Brain, Behavior, & Immunity - Health 35 (2024) 100701

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Brain, Behavior, & Immunity - Health

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SARS-CoV-2 infection and cognition in community-dwelling and nursing

home residents in southern Switzerland
Greta Rizzi a, Deborah Pacifico a, Serena Sabatini b, Anna Maria Annoni a, Federico Mele c,
Sandra Jovic c, Luca Piccoli d, Laurie Corna e, Rebecca Amati a, William Pertoldi f,
Maddalena Fiordelli a, Federica Sallusto c, g, Emiliano Albanese a, *
a
Institute of Public Health, Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
b
Institute of Mental Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom
c
Institute for Research in Biomedicine, Università Della Svizzera Italiana, Bellinzona, Switzerland
d
Humabs BioMed SA, a Subsidiary of Vir Biotechnology, Bellinzona, Switzerland
e
Centre of Competence on Ageing, Department of Business Economics, Health & Social Care, University of Applied Sciences & Arts of Southern Switzerland, Manno,
Switzerland
f
Istituti Sociali, Chiasso, Switzerland
g
Institute of Microbiology, ETH Zurich, Switzerland

A R T I C L E I N F O A B S T R A C T

Keywords: Background: COVID-19 patients can report ‘brain fog’ and may exhibit cognitive symptoms for months after
Cognitive COVID recovery (Cognitive COVID). However, evidence on whether and the extent to which SARS-CoV-2 infection
SARS-CoV-2 infection impacts cognition irrespective of COVID-19 course and severity is limited to clinical samples and mainly comes
Cognitive decline
from prognostic studies. We aimed to explore the association between serologically confirmed SARS-CoV-2
Serological assessment
Neuropsychological assessment
infection and cognitive functioning in community-based and institutionalized older adults, irrespective of
Long COVID COVID-19 symptoms.
Methods: We conducted a case-control study nested into two cohorts in Southern Switzerland. Eligible subjects
were Italian speaking older adults, without a previous diagnosis of dementia, who underwent serological testing
for anti-SARS-CoV-2 antibodies between November 2020 and July 2021. We manually selected age-, sex- and
education-matched cases (i.e., individuals with a serologically confirmed SARS-CoV-2 infection), with sero­
negative controls, and we conducted in-person neuropsychological assessments using validated, highly sensitive
cognitive tests.
Results: We completed 38 neuropsychological assessments in a mostly female sample of older adults (Mean age:
83.13 ± 8.95; 86.8% women). 17 were community dwelling individuals while 21 lived in a nursing home. As
expected, socio-demographic characteristics of age, gender and educational level were similarly distributed
between cases (n = 14) and controls (n = 24). In linear regression models, cases had significantly lower scores in
cognitive tasks of memory (β = − 0.367, p = 0.023), attention (β = 0.428, p = 0.008) and executive functions (β
= 0.326, p = 0.046). We found no significant difference in tests of language and spatial-temporal orientation (all
p values > 0.05).
Conclusions: SARS-CoV-2 infection was associated with cognitive impairment in memory, attention, and execu­
tive functions in older adults. Our findings are consistent with mechanistic evidence of the neurotropism of the
virus and provide empirical support for the “Cognitive COVID” construct also in non-clinical samples. With
nearly 800 million COVID-19 cases (in April 2023), and many more infections worldwide, the clinical and public
health implications of Cognitive COVID due to SARS-CoV-2 infection may be massive and warrant further
epidemiological investigations.

* Corresponding author. Institute of Public Health, Faculty of Biomedical Sciences, Università della Svizzera Italiana, Via Buffi 13, Lugano, Switzerland.
E-mail addresses: [email protected] (G. Rizzi), [email protected] (D. Pacifico), [email protected] (S. Sabatini), [email protected]
(A.M. Annoni), [email protected] (F. Mele), [email protected] (S. Jovic), [email protected] (L. Piccoli), [email protected] (L. Corna), rebecca.
[email protected] (R. Amati), [email protected] (W. Pertoldi), [email protected] (M. Fiordelli), [email protected] (F. Sallusto),
[email protected] (E. Albanese).

https://doi.org/10.1016/j.bbih.2023.100701
Received 13 September 2023; Received in revised form 25 October 2023; Accepted 28 October 2023
Available online 7 November 2023
2666-3546/© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
G. Rizzi et al. Brain, Behavior, & Immunity - Health 35 (2024) 100701

1. Introduction Finally, evidence in older adults who live in long-term care facilities, in
whom both cognitive impairment and SARS-CoV-2 infections are very
COVID-19, the disease caused by SARS-CoV-2 infection, can cause common, is non-existent.
brain fog, or Cognitive COVID which refers to the medium- and long- Our aim was to study the association of SARS-CoV-2 infection with
term sequelae of SARS-CoV-2 infection on cognitive functions cognitive sequelae, overcoming the above listed limitations and
including attention, memory, and language (Ritchie and Chan, 2021). reducing proneness to biases of previous studies. We conducted a case-
Although, the pathophysiological mechanisms of Cognitive COVID are control study at the community level and in a nursing home for older
not yet well known, it has been hypothesized that cognitive deficits may adults. We hypothesized that there is an association between serologi­
be the consequences of an immune dysfunction, including a non-specific cally confirmed infections and cognitive impairment, irrespective of
neuroinflammation (Spudich and Nath, 2022) or of the neurotropism of COVID-19 symptoms and severity. In order to provide empirical evi­
SARS-CoV-2, i.e., the ability of the virus to invade and infect the neural dence to better define the Cognitive COVID construct, we also sought to
tissue (Desai et al., 2022; Hu et al., 2020). Recent estimations suggest describe the cognitive profile of people over the age of 65 previously
that about 45% of people with a SARS-CoV-2 infection may have Long affected by COVID-19.
COVID (O’Mahoney et al., 2023), defined as the persistence of symp­
toms for 12 or more weeks after recovery from COVID-19 (Bellan et al., 2. Methods
2021). Moreover, evidence is rapidly expanding about the long-term
neurological (headache, smell or taste disorders) (Chen et al., 2021; 2.1. Study design and setting
Nalleballe et al., 2020), neuropsychiatric, and psychological (Mazza
et al., 2021; Nalleballe et al., 2020; Vindegaard and Benros, 2020) We conducted a nested case-control study within the Corona
complications of SARS-CoV-2 virus. However, the mid-to long-term Immunitas Ticino and Cov-risk nursing homes cohort studies in South­
consequences on cognition have received comparatively less attention. ern, Italian-speaking Switzerland (i.e., Ticino canton). Both studies have
Limited evidence available suggests that COVID-19 may impair several been previously described (West et al., 2020) and entail repeated sero­
cognitive abilities, particularly memory, attention and executive func­ logical ELISA tests of anti-SARS-CoV-2 antibodies, and an array of
tions (Alemanno et al., 2021a; Almeria et al., 2020; Chaumont et al., COVID-19 related measures, including exposure to infection, symptoms,
2020; Helms et al., 2020; Premraj et al., 2022; Reford et al., 2022). and impact.
Evidence is not only sparse but also somewhat inconsistent (Zhou et al., Between July 2021 and January 2022, we drew cases (i.e., people
2021). Although decreased verbal fluency (Beaud et al., 2021) and with a serologically confirmed infection, irrespective of symptoms) and
reduced processing speed may be part of Cognitive COVID (Almeria manually matched them with controls (i.e., people without SARS-CoV-2
et al., 2020; Iodice et al., 2021), memory deficits, attentional disorders, antibodies due to infection, in their serum) and conducted in depth, in-
and mental fog are the most commonly self-reported symptoms (Davis person neuropsychological assessments. Interviews lasted 45 min on
et al., 2021a; Misra et al., 2021; Premraj et al., 2022). Cognitive COVID average and were all conducted by a purposely trained junior psychol­
is very common. Estimations based on both objective cognitive assess­ ogist (GR).
ments (Almeria et al., 2020) and self-reported cognitive difficulties The study was approved by the Ticino Cantonal Ethics Committee
(Davis et al., 2021a; Liguori et al., 2020) suggest that Cognitive COVID (Project ID, 2021-00742) and found to comply with the principles of
may be experienced by up to a third of COVID-19 patients after recovery, research involving human people.
but current prevalence estimates vary considerably between 40%
(Reford et al., 2022) and 88% in the Long COVID population (Davis 2.2. Study population
et al., 2021a). Cognitive difficulties may endure several months
(Almeria et al., 2020; Ferrucci et al., 2021), interfere with the ability of Participants were Italian speaking older adults (≥65 years) without a
individuals to conduct daily activities (Reford et al., 2022), and lead to previous diagnosis of dementia, who underwent serological testing be­
increased use of healthcare facilities in terms of increased help-seeking tween November 2020 and July 2021.
behavior to obtain pharmacological treatments for symptoms We selected cases (seropositives) in the source populations using a
(McNaughton et al., 2022). Therefore, Cognitive COVID likely exacer­ Simple Random Sampling technique. We manually matched seronegative
bates the societal and economic impact of the COVID-19 pandemic controls with cases based on age, gender, and years of education, with a
irrespective of the dynamics and spreading of infections. planned one-to-one control to case ratio. We included both community-
Cognitive COVID is important but difficult to investigate both from a dwelling older adults and residents living in a nursing home. The
clinical and public health perspective. As said, current evidence on planned sample size was 35 participants, based on a priori power
Cognitive COVID remains limited, and it is mainly based on data analysis implemented in Statulator (2014) (http://statulator.com/S
collected in hospitalized patients in the post-acute phase of the infection ampleSize/ss2M.html) using the following parameters: probability
(Almeria et al., 2020; Ferrucci et al., 2021; Mazza et al., 2021), despite level (α) 0.05, and statistical power (1 - β) 0.80. We sampled and con­
only a minority of COVID-19 patients are hospitalized. This clinical tacted 50 people, and 38 agreed to take part in the study.
perspective may be biased, and we still know very little on the conse­ All participants (or a legal representative) provided handwritten
quences of SARS-CoV-2 on cognition in asymptomatic or mild signing of the informed consent document before the interviews.
non-hospitalized cases. Comprehensive monitoring of cognitive deficits
should be extended to infected individuals irrespective of COVID-19 2.3. Variables and measures
symptoms. Measurement bias may not be excluded either because
existing studies mainly relied on participants’ performance on general We collected socio-demographic characteristics (age, date of birth,
neuropsychological screening tests such as the Mini Mental State Ex­ gender, and educational level), and information related to COVID-19
amination (MMSE) or the Montreal Cognitive Assessment (MoCA) plausible symptoms (fever, cough, sore throat, loss of taste and/or
(Alemanno et al., 2021a; Patel et al., 2021) although these may prove smell etc.) and severity of disease with online self-reported question­
insensitive to subtle changes in cognition, particularly if impairment is naires. Healthcare staff could assist older adults in data collection based
mild and selective (Beaud et al., 2021; Lynch et al., 2022). Furthermore, on need. For residents living in a nursing home a staff member
older adults are often underrepresented in studies evaluating the po­ completed the questionnaires on their behalf. For the cognitive assess­
tential consequences of COVID-19 on cognition because of a supposed ment schedule, we assembled a battery of cognitive tests related to the
difficulty in disentangling age-related cognitive changes or impairments Cognitive COVID construct (Ritchie and Chan, 2021). We used previ­
from cognitive difficulties due to COVID-19 (Prendki et al., 2020). ously validated and highly sensitive neuropsychological tests to

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G. Rizzi et al. Brain, Behavior, & Immunity - Health 35 (2024) 100701

comprehensively assess cognitive functioning. The battery assessed the Table 1

following cognitive domains: (a) memory, with the CERAD 10 words list Sociodemographic characteristics of cases and controls.
learning test (Sosa et al., 2009); (b) attention, with Trail Making test part SARS-CoV-2 infection Statistics
A and B (TMT) (Siciliano et al., 2019), (c) executive functions with the
Cases (n Controls (n p-valuea
shortened version of the Stroop test (Caffarra et al., 2002), (d) language, = 14) = 24)
with semantic and phonemic verbal fluency tasks (e.g. Number of words
Age, mean ± SD 88.21 ± 80.17 ± 0.309
in 1 min) (Costa et al., 2014; Sosa et al., 2009); (e) visual-spatial 5.09 9.44
perception through the Clock drawing test (Shulman, 2000), and
bespoken standard questions about spatial-temporal orientation. We Gender, % (n) Male 14.3% (2) 12.5% (3) 0.875
favored instruments with little ceiling effects, and minimally age Female 85.7% 87.5% (21)
(12)
confounded. We accounted for age and years of education in test
execution using normative data and standardized the cognitive test Years of education, 1–5 years 28.6% (4) 12.5% (3) 0.559
scores accordingly. We also administered the EURO-D scale from the % (n) 6–8 years 28.6% (4) 45.8% (11)
Geriatric Mental State exam (Copeland et al., 2002) to enquire about 9–13 years 35.7% (5) 37.5% (9)
participants’ mental health status. The EURO-D is a validated, 12-item >13 years 7.1% (1) 4.2% (1)

scale (Castro-Costa et al., 2008) for the evaluation of depression in EURO-D – 4.42 ± 3.13 ± 2.53 0.089
later life. Depression, mean 2.91
To minimize bias, the interviewer was blinded by design about ± SD
grouping of participants (serologically confirmed SARS-CoV-2
Place of residence, Nursing home 85.7% 37.5% (9) 0.004
infection).
% (n) (12)
Community- 14.3% (2) 62.5% (15)
2.4. Statistical analysis dwelling
a
A Student’s T-test for independent samples or a Chi-square test was run
We used IBM® SPSS Statistics version 25 (IBM Corp. Released, 2019. according to the variables.
IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.)
for all statistical analysis and set statistical significance at 0.05.
3.2. Neuropsychological findings
We computed summary statistics for normally distributed contin­
uous variables as means ± standard deviation (SD), or medians with
We completed the full neuropsychological battery with all partici­
min/max ranges in case of a skewed distribution and conducted between
pants, except for one of them who could not complete the Trail Making
groups comparisons using Student’s T-test for independent samples, or
Test Part A, and 10 participants who could not finish the Trail Making
the Mann–Whitney non-parametric test, based on departure from
Test Part B. Because participants were not able to perform the tests, we
normality.
coded missing values as impaired scores. In linear regression models,
Next, we ran separate linear regressions models to investigate the
cases obtained considerably lower scores in attention (β = 0.428, p =
relationships between seropositivity (independent variable) and cogni­
0.008), executive functions (β = 0.326, p = 0.046), and memory tasks (β
tive test performance (continuously distributed dependent variables of
= − 0.367, p = 0.023). We found no significant differences between
cognitive tests).
cases and controls in language and orientation tasks. Detailed neuro­
TMT and Stroop test outcomes were considered as binary variables
psychological test battery results, adjusted by age and years of educa­
(normal vs impaired score), based on their respective normative grids
tion, are reported as mean ± SD in Table 2. Then, we calculated Odd
(Caffarra et al., 2002; Siciliano et al., 2019). For binary outcome mea­
Ratios for impaired execution of the Trail Making Test and Stroop Test,
sures we computed Odd Ratios (ORs) to compare the frequency of the
respectively using normative cut-offs of normal and impaired perfor­
cognitive outcome in subjects with and without a previous SARS-CoV-2
mance. Based on the Italian normative cut-off (Siciliano et al., 2019), at
infection.
the Trail Making Test, 64.3% of cases obtained an impaired score
compared to 17.39% in controls. Similarly, at the Stroop test (Caffarra
2.5. Data availability
et al., 2002), 64.3% of cases obtained a score below the threshold; the
percentage dropped to 20.8% in controls. After adjustment for age and
Anonymized data, including raw and analyzed data, and materials
education, SARS-CoV-2 infection was associated with an increased
not published within this article will be made available by request from
likelihood of an impaired test performance both in the Trail Making Test
any qualified investigator for bona fide uses.
(OR: 6.84, 95% CI: 1.57–29.80) and the Stroop test (OR: 2.52, 95% CI:
0.65–9.83).
3. Results
Age did not significantly modify the association of seropositivity
with cognitive functions, for all cognitive tests.
3.1. Study sample: descriptive statistics
4. Discussion
A total of 38 older adults took part in the study between July 2021
and January 2022; 21 were nursing homes’ residents, 17 lived in the
Our observations seem to confirm that SARS-CoV-2 infection may
community. Mean age was 83.13 (SD: ± 8.95), ranging between 68 and
lead to long-term sequalae and affect cognition. The cognitive effects of
99 years. Most of the study participants were women (86.8%). The
SARS-CoV-2 are common even if it is still not clear how cognitive
characteristics of the actual sample cases (n = 14) and matched controls
impairment evolves after recovery from infection. In this nested case-
(n = 24) are summarized in Table 1. By design, cases and controls had
control study, we assessed the association between serologically
similar socio-demographic characteristics of age, gender, and years of
confirmed SARS-CoV-2 infection and cognitive functions in an older
education and similar EURO-D total scale score distributions for
adults’ sample. The study aimed at exploring if and which cognitive
depression assessment (all p values > 0.05). However, our actual sample
domains were affected by the virus up to several months following the
was significantly differently distributed according to the place of resi­
infection and irrespective of COVID-19 symptoms in both community-
dence (p value = 0.004) and most cases lived in a nursing home (85.7%).
dwelling and nursing homes’ residents older adults. The neurotropism
Cases were all in the range from asymptomatic to moderate symptoms
of SARS-CoV-2 provides a solid mechanistic presumption for our
and did not require hospitalization for treatment of COVID-19.

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G. Rizzi et al. Brain, Behavior, & Immunity - Health 35 (2024) 100701

Table 2
Cognitive outcomes in cases and controls (reported as mean ± SD) by cognitive domain and neuropsychological testsa.
Cognitive domains (Test) SARS-CoV-2 infection Statistics
2
Cases Controls Beta R F p value 95% CI

Lower Upper

Memory (10-words list learning test)

- Immediate recall 9.50 (6.89) 14.25 (5.51) − 0.363 0.132 5.457 0.025 − 8.87 − 0.63
- Delayed recall 2.14 (2.54) 3.88 (2.51) − 0.323 0.104 4.183 0.048 − 3.45 − 0.01
- Total Memory Index 11.64 (9.06) 18.25 (7.83) − 0.367 0.135 5.613 0.023 − 12.26 − 0.95
Attention (Trail Making test)
- Part A 211.50 (252.08) 52.08 (85.12) 0.428 0.183 7.854 0.008 43.94 274.89
- Part B 181.00 (186.75) 78.90 (117.49) 0.318 0.101 2.931 0.099 − 20.48 224.67
- B-A 23.00 (130.35) 48.42 (85.15) − 0.116 0.014 0.357 0.555 − 112.86 62.01
Executive functions (Stroop test)
- Interference of time 88.18 (48.36) 56.80 (42.90) 0.326 0.106 4.274 0.046 0.60 62.18
Language (fluency)
- Semantic fluency 11.38 (6.41) 15.46 (7.63) − 0.266 0.071 2.672 0.111 − 9.13 0.99
- Phonemic fluency 9.71 (5.55) 13.13 (4.87) − 0.315 0.099 3.849 0.058 − 6.95 0.12
Orientation
- Spatial orientation 1.79 (0.58) 1.87 (0.45) − 0.088 0.008 0.283 0.598 − 0.43 0.25
- Temporal orientation 2.36 (1.55) 3.04 (1.37) − 0.230 0.053 2.011 0.165 − 1.66 0.29
a
All tests were age-, sex- and education-standardized, based on normative data.

research hypotheses. excluded). Nevertheless, there is ample evidence that older adults are
In a mostly female sample of asymptomatic to moderate COVID-19 more likely to suffer not only from a more severe course of COVID-19
older adults’ cases and matched seronegative controls, we found that and more severe respiratory symptoms but also delirium (Batty et al.,
previously infected individuals exhibited cognitive impairment entail­ 2020; Misra et al., 2021), which may precede or co-occur with dementia,
ing fewer words remembered in memory tasks and more time required and impact on cognitive test results. Whether and the extent to which
to complete attention and executive functions tasks. Lower cognitive Cognitive COVID and dementia share similar underpinning structural
performance in cases was up to 4-fold compared to what we observed in and functional brain damages is worth investigating, not least because
controls, independent from the age of participants. The present findings the former might exacerbate the latter. Furthermore, our results suggest
are consistent with previous demonstration of the neurotropism of that older adults who contracted the SARS-CoV-2 virus may be more
SARS-CoV-2 (Stein et al., 2022; Sun et al., 2020), which can invade and vulnerable to cognitive decline, irrespective of COVID-19 symptoms and
affect the central nervous system (Desai et al., 2022; Poyiadji et al., up to several months after recovery from the disease. Should
2020), causing long-term sequelae, including cognitive impairment SARS-CoV-2 infection increase dementia risk, the public health impli­
(Desai et al., 2022). Our observations on the most affected cognitive cations would be enormous, because billions of people have been
domains (i.e. memory, attention and executive functions) are in line infected worldwide.
with what has been found in different COVID-19 patients (Alemanno Epidemiological research on Cognitive COVID is in its infancy, but
et al., 2021a; Almeria et al., 2020; Helms et al., 2020; Mazza et al., 2021; inconsistent results are likely attributable to measurement. Most of
Pinna et al., 2020). However, a medium-long term impact of the virus previous studies assessed cognitive deficits following COVID-19 based
more widely distributed on cognition cannot be excluded, including on self-reporting of both infection and perceived cognitive functioning
deficits in information processing speed and language, as already re­ (Ceban et al., 2022; Crivelli et al., 2022; Premraj et al., 2022) or used
ported by other studies (Almeria et al., 2020; Beaud et al., 2021; Iodice generic screening cognitive tests (Mattioli et al., 2021; Patel et al.,
et al., 2021). Even if neuropsychological testing across cognitive do­ 2021). Information and measurement bias are likely. We sought to
mains is taxonomic in nature, it may not reflect the complexity of overcome these biases in our study. We established caseness, that is
brain-behavior relationships. For example, the Trail Making Test - often previous infection, based on a valid and reliable serological test, and
used to evaluate attentional skills - involves other cognitive functions conducted in-person cognitive assessments using objective and vali­
such as visuospatial processing, coordination, and graphomotor speed dated neuropsychological measures chosen based on their reliability and
(Bowie and Harvey, 2006). Furthermore, whether infection is associated sensitivity.
with difficulties in different cognitive domains has not yet been estab­ Our study has some worth noting limitations. First, the small sample
lished and requires further investigation. size of our study may have hindered our ability to detect all true virus-
Comparisons with other studies are not straightforward because of cognition associations. Even if we used a multi-stage approach to contact
the methodological heterogeneity. After the first pandemic wave, liter­ and attempt to recruit one control per case from the source population,
ature was largely dominated by case reports and small case series con­ response rate was not high enough to maintain the anticipated ratio and
ducted in COVID-19 hospitalized patients with moderate to severe matching of cases and controls in the study sample. Based on the limited
symptoms (Almeria et al., 2020; Chaumont et al., 2020; Mazza et al., number of cases, we selected more controls per case ended up with an
2021; Woo et al., 2020). We focused on SARS-CoV-2 infection not on almost 1:2 ratio, in order to maximizing the statistical power of the study
COVID-19, and our cases were mainly a- or pauci-symptomatic older (Setia, 2016). This is a case control study, with limited external validity
adults. Our findings suggest that Cognitive COVID can occur in previ­ by design. Our findings are somewhat preliminary and should be
ously infected individuals irrespective of the course and severity of generalized with caution and only to similar populations.
COVID-19. Null associations between SARC-CoV-2 infection and Second, baseline measures of the study participants’ cognitive
cognitive impairment have been previously reported but may be spuri­ functioning were not available. Issues of directionality may exist that
ously due to the young age of the study samples (between 30 and 64 limit any causal speculations for the association between SARS-CoV-2
years) (Mattioli et al., 2021; Zhou et al., 2021). While the occurrence of infection and cognitive deficits. Nevertheless, reverse causality, that is
Cognitive COVID in infected individuals may increase with age, it is also cognitive impairment leading to infection, seems unlikely in our sample
possible that subtle cognitive impairments are more difficult to detect at because we excluded people with dementia by design. We acknowledge
younger ages (‘floor effect’, opposite of the ceiling effect, may not be that whether those with poorer cognition were at greater risk of

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G. Rizzi et al. Brain, Behavior, & Immunity - Health 35 (2024) 100701

infection because of general poor health may be difficult to disentangle, construct in a non-clinical sample of older adults, supporting the rela­
and evidence is lacking on the association of poor health with adherence tionship between poor cognition and infection, irrespective of the
to infection preventive measures. Furthermore, although the age dif­ severity of symptoms. With nearly 800 million COVID-19 cases, Cogni­
ference between cases and controls was not significant and tests were all tive COVID societal impact may be massive. We need more longitudinal
age-standardized, it cannot be ruled out that age played a role in subtle data on the distribution, frequency, and impact of the cognitive post-
differences in neuropsychological performance. infection manifestations, as well as on their determinants and modula­
Third, most of our cases were nursing home residents, reflecting tors to address epidemiological and mechanistic gaps. This knowledge
greater spread and circulation of infection in long-term residential set­ can inform future studies, and surveillance strategies for Cognitive
tings compared to communities (Amati et al., 2023; Corna et al., 2022). COVID, as well as help in clinical practice in terms of timely diagnosis
However, place of residence may have had an impact on cognitive and treatment options.
performance and the cognitive decline could be a consequence of social
isolation and the strict confinement measures adopted to prevent Funding
contagion (Pérez-Rodríguez et al., 2021).
Again, we did not have and could not adjust our statistical models for This research did not receive any specific grant from funding
dysmetabolic measures (including high Body Mass Index, an indicator of agencies in the public, commercial, or not-for-profit sectors.
global adiposity) or comorbid conditions (such as cardiovascular dis­
eases, diabetes, and hypertension) that may be associated with poorer
cognition and cognitive decline (Dye et al., 2017; Livingston et al., Declaration of competing interest
2020). This is a limitation that we share with previous studies (Almeria
et al., 2020) which is though unlikely to contribute significantly to re­ The authors have no declaration of competing interest.
sidual confounding. While poor health in older adults is associated with
more severe courses of COVID-19, evidence about risk of SARS-CoV-2 Data availability
infection remains highly erratic (Vulturar et al., 2022).
We found that non-hospitalized, SARS-CoV-2 positive older adults Data will be made available on request.
had worse cognitive performance compared to immunonaive counter­
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