Researchers have found that individuals who experienced anosmia—the sudden loss of smell—during their COVID-19 infection exhibit significant alterations in both brain functionality and physical structure during their recovery.
A groundbreaking study, recently published in Scientific Reports, has unveiled alarming new insights into the long-term neurological impacts of COVID-19. Researchers have found that individuals who experienced anosmia—the sudden loss of smell—during their COVID-19 infection exhibit significant alterations in both brain functionality and physical structure during their recovery. This research marks one of the earliest investigations into the direct link between COVID-related olfactory loss and measurable changes within the brain.
Although the SARS-CoV-2 virus has predominantly been associated with respiratory issues, a growing number of survivors, even those who experienced only mild symptoms, have reported troubling cognitive problems. Symptoms such as memory loss, confusion, and difficulty concentrating have raised red flags about the virus’s effects on the brain. Among these neurological symptoms, anosmia stood out as one of the most prevalent and identifiable signs of COVID-19.
The sudden onset of smell loss became a hallmark of COVID-19, but while many regained their sense of smell within weeks, others suffered from more prolonged disruptions. Previous research had already hinted that anosmia could indicate broader neurological implications, similar to those seen in conditions like Alzheimer’s and Parkinson’s. Motivated by this connection, scientists sought to determine whether anosmia during COVID-19 left behind lasting damage in the brains of those recovering from the virus.
“Our laboratory studies the neurobiological mechanisms underlying complex social behavior and decision-making. During the pandemic, it was very challenging to halt our experimental activities due to health restrictions,” said Pablo Billeke, one of the study’s lead authors and a researcher at the Center for Research in Social Complexity at the University for Development in Chile, reported PsyPost.
“In this context, and given the early reports of neurological symptoms in patients affected by COVID-19, we wanted to contribute from our unique perspective to understanding the potential damage caused by SARS-CoV-2 infection in the central nervous system. This led us to initiate this study,” Billeke continued.
The team recruited 100 adults in Santiago, Chile, who had recovered from respiratory infections between February 2020 and May 2023. Out of these, 73 had confirmed cases of COVID-19, while the others were diagnosed with non-COVID respiratory infections, confirmed through negative PCR tests. Over two separate sessions, the researchers conducted a range of cognitive tests and brain scans to investigate how the infection had impacted brain function and structure.
Strikingly, individuals who reported anosmia during their illness displayed a tendency toward more impulsive decision-making in cognitive tests compared to those who retained their sense of smell. These participants often changed their choices more quickly following negative feedback, particularly in tasks that required learning and adapting to shifting probabilities of rewards. This behavioral shift pointed to a possible alteration in how the brain processes rewards and risks.
On a functional level, patients with a history of anosmia showed reduced brain activity in areas responsible for decision-making, including the lateral prefrontal cortex and temporoparietal regions. Structurally, the study revealed thinning in specific regions of the brain, particularly in the parietal lobe—responsible for sensory processing and spatial awareness. This thinning indicates potential long-term structural changes in the brains of individuals affected by anosmia.
The findings also extended to white matter integrity. White matter is crucial for the communication between various regions of the brain, and disruptions in its integrity can lead to cognitive impairments. Individuals who had anosmia showed decreased white matter integrity in brain regions involved in higher cognitive functions.
“In the current context, where we know that a significant percentage of the population has contracted COVID-19 at some point, it is crucial to identify the factors that may make certain individuals more susceptible to developing brain alterations after infection,” Billeke explained. He noted that those who experienced anosmia demonstrated detectable changes in brain structure and displayed distinctive patterns of behavior during decision-making tasks, particularly when it came to adapting to changing environments.
Interestingly, the study also found that the severity of respiratory symptoms did not correlate with the degree of neurological impact. In fact, brain alterations were less pronounced in individuals who had more severe respiratory symptoms, including those who required hospitalization. This suggests that anosmia might be a more telling sign of neurological involvement than the severity of respiratory distress.
“What surprised us the most was how consistent the findings were in patients with anosmia compared to other patients, regardless of the severity of their respiratory symptoms,” said Billeke. “These individuals exhibited detectable alterations at the behavioral level and in brain function and structure, affecting white matter and gray matter.”
While the study presents compelling data, it does come with limitations. The reliance on self-reported anosmia symptoms and the use of screening tools like the KOR test may benefit from further objective clinical evaluations. Moreover, the absence of pre-COVID brain scans makes it challenging to establish a direct causal link between infection and brain changes. However, when combined with existing research, these findings contribute to mounting evidence that COVID-19 can indeed cause neurological damage.
As the researchers move forward, they plan to continue monitoring the study participants to determine whether these brain changes persist over time and impact daily life. In the future, they hope to explore brain stimulation therapies as a potential treatment for individuals suffering from post-COVID cognitive impairments.
“We aim to identify the oscillatory patterns related to these alterations, which is the focus of our ongoing electroencephalography (EEG) studies,” Billeke said. “By identifying these altered patterns, we hope to develop brain stimulation therapies, such as transcranial electrical or magnetic stimulation, to alleviate symptoms.”
With the lingering impact of COVID-19 on the global population, these findings emphasize the urgent need for further research into how the virus affects brain health and long-term cognitive function.
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