Corrigendum: A prospective cohort study on cognitive and psychological outcomes in COVID-19 ICU survivors at 3 months of follow up

Significant advancements in critical care medicine have yielded a growing cohort of Intensive Care Unit (ICU) survivors, giving rise to a spectrum of short and long-term health and socioeconomic effects (1). These consequences extend beyond acute respiratory distress syndrome (ARDS) survivors to other ICU treated diseases as well (2). Within this population, mental health repercussions, ranging from depression and anxiety to post-traumatic stress disorder (PTSD), have been reported in varying percentages, spanning from 8 to 57% (3,4). Concurrently, cognitive impairment, persisting for months to years, affects a considerable proportion, with prevalence rates ranging from 30 to 80% (1,5). The onset of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shed further light on the lingering neuropsychiatric and cognitive effects that may persist after recovery from intensive care or a critical illness (3). Long-lasting neuropsychiatric and cognitive effects, such as mental fatigue, PTSD, depression, and anxiety (4-23%), can manifest 2 to 12 months following COVID-19 (6,7). COVID-19 ICU survivors exhibit distinct features due to the specific pathophysiology of COVID-19. Factors such as inflammation, endothelial dysfunction, and microthrombi contribute to this uniqueness (8). Additionally, the severity of illness in COVID-19 patients often surpasses that of non-COVID-19 ICU survivors, resulting in divergent recovery trajectories.Long-term outcomes are shaped by a combination of both ICU-related factors and COVID-19-specific elements. Researchers continue to investigate the intricate interplay between COVID-19 and its impact on ICU survivors.Cognitive and psychological outcomes are influenced by various factors, such as genetics, social and cultural aspects, prior psychological disorders, occupational and financial stability, among others (8). As a result, findings from a particular study may not be applicable to populations in different geographical areas. Gulf Cooperation Council countries, including Qatar, have distinct population demographics. Qatar's population predominantly comprises expatriates from over a hundred nationalities, representing a diverse tapestry of cultural and ethnic backgrounds, with the majority being male and below 60 years of age (9). Furthermore, Qatar boasts one of the lowest recorded COVID-19 mortality rates, with 682 deaths out of a total of 0.45 million cases as of September 2022 (10).However, the COVID-19 pandemic has presented unique stressors for the majority expatriate population in Qatar. These stressors include fear of serious illness and death without close family support, financial fragility due to income loss, increased isolation due to social distancing rules and heightened travel restrictions limiting face-to-face interactions with families and loved ones. Our study, Outcomes-Short and Long term in ICU patient with COVID-19 "OUTSTRIP COVID-19" evaluated the patients' mortality, co-morbidities, lung function, physical and psychiatric co-morbidities, and work capacity after ICU discharge. This paper from OUTSTRIP COVID-19, seeks to examine the cognitive and psychological outcomes in COVID-19 patients admitted to ICUs in Qatar. The research aims to assess the prevalence of cognitive impairment, depression, anxiety, and stress at baseline and 3 months after ICU discharge, with a focus on the short-term follow-up.We conducted a single-center prospective observational cohort study at Hamad Medical dyspnea (respiratory rate ≥ 30 breath/min), hypoxia (SpO2 ≤ 93% on room air), radiological changes affecting ≥ 50% of the lung, or severe disease complications such as respiratory failure, the need for mechanical ventilation, septic shock, or nonrespiratory organ failure.The second follow-up was conducted at 3 months after their discharge from the ICU.Detailed information about the inclusion and exclusion criteria, as well as study definitions, can be found in a previous paper published by the same study group (11).Baseline data and demographic information were collected when patients were admitted to the Intensive Care Unit (ICU) using a case record form. This comprehensive data encompassed various variables, including patient characteristics such as age and nationality, body mass index, results of blood tests and radiological examinations, presence of other medical conditions, length of hospital and ICU stay, total days on ventilator support, Acute Physiology and Chronic Health Evaluation (APACHE) score after 24 h, oxygen saturation index, and the ratio of arterial oxygen tension to the fraction of inspired oxygen (PaO2/FiO2 ratio).To assess cognitive and psychological outcomes, two physicians and one research assistant utilized the following tools:• (a) Montreal Cognitive Assessment-Basic (MoCA-B): A validated screening tool used to evaluate mild cognitive impairment in populations with varying literacy and low education levels (12). The MoCA-B scores range from 0 to 30 points, encompassing visual perception, executive functioning, language, attention, memory, and orientation. The MoCA-B is available in English, Hindi, Bengali, and Arabic (13). A score of < 24/30 (with 81% sensitivity and 86% specificity) was considered the cut-off for mild cognitive impairment (12). The validity and reliability of the Montreal Cognitive Assessment-Basic (MoCA-B) have been investigated in both the Middle East and North Africa (MENA) region and the Indian population. This is particularly relevant as the Indian population constitutes a major demographic group in Qatar (14, 15). Data was managed and analyzed using Microsoft Excel and SPSS version 28 (IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp). Descriptive statistics using mean (SD) and frequency (%) were used to describe the data. Mean and standard deviations were calculated for interval variables, while frequency distribution with percentages was computed for categorical variables in the study. Paired student t-tests were utilized to assess mean significant differences in variables, including MOCA score, MOCA time, DASS depression, DASS stress, and DASS anxiety scores at baseline and three months. Chi-square tests (McNemar) were employed for all categorical variables. A p-value of 0.05 (two-tailed) was considered as the level of statistical significance. To account for important confounders such as age and gender, a multivariate mixed-method model with repeated measures ANOVA and post-hoc analysis using Bonferroni was conducted to examine the effect of anxiety scores from baseline to 3 months.A total of 100 ICU survivors were reviewed at baseline within 7 weeks of discharge from the ICU, among whom 24 survivors did not attend visit 2 at 3 months due to logistical reasons related to work, transport, and travel. One participant dropped out of the study as indicated in Figure 1.Demographics and clinical characteristics of the cohort of ICU survivors are presented in Table 1. In accordance with the inclusion-exclusion criteria, there were no known cognitive, psychiatric, or psychological illnesses prior to ICU admission for COVID-19.The participants' mean age was 47.87 ± 8.4 years, with the majority being males (82%) and nonsmokers (94%). Major co-morbidities included diabetes mellitus (56%) and hypertension (44%).During their hospital course, 20% of the patients required invasive mechanical ventilation, while the majority 80% were managed with noninvasive ventilation or supplemental oxygen therapy. The mean duration of stay in the ICU was 10.7 ± 12.3 days, while the total duration of hospital stay was 19.7 ± 17.5 days. Among the participants, 43% received convalescent plasma, and 6% required blood transfusion. In terms of sedatives and analgesics, narcotics were administered to 21 patients for an average of 6.9 ± 3.8 days, benzodiazepines to 21% of patients for 5.04 ± 3.06 days, and neuroleptics to 9% of patients for 6.4 ± 4.5 days. Delirium was observed in 9% of the ICU survivors.The mean depression score remained within the normal scale (below 9) at 5.64 ± 6.90, with no significant improvement noted at 3 months, as shown in Table 2. However, at baseline, 25% of the 100 survivors exhibited clinical depression ranging from mild to extremely severe. This percentage reduced to 16% (12 survivors) at 3 months, as indicated in Table 3.The mean anxiety score exceeded the normal value of 7, with a significant improvement from baseline to 3 months (9.35 ± 8.50 versus 6.51 ± 7.74; p = 0.002). At baseline, 48% of survivors did not report anxiety, and this percentage increased to 66% (50 survivors) at the 3-month follow-up. However, severe to extremely severe anxiety was noted in 19% of survivors at baseline and decreased to 12% (9 survivors) at 3 months.The mean stress score at baseline was 8.34 ± 8.07, falling within the normal range of less than 14, with no significant improvement at 3 months. However, 18% of patients experienced some degree of stress at baseline, with 5% facing severe to extremely severe stress. At the 3-month follow-up, only 12% of the patients still experienced stress, and out of those, 5.3% had severe to extremely severe stress.The majority of the patients (72%) exhibited mild cognitive impairment, which showed significant improvement of 1 point (p < 0.001) at 3 months, as indicated in Table 2. The time taken to complete the MOCA-B questionnaire also significantly decreased by 1.6 minutes (p < 0.001) at 3 months. However, severe cognitive impairment observed in 28% of survivors at baseline persisted in 20% of survivors at 3 months, while 56% continued to have mild cognitive impairment at 3 months, compared to 72% of survivors at baseline.Further correlation with invasive mechanical ventilation did not show any significant impact on the mean changes in MOCA-B and DASS-21 scores.Within the analysis, the effect of anxiety (F: 4.84, p = 0.03) and the interaction between anxiety and age (F: 7.72, p = 0.007) were found to be significant, while the interaction between anxiety and sex was not significant (F: 0.24, p = 0.63). Regarding between subjects' effect, age was not significant (F: 0.04, p = 0.84), but the effect size was significant between males and females (F: 5.45, p = 0.01), with estimated marginal means of 12.2 ± SE (1.92) and 6.8 ± SE (0.92), respectively.However, parameters such as depression and stress were not found to be significant from baseline to 3 months, thus multivariate mixed-method model repeated measures ANOVA was not performed for these parameters.Our investigation enhances the comprehension of the psychological well-being and cognitive status exhibited by individuals with COVID-19 who underwent admission to the ICU, revealing, that a substantial number of ICU patients exhibited cognitive impairment both at the baseline assessment and at the 3-month follow-up. This persistent cognitive impairment highlights the complex interplay between critical illness, COVID-19 infection, and potential neurological effects. Importantly, while the prevalence of depression and stress was reported by approximately one-quarter of the patients during the baseline assessment, more than half of the participants experienced notable levels of anxiety. This underscores the considerable psychological distress experienced by these patients during their ICU stay and its potential lingering impact. Although a trend towards improvement was observed in all parameters at 3 months, significant improvements were noted only in cognitive measurement and anxiety.In a systematic review conducted by Renaud-Charest et al., it was demonstrated that the prevalence of depressive symptoms beyond 12 weeks following SARS-CoV-2 infection spanned from 11 to 28% (16). In line with these findings, our study echoed similar results, reporting depression symptoms in 16% of our cohort at the 12-week mark. The literature offers diverse insights into the factors linked with depression and anxiety, yielding contrasting outcomes. Some studies point to sex, previous psychiatric history, psychopathology at the one-month follow-up, and acute-phase systemic inflammation as potential contributors, while age emerges as a tentative factor and the severity of acute COVID-19 appears non-contributory.and depressive symptoms, with age showing no significant correlation (18,19).Conversely, Morin et al. (20) identified age over 75 as a significant risk factor for depression (21). Interestingly, the severity of acute COVID-19, encompassing symptomatology and treatment intensity, including intubation, did not exert influence over the occurrence of depressive symptoms, as indicated by some studies integrated into Renaud-Charest et al.'s systematic review. Similarly, the long-term rates of depressive symptoms did not show significant elevation in hospitalizations for COVID-19 with neurological complications compared to those without such complications.As our study's trajectory extends to the 3-month mark, a significant improvement in anxiety was evident; however, a notable 12% (comprising 9 survivors) continued to experience severe to extremely severe anxiety. Notably, Zhang et al. (22) presented a different facet, revealing no statistically significant disparity in the prevalence of anxiety among COVID-19-infected individuals, those in quarantine, and the general population (20). Yuan et al. (23), in their meticulous systematic review and meta-analysis, unveiled a pertinent trend: the prevalence of depression, anxiety, and insomnia witnessed an uptick during the COVID-19 epidemic across various demographic subsets, spanning the public, healthcare professionals, university students, older adults, infected patients, survivors, and pregnant women. Intriguingly, while university students reported the highest pooled prevalence of depression, survivors of COVID-19 exhibited the lowest prevalence. Within this tapestry, anxiety garnered a high prevalence rate among pregnant women, while older adults reported the lowest levels. Our findings reveal a significant interaction between anxiety and age (F: 7.72, p = 0.007), suggesting that age modifies how anxiety affects cognitive and emotional outcomes in post-ICU COVID-19 patients. The influence of age on psychological recovery has also been noted in other studies, with older adults often exhibiting greater resilience in psychological outcomes post-critical illness and severe COVID-19 (20,24). However, the trajectory of recovery can vary, and certain age groups may experience prolonged anxiety symptoms, potentially due to pre-existing conditions, the severity of the illness, or social factors such as isolation (25).Interestingly, our analysis showed a significant effect size between males and females concerning the impact of anxiety on outcomes (F: 5.45, p = 0.01). This observation is crucial, as it aligns with literature suggesting that sex differences may influence the prevalence and manifestation of psychological symptoms after traumatic health events.Females often experience longer and more severe post-COVID-19 syndrome, with a higher incidence of depression compared to males (26). Additionally, in a Swedish cohort followed for one year after ICU admission with COVID-19, female sex was a predictor of depression (27). Our results indicate that males might also be significantly impacted, potentially due to socio-cultural roles or differences in coping mechanisms (28). Female gender could be emerging as a risk factor for depression likely due to other factors such as pre-existing depression, cultural norms, gender-based biases and expectations, and hormonal changes in women, particularly those in the perimenopausal age group (27). However, we have a relatively young cohort of mixed nationalities and predominantly male participants, resulting in unique findings.The overarching prevalence of mental health concerns during the COVID-19 epidemic exhibited variability across different countries (29). Within this complex framework, the extent to which the amplified media coverage of COVID-19 shapes the articulation of symptoms remains enigmatic, holding the potential to temper or intensify symptom severity and overall quality of life reporting. A realm of speculation also emerges, pondering whether COVID-19 survivors might have benefited from augmented clinical and social support, including concentrated attention on post-discharge education, thereby potentially leading to a diminished prevalence of anxiety and depression. This could potentially be true for our cohort as Qatar had launched a robust mental health services program targeting the public, covid-19 patients in quarantine and inpatients from admission to discharge and follow up (22). Indeed, the socioeconomic ripple effects of the pandemic could potentially shape the frequency and severity of depression, necessitating a more in-depth investigation.Amidst the direct specter of the virus, the pandemic has catalyzed a cascade of uncertainties, spanning employment, housing, education disruptions due to school closures, and the amplification of social isolation, yet the complete complexion of these dynamics remains to be meticulously elucidated.Most of our patients (72%) displayed mild cognitive impairment, while 28% presented with severe impairment; however, both groups demonstrated significant enhancement in cognitive function at the 3-month follow-up. Notably, participants exhibited a reduced completion time for the questionnaire compared to baseline, potentially attributed to substantial advancements in visual memory, processing speed, and attention over the observation period (23). Ceban et al. 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