Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge

Background: Emerging evidence shows that cognitive dysfunction may occur following coronavirus disease 19 (COVID-19) infection which is one of the most common symptoms reported in researches of "Long COVID". Several inflammatory markers are known to be elevated in COVID-19 survivors and the relationship between long-term inflammation changes and cognitive function remains unknown.Methods: We assessed cognitive function and neuropsychiatric symptoms of 66 COVID-19 survivors and 79 healthy controls (HCs) matched with sex, age, and education level using a digital, gamified cognitive function evaluation tool and questionnaires at 15 months after discharge. Venous blood samples were collected to measure cytokine levels. We performed correlation analyses and multiple linear regression analysis to identify the factors potentially related to cognitive function.Results: The COVID-19 survivors performed less well on the Trails (p=0.047) than the HCs, but most of them did not report subjective neuropsychiatric symptoms. Intensive care unit experience (13=-2.247, p < 0.0001) and self-perceived disease severity (13=-1.522, p=0.007) were positively correlated, whereas years of education (13=0.098, p=0.013) was negatively associated with the performance on the Trails. Moreover, the abnormally elevated TNF-alpha levels (r=-0.19, p=0.040) were negatively correlated with performance on the Trails in COVID-19 group.Conclusion: Our findings suggest that COVID-19 survivors show long-term cognitive impairment in executive function, even at 15 months after discharge. Serum TNF-alpha levels may be an underlying mechanism of long-term cognitive impairment in patients recovering from COVID-19.