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Chronic Inflammation and Altered Immune Responses in LongCOVID Associate with Neurological Manifestations and Accelerated Aging

Year: 2025

Type: article

Abstract: There is a subgroup of people infected with the SARS-CoV-2 virus who manifest lingering sequelae (LongC), with neurological symptoms (nLongC). We recruited 86 COVID-19 volunteers, 35 of whom were fully recovered (Cov) and 51 who had neurological symptoms (nLongC) 4-53 months after infection and compared them to 51 healthy pre-pandemic controls (HC). Thirty-five percent of nLongC individuals carried the apolipoprotein E4 (APOE4) gene, compared to 11% of Cov. Four plasma proteins, interleukin 1 beta (IL-1β), interleukin 8 (IL-8), glial fibrillary acidic protein (GFAP), and hemopexin, continued to be elevated in both Cov and nLongC compared to HC. Soluble CD14 was elevated in nLongC but not Cov. As a group, IL-1β decreased over time in Cov but not nLongC. Two of the elevated proteins, IL-8 and GFAP, correlated with age, with both Cov and nLongC showing higher levels than HC. Using a combination of four plasma proteins, along with age, body mass index, and APOE4 presence, we were able to achieve an area under the curve (AUC) of 0.81. These results suggest that SARS-CoV-2 infection causes a low-grade inflammatory process that, even months or years after infection, does not return to pre-COVID-19 levels, which may contribute to neurologic sequelae and accelerated aging.

Source: Cells

DOI: 10.3390/cells14231875

Authors: Norina Tang, Judith M. Ford, Kaitlyn Dal Bon, Lynn Pulliam

Institutions: San Francisco VA Medical Center, San Francisco VA Health Care System, University of California, San Francisco

Language: English

Topic: Long-Term Effects of COVID-19

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258