Long Covid symptoms such as intense fatigue, brain fog, sleep disorders, fever, loss of smell and/or taste, headaches, tremors and others, even after mild infection are common and are not trivial. These can be devastating and can last for prolonged time frames, often waxing and waning and often exacerbated by physical or mental exercise or by stress. Unfortunately, it is often not recognized by patient or physician as related to the prior infection. The specific causes are likewise not clear and so treatment often is rather ad hoc.

In this article, the third in a series, I will focus on cognitive and mental health disorders that frequently appear well after a Covid infection has cleared.

Many people during and after infection refer to “brain fog,” an inability to think as clearly and rapidly as pre infection. Often it clears spontaneously but for some it persists and for others it occurs much later, weeks or months later. Now there is evidence that the brain is damaged even in individuals with mild Covid-19.

A large ongoing study at Oxford University indicates from MRI brain scans that individuals post Covid-19 may have gray matter loss and brain size shrinkage when compared to those who did not get infected during the same time period.

In the UK Biobank of over 500 million volunteers, many have had MRI scans of the brain done between 2014 and the onset of the pandemic. The study investigators invited those aged 51 to 81 to have a repeat scan in early 2021. There were 401 volunteers that had Covid-19. The great majority had “mild” Covid with only 15 hospitalized. They were re-scanned, on average, 4.5 months after infection. As controls, 384 volunteers were selected to match the infected group for age, sex, and a variety of risk factors such as obesity and diabetes.

They found, on average, that the infected individuals had reduced gray matter especially in the areas related to smell, evidence of tissue damage in the same areas, and cognitive decline as measured by standard tests with anatomic correlation of shrinkage of brain tissue in areas known to be important for cognitive abilities.

It is still unclear if these changes will or can be reversed.

An investigation from Wuhan, China that studied 3233 Covid-19 survivors over the age of 60 hospitalized during the early months of the pandemic and evaluated for cognitive function 6 and 12 months after infection and compared them to uninfected spouses. Those with severe disease had a higher risk compared to the controls of early onset cognitive decline, late-onset decline and progressive decline. Importantly, it was found that those with non-severe infection had a higher risk than controls of early progressive cognitive decline.

These and other studies make clear that cognitive decline post Covid-19 is real, not uncommon and can be persistent. It is also becoming clear that various neuropsychiatric symptoms also occur after Covid-19 infection. My prior article reviewed a Veterans Affairs study that assessed Long Covid cardiovascular syndromes.

The same group of epidemiologists did a concurrent study of neuropsychiatric issues such as anxiety, depression, cognitive decline, brain fog, sleep disorders, stress and adjustment disorders, and substance abuse post Covid-19. The ~154,000 veterans who visited a VA health facility who tested positive for Covid-19 during the first 10 ½ months of the pandemic and who were still alive 30 days later were studied over the next 12 months and compared to the over 5 million veterans seen at the VA health centers who never had a positive test.

There were many that developed one or more neuropsychiatric symptoms in both groups. The larger group served as the baseline control yielding the expected number of veterans during that time frame who would develop one or more mental health syndromes. The Covid-19 positive patients neuropsychiatric syndrome frequency was compared to the control group.

Bottom line- those with a positive test for Covid-19 had more syndromes develop than did those who never tested positive.

Among the ~154,000 veterans who were Covid-19 test positive were those who were asymptomatic or had “mild” Covid and were never hospitalized (~133,000) and those who required hospitalization (~21,000.)

Perhaps not surprisingly, those who had been hospitalized and those treated in the ICU had a much higher frequency of post Covid mental health syndromes than the control group. They also had a higher incidence than those who were not hospitalized.

This difference can be easily observed on the graphic below. The upper dotted line represents the mental health issues when first diagnosed among the control group. The solid line plots the first diagnosis for those with Covid who were not hospitalized. Finally, the lower line indicates that those hospitalized developed neuropsychiatric syndromes at a much higher rate than the control or the mild Covid patients.

Look again at the line representing the non-hospitalized patients with Covid-19. It may not appear to be that much different than the control group, but it is. The risk for any mental health syndrome developing after Covid-19 for these non-hospitalized individuals was greater than the controls by 32 per thousand. Multiplying just within this group of 133,000 veterans yields about 4250 more cases than expected among these veterans.

Consider for a moment the implications of these numbers. About 80 million Americans have had Covid; most have been mild. Will the healthcare system be overwhelmed with Long Covid patients, even just those with neuropsychiatric syndromes? Most likely.

The cause or causes are not understood although there are many possibilities including the social impact of the infection with isolation, loss of normal employment, family impacts, etc. Among the proposed biologic causes are direct damage to the brain by the virus, immune cells traveling to the brain and causing damage, brain cell inflammation from some other mechanism, and an overall immune system dysfunction that also impacts the brain. But even if one or more of these are correct, it leaves open the question as to why some develop mental health issues after mild Covid-19 and others do not.

Without a unifying causation concept, treatment will be symptomatic rather than attacking the specific cause or causes.

This much is certain. The development of cognitive decline and mental health syndromes after mild Covid is one more reason, if one is still needed, to discount the idea that getting infected can be useful.