Harvard Health Blog
The hidden long-term cognitive effects of COVID-19
The COVID pandemic has now claimed as many American lives as World War I, the Vietnam War, and the Korean War combined. Most of these deaths are due to the well-known pulmonary complications of the coronavirus. It has become increasingly recognized, however, that the virus also attacks the nervous system. Doctors in a large Chicago medical center found that more than 40% of patients with COVID showed neurologic manifestations at the outset, and more than 30% of those had impaired cognition. Sometimes the neurological manifestations can be devastating and can even lead to death.
However, new research is now suggesting that there may be long-term neurologic consequences in those who survive COVID infections, including more than seven million Americans and another 27 million people worldwide. Particularly troubling is increasing evidence that there may be mild — but very real — brain damage that occurs in many survivors, causing pervasive yet subtle cognitive, behavioral, and psychological problems.
How COVID damages the brain
COVID can cause damage to the brain directly by encephalitis, which may have devastating or subtle consequences. In one British study of 12 patients with encephalitis, one made a full recovery, 10 made a partial recovery, and one died. This study also found that a number of patients with COVID suffered strokes. In fact, COVID infection is a risk factor for strokes. A group of Canadian doctors found that individuals over 70 years of age were at particularly high risk for stroke related to COVID infection, but even young individuals are seven times more likely to have a stroke from this coronavirus versus a typical flu virus.
Autopsy data from COVID patients in Finland suggests that another major cause of brain damage is lack of oxygen. Particularly worrisome is that several of the patients who were autopsied did not show any signs of brain injury during the course of their COVID infection — yet all had brain damage. In one patient there was loss of taste, and in two there was “minimal respiratory distress,” but none of these patients were thought to have any brain damage while alive.
A new study by doctors from Johns Hopkins University and Harvard Medical School found that large cells called megakaryocytes may be found in the brain capillaries of individuals who died from COVID-19 infection. Megakaryocytes make platelets — part of the body’s clotting system — and these cells should not be there. In fact, these neuropathologists had never seen megakaryocytes in the brain before, and this observation had never before been reported in the medical literature. These cells could be related to strokes observed in individuals with COVID-19.
Major cognitive effects of COVID
In survivors of intensive care unit (ICU) stays due to acute respiratory failure or shock from any cause, one-third of people show such a profound degree of cognitive impairment that performance on neuropsychological testing is comparable to those with moderate traumatic brain injury. In daily life, such cognitive effects on memory, attention, and executive function can lead to difficulties managing medications, managing finances, comprehending written materials, and even carrying on conversations with friends and family. Commonly observed long-term psychological effects of ICU stays include anxiety, depression, and post-traumatic stress disorder (PTSD). Effects due to COVID ICU stays are expected to be similar — a prediction that has already been confirmed by the studies in Britain, Canada, and Finland reviewed above.
Subtle cognitive effects of COVID
It is clear that COVID can cause brain damage by direct infection (encephalitis), by strokes, and by lack of oxygen. It is also clear that when patients experience severe illness requiring an ICU stay, brain damage is highly likely to occur, and its effects are typically obvious. But what if the COVID illness is not so severe? Can brain damage still occur?
A Chinese group of doctors and researchers examined several aspects of cognitive function in 29 individuals who were thought to have fully recovered from COVID infection. They found persistent impairment in sustained attention — the ability to attend to important information for as long as it is relevant.
Long-term cognitive effects of COVID infection
Why would sustained attention be persistently impaired in individuals who were thought to have fully recovered from COVID? The Chinese group thought it might be linked to underlying inflammatory processes. But it is equally likely that patients with COVID suffered silent strokes or lack of oxygen that damaged their brains. As discussed above, strokes due to COVID are common, particularly in those over 70. We know that silent strokes frequently occur, and are a risk factor for both large strokes and dementia. Silent strokes typically affect the brain’s white matter — the wiring between brain cells that enables different parts of the brain to communicate with each other. This wiring is essential for attention, and when it is damaged, sustained attention is impaired.
The bottom line
There is one inevitable conclusion from these studies: COVID infection frequently leads to brain damage — particularly in those over 70. While sometimes the brain damage is obvious and leads to major cognitive impairment, more frequently the damage is mild, leading to difficulties with sustained attention.
Although many people who have recovered from COVID can resume their daily lives without difficulty — even if they have some deficits in attention — there are a number of people who may experience difficulty now or later. One recently published paper from a group of German and American doctors concluded that the combination of direct effects of the virus, systemic inflammation, strokes, and damage to bodily organs (like lungs and liver) could even make COVID survivors at high risk for Alzheimer’s disease in the future. Individuals whose professions involve medical care, legal advice, financial planning, or leadership — including political leaders — may need to be carefully evaluated with formal neuropsychological testing, including measures of sustained attention, to assure that their cognition has not been compromised.
About the Author
Andrew E. Budson, MD, Contributor; Editorial Advisory Board Member, Harvard Health Publishing
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