Hyperinflammation triggers long COVID headaches

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Hyperinflammation triggers long COVID headaches
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Hyperinflammation triggers long COVID headaches Coronavirus Disease COVID PASC LongCOVID biorxivpreprint ClevelandClinic

By Pooja Toshniwal PahariaMar 13 2023Reviewed by Benedette Cuffari, M.Sc. *Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background COVID-19 patients may experience persistent symptoms, which is often referred to as post-COVID-19 condition , PASC, or long COVID. Among the long-term neurological symptoms, chronic headache is most commonly reported. Blood samples were obtained between May 2020 to October 2021 from adults with long COVID [LC]-associated chronic headaches and without long COVID [LC] in the post-acute COVID-19 period. The time points for blood collection following headache onset were -8 days, -7 to seven days, eight to 30 days, one to three months, and over three months. Study participants were registered with the Cleveland Clinic COVID registry and Cleveland Clinic BioRepository .

Results Hyperinflammation was involved in triggering the onset of PCC-associated headache symptoms, with sustained inflammation potentially contributing to the development of persistent long COVID headaches. Immuno-metabolic reprogramming among PCC-headache patients may be responsible for the accumulation of lipid and arginine metabolites that contribute to long-term inflammation. The dysregulated metabolism of multiple neurotransmitters could be the hallmark of PCC-associated chronic headaches.

The study findings indicate that chronic generalized inflammation drives COVID headaches, irrespective of COVID-19 severity. Enhanced glucose metabolism and inflammation were also observed among PCC headache patients before headache onset, which likely served as an energy source that subsequently led to a hyper-inflammatory state.

In addition to M1 macrophage-skewing and lipidomic-type profiles among PCC-headache patients, increased arginine and oxo-arginine were observed, with lower expression of nitric oxide synthase inhibitors, asymmetric and symmetric dimethylarginine , and urea. These observations emphasize the essential roles of M1-type macrophage-mediated persistent inflammation among long COVID headache patients.

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