Post-mortem studies have shown that patients dying from SARS-CoV-2 infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. In this study the authors proposed that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. They used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. 7 T QSM data from 30 patients were used, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. The authors correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. The authors concluded underlying that this study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, they show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.
Rua C, Raman B, Rodgers CT, Newcombe VFJ, Manktelow A, Chatfield DA, Sawcer SJ, Outtrim JG, Lupson VC, Stamatakis EA, Williams GB, Clarke WT, Qiu L, Ezra M, McDonald R, Clare S, Cassar M, Neubauer S, Ersche KD, Bullmore ET, Menon DK, Pattinson K, Rowe JB. Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations. Brain. 2024 Oct 7:awae215. doi: 10.1093/brain/awae215. Epub ahead of print. PMID: 39375207.