The Impact of COVID-19 on Cognitive Development and Executive Functioning in Adolescents: A First Exploratory Investigation

Background: The rapid expansion and severity of the COVID-19 contagion has had negative physical and psychological health implications for millions of people around the world, but even more so among children and adolescents. Given the severity of the situation and the small number of studies on the direct influence of viral infection on the cognitive development within adolescents, the present study aims at understanding the consequences of contracting the virus and being hospitalized in relation to cognitive functioning, in particular, for executive functioning, among adolescents. Methods: To all subjects included in the sample, divided into four groups based on the severity of the COVID-19 infection, were administered the WISC-IV in order to evaluate the global cognitive functioning, and subsequently, the subtests Courses and Tower of London (ToL), both part of the BVN 12–18, were administered for the evaluation of executive operation. Results: Our analyses showed that between subjects who did not contract the viral infection and those who contracted it in an asymptomatic form, there are no significant differences in cognitive functioning, but only in executive functioning. Furthermore, in both hospitalized and non-hospitalized subjects, we found lower scores especially for WM skills, while IQ scores are in a medium range. Conclusion: the present study shows that contracting the viral infection and, thus, being hospitalized, caused greater problems and difficulties as compared to those who were not hospitalized, impacting global cognitive (and executive) functioning, especially the WM. We believe that these results could allow an early detection of alterations in cognitive and executive functioning, a fundamental aspect of the interventions that occur in evolutionary phases such as those related to pre-adolescence, allowing, therefore, the activation of functional recovery pathways in a short time.


Introduction
Coronavirus disease 2019 (COVID- 19) was first identified in late December 2019, in a cluster of atypical pneumonia cases in Wuhan (China). Infections have increased and quickly spread to other nations, prompting the World Health Organization (WHO) to declare the status of a Global Pandemic [1]. The rapid expansion and severity of the COVID-19 contagion have had negative physical and psychological health implications for millions of people around the world [2]. Efforts to suppress its spread have resulted in significant disruptions to daily life, the education system and the delivery of health services [3]. Some research [4,5] suggests that these limitations can have particularly negative effects on the mental health (HD) of children and adolescents, as well as their parents. In particular, some studies have shown how these types of epidemics lead people to experience psychological problems such as Post-Traumatic Stress Disorder (PTSD), psychological distress, depression and anxiety [5,6].
Recent research has especially highlighted a worsening of emotional and behavioral health among children and adolescents, both internalizing [4] and externalizing [5,7] problems. Indeed, the social isolation, forced closure of schools and hospitalization orders are conditions that have been linked to the mental health problems of children and adolescents [8]. In particular, it is the child population that is most affected, given the vulnerability it presents to the alteration of everyday contexts. Indeed, a large body of research shows that children and adolescents in prolonged stressful situations can experience immediate or long-term mental health problems [9][10][11][12][13]. The National Child Traumatic Stress Network [14] states that the psychological response to COVID-19 varies with age. In the preschool stage, manifestations of fear, loss of appetite, increased outbursts and complaints or ambivalent anxious attachment behaviors are expected. Between the ages of 6 and 12, higher rates of irritability, nightmares, sleep and appetite disturbances, somatic symptoms or loss of interest in peers, as well as excessive attachment to parents can occur. In adolescents aged 13 to 18 years, in addition to physical symptoms, problems with sleep disturbance, or isolation, increased or decreased energy, higher rates of apathy or inattention are also expected [15]. In particular, the authors show that in situations of confinement, sleep-related problems can have an impact; it has been shown that sleep-related problems can have a significant impact on both emotional and cognitive levels, as well as on learning and learning. Therefore, cognitive processes are influenced in situations of confinement [15]. Additionally, these data show that although the discomfort caused by the pandemic affects mental health, in general, there are also negative consequences on attention and cognitive functioning.
Furthermore, it has been observed that both chronic and acute stress affects the cognitive processes governed by the prefrontal cortex [16], as working memory (WM), emotion regulation, cognitive flexibility, organization and planning, and goal-oriented behaviors [17,18]. Several authors underline the role of these functions, in particular those related to planning, as possible mediators between perceived stress and subjective memory disorders [19,20].
As mentioned in the studies cited above, the discomfort caused by the pandemic also concerns stress [5,6] and adolescents are affected with important consequences in relation to attention and cognitive functioning, causing possible difficulties in the academic field [15]. Therefore, given the severity of the situation regarding adolescent mental health and given the small number of studies on the direct influence of viral infection on cognitive development and overall executive functioning in adolescents, we decided to conduct the present study with the " objective to understand the consequences, in subjects aged between 12 and 13 who have contracted the virus (and not), for cognitive functioning and, in particular, on executive functioning (planning, self-regulation of emotions, cognitive flexibility, problem-solving), all variables that affect school performance and quality of life. The hypotheses underlying our study are the following: highlight how the COVID-19 infection influenced the cognitive performance of the subjects, and to what extent it impacted cognitive and executive functioning. We also hypothesize differences between children who have been infected and hospitalized, children who have not been hospitalized and children who have not contracted the virus.

Participants
Subjects aged between 12 and 13 years (15 from lower secondary schools, 10 in the province of Naples and 5 in the province of Caserta) were recruited for the present study. The schools were chosen at random. The inclusion criteria were: (a) age between 12 and 13; (b) absence of psychiatric or neurological pathologies; (c) absence of any other chronic pathologies that may interfere with normal cognitive development. For the evaluation of these criteria, an anamnestic interview was carried out and the K-SADS-PL DSM 5 diagnostic interview [21] was administered to the parents. The data collected from this interview did not reveal any comorbidities with psychiatric pathologies.
The overall sample was made up of 100 subjects attending the 2nd grade; the subjects were divided into 4 groups, with the aim of discriminating between alterations induced by stress and alterations induced by viral infection: Gr1 (control group), composed of 25 subjects who did not contract the infection; Gr2 composed of 25 subjects who contracted the infection in an asymptomatic form; Gr3 composed of 25 subjects who contracted the infection in a symptomatic form but whose symptoms did not require hospitalization; Gr4 composed of 25 subjects who contracted the infection in a symptomatic form and in which the severity of the symptoms led to hospitalization but not hospitalization in TI. In All groups were subjected to the administration of Wechsler Intelligence Scale for Children-IV (WISC-IV) [22] in the school environment anonymously, by qualified psychologists belonging to the reference clinic (FINDS). Subsequently, the Corsi and Tower of London (ToL) subtests, as part of the Neuropsychological evaluation battery (BVN 12-18) [23] were administered. Both recruitment and evaluation procedures lasted 6 months. It is also underlined that the 4 groups were homogeneous in relation to the socio-cultural background of the parents, and the family/environmental context did not represent an influencing factor on the level of education in any of the 4 groups. The assessment of the socio-economic level was carried out by administering the scale for the assessment of the socio-economic level (SES) to both parents [24].
More specifically the Gr1 had a score of 7.2 (SD = 0.5), the Gr2 had a score of 7.4 (SD = 0.2), the Gr3 had a score of 7.3 (SD = 0.4) and the Gr4 had a score of 7.5 (SD = 0.3). Moreover, in each group there were subjects from all schools in an equally distributed and randomized manner.
The study was conducted at the Developmental Psychology Laboratory of the University of International Studies of Rome in collaboration with the Italian Foundation for Neuroscience and Developmental Disorders (FINDS) and the Campania Regional School Office (USR Campania). The study protocol was approved by the Academic Senate and the Ethics Committee of UNINT (University of International Studies of Rome). The data was collected anonymously after obtaining a written informed consent by the parents.

Tasks and Procedures
The protocol used is composed of the following measures: the WISC IV [21], the Corsi and Tower of London subtest (ToL) of Battery BVN 12-18 [22] and Scale for the evaluation of the socio-economic level (SES) [23]. For the evaluation of the inclusion criteria the Diagnostic Interview for Evaluation of Psychopathological Disorders (K-SADS-PL DSM-5) [21] was used.
WISC-IV: It is a clinical and diagnostic tool used to assess the intellectual abilities of children aged 6 to 16. It consists of 15 tests (10 main and 5 supplementary) divided into 4 indices. The 10 main tests are represented by: block design (BD), similarities (SI), digit span (DS), picture concepts (PCN), coding (CD), vocabulary (VC), letter-number sequencing (LN), matrix reasoning (MR), comprehension (CO), and symbols search (SS). They are divided into 4 indices: The perceptual reasoning index (PRI), which includes BD, PCN, and MR; the verbal comprehension index (VCI), which includes SI, VC, and CO; the working memory index (WMI), which includes DS and LN; and the processing speed index (PSI), which includes CD and SS. : It is a test battery for neuropsychological evaluation aimed at identifying single disorders in specific areas. In particular, the Tower of London (ToL) subtest evaluates higher executive functions such as planning and problem-solving skills. The Corsi subtest, on the other hand, allows us to evaluate the span of visuospatial memory, that is, the amount of visuospatial information that can be retained in short-term memory (MBT). SES: It is a self-administered questionnaire that allows the collection of information about the level of education and professional level of the parents, by indicating their position within the social system.
K-SADS-PL DSM 5: The K-SADS-PL consists of a diagnostic interview and detects the presence of psychopathological disorders in children and adolescents, referred to the criteria of DSM 5. It consists of the following parts: an unstructured introductory interview, a screening diagnostic interview, a checklist for administration of diagnostic supplements, 5 diagnostic supplements (mood disorders, psychotic disorders, anxiety disorders, attention deficit and disruptive behavior disorders, substance abuse disorders) for each of the criteria required by DSM 5 are provided, one comprehensive checklist of the patient's medical history and a scale for the overall assessment of the child's current functioning. The K-SADS-PL allows researchers to detect the presence of psychopathological frameworks and to code the symptoms of the subject.
The subjects who had contracted the virus were all evaluated 3 months after the infection (negative swab for three months). All groups were administered the WISC-IV in its Italian standardization [21]. The scores on the individual tasks were analyzed, in particular, the main indices (VCI, PRI, WMI, PSI and IQ). The aim was to assess whether there were performance differences between the groups and to identify which groups had a possible difficulty in the tasks of working memory (WMI) and processing speed (PSI) with a consequent impact on the intellectual quotient (IQ). We then administered the subtests of BVN 12-18 for an in-depth study of memory skills (visuo-spatial). We refer to the Corsi and ToL subtests.

Methods
Data analyses were performed using SPSS 26.0 statistical survey software [25]. Significance was accepted at the 5% level (α < 0.05). We compared the weighted scores of the groups at the indices (VCI, PRI, WMI, PSI, IQ) of the WISC-IV, the scores emerged at the ToL and Corsi subtests using the one-way analysis of variance (ANOVA) test: one for the WISC-IV test, one for the ToL subtest and one for the Corsi subtest. To understand the differences between the groups (and verify our hypothesis), we performed the post hoc tests (Bonferroni).

Results
The comparison between the 4 groups regarding WISC-IV showed a significant effect of the group at the following indices:  (Table 1).
Our analyses did not reveal any significant effects between the 4 groups and the VCI index, demonstrating that there are no significant differences in verbal understanding between subjects who did not contract the infection and those who contracted the infection.
No significant differences emerged from the comparison between Gr1 and Gr2, demonstrating that performance was not different between subjects who did not contract the infection and subjects who contracted the infection in an asymptomatic form.
From the comparison between Gr1 and Gr3 no significant differences emerged at WISC IV, demonstrating that cognitive functioning was not impaired in subjects who contracted the infection in a symptomatic form but whose symptoms did not require hospitalization compared to those who did not contract the infection. We then compared the performances at the subtest ToL [F (3,99) = −1.160, p < 0.05] and at Corsi [F (3,99) = −1.520, p < 0.05] and significant differences emerged. These results show that scores for visuospatial planning and memory skills were lower in subjects who contracted the infection symptomatically but whose symptoms did not require hospitalization, compared to those who did not contract the infection (Table 2).   The skill scores of PRI, WMI and PSI were lower in subjects who contracted the infection in symptomatic form and in who the severity of symptoms led to hospitalization (but not to hospitalization in TI, also impacting on IQ). We then compared the performances at the ToL subtest [F (3,99) = −1.200, p < 0.05] and at Corsi [F (3,99) = −1.880, p < 0.05] and significant differences emerged. These results show that scores related to visuospatial planning and memory skills were lower in subjects who contracted the infection in a symptomatic form and in who the severity of symptoms led to hospitalization but not hospitalization in IC, compared to those who contracted infection (Table 3). From these analyses, it emerged that the scores of Gr2 differ significantly from those of Gr3 at the WMI index [F (3,99) = −4.680, p < 0.05]. These scores were lower in subjects who contracted the infection in a symptomatic form but whose symptoms did not require hospitalization compared to subjects who contracted the infection in an asymptomatic form, but not impacting on IQ. However, significant differences also emerged at the ToL subtest [F (3,99) = −1.160, p < 0.05] and at Corsi [F (3,99) = −1.440, p < 0.05]. These results show that the scores related to visuospatial planning and memory skills are lower in subjects who contracted the infection in symptomatic form but whose symptoms did not require hospitalization compared to subjects who contracted the infection in asymptomatic form ( Table 4).  These results demonstrate the scores related to planning and visuospatial memory skills are lower in subjects who contracted the infection in a symptomatic form and in who the severity of symptoms led to hospitalization but not hospitalization in IC compared to subjects. who contracted the infection asymptomatically (Table 5).  ]. It appears that the scores related to the PRI, WMI and PSI abilities are lower in subjects who contracted the infection in a symptomatic form and in who the severity of symptoms led to hospitalization but not hospitalization in IC compared to subjects who contracted the infection in a symptomatic form but whose symptoms did not require hospitalization, also impacting on IQ. However, in the analyses, no significant differences emerged in the performance of the ToL and Corsi subtests (Table 6).

Discussion
The COVID-19 pandemic is one of the very few social events to have had such a major impact on human psychology, mainly due to the number of people affected and the influence it has had on all spheres of life [26]. Many people have experienced alterations in their work, financial and personal circumstances. Furthermore, children and adolescents have completely limited social contact with their peers and significantly limited their physical activity [27], causing major changes in their daily routines. In fact, a highly vulnerable part of the population is that of the child and adolescent population since the contexts in which they live and develop are altered. Although there are few studies on the responses of this population to epidemics [28], a large body of research shows that children and adolescents in prolonged stressful situations may have immediate or long-term mental health problems [10][11][12][13]. Therefore, we believe that the current pandemic may constitute an example of a prolonged and highly stressful situation; in fact, living for more than a year with the stress of a pandemic and the resultant social restrictions has caused a high level of psychological pressure on people in several countries [29], with a decrease in the mental health of adults, children and adolescents, producing changes in mood, behavior and other daily activities [30][31][32]. Emotional stress has neurobiological consequences that increase the likelihood of exacerbating concomitant illnesses and the vulnerability to meet criteria for a mental disorder such as anxiety disorders, depression, sleep disturbances, and acute stress, among others [12,[33][34][35]. Alongside emotional and sleep difficulties, cognitive processes can also be compromised in situations of confinement and restrictions such as those resulting from the COVID-19 pandemic. It has been observed that stress, both chronic and acute, affects the cognitive processes governed by the Prefrontal Cortex (PFC) [16]. This area dominates the processes and functions of the executive system, including WM, the processes of self-regulation of emotions, cognitive flexibility, organization and planning, decision-making and goal-oriented behaviors, among others [17,18,36]. Several authors highlight the role of these functions, particularly those related to planning, as possible mediators between perceived stress and subjective memory disorders [19,20].  also reveal that in stressful situations, perceived stress would be inversely related to the level of executive control and attention problems. Another study found that hospitalized patients exhibited high levels of concern about infection, resistance to existing treatments, greater socialization difficulties [38], and a lower immune response [39] than to those who maintained social contacts and had not been hospitalized. A recent review showed that social isolation has a detrimental effect on cognitive abilities, such as executive functions and memory [40], leading to an unknown scenario on the cognitive consequences of prolonged periods of social isolation, such as those imposed by national policy to control the COVID-19 pandemic. Young adults have been identified by previous studies as being more vulnerable to mental health disorders during the COVID-19 pandemic [41]. In this study, we wanted to investigate the influence of viral infection on the development of adolescents and on global cognitive functioning, with the aim of understanding the consequences for subjects who have contracted the virus, for their cognitive functioning and, in particular, in relation to executive functions. In fact, our results revealed a difference in cognitive performance between subjects who contracted the infection in a symptomatic form and those who had not contracted it. More specifically, we found no differences in global cognitive functioning between subjects who did not contract the infection (Gr1) and those who contracted the infection in an asymptomatic form (Gr2). Differences on executive functioning, (leaving the IQ intact) emerged between Gr3 and Gr1, respectively, and between those subjects who contracted the infection in a symptomatic form but whose symptoms did not require hospitalization (Gr3) and those who had not contracted the infection (Gr1).
Significant differences emerged between subjects who did not contract the infection (Gr1) and subjects who were hospitalized but not in IC (Gr4) for both cognitive and executive functioning. That is, the infection and hospitalization affected the executive performance and the overall cognitive functioning of these subjects. We also found that the performance of the latter subjects (Gr3 and Gr4) was lower even compared to those who had contracted the infection symptomatically but without hospitalization (Gr2), but Gr3 compared to Gr2 only at the WMI index and on the executive operation. Therefore, hospitalization had affected cognitive and executive functioning to a greater extent.
Finally, we found a worse performance of cognitive and executive functioning in subjects who had contracted the infection symptomatically with hospitalization (Gr4) compared to subjects who had not been hospitalized despite having contracted the infection. Therefore, our data suggest that being hospitalized for contracting the virus caused greater problems and difficulties in individuals, especially the skills of WM. An element of difference that we found in this study compared to previous studies is highlighted by the fact that having contracted the virus (both in hospitalized and non-hospitalized subjects) mainly affected the ability of WM without causing consequences in relation to IQ, which is in keeping with an average range in such subjects. Long-term monitoring would be useful to assess the possible consequences of these results.

Conclusions and Limits
Due to the confinement caused by the current pandemic, numerous changes and disturbances (mood, emotional state, behavioral etc.) have been detected in the entire population, but particularly in the age groups from 6 to 18 years [15,42]. Within this context, the results of the present study contribute to increasing knowledge on the neurocognitive consequences in adolescents affected by Covid-19 infection.
Moreover, we believe that our results could allow an early detection of alterations in cognitive and executive functioning, allowing the activation of functional recovery pathways in a phase of important psychological growth such as in adolescence. We hope that medical assistance to adolescents hospitalized due to Covid-19 infection may include keeping an eye on psychological aspects, such as those related to cognitive functioning, which impact not only the present but also the future. However, limitations of the present study are represented by the small number of the sample and the lack of follow-up. Therefore, we hope that future investigations may include longitudinal studies that could evaluate the neurocognitive consequences, not only in the short-term perspective but also medium and long-term of the sample examined. A further limitation of this study is also represented by the lack of an assessment before the contagion (T0), which would provide a measure of the skills possessed in a time prior to the infection and would clarify to a greater extent the impact that COVID-19 had on the cognitive functioning. Furthermore, it would be interesting for future studies to analyze gender differences in neurocognitive assessment, or even to recruit a lower age population (3-6 years old) that has been most affected by this difficult period, and to evaluate the neurocognitive consequences in an earlier age group. Informed Consent Statement: Informed consent was obtained from all parents of the adolescents involved in the study.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.