The recent surge of the FLiRT variant reminds us that clinicians are not only dealing with the immediate health impacts of COVID-19 infections, but also, in many patients, they’re grappling with persistent neurocognitive and neuropsychiatric effects that the illness may include. As the nation treats more and more of these patients, a critical question has emerged: Are the post-COVID cognitive and psychiatric challenges uniform, or do they present in distinct, differentiated groups?
A recently published Mayo Clinic study involving 205 individuals recovering from SARS-CoV-2 infection aimed to decode post-acute neuropsychological profiles and potentially categorize them into neurophenotypes. Researchers gathered multiple data points, including cognitive assessments performed with the CNS Vital Signs platform, and then applied advanced machine learning techniques to analyze an array of objective and subjective measures. Three distinctive post-COVID neurophenotypes emerged, each with a unique set of risk factors and recovery outcomes.
Three Distinct Phenotypes
The first and largest neurophenotype, encompassing 69% of the participants, exhibited cognitive functions within normal limits, albeit with mild subjective attention and memory complaints lingering. Those vaccinated against COVID-19 were more likely to belong to this "normal cognition" group, suggesting a link between vaccination and cognitive recovery.
For the remaining 31% of participants experiencing cognitive impairment, two distinct clusters emerged. The first cluster (16% of participants) showcased prominent memory deficits, slowed processing speed, and fatigue. Anosmia and a history of severe COVID-19 infection were identified as risk factors for this "memory-speed impaired" neurophenotype. On the other hand, the second cluster (15% of participants) displayed executive dysfunction (the “dysexecutive” neurophenotype) as a primary feature, with risk factors encompassing disease-nonspecific factors like neighborhood deprivation and obesity.
Specific Cognitive Domains Impacted in Post-COVID Neurophenotypes
In this study, impairment in specific CNS Vital Signs-measured cognitive domains were observed in each cluster, providing a preliminary understanding of the cognitive challenges faced by each neurophenotype:
1. “Normal Cognition” Neurophenotype:
- Verbal Memory
- Psychomotor Speed
- Attention
2. “Memory-Speed Impaired” Neurophenotype:
- Verbal and Visual Memory
- Psychomotor Speed
- Reaction Time
3. “Dysexecutive” Neurophenotype:
- Complex Attention
- Cognitive Flexibility
Understanding the specific cognitive domains affected in each neurophenotype is crucial for tailoring rehabilitation strategies.
Outcomes & Treatment Considerations
Looking six months ahead into recovery outcomes, the neurophenotypes demonstrated varied trajectories.
The "normal cognition" group displayed improvements in verbal memory and psychomotor speed, hinting at a promising recovery.
Similarly, the “dysexecutive” group also displayed broad recovery at the same point.
In contrast, the "memory-speed impaired" group did not exhibit the same objective improvement and faced relatively worse functional outcomes.
These findings underscore the importance of identifying the specific neurophenotype in which a post-COVID patient is included and tailoring rehabilitation accordingly. For the “memory-speed impaired” neurophenotype, targeted cognitive rehabilitation focusing on memory and processing speed may be particularly beneficial. Meanwhile, the “dysexecutive” neurophenotype may benefit from interventions that enhance attention and cognitive flexibility. Personalized approaches, considering these distinct cognitive profiles, can significantly improve outcomes and the quality of life for individuals grappling with post-COVID cognitive challenges.
Conclusion
The identification of distinct neurophenotypes among post-COVID individuals sheds light on potential pathways for understanding and addressing persistent cognitive challenges. As we move forward, understanding these nuances can help pave the way for targeted treatments, personalized rehabilitation plans, and improved outcomes for those grappling with the aftermath of a COVID-19 infection.
Source:
Prabhakaran D, Day GS, Munipalli B, Rush BK, Pudalov L, Niazi SK, Brennan E, Powers HR, Durvasula R, Athreya A, Blackmon K. Neurophenotypes of COVID-19: Risk factors and recovery outcomes. Brain Behav Immun Health. 2023 Jul;30:100648. doi: 10.1016/j.bbih.2023.100648. Epub 2023 Jun 4. PMID: 37293441; PMCID: PMC10239310.