COVID-19 patients may experience persistent symptoms, which is often referred to as post-COVID-19 condition (PCC), PASC, or long COVID. Among the long-term neurological symptoms, chronic headache is most commonly reported.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for COVID-19, induces inflammation. However, immunological, biological, and metabolomic and factors associated with long COVID headaches are not well-characterized.
Researchers in the current study assess the immuno-metabolomic alterations in long COVID patients who suffer from persistent headaches.
Adults with long COVID [(+)LC]-associated chronic headaches and those without long COVID [(-)LC] in the post-acute COVID-19 period provided blood samples between May 2020 and October 2021. 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. Cleveland Clinic COVID registry and Cleveland Clinic BioRepository registrations were made for study participants (CC-BioR).
A quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay was used to confirm the diagnosis of COVID-19. Complete blood count (CBC) analysis, multi-omics analyses, including transcriptomics, metabolomics, bulk ribonucleic acid (RNA) sequencing (RNAseq) and proteomics, were also performed. In addition, bulk RNAseq analysis was performed on isolated white blood cells to assess immunological responses triggering the onset of PCC headaches.
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.
