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. 2025 Oct 27;15(1):37381.
doi: 10.1038/s41598-025-19984-7.

Co-occurrence of memory impairment and fatigue distinguishes post COVID from pandemic-related health effects in the 4-year CON-VINCE cohort study

Patricia Martins Conde #  1 , Dmitry Bulaev #  2 , Armin Rauschenberger  3   2 , Jochen Ohnmacht  2 , Joëlle V Fritz  2 , Marc P O'Sullivan  2   4 , François Ancien  3 , Soumyabrata Ghosh  3 , Olena Tsurkalenko  2   5 , Alexey Kolodkin  2 , Venkata Satagopam  3 , Michel Vaillant  2 , Jochen Klucken  3   5 , Rejko Krüger  3   2   5 ; CON-VINCE/ORCHESTRA Study Consortium
Collaborators, Affiliations

Co-occurrence of memory impairment and fatigue distinguishes post COVID from pandemic-related health effects in the 4-year CON-VINCE cohort study

Patricia Martins Conde et al. Sci Rep. .

Abstract

A major challenge in diagnosing post COVID lies in differentiating symptoms following a confirmed SARS-CoV-2 infection from those that may also occur in uninfected individuals (post COVID mimics) and be associated with a broader impact of the pandemic. The WHO post COVID definition was applied to the Luxembourgish longitudinal CON-VINCE cohort, where SARS-CoV-2 infection was confirmed via either a positive RT-qPCR or a serology test. Risk factor analysis was conducted on 1,865 individuals. Female gender, lower resilience, greater loneliness, and a higher number of comorbidities were associated with symptoms persistence. The symptomatology and comorbidity profiles of 559 participants (including 50 post COVID and 66 post COVID mimics) were investigated. Two distinct clusters of persistent symptoms were identified: (1) depression with anxiety, present in both infected and non-infected groups, and (2) memory impairment with fatigue, unique to the post COVID group. Therefore, presence of both memory impairment and fatigue may help differentiate post COVID patients from post COVID mimics. Yet, verification that memory impairment was newly developed was not possible, as this symptom was not recorded at baseline. Our findings suggest that future studies should consider factors affecting development of persistent post COVID-like symptoms observed in individuals that were never infected.

Keywords: Cohort; Long COVID; Long COVID mimics; PASC; Post COVID syndrome; SARS-CoV-2.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was conducted according to the Ethical Principles for Medical Research Involving Human Subjects, as stated in the 2013 revised version of the 1964 World Medical Association Declaration of Helsinki. The national research ethics committee (Comité National d’Ethique de Recherche, CNER) and the Luxembourgish Ministry of Health (references 202004/01 and 831x6ce0d, respectively) approved the study. Trial registration number is NCT04379297. The ORCHESTRA study was approved by the national research ethics committee (CNER No 202106/03). Consent to participate: All participants completed an electronic Informed Consent Form and had the right to withdraw from the study at any time. Consent for publication: Every study participant accepted that the results of this study may be the subject of scientific communications or publications, under the condition that presentation of the study results can in no way allow direct or indirect identification of the consenting participant.

Figures

Fig. 1
Fig. 1
Evolution of the distribution of participants by infection status and by presence of persistent symptoms at different study visits. Most prevalent SARS-CoV-2 variants were obtained from Our World in Data website and based on GISAID datasets.
Fig. 2
Fig. 2
Forest plots. Odds ratios (ORs), odds and p-values of persistent symptoms between infected and non-infected participants at CON-VINCE visit 8. Only the odds ratios of the 5 symptoms with the 5 lowest p-values in the associated Fisher’s exact test are plotted. All SARS-CoV-2 infected and all non-infected participants with a known symptom status are presented. The odds represent the number of individuals with the persistent symptom divided by the number of individuals without the persistent symptom in the subgroup. The resulting ORs are presented in the forest plots. * Significantly different symptoms between the subgroups before adjustment for multiplicity at 5% confidence level.
Fig. 3
Fig. 3
Forest plots. Odds ratios (ORs), odds and p-values of persistent symptoms between males and females, stratified by infection status at CON-VINCE visit 8. Only the odds ratios of the 5 symptoms with the 5 lowest p-values in the associated Fisher’s exact test within each group are plotted-infected at the top and non-infected at the bottom. The odds represent the number of males or females with the persistent symptom divided by the number of males or females without the persistent symptom, within the infected or non-infected subgroup. * Significantly different symptoms between the two genders before adjustment for multiplicity at 5% confidence level.
Fig. 4
Fig. 4
Pairwise combinations of persistent symptoms in SARS-CoV-2 infected individuals (top) and in non-infected individuals (bottom) at CON-VINCE visit 8. Only the symptoms present in at least one individual in any of the two groups (infected/non-infected) are plotted. Heat maps based on the Jaccard similarity index between symptoms. The Jaccard index ranges from zero for dissimilar (white) to one for similar (dark red), and it is not defined if both symptoms never occur. Significant at 5% level, FDR-adjusted p-values from a Fisher’s exact test are indicated by a green circle. The values on the right and at the bottom indicate the number of individuals with the given symptom, with the proportion of individuals with this symptom in the considered subgroup in brackets.
Fig. 5
Fig. 5
Forest plots. Odds ratios (ORs), odds and p-values of presenting any persistent symptoms at CON-VINCE visit 8 between comorbid and non-comorbid participants at baseline visit 0. Only the odds ratios of the 5 comorbidities with the 5 lowest p-values in the associated Fisher’s exact test are plotted. The values represent the number of individuals with any persistent symptom divided by the number of individuals without any persistent symptom at visit 8 in the comorbid or non-comorbid subgroups. * Significantly different comorbidities between the subgroups before adjustment for multiplicity at 5% confidence level.
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