key: cord-0887634-ueqoqp5r authors: Almeria, M.; Cejudo, J.C.; Sotoca, J.; Deus, J.; Krupinski, J. title: Cognitive profile following COVID-19 infection: Clinical predictors leading to neuropsychological impairment date: 2020-10-22 journal: Brain Behav Immun Health DOI: 10.1016/j.bbih.2020.100163 sha: 1e95896c61e43bc53e391ed4cb8f0a8220267621 doc_id: 887634 cord_uid: ueqoqp5r BACKGROUND: Cognitive manifestations associated with the severity of a novel coronavirus (COVID-19) infection are unknown. An early detection of neuropsychological manifestations could modify the risk of subsequent irreversible impairment and further neurocognitive decline. METHODS: In our single-center cohort study, we included all consecutive adult patients, aged between 20 and 60 years old with confirmed COVID-19 infection. Neuropsychological assessment was performed by the same trained neuropsychologist from April, 22nd through June, 16th 2020. Patients with previous known cognitive impairment, any central nervous system or psychiatric disease were excluded. Demographic, clinical, pharmacological and laboratory data were extracted from medical records. RESULTS: Thirty-five patients met inclusion criteria and were included in the study. Patients presenting headache, anosmia, dysgeusia, diarrhea and those who required oxygen therapy had lower scores in memory, attention and executive function subtests as compared to asymptomatic patients. Patients with headache and clinical hypoxia scored lower in the global Cognitive Index (P = 0.002, P = 0.010). A T score lower than 30 was observed in memory domains, attention and semantic fluency (2 [5.7%]) in working memory and mental flexibility (3 [8.6%]) and in phonetic fluency (4 [11.4%]). Higher scores in anxiety and depression (P = 0.047, P = 0.008) were found in patients with cognitive complaints. CONCLUSIONS: In our cohort of COVID-19 patients neurologic manifestations were frequent, including cognitive impairment. Neurological symptoms during infection, diarrhea and oxygen therapy were risk factors for neurocognitive impairment. Cognitive complaints were associated with anxiety and depression. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the current rapidly growing outbreak of coronavirus disease . Common symptoms include fever, dry cough, fatigue and dyspnea, whereas respiratory failure and subsequent pneumonia frequently leads to hospitalization. Neurological manifestations are being recognized increasingly. The most frequent being headache, myalgias or loss of burst and smell (Mao et There are no studies to our knowledge on the co-existence and clinical definition of cognitive impairment related to COVID-19 infection. As COVID-19 outbreak may directly impact on CNS, it is likely that we will face more neurocognitive complaints once severe respiratory syndrome is resolved. It is of great scientific and clinical relevance to describe COVID-19 related cognitive symptoms due to its possible reversibility and the differences from the impairment caused by neurodegenerative disease. In this study, we aimed to evaluate the impact of COVID-19 on neurocognitive performance. J o u r n a l P r e -p r o o f Almeria, M. 5 This is our cohort study, we included consecutive adult patients evaluated in Hospital Universitari MútuaTerrassa (HUMT) from April 21 (date of first specimen assessed) to June 16, 2020. All patients included in the study had SARS-Cov-2 infection confirmed by positive PCR from nasopharyngeal swab and/or positive serology. Patients aged from 24 to 60 years old. Subjects with previous cognitive impairment and any other CNS disease were excluded. The study was approved by the local ethic committee and all subjects signed the informed consent. Clinical data was collected prospectively in HUMT and we retrospectively reviewed electronic health records database for all patients with laboratory-confirmed SARS-CoV-2 infection. Demographic data, comorbidities, blood test results that included ferritin and D-Dimer, symptoms and signs at presentation, complications, treatment, previous cognitive impairment or cognitive complaints after infection and outcomes were collected and evaluated. Complications the data greater compliance with the Normal Distribution, specifically used the T note (PT) (mean 50 points and standard deviation of 10 points). Additionally, a total cognitive performance score was created by obtaining an arithmetic mean of the standardized scores of the different cognitive tests used, called the Cognitive Index (ICog). Also Hospital Anxiety and Depression Scale (HAD) was administered to assess symptoms of anxiety and depression. All the assessments were performed between 10 and 35 days from hospital discharge by the same trained neuropsychologist and cognitive evaluation lasted approximately one hour. In a first level of analysis the sample data and cognitive results were described assuming Normal Distribution, knowing its performance in larger samples and being standardized in our population. Standardized punctuations (T scores) for different cognitive tests were expressed in frequencies as well as the Cognitive Index as an expression of pathological results in those with scores equal to or less than 30 in their T score (corresponding to 2 standard deviations or less). In a second level of analysis, inferential tests were performed to compare cognitive performance according to other characteristics of the sample of clinical relevance. Comparisons between cohorts were analyzed using the t-Student Test (independent variables), and Levene test was used to assume equal variances or not on groups of comparison analysis. Due to sample size, comparisons between groups have been made only if they had more than 5 subjects per group All study data, including raw and analyzed data and materials will available from the corresponding author on reasonable request. Between April and June 2020, 454 patients tested positive for SARS-CoV-2 at HUMT. Of these patients, subjects older than 60 were excluded from the study to avoid cognitive impairment due to age-related cognitive decline. Patients with previous cognitive impairment and any other CNS or psychiatric affection were also excluded from the study. Neuropsychological study was performed between 10 and 35 days after hospital discharge to have the most recent possible cognitive profile related to the infection. A total of thirty-five patients were included in the study. Their demographic and clinical characteristics are described in Table 1 . 19 subjects were female (54.3%) with mean (SD) age of 47.6 (8.9) years. Most common symptoms at onset of illness were fever ( Neuropsychological characteristics are described in Table 2 No differences in neuropsychological tests were found between patients that expressed cognitive deficits after COVID-19 infection than patients who didn't. Nevertheless, higher scores in Anxiety and Depression test (P = 0.047, P = 0.008 respectively) were found in the group with cognitive complaints. Association between COVID-19 and cognitive impairment was not previously reported. Considering that COVID-19 had known neurotropism and that cognitive deficits are seen in other viral infections, we believed that the association is very likely. We found COVID-19 infection profile to be consistent with that described in general population. In our cohort, fever was the predominant symptom in all patients, followed by cough, myalgias, fatigue and headache as described in previous studies (Li et This study has several limitations. Only 35 patients were included. It would be better to include more patients in order to assess potential cognitive differences associated with other symptoms such as myalgia or fatigue. It is important to note that older population were excluded to avoid age-related cognitive impairment. Neuropsychological assessment was performed in early period after hospitalization in order to have the most recent possible cognitive profile related to the infection and its possible temporal relationship with the resolution. Some of the data was extracted from the electronical medical records; some manifestations might not be captured if they were too mild or not easily referred by the patient, such as taste and smell impairment or diarrhea. We probably missed some of the patients with MRI hypoxic lesions. Future studies should include advanced neuroimaging and a long term follow up assessment of the deficits to determine whether this could precipitate the onset of neurodegenerative or cerebrovascular disease. 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Funding: This research did not receive any specific grant from funding agencies in the public, o This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue.