TY - JOUR
T1 - The pandemic brain
T2 - Neuroinflammation in non-infected individuals during the COVID-19 pandemic
AU - Brusaferri, Ludovica
AU - Alshelh, Zeynab
AU - Martins, Daniel
AU - Kim, Minhae
AU - Weerasekera, Akila
AU - Housman, Hope
AU - Morrissey, Erin J.
AU - Knight, Paulina C.
AU - Castro-Blanco, Kelly A.
AU - Albrecht, Daniel S.
AU - Tseng, Chieh En
AU - Zürcher, Nicole R.
AU - Ratai, Eva Maria
AU - Akeju, Oluwaseun
AU - Makary, Meena M.
AU - Catana, Ciprian
AU - Mercaldo, Nathaniel D.
AU - Hadjikhani, Nouchine
AU - Veronese, Mattia
AU - Turkheimer, Federico
AU - Rosen, Bruce R.
AU - Hooker, Jacob M.
AU - Loggia, Marco L.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/2/13
Y1 - 2022/2/13
N2 - While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.
AB - While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.
KW - Mental health
KW - MRS
KW - Neuroimaging
KW - Pandemic
KW - PET
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=85124838922&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2022.02.018
DO - 10.1016/j.bbi.2022.02.018
M3 - Article
SN - 0889-1591
VL - 102
SP - 89
EP - 97
JO - Brain, behavior, and immunity
JF - Brain, behavior, and immunity
ER -
