Prolonged exposure to lung-derived cytokines is associated with inflammatory activation of microglia in patients with COVID-19.
Rogan A GrantTaylor A PoorLango SichizyaEstefani DiazJoseph Isaac BaileySahil SoniKarolina J SenkowXóchitl G Pérez-LeonorHiam Abdala-ValenciaZiyan LuHelen K DonnellyRobert M TigheJon W LomasneyRichard G WunderinkBenjamin David SingerAlexander V MisharinG R Scott Budingernull nullPublished in: bioRxiv : the preprint server for biology (2023)
Neurological impairment is the most common finding in patients with post-acute sequelae of COVID-19. Furthermore, survivors of pneumonia from any cause have an elevated risk of dementia 1-4 . Dysfunction in microglia, the primary immune cell in the brain, has been linked to cognitive impairment in murine models of dementia and in humans 5 . Here, we report a transcriptional response in human microglia collected from patients who died following COVID-19 suggestive of their activation by TNF-ɑ and other circulating pro-inflammatory cytokines. Consistent with these findings, the levels of 55 alveolar and plasma cytokines were elevated in a cohort of 341 patients with respiratory failure, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. While peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, cumulative cytokine exposure was higher in patients with COVID-19. Corticosteroid treatment, which has been shown to be beneficial in patients with COVID-19 6 , was associated with lower levels of CXCL10, CCL8, and CCL2-molecules that sustain inflammatory circuits between alveolar macrophages harboring SARS-CoV-2 and activated T cells 7 . These findings suggest that corticosteroids may break this cycle and decrease systemic exposure to lung-derived cytokines and inflammatory activation of microglia in patients with COVID-19.
Keyphrases
- respiratory failure
- sars cov
- cognitive impairment
- inflammatory response
- extracorporeal membrane oxygenation
- oxidative stress
- coronavirus disease
- neuropathic pain
- mechanical ventilation
- mild cognitive impairment
- respiratory syndrome coronavirus
- endothelial cells
- rheumatoid arthritis
- liver injury
- young adults
- gene expression
- drug induced
- anti inflammatory
- liver fibrosis
- liver failure
- transcription factor
- white matter
- spinal cord
- multiple sclerosis
- resting state
- spinal cord injury
- cerebral ischemia
- community acquired pneumonia
- heat stress
- replacement therapy
- combination therapy