COVID-19 Brain Changes: New Evidence Details Long-Term Effects of Infection

Kevin Kavanagh, MD

Up to 60% of patients with SARS-CoV-2 experience a loss of smell and taste (it should be noted that the perception of taste is markedly affected with the loss of smell). Many have assumed this symptom is because of nasal congestion or damage to the nerve receptors in the nose. However, data from a recent study published in the journal Nature support a more chilling prospect—that this symptom is caused by spread of the infection to the brain’s olfactory cortex, and from there the virus can spread to other structures causing memory and cognitive impairment.
 
The newly published peer-reviewed study by Gwemaëlla Douaund, et al., documented changes in brain scan images of patients with SARS-CoV-2. Some of the most telling findings were a reduction in grey matter thickness in the orbitofrontal cortex and “tissue damage in regions functionally-connected to the primary olfactory cortex,” along with a reduction in brain size. The orbitofrontal cortex has extensive connections to the olfactory cortex and limbic system structures involved in memory and emotions. Damage was more extensive in the 15 patients who were hospitalized but, even with their exclusion, there was still a significant cognitive decline in the SARS-CoV-2–positive patients. The lasting clinical impact of these changes is not known, but some are concerned that they may contribute to the onset of Alzheimer disease. The authors note that these changes represent statistical averages and “not every infected participant will display brain longitudinal abnormalities.”

Many articles have been written on the crippling pulmonary effects of COVID-19. But long-term effects on the heart and central nervous system (CNS) are of grave concern. Early in the pandemic, frequent anecdotal reports of brain fog and difficulties with concentration started to surface and were common symptoms in patients afflicted with long COVID. Overall, between 10 to 30% of patients with COVID-19 develop long COVID.
 
The frequency of CNS and cognitive symptoms has been reported by a number of authors using a variety of experimental designs and surveys.
 
One of the first clinical studies regarding SARS-CoV-2’s effect on the brain was published in July 2020 by Ross Paterson, et al. The investigators studied 43 patients with COVID-19 (“29 were SARS-CoV-2 PCR positive and definite, 8 probable, and 6 possible”) and found inflammatory CNS syndromes in 12. The authors concluded that “SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis.”

Figure courtesy of Kevin Kavanagh, MD

In February 2021, Jennifer Logue, et al., observed that symptoms of COVID-19 can last up to 9 months in 30% of 177 patients. Additionally, 85% of the patients were outpatients with mild disease. The most common symptom was fatigue, which was reported in 13.6% of the total patients (24 of 177) and brain fog which was reported in 2.3% of the total patients (4 of 177).

In June 2021, Bjorn Blomberg, et al., reported long-term sequelae in 61 home-isolated patients with COVID-19. At 6 months, 52% had persistent symptoms (32 of 61), with 13% (8 of 61) reporting impaired concentration and 11% (7 of 61) reporting memory problems.
 
In July 2021, Jennifer Frontera, et al. reported the results of an online survey of self-reported patients with COVID-19. Long COVID-19 was defined as symptoms persisting greater than 1 month after the initial diagnosis. The NIH/NINDS PROMIS Quality of Life in Neurological Disorders survey results were analyzed from 999 respondents. A total of 76 (7.6%) reported having COVID-19. The investigators found prolonged symptoms existed in 25% of patients with COVID-19 and that neuro quality of life cognitive dysfunction was more than 11 times more common in the COVID-19–positive group. Of the 19 patients with long COVID, 42% reported experiencing “brain fog.”
 
Also in July 2021, a large online survey by Hannah Davis, et al., studied 3762 patients with COVID-19 symptoms lasting more than 28 days. The authors reported 85% of respondents (3203) experienced “brain fog and cognitive dysfunction, including poor attention, executive functioning, problem solving, and decision making.” In addition, 72% experienced memory impairment.
 
As time progresses, it is becoming more apparent that prevention of the dangers and disability of long COVID should be of paramount importance. The prevention of hospitalizations and severe COVID-19 as a primary goal is no longer acceptable. We must also prevent the occurrence of long-term pulmonary, cardiac, and central nervous system disability. The peer-reviewed study by Gwemaëlla Douaund, et al., supports the conclusion that the “brain fog,” as reported by many who have recovered from mild infections, is real and has an anatomical basis.

Unfortunately, the COVID-19 pandemic does not appear to be over. SARS-CoV-2 cases in the United Kingdom have recently started to tick upward, and the country’s 7-day hospitalization rate has increased 13.1% from the previous week (Figure). The United States has all but declared victory and followed the United Kingdom’s example by rapidly relaxing public health strategies, including masking. The BA.2 (Stealth) variant could prove more infectious than Omicron (BA.1) and is ravaging Denmark and Hong Kong. This variant is also increasing in our country. A finding that, combined with the increased concerns over the impact of long COVID, dictates that a more careful approach to relaxation of mitigation strategies may be warranted.