Systemic cytokines related to memory function 6-9 months and 12-15 months after SARS-CoV-2 infection

Abstract

Cognitive symptoms persisting beyond the acute phase of COVID-19 infection are commonly described for up to 2 years after infection. The relationship between cognitive performance, in particular episodic memory processes observed chronically after infection, and cytokine levels in the acute phase of COVID-19 has not yet been identified in humans. To determine whether the levels of cytokines IL1β, IL-6 and TNFα secreted in the acute phase of SARS-CoV-2 infection are associated and predict verbal and visuospatial episodic memory performance in humans 6 to 9 months and 12 to 15 months post-infection. The associations and predictive value of the concentration of cytokines measured in acute phase (IL-1β, IL-6, TNFα) from plasma samples of N = 33 hospitalized COVID-19 patients (mean age 61 years, 39-78, 65% in intensive care) in relation to their verbal and visuospatial episodic memory performance measured at 6-9 months and 12-15 months post-infection were analyzed. To do this, we used Spearman correlations and generalised linear mixed models. IL-1β levels were associated with verbal episodic memory total recall scores 6-9 months post-infection. At 12-15 months post-infection IL-6 predicted verbal episodic memory score. This study demonstrated that the severity of inflammatory reaction at acute phase of SARS-CoV-2 infection predicts verbal episodic memory performance in the long-term post-infection.

Keywords: COVID-19; Cognition; Immunity; Long COVID; Memory; Post-COVID; SARS-CoV-2.

Fig. 1

Semi-log association between IL-1β secreted during the acute phase of SARS-CoV-2 infection and episodic memory performance 6–9 months and 12–15 months post-infection. (a) Semi-log association between Log IL-1β and the total of the three RLRI total scores 6–9 months post infection. (b) Semi-log association between Log IL-1β and the addition of the three RLRI free recall scores 12–15 months post-infection. Log logarithmic, RLRI free/cued recall paradigm.

Fig. 2

Study flowchart. In this study, we included 33 patients hospitalized in the acute phase of SARS-CoV-2 infection for whom a blood sample and cytokine analysis had been performed and who were assessed a neuropsychological examination at 6–9 months and 12–15 months post-infection. We excluded 88 patients from the cohort, who had not been hospitalized due to the absence of a blood sample, patients who had been hospitalized without a viable blood sample for cytokine analysis and patients who had not completed a follow-up neuropsychological examination 12–15 months post-infection. ICU intensive care unit.