Survivors of SARS-CoV-2 Infection Show Neuropsychiatric Sequelae Measured by Surveys, Neurocognitive Testing, and Magnetic Resonance Imaging: Preliminary Results

A significant number of individuals experience physical, cognitive, and mental health symptoms in the months after acute infection with SARS-CoV-2, the virus that causes COVID-19. This study assessed depressive and anxious symptoms, cognition, and brain structure and function in participants with symptomatic COVID-19 confirmed by PCR testing (n=100) approximately three months following infection, leveraging self-report questionnaires, objective neurocognitive testing, and structural and functional neuroimaging data. Preliminary results demonstrated that over 1/5 of our cohort endorsed clinically significant depressive and/or anxious symptoms, and >40% of participants had cognitive impairment on objective testing across multiple domains, consistent with ‘brain-fog’. While depression and one domain of quality of life (physical functioning) were significantly different between hospitalized and non-hospitalized participants, anxiety, cognitive impairment, and most domains of functioning were not, suggesting that the severity of SARS-CoV-2 infection does not necessarily relate to the severity of neuropsychiatric outcomes and impaired functioning in the months after infection. Furthermore, we found that the majority of participants in a subset of our cohort who completed structural and functional neuroimaging (n=15) had smaller olfactory bulbs and sulci in conjunction with anosmia. We also showed that this subset of participants had dysfunction in attention network functional connectivity and ventromedial prefrontal cortex seed-based functional connectivity. These functional imaging dysfunctions have been observed previously in depression and correlated with levels of inflammation. Our results support and extend previous findings in the literature concerning the neuropsychiatric sequelae associated with long COVID. Ongoing data collection and analyses within this cohort will allow for a more comprehensive understanding of the longitudinal relationships between neuropsychiatric symptoms, neurocognitive performance, brain structure and function, and inflammatory and immune profiles.

A - 26 AMPAR as a Sports Concussion Biomarker and Its Relationship to Neurocognitive Functioning in Collegiate Athletes

Objective This prospective controlled observational cohort pilot study investigated a potential blood-based biomarker [α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] and relationship to neurocognitive testing in collegiate athletes. Methods A multisport sample of 60 collegiate athletes (53% female; 44 contact, 16 non-contact controls) completed ImPACT testing and provided blood samples at a pre-season baseline and within 4 weeks post-season. Plasma and serum samples were processed for AMPAR peptides and antibodies. Twelve athletes did not complete all procedures and were excluded from the final analysis (final n = 48; 36 contact; 12 controls). Results Contact athletes demonstrated greater increases in serum AMPAR antibodies compared to controls (t(46) = 3.24;p < 0.01). On neurocognitive testing, controls had a faster reaction time than contact athletes at baseline (p < 0.05); however, this increased post season (p < 0.01), with the mean change in reaction time (contact: M = 0.06, SD = 0.19; control: M = 0.00, SD = 0.04) approaching significance (t(37.23) = 1.54; p < 0.15). Additionally, ImPACT reaction time was correlated (r = 0.37;p < 0.05) with serum AMPAR antibodies, with slowed reaction time related to increased AMPAR in contact athletes only and only post-season. Conclusions Serum AMPAR antibody levels significantly increased in the contact group and were correlated with reaction time on contact athlete neurocognitive testing at post-season only, with contact athletes showing both slower reaction time and increased levels of AMPAR antibodies compared to controls. No findings were identified in plasma AMPAR peptides, possibly related to sample processing which could not be done immediately in this pilot study. Future research and replication is needed; however, AMPAR may represent a blood-based concussion biomarker, with potential for clinical utility in athletes.

The association of genetic polymorphisms with neuroconnectivity in breast cancer patients

Genetic polymorphisms in select genes, including APOE (apolipoprotein E), COMT (Catechol-O-Methyltransferase), MDR1 (multi-drug resistance 1), BDNF (brain derived neurotrophic factor), and GST (glutathione-S-transferase), have been associated with vulnerability to cognitive impairment. In this study, we evaluated the relationship of these genetic variants to measures of brain health in patients with breast cancer, including neurocognitive testing and functional connectome analysis. Women with breast cancer (n = 83) and female healthy controls (n = 53) were evaluated. They underwent resting-state functional MRI scans and neurocognitive testing. Polymerase chain reaction (PCR) was performed on saliva samples to identify single nucleotide polymorphisms (SNPs) in candidate genes: APOE, COMT, MDR1, BDNF, and GST. Breast cancer patients treated with chemotherapy had slower processing speed (p = 0.04) and poorer reported executive function (p < 0.0001) than healthy controls. Those chemotherapy-treated patients that were APOE e4 carriers had significantly slower processing speed. A greater number of risk-related alleles was associated with poorer connectivity in the regions of the left cuneus and left calcarine. While breast cancer patients that are APOE e4 carriers may have a select vulnerability to processing speed impairments, other risk-related alleles were not found to influence cognitive test performance in this population. Conversely, regions of impaired functional connectivity appeared to be related to risk-related genetic polymorphisms in breast cancer patients. This suggests that a cancer patient’s SNPs in candidate genes may influence the risk of neurotoxicity. Further study evaluating the impact of genotype on biomarkers of brain health in cancer survivors is warranted.