key: cord-0868389-y7xm9e4w
authors: Soraas, A.; Ro, R.; Kalleberg, K. T.; Ellingjord-Dale, M.; Landro, N. I.
title: Self-reported Memory Problems Eight Months after Non-Hospitalized COVID-19 in a Large Cohort
date: 2021-02-26
journal: nan
DOI: 10.1101/2021.02.25.21252151
sha: 695e0f0fca4c342c564a4728d7d02ca6fb7b8fa6
doc_id: 868389
cord_uid: y7xm9e4w

Background: Neurological manifestations of COVID-19 range from ageusia and anosmia, experienced by most patients, to altered consciousness and rare and severe encephalopathy. A direct affection of the central nervous system (CNS) in the disease has been supported by animal models and MRI findings in patients with mild and severe symptoms. Here we report eight-month data on memory problems for non-hospitalized COVID-19 patients compared to SARS-CoV-2 negative patients and untested volunteers. Objective: To explore the association between non-hospitalized COVID-19 eight months previously and self-reported memory problems. Methods: We followed a cohort of 13156 participants that was invited after (1) being tested for SARS-CoV-2 with a combined oropharyngeal- and nasopharyngeal swab or (2) randomly selected from the Norwegian population (untested). Participants completed online baseline- and follow-up questionnaires detailing underlying medical conditions, demographics, symptoms, and items from the RAND-36 questionnaire on health-related quality of life and known confounders for memory problems. Results: After repeated invitations, the participation rate was 40% (N=794) of SARS-CoV-2 positive, 26% (N=7993) of negative, and 22% (N=4369) of untested randomly selected invitees. All participants completed the baseline questionnaire as a part of inclusion. The follow-up period was 248 days (SD=18) from baseline, and the follow-up questionnaire was completed by 75% of SARS-CoV-2 positive participants, 65% of negative participants, and 73% of untested randomly selected participants. At follow-up, 49 (11.5%) of the SARS-CoV-2 positive participants reported memory problems in contrast to 173 (4.1%) of the SARS-CoV-2 negative participants and 65 (2.4%) of the untested randomly selected participants. In a multivariate model, SARS-CoV-2 positivity remained strongly associated with reporting memory problems at eight months follow-up compared to the SARS-CoV-2 negative group (odds ratio (OR) 4.0, 95% confidence interval (CI) 2.8-5.2) and the untested group (OR 4.9, 95% CI 3.4-7.2). Compared to the other groups, SARS-CoV-2 positive participants also reported more concentration problems and a significant worsening of health compared to one year ago at follow-up. Feeling depressed, less energy, or pain were reported relatively equally by the different groups. Summary: We find that 11.5% of COVID-19 patients experience memory problems eight months after the disease. SARS-CoV-2 is a new virus, and the long-term consequences of infections are therefore unknown. Our results show that a relatively high proportion of non-hospitalized COVID-19 patients report memory problems eight months after the disease.

In a multivariate model, SARS-CoV-2 positivity remained strongly associated with reporting memory problems at eight months follow-up compared to the SARS-CoV-2 negative group (odds ratio (OR) 4.0, 95% confidence interval (CI) 2. 8-5.2) and the untested group (OR 4.9, 95% CI 3.4-7.2).

Compared to the other groups, SARS-CoV-2 positive participants also reported more concentration problems and a significant worsening of health compared to one year ago at follow-up. Feeling depressed, less energy, or pain were reported relatively equally by the different groups.

Summary: We find that 11.5% of COVID-19 patients experience memory problems eight months after the disease. SARS-CoV-2 is a new virus, and the long-term consequences of infections are therefore unknown. Our results show that a relatively high proportion of nonhospitalized COVID-19 patients report memory problems eight months after the disease.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted February 26, 2021. ; https://doi.org/10.1101/2021.02.25.21252151 doi: medRxiv preprint

Background: Neurological manifestations of COVID-19 range from ageusia and anosmia, experienced by most patients, to altered consciousness and rare and severe encephalopathy (1) . A direct affection of the central nervous system (CNS) in the disease has been supported by animal models and MRI findings in patients with mild and severe symptoms (2) (3) (4) .

Damage to the CNS can lead to long-lasting sequela and a large project on dementia after COVID-19 has been established (5). Many COVID-19 survivors are now at risk for sequelae, and there is an urgent need for a detailed description of the long-term complication (6) . Here we report eight-month data on memory problems for non-hospitalized COVID-19 patients compared to SARS-CoV-2 negative patients and untested volunteers.

Objective: To explore the association between non-hospitalized COVID-19 eight months previously and self-reported memory problems.

We followed a cohort of 13156 participants that was invited after (1) being tested for SARS-CoV-2 with a combined oropharyngeal-and nasopharyngeal swab or (2) randomly selected from the Norwegian population (untested). SARS-CoV-2 testing was performed using real-time RT-PCR in four large accredited laboratories in Norway between February 1 and April 15, 2020 (7) . Nearly all testing in Norway during the time-period was on symptomatic patients and all adults tested at the four laboratories were invited. Willing participants signed an online electronic consent form. Participants completed online baselineand follow-up questionnaires detailing underlying medical conditions, demographics, symptoms, and items from the RAND-36 questionnaire on health-related quality of life and known confounders for memory problems. Hospitalized participants are not reported here.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted February 26, 2021. ; https://doi.org/10.1101/2021.02.25.21252151 doi: medRxiv preprint

The Ethics and ClinicalTrials approval number-and identifiers were REK124170 and NCT04320732.

To determine whether differences between the SARS-CoV-2 positive and negative or untested participants remained after adjustment for confounding, we applied a multivariate logistic regression model that included age, gender, and known confounders for memory problems (RAND-36 items for physical health limitation, pain, feeling energetic, and feeling depressed).

Results: After repeated invitations, the participation rate was 40% (N=794) of SARS-CoV-2 positive, 26% (N=7993) of negative, and 22% (N=4369) of untested randomly selected invitees. All participants completed the baseline questionnaire as a part of inclusion ( Table 1 ).

The follow-up period was 248 days (SD=18) from baseline, and the follow-up questionnaire was completed by 75% of SARS-CoV-2 positive participants, 65% of negative participants, and 73% of untested randomly selected participants. Compared to the other groups, SARS-CoV-2 positive participants also reported more concentration problems and a significant worsening of health compared to one year ago at . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted February 26, 2021. ; https://doi.org/10.1101/2021.02.25.21252151 doi: medRxiv preprint follow-up. Feeling depressed, less energy, or pain were reported relatively equally by the different groups (Table 1) .

Patients reporting dyspnea during COVID-19 disease had more memory problems than those not reporting dyspnea (OR 1.5, 95% CI 1.2-1.9).

Discussion: We find that 11.5% of COVID-19 patients experience memory problems eight months after the disease. Or results are consistent with unpublished surveys without control grops in non-hospitalized and hospitalized patients (8, 9) .

Although we ran multivariate models adjusting for several likely confounders, there may still have been unmeasured or residual confounding in the association observed between SARS-CoV-2 status and memory problems at follow-up. An additional limitation of the study is that knowledge of COVID-19 status at baseline could have led to participation or response bias in the follow-up round. A strength is that memory problems have not yet been reported as part of the "long-COVID" syndrome by Norwegian media. Importantly, memory complaints are known to reflect objective problems and observable changes in everyday function even when controlling for factors associated with self-reported memory problems, such as depression (10, 11) .

SARS-CoV-2 is a new virus, and the long-term consequences of infections are therefore unknown. Our results show that a relatively high proportion of non-hospitalized COVID-19 patients report memory problems eight months after the disease.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Not applicable . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted February 26, 2021. ; https://doi.org/10.1101/2021.02.25.21252151 doi: medRxiv preprint

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