioning. As senior author of the paper Joanna Hellmuth, MD, MHS, of the UCSF Memory and Aging Center says, the symptoms “manifest as problems remembering recent events, coming up with names or words, staying focused,and issues with holding onto and manipulating information, as well as slowed processing speed”.

“If people tell us they have new thinking and memory issues, I think we should believe them rather than require that they meet certain severity criteria”, she added.

Effects on the immune system

One explanation for coronavirus’ long-term impact on health is related to its effect on immune functioning. “It’s possible that the immune system, stimulated by the virus, may be functioning in an unintended pathological way,” said Hellmuth. “This would be the case even though the individuals did not have the virus in their bodies,” she said, considering that the cerebrospinal fluid collection occurred an average of 10 months after the emergence of each participant’s first COVID symptom.

Indeed, the underlying cause of long COVID is though not to be coronavirus itself, but rather the immune system’s response to infection. The immune system comprises the innate response and the adaptive response, which work to protect against invading pathogens.

An unfortunate side effect of activating the immune response is increased inflammation in the body, which can have negative side effects like swelling, pain, loss of tissue function and pathology. Occasionally, infections can cause long lasting systems especially when they effect the brain.

Remaining fragments of SARS-CoV-2 in the body post-infection may change inflammatory markers and cause the body to attack itself as seen in autoimmune diseases like chronic fatigue symptoms (CFS) and myalgic encephalitis (ME) [3]. This new study offers convincing evidence that coronavirus infection can cause the immune system to overreact, leaving individuals with cognitive symptoms from long COVID after recovering from the virus.