Disentangling the cognitive, physical, and mental health sequelae of COVID-19

Abstract

As COVID-19 cases exceed hundreds of millions globally, many survivors face cognitive challenges and prolonged symptoms. However, important questions about the cognitive effects of COVID-19 remain unresolved. In this cross-sectional online study, 478 adult volunteers who self-reported a positive test for COVID-19 (mean = 30 days since most recent test) perform significantly worse than pre-pandemic norms on cognitive measures of processing speed, reasoning, verbal, and overall performance, but not short-term memory, suggesting domain-specific deficits. Cognitive differences are even observed in participants who did not require hospitalization. Factor analysis of health- and COVID-related questionnaires reveals two clusters of symptoms-one that varies mostly with physical symptoms and illness severity, and one with mental health. Cognitive performance is positively correlated with the global measure encompassing physical symptoms, but not the one that broadly describes mental health, suggesting that the subjective experience of "long COVID" relates to physical symptoms and cognitive deficits, especially executive dysfunction.

Keywords: COVID-19; cognition; cross-sectional online study; long COVID; mental health; physical health.

Graphical abstract

Figure 1

Factor analyses of cognitive test scores and health-related measures (A) Twelve cognitive test scores from normative data (N = 7,832) and (B) health-related measures in COVID⁺ participants (N = 478). Concentric rings represent factors, ordered by decreasing variance explained from inside to outside. Colored cells show the loadings of observed variables on each factor. Curves connecting observed variables indicate pairwise correlations. Pink indicates positive relationships, whereas blues indicate negative correlations. (A) 3 (of 5) composite cognitive scores analyzed in this study were derived from a factor analysis of 12 cognitive tasks: STM (inner ring), reasoning (center), and verbal (outer) domains. (B) Two factors explained health-related questionnaire variables: overall physical health, including COVID severity (F1; inner ring), and mental health and wellness (F2; outer ring). Note that the GAD2 and PHQ2 scales were reversed to make higher scores correspond to better health, like other measures (except disease severity).

Figure 2

Within-group associations between physical health and cognition Participants in the COVID⁺ sample were grouped into tercile bins based on their F1 scores: Below average (“worse”; left group, green traces), average (center group, blue traces), and above average (“better”; right group, purple traces) physical health (F1). Cognitive scores (corrected for nuisance variables) are relative to the normative sample mean (Y = 0.0). Boxes span from the 1st to 3rd quartiles, horizontal lines within a box indicate the median, whiskers span 1.5 times the interquartile range (limited to minimum/maximum of the sample), and points outside the whiskers (i.e., outliers) are individually plotted. Double asterisks below a box trace indicate a significant difference between that COVID⁺ subgroup and the norms (p < 0.05 corrected for 15 comparisons).

Figure 3

Does hospitalization explain physical/cognitive associations? (A) Distributions of health factor scores—physical (F1) and mental (F2) health—in the hospitalized (N = 66) and non-hospitalized (N = 412) COVID⁺ subgroup. The x axis (Y = 0) corresponds to the COVID⁺ sample mean. The brace and asterisks indicate a significant group difference (p < 0.001). (B) Cognitive scores (corrected for nuisance variables), for which Y = 0 indicates the normative sample mean. Double asterisks below boxes indicate significant differences between the COVID⁺ subgroup and the normative sample (p < 0.05 corrected for 10 comparisons). No cognitive differences between hospitalized and non-hospitalized groups were significant at a corrected level. Boxes span from the 1st to 3rd quartiles, horizontal lines within a box indicate the median, whiskers span 1.5 times the interquartile range (limited to minimum/maximum of the sample), and points outside the whiskers (i.e., outliers) are individually plotted.