COGNITIVE DISORDERS IN PATIENTS INFECTED WITH COVID-19: A NARRATIVE REVIEW TRASTORNOS COGNITIVOS EN PACIENTES INFECTADOS POR COVID-19: UNA REVISIÓN NARRATIVA TRANSTORNOS COGNITIVOS EM PACIENTES INFECTADOS COM COVID-19: UMA REVISÃO NARRATIVA

Objective: The overactivated immune system due to COVID-19 may be responsible for most of its physiological manifestations, including the neurological ones. Methods: The scientific articles were searched by two independent researchers in the MEDLINE (PubMed), LILACS, SciELO, Scopus, Web of Science, and BIREME databases, with no restriction of language, period, or place of publication. To complement and avoid the bias of risk, gray literature was searched in Google Scholar. The narrative review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The studies included in the research had scored ≥ 6 points in the qualitative protocol proposed by Pithon et al. (2015). Results: COVID-19 patients commonly have neurological manifestations. The patients’ age was an important risk factor for neuropsychological deficiencies due to COVID-19. Increased fatigability and deficits in concentration, memory, and overall cognitive speed are reported months after hospital discharge. Also, the studies showed that the phase of the disease in which the patient is found directly interferes with the manifestation of the cognitive changes. Conclusion: Cognitive changes are frequently found months after hospital discharge in COVID-19 patients. A slower cognitive processing speed and impaired memory may interfere with the patients’ daily functioning and their capacity to return to work. Hence, cognitive rehabilitation interventions aiming to increase the processing speed and memory must also be considered for this population.


INTRODUCTION
The disease named 2019 coronavirus (COVID-19) is a respiratory condition caused by the RNA virus.
It is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can result in various syndromes due to long-term effects and variables in the person's body. The diversified changes caused by SARS-CoV-2 are the main reasons why the disease has long-term physiological effects. 1 On January 30, 2020, the COVID-19 outbreak was classified as a Public Health Emergency of International Concern. COVID-19 infection generally has a range of manifestations, from initial signs and symptoms related to upper respiratory tract infection (such as rhinorrhea and sore throat) to cough, fever, dyspnea, and difficulty breathing. 2 The coronavirus is an important virus that affects mainly the human respiratory system, although it also has a neuroinvasive capacity and can expand from the respiratory tract to the central nervous system (CNS). 3 It is hypothesized in the literature that SARS-CoV-2 is transmitted to the CNS via the hematogenous route, invasion of the olfactory bulb, and retrograde axonal transport. 3 The overactivated immune system due to COVID-19 is believed to be responsible for most of its physiological manifestations, including the neurological ones. The severe cases of the disease are more prone to manifesting severe neurological syndromes. Another situation to be considered is the endothelial dysfunction caused by SARS-CoV-2, which can occur in different organs of the body, resulting in ischemia/infarction and hemorrhage. 4 Previous observations led to increasing research characterizing the neurological ramifications due to SARS-CoV-2. However, the data on the cognitive effects of the disease have not been fully clarified yet. 1 Given the above, this research aims to verify scientific evidence of cognitive disorders in patients infected with COVID-19 to answer the following research question: "What are the cognitive disorders present in patients infected with COVID-19?"

Protocol
This narrative review, aiming to verify the cognitive disorders in patients infected with COVID-19, was conducted according to the PRISMA recommendations (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). 5 The scientific articles were searched by two independent reviewers in the MEDLINE (PubMed), LILACS, SciELO, Scopus, Web of Science, and BIREME databases, with no restriction of language, time, and place of publication. The research was structured and organized in the PICOS framework, which is an acronym standing for Target

Research strategy
The descriptors were selected based on controlled vocabulary in the Health Sciences Descriptors

Eligibility criteria
The studies were included with no restriction of language, time, and place of publication. Table 2 shows the inclusion and exclusion criteria developed for this research. The studies scored 12 in the modified protocol by Pithon et al. (2015), 6 which assesses their quality. 5

Risk of bias
The quality of the methods used in the studies included here was independently assessed by the reviewer (XX), following the PRISMA recommendations (Moher et al., 2015). The assessment gave priority to clearly described information. At this point, the review was blind, masking the names of authors and journals to avoid any potential bias and conflict of interest.

Exclusion criteria
Studies published as letters to the editor, guidelines, literature reviews, narrative reviews, systematic reviews, meta-analyses, and abstracts were excluded, as well as studies not fully available ( Table 2).

Data analysis
For the eligibility process, the data were extracted from the studies by two researchers with a spreadsheet specifically developed for narrative reviews in Excel ® version 16.0 (Microsoft, USA). The extracted data were entered in it by one of the researchers and then checked by another one. The studies were first selected by title; then, the abstracts were analyzed, and only the potentially eligible ones were selected. Based on the abstracts, articles were set apart to be read in full, and those that met all the pre-established criteria were included.

Selection of the studies
Initially, the eligibility reviewer (XXX) was calibrated by XX to conduct the narrative review. After calibrating and answering questions, the titles and abstracts were independently examined, not blind to the names of authors and journals. Those whose title was within the scope but the abstract was unavailable were also obtained and analyzed in full. Studies not within the scope, and the case reports, letters to the editor and/or editorials, literature reviews, indexes, abstracts, systematic reviews, and meta-analyses were excluded. Afterward, the preliminarily eligible studies had their full text obtained and evaluated.

Collected data
After the screening, the text of the selected articles was reviewed and extracted by one of the authors (XXX) supervised by XX, following a standard with the identification of year of publication, place of the research, language of publication, type of study, sample, method, result, and conclusion of the study.

Clinical result
The clinical result of interest consisted in verifying the cognitive disorders in patients infected with COVID-19. Those with a different approach from what had been defined were not included in the sample of this narrative review.

RESULTS
At first, 142 articles were selected, narrowed down to 139 after excluding the duplicate ones. Then, the titles and abstracts were analyzed, and 135 papers were excluded for not being within the scope approached in this research. Hence, four articles were included in the final analysis, as all of them answered the research question ( Figure 1). Their study design was cross-sectional. Based on the descriptors selected, the databases were consulted, returning the results made available in  8

RECIMA21 -REVISTA CIENTÍFICA MULTIDISCIPLINAR ISSN 2675-6218 COGNITIVE DISORDERS IN PATIENTS INFECTED WITH COVID-19: A NARRATIVE REVIEW Laura Faustino Gonçalves, Patrícia
The studies selected for the present research were described in Table 4.

Study design
The first study 7 was conducted in three centers of a hospital in China. The authors retrospectively analyzed patients diagnosed with COVID-19. A total of 214 hospitalized patients with laboratory confirmation of SARS-CoV-2 were included in the analysis. The collected data encompassed age, sex, comorbidities (such as hypertension, diabetes, cardiac, cerebrovascular, malignant, or chronic renal diseases), and typical symptoms from the onset to hospitalization (including fever, cough, anorexia, diarrhea, sore throat, abdominal pain, symptoms of the nervous system, and laboratory and CT scan findings). The subjective symptoms were provided by the patients who were awake to answer the interview. 7 The neurological manifestations were categorized into groups: CNS manifestations (such as dizziness, headache, impaired awareness, acute cerebrovascular disease, ataxia, and convulsions), 10 in those with PNS symptoms, the most often reported ones were impaired taste (12.6%) and smell (5.1%). 7 The second study 8

Neuropsychological Assessments
The TMT traces visual sweeping and visual movement, reflecting the people's information processing speed. The SCT is used to investigate visual perception, visual sweeping, eye movement, and memory.
The CPT measures impulse and continuous and selective attention. And the DST assesses concentration, instantaneous memory, and resistance to information interference. 8 The had some deficit. Group 1 had higher scores than Group 3. Significant differences between these two groups were observed in the subdomains of short-term memory, attention, abstraction, long-term memory, space, and time orientation. 9 The analysis of the Mini-Mental State Examination (MMSE) showed that 12.9% of the patients in Group 1 had mild to severe deficits; 55.6% of those in Group 2 had mild to moderate deficits; 48.3% of those in Group 3 had mild to severe deficits; and 44.4% of the ones in Group 4 had moderate deficits. Group 1 had higher scores than Group 3. These differences were significant in the domain of attention, calculation, memory, and language. 9 The participants were submitted to neuropsychological assessment within 4 to 5 months after hospital discharge. Before proceeding to complete neuropsychological assessment, the patients were selected 11 The nervous system manifestations were significantly more common in severe infections than in nonsevere ones (45.5% vs. 30.2%). Hence, the authors reported that SARS-CoV-2 can infect the nervous system. In patients with a severe infection, there is a greater neurological involvement, which includes acute cerebrovascular diseases and impaired awareness. Their quick deterioration and or clinical worsening may be associated with a neurological event, such as a stroke, which would contribute to their high mortality rate. 7 The results were based on the four tests they applied. In the CPT, the patients with COVID-19 had a lower score than the control group. Likewise, there was a significant difference in the responses of the COVID-19 patients in the CPT 2 and CPT 3 tests in comparison with the control group. 8 Approximately 80% of the patients had cognitive deficits in the subacute phase of the disease, and approximately 40% of the patients suffered from mild to moderate depression; these deficits were more significant in older patients. The patients' age proved to be a risk factor for neuropsychological deficiencies due to COVID-19. 9 Thirty participants answered the SSD. Of these, 50% reported a moderate to high increase in fatigability; In another study present in this analysis, the patients in the subacute phase of the disease had cognitive deficits, which were more significant in older patients. 9 This corroborates with another study included here, 7 in which the authors report that nervous system manifestations were significantly more common in severe infections. In such patients, there is a greater neurological involvement, including acute cerebrovascular disease and impaired awareness.
There are currently few studies in the literature approaching cognitive sequelae of COVID-19 infection.

COVID-19 infection results from a combination of respiratory infection and mechanical ventilation
secondary to inadequate oxygenation, the reactivity of the inflammatory system, and an increase in the blood coagulation factors. These can affect the CNS function, resulting in long-term cognitive communication impairment in a proportion of the survivors. 13 In a study, the overall cognitive deficit was observed in 33.3% of those with a pathological score in the MMSE, with a specific decline in attention, memory, language, and praxis skills. Poor cognitive functioning seems to be linearly associated with ICU length of stay. 14 Brain vascular disease is emerging as one of the main COVID-19 complications in its severe conditions, thus increasing the risks of lasting brain damage, such as stroke and vascular cognitive deficiency.
Many of the metabolic abnormalities that affect COVID-19 patients may also increase their risk of developing dementiawhich has comorbidities and risk factors similar to those of COVID-19, including age, sex, hypertension, diabetes, and obesity. These similar comorbidities and mechanisms may also explain the high incidence and increase in mortality rates in people with dementia. 15 Older adults, particularly those with comorbidities, make up a vulnerable group at greater risk of acquiring the disease and presenting more severe outcomes, including death. Therefore, post-COVID-19 infection follow-up with encompassing cognitive and neuropsychiatric assessments is essential, along with brain imaging, especially for those who developed the severe stage of the disease. It is thus necessary to dismiss long-term sequelae and provide mental health support and cognitive rehabilitation to minimize potential negative effects on the survivors' psychosocial functioning and quality of life. 16 In another research 8 present in this analysis, the results show that COVID-19 patients had a lower score than the control group in the neuropsychological tests. The careful comparison with the neuropathological findings in people not infected with COVID-19 may be critical to determine whether many findings common to autopsies are substantially more likely in the disease and whether they can

CONCLUSION
Cognitive changes are frequently found in patients diagnosed with COVID-19 months after hospital discharge. The slower cognitive processing speed and impaired memory may interfere with the functioning of these patients' quality of life. Hence, cognitive rehabilitation interventions aiming to increase processing speed and memory must also be considered. Therefore, the long-term follow-up of neurological deficits is an essential element, along with the imminently necessary follow-up of the rehabilitation health team.