Nearly a year and a half after initial infection, a new study has found no measurable signs of inflammation or neuronal damage in the blood of patients with long COVID. The research, published in Scientific Reports, challenges previous assumptions about ongoing immune activation in people experiencing persistent symptoms after COVID-19.
The study was conducted at a Norwegian hospital between January 2022 and April 2024. Researchers analyzed circulating biomarkers associated with systemic inflammation and neuroinflammation in adults who had confirmed SARS-CoV-2 infection. Participants included both individuals who met the National Institute for Health and Care Excellence (NICE) criteria for long COVID—defined as symptoms lasting more than 12 weeks without another explanation—and those who had fully recovered from the virus.
A total of 96 participants were included in the final analysis, with an average age of nearly 47 years. Most were women, and the median time since their COVID-19 diagnosis was 69 weeks. The two groups—long COVID cases and recovered controls—were closely matched by sex, age, and time since infection.
Blood tests measured routine markers such as C-reactive protein (CRP), as well as specific proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Additional markers related to neuroinflammation and neuronal damage—including glial fibrillary acidic protein (GFAP) and neurofilament light (NfL)—were also assessed.
The results showed that CRP levels did not differ significantly between long COVID patients and recovered controls. While TNF-α and IL-6 were slightly higher among those with long COVID, these differences disappeared after statistical correction for multiple comparisons. Other markers of neurological injury also showed no significant difference between groups.
"Taken together, the study found no significant differences in neurological and inflammatory biomarkers between LC cases and recovered controls at 69 weeks after SARS-CoV-2 infection," the authors stated. "These results do not support evidence of overt immune activation, inflammation, or neuronal injury in the studied cohort at this late stage of infection."
The researchers noted that earlier studies may have detected signs of ongoing inflammation because they often included people with preexisting chronic inflammatory or autoimmune conditions, which can confound results. By excluding such individuals from this study, the team aimed to better isolate biological signals specifically linked to long COVID.
However, the authors acknowledged several limitations: "The study’s limitations include its small sample size, cross-sectional design that precludes causal inference, use of a select biomarker panel that may mean other inflammatory pathways are active, and reliance on blood-based biomarkers with no paired cerebrospinal fluid or neuroimaging data, as well as the use of assay outputs reported in normalized protein expression units rather than absolute concentrations, which may limit comparisons with external reference values."
Overall, while the findings do not indicate persistent systemic inflammation or neuronal injury detectable through blood tests at this stage of long COVID, researchers caution that very low-level immune activity or other mechanisms could still be involved. They recommend further investigation using larger cohorts to better understand lingering symptoms following SARS-CoV-2 infection.
