COVID-19 does mess with the brain even years after infection

A long-term study showed that individuals who have recovered from COVID-19 continued to experience cognitive, psychiatric, and neurological issues, as well as brain functional alteration, even 2 years after being infected.

“[C]ognitive, psychiatric, and neurological symptoms may persist for a long time among individuals recovering from COVID-19, [but] the underlying mechanism of these brain abnormalities remains unclear,” said the researchers.

Using resting-state functional MRI (rs-fMRI), the team assessed the long-term neuroimaging effects of COVID-19 infection among 52 survivors (n=25 [mild-moderate disease] and 27 [severe-critical]) 27 months after infection and compared it against a group of healthy individuals (n=35). Subjective assessments were done using the CFQ-14* and FS-14**. [Lancet Reg Health West Pac 2024;doi:10.1016/j.lanwpc.2024.101086]

Cognitive complaints

Compared with the control group, participants who had mild-moderate and severe-critical COVID-19 had significantly higher scores in the CFQ-14 (32.14 and 30.36 vs 19.64; p=0.006) and FS-14 (10 and 10 vs 5; p<0.001).

Post hoc analyses also saw higher levels of cognitive failure and fatigue in the mild-moderate subgroup vs controls (p=0.007 and p<0.001, respectively). A similar trend was seen among those who had severe-critical disease (p=0.002 and p<0.001).

Psychiatric, neurological symptoms

Compared with controls, more participants in the mild-moderate and severe-critical groups reported psychiatric symptoms of depression (80 percent and 74 percent vs 37 percent), anxiety (60 percent and 59 percent vs 26 percent), post-traumatic stress disorder (24 percent and 22 percent vs 0 percent), and insomnia (68 percent and 74 percent vs 31 percent).

The incidence of neurological symptoms was also higher among COVID-19 survivors vs healthy participants (60 percent and 59 percent vs 14 percent [smell disorder] and 48 percent and 41 percent vs 3 percent [taste disorder]).

According to the investigators, the comparisons between the mild-moderate and control groups and between the severe-critical and control groups yielded statistically significant differences across these psychiatric and neurological outcomes.

rs-fMRI findings

COVID-19 survivors demonstrated significantly increased ALFF** values in the left putamen, right inferior temporal gyrus, and right pallidum vs the control group.

The putamen plays a vital role in motor execution and learning and is apparently involved in learning and memory processes that are not directly associated with motor functioning. [Horizons in Neuroscience Research 2004:7;29-52] “[O]ur findings may be related to the compensatory repair of brain tissue, but the specific underlying mechanism behind the impaired putamen remains unclear,” the researchers explained.

Conversely, ALFF values in the right superior parietal gyrus (SPG) were lower among COVID-19 survivors vs controls, they said.

The superior parietal cortex plays an essential role in visuospatial and attentional processing, as well as working memory. [Science 1995;270:802-805; J Neurosci 2009;29:14980-14986] In a study, COVID-19 survivors seemed to have experienced impairments in memory, attention, and executive function, which could signal more brain damage. [Front Neurol 2021;12:699582]

“Our findings align with a recent Mendelian randomization study that suggested a nominal association between the severe COVID-19 phenotype and reduced cortical surface area in the SPG, pericalcarine and parahippocampal gyrus,” said the researchers. [BMC Med 2023;21:261] “Taken together, these evidence indicate that the SPG may be vulnerable to COVID-19 infection, but the precise mechanism is unclear.”

Offers potential targets for long COVID management

“[This] fMRI study identified specific brain functional regions that were particularly susceptible to COVID-19, including the putamen, temporal lobe, and SPG, along with other brain regions. These regions have a comprehensive impact on cognitive function and emotional regulation,” said the researchers.

“These findings provide valuable neuroimaging insights into the cognitive complaints of long COVID, thereby offering potential targets for treatment and intervention in individuals with brain fog [due to] long COVID,” they concluded.

They called for long-term follow-up trials to shed light on the trajectory of cognitive, psychiatric, and neurological issues in SARS-CoV-2 infection, and on the mechanisms that could explain for these effects.