Brainstem neurochemical profiles after hospitalisation for COVID-19: a 7T MR spectroscopy study
Graf C., Raman B., Manktelow A., Chatfield DA., Clarke WT., Rua C., Newcombe VFJ., Lupson VC., Sawcer SJ., Outtrim JG., Ersche KD., Qiu L., Ezra M., McDonald R., Clare S., Cassar MP., Neubauer S., Bullmore ET., Menon DK., Rowe JB., Pattinson K., Rodgers CT., Allinson K., Anwar F., Bhatti J., Bullmore ET., Chatfield DA., Christmas D., Coles AJ., Coles JP., Correia M., Das T., Elmer A., Fletcher PC., Jubb AW., Manktelow A., Menon DK., Michell A., Needham E., Newcombe VFJ., Pointon L., Rodgers CT., Rowe JB., Rua C., Sawcer SJ., Sithole N., Spindler LRB., Stamatakis EA., Taylor J., Valerio F., Widmer B., Williams GB., Allison J., Alvio G., Baker S., Baker S., Bergamashi L., Beristain-Covarrubias N., Bermperi A., Betancourt A., Biggs H., Booth L., Boston R., Bower G., Bradley J., Brookes K., Bucke A., Bullman B., Butcher H., Caddy SL., Calder J., Caller LG., Canna L., Caputo D., Chandler M., Chaudhry Y., Chinnery P., Clapham-Riley D., Cooper D., Cossetti C., Crucusio C., Cruz I., Curran MD., Jesus RD., Sa AD., Dempsey K., Dewhurst E., Stephano GD., Domingo J., Dougan G., Dunmore BJ., Epping M., Fawke S., Feltwell T., Fernandez C., Ferreira A., Fuller S., Furlong A.
Background: Somatic, cognitive and mental health issues have been identified in three-quarters of people 5 months after hospitalisation for severe acute SARS-CoV-2 (COVID-19) infection. The underlying neuroanatomical basis of these symptoms remains unclear, but recent studies suggest a role for altered brainstem physiology. We aimed to test the hypothesis that brainstem neurochemical profiles differ in patients who had been hospitalised for COVID-19 compared to matched controls using 7T magnetic resonance spectroscopy (MRS). Methods: This prospective case–control study recruited 34 individuals who were hospitalised for COVID-19 and 15 healthy controls with no history of COVID-19 infection from two major UK hospitals before vaccines became available. The participants underwent 7T semi-adiabatic localization by adiabatic selective refocusing (sLASER) 1H-MRS at the ponto-medullary junction. Water-referenced metabolite concentrations were compared between the patients and controls and correlated with infection severity, as measured by maximum C-reactive protein (CRPmax) assay during inpatient admission. Linear mixed modelling was used with a 0.05 significance level. Results: Spectral quality was high/acceptable in 44/49 participants according to the MRS Consensus criteria. The magnitude of inflammation during patient admission (i.e., CRPmax) correlated positively with myo-inositol concentration (β = 0.005, p = 0.035), as did patient-reported symptoms (β = −0.564, p = 0.023). However, metabolite concentrations were not significantly different between the patients and controls. Conclusion: We show the feasibility of assessing brainstem neurochemical profiles using 7T 1H-MRS in a multi-centre study. Technical limitations at one site’s 7T MRI led to variable repetition times, which limited our statistical power and should be avoided in future studies. Our findings highlight the need for further investigation into the role of neuroinflammation in post-acute COVID-19.