The Burden of Survivorship: Survivor Guilt and Its Association with Psychiatric Sequelae in COVID-19 Patients.

COVID-19 survivors struggle with intense depressive and post-traumatic symptoms in sub-acute stages. Survivor guilt may affect post-acute psychopathology. Herein, we aim to unveil the potential affective mechanism underpinning post-COVID psychiatric implications by focusing on the association of survivor guilt with psychopathology and maladaptive attributional style. At one month after discharge, we evaluated symptoms of depression on The Zung Severity Rating Scale (ZSDS), post-traumatic distress on Impact of Event Scale-Revised (IES-R), and sleep disturbances on the Women's Health Initiative Insomnia Rating Scale (WHIIRS) in 195 COVID-19 survivors. Interpersonal Guilt Rating Scale (IGRS-15) rated survivor guilt. A discrepancy score between the burden of depression and post-traumatic distress symptoms was computed individually. Dysfunctional depressive attributions were assessed through the Cognition Questionnaire (CQ). Survivor guilt significantly predicts all evaluated psychopathological dimensions. Moreover, higher rates of survivor guilt were associated with an overlap between post-traumatic and depressive symptomatology, thus suggesting that survivor guilt equally sustains both psychiatric manifestations. Finally, survivor guilt fully mediated the relationship between dysfunctional depressive attributions and the discrepancy index. Our results confirm survivor guilt as a clinically relevant form of suffering related to psychopathological dimensions of post COVID-19 infection, gaining the status of a specific phenomenon and a promising treatment target.

Immunopsychiatry after COVID-19

Immunopsychiatry can be defined as the study of immune-inflammatory pathways in order to identify pathogenetic mechanisms, and targets for treatment, in psychiatric conditions: under the premises that interactions between the immune system and the central nervous system are crucial for brain homeostasis and function, and their disruption has major consequences on mental health. With its terrible burden of disease inflicted on mankind, the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection provided a natural experiment, to provocatively test the relationship between inflammation and mood disorders. Consistent systematic reviews and meta-analyses now affirm that COVID-19 survivors show persistent psychopathology and neurocognitive impairment, with clinically significant depressive psychopathology being reported in around 35% of patients. The cluster of Post-Acute Sequelae of COVID-19 (PASC) symptoms typically emerge after the acute phase of illness, when patients are no longer positive to SARS-CoV-2, including dyspnoea, hypoxia, joint and muscle pain, paraesthesia, dysgeusia, anosmia, fatigue;and, unrelated to the above, neuropsychiatric and neurocognitive symptoms with depression, anxiety, insomnia, difficulties in sustained attention and memory, which worsen over the months. Psychopathological features are the same observed in Major Depressive Disorder, distributing along the same gradient of severity, and including a typically melancholic cognitive vulnerability with self-reproach and depressive cognitive style in evaluating events. Neurocognitive impairment could possibly separate from depression in the long term, but not in the first 6 months after infection, and it is largely overlapping with persistent cognitive deficits described in severe mood disorders. Brain correlates are the same observed in Major Depressive Disorder and in Bipolar Disorder, involving spread disruption of white matter microstructure, reduced grey matter volumes in anterior cingulate cortex, and abnormal functional connectivity in the cortico-limbic circuitries: all the above, being proportional to the degree of persistent systemic inflammation, and not to the severity of the acute illness and of the breadth of exposure to stressful events during the pandemic. We suggest that post-COVID depression provides an invaluable model illness for the study of immune-inflammatory mechanisms involved in the pathogenesis of mood disorders, to identify new targets for treatment, with the aim of restoring mental health and brain homeostasis.

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness's resolution, mainly related to neurological and neuropsychiatric consequences. Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach. Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest. Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.

A Nomogram-Based Model to Predict Respiratory Dysfunction at 6 Months in Non-Critical COVID-19 Survivors.

Objective: To assess the prevalence of respiratory sequelae of Coronavirus disease 2019 (COVID-19) survivors at 6 months after hospital discharge and develop a model to identify at-risk patients. Patients and Methods: In this prospective cohort study, hospitalized, non-critical COVID-19 patients evaluated at 6-month follow-up between 26 August, 2020 and 16 December, 2020 were included. Primary outcome was respiratory dysfunction at 6 months, defined as at least one among tachypnea at rest, percent predicted 6-min walking distance at 6-min walking test (6MWT) ≤ 70%, pre-post 6MWT difference in Borg score ≥ 1 or a difference between pre- and post-6MWT oxygen saturation ≥ 5%. A nomogram-based multivariable logistic regression model was built to predict primary outcome. Validation relied on 2000-resample bootstrap. The model was compared to one based uniquely on degree of hypoxemia at admission. Results: Overall, 316 patients were included, of whom 118 (37.3%) showed respiratory dysfunction at 6 months. The nomogram relied on sex, obesity, chronic obstructive pulmonary disease, degree of hypoxemia at admission, and non-invasive ventilation. It was 73.0% (95% confidence interval 67.3-78.4%) accurate in predicting primary outcome and exhibited minimal departure from ideal prediction. Compared to the model including only hypoxemia at admission, the nomogram showed higher accuracy (73.0 vs 59.1%, P < 0.001) and greater net-benefit in decision curve analyses. When the model included also respiratory data at 1 month, it yielded better accuracy (78.2 vs. 73.2%) and more favorable net-benefit than the original model. Conclusion: The newly developed nomograms accurately identify patients at risk of persistent respiratory dysfunction and may help inform clinical priorities.

Interactions between Severe Allergy and Anxiety in Anti-SARS-CoV-2 Vaccinees.

Severe drug allergy affects patient hesitancy to new treatments, posing unprecedented challenges to anti-SARS-CoV-2 vaccination campaigns. We aimed to analyze the psychological profile of vaccinees with a history of severe allergy in comparison to subjects with a milder allergy history. Patients attending a dedicated vaccination setting were administered an anonymized questionnaire including clinical data and the State-Trait Anxiety Inventory (STAI) scale (score range 20−80). Patients were also asked whether being in a protected setting affected their attitude toward vaccination. Data are expressed as median (interquartile range). We enrolled 116 patients (78% women), of whom 79% had a history of drug anaphylaxis. The median state anxiety score was 36.5 (30−47.2), while the trait anxiety score was 37 (32−48). State anxiety was higher in those with severe than mild allergy [39 (32−50) vs. 30 (25−37); p < 0.001], with the highest score found in a patient with previous drug anaphylaxis (42.5 [32−51.7]). More than 50% of patients reported that being in a protected setting had lowered their anxiety. Severe allergy is associated with a higher burden of situational anxiety in the setting of vaccination without affecting patient constitutional (trait) levels of anxiety. Vaccination in dedicated facilities might overcome issues related to hesitancy and improve patients' quality of life.

Prevalence of depression in SARS-CoV-2 infected patients: An umbrella review of meta-analyses.

OBJECTIVE: The COVID-19 pandemic is still spreading worldwide two years after its outbreak. Depression has been reported in around 30% of SARS-CoV-2 infected patients. We aim to synthesize the available meta-analytical evidence in an umbrella review exploring the prevalence of depression during and after SARS-CoV-2 infection. METHODS: First, we performed a narrative umbrella review including only meta-analyses providing a quantitative summary of the prevalence of depression during or after SARS-CoV-2 infection. Then we extracted the prevalence and sample size from the original studies included in each meta-analysis, and after removing duplicate studies, we performed a random-effects model meta-analysis based on single original study estimates. Heterogeneity, publication bias, leave-one-out sensitivity, and subgroup analyses were performed. RESULTS: 14 meta-analyses were included in the umbrella review. The prevalence of depression ranged from 12% to 55% in the presence of high heterogeneity. The meta-analysis based on 85 original studies derived from the included 14 meta-analyses showed a pooled prevalence of depression of 31% (95% CI:25-38%) in the presence of high and significant heterogeneity (Q = 8988; p < 10-6; I2 = 99%) and publication bias (p < 0.001). CONCLUSION: The burden of post-COVID depression substantially exceeds the pre-pandemic prevalence. Health care services for COVID-19 survivors should monitor and treat emergent depression, reducing its potential detrimental long-term effects.

Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients.

Background: A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals. Methods: This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia. Results: A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23-1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B -5.63, 95% CI -8.39 to -2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10-15.13, p = 0.003), impaired muscle performance (SPPB: B -3.47, 95% CI -6.33 to -0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52-619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37-813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87-1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32-8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17-12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44-1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009). Conclusion: The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.

Prevalence, trajectory over time, and risk factor of post-COVID-19 fatigue.

Fatigue is one of the most commonly reported symptoms in the context of the post-COVID-19 syndrome. Notably, fatigue is characterised by overlapping physical and psychopathological symptoms, and questions about its trajectory over time and possible predictors remained unanswered. Thus, in the present study we aim to investigate the prevalence, the course over time, and the risk factors of post-COVID fatigue. We included 495 patients recovered from COVID-19. For all of them we collected one month demographic, clinical and psychopathological characteristics. We evaluated fatigue severity at one, three, six, and twelve-months according to Fatigue Severity Scale (FSS). We explored the potential predictor of long-term post-COVID fatigue (six or twelve months FSS) by implementing 5000 non-parametric bootstraps enhanced elastic net penalised regression. We found that 22%, 27%, 30%, and 34% of patients self-rated fatigue symptoms in the pathological range at one, three, six, and twelve months respectively. We detected a worsening of fatigue symptomatology over time. From the elastic net regression results, only depressive symptomatology at one month (ZSDS and BDI-13) predicted the presence of post-COVID-19 long-term fatigue. No other clinical or demographic variable was found to predict post-COVID fatigue. We suggest that, rather independent of COVID-19 severity, depression after COVID-19 is associated with persistent fatigue. Clarifying mechanisms and risk factors of post-COVID fatigue will allow to identify the target population and to tailor specific treatment and rehabilitation interventions to foster recovery.

Joint European policy on the COVID-19 risks for people with mental disorders: An umbrella review and evidence- and consensus-based recommendations for mental and public health.

As COVID-19 becomes endemic, identifying vulnerable population groups for severe infection outcomes and defining rapid and effective preventive and therapeutic strategies remains a public health priority. We performed an umbrella review, including comprehensive studies (meta-analyses and systematic reviews) investigating COVID-19 risk for infection, hospitalization, intensive care unit (ICU) admission, and mortality in people with psychiatric disorders, and outlined evidence- and consensus-based recommendations for overcoming potential barriers that psychiatric patients may experience in preventing and managing COVID-19, and defining optimal therapeutic options and current research priorities in psychiatry. We searched Web of Science, PubMed, and Ovid/PsycINFO databases up to 17 January 2022 for the umbrella review. We synthesized evidence, extracting when available pooled odd ratio estimates for the categories "any mental disorder" and "severe mental disorders." The quality of each study was assessed using the AMSTAR-2 approach and ranking evidence quality. We identified four systematic review/meta-analysis combinations, one meta-analysis, and three systematic reviews, each including up to 28 original studies. Although we rated the quality of studies from moderate to low and the evidence ranged from highly suggestive to non-significant, we found consistent evidence that people with mental illness are at increased risk of COVID-19 infection, hospitalization, and most importantly mortality, but not of ICU admission. The risk and the burden of COVID-19 in people with mental disorders, in particular those with severe mental illness, can no longer be ignored but demands urgent targeted and persistent action. Twenty-two recommendations are proposed to facilitate this process.

Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients

Background A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals. Methods This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia. Results A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23–1432.49, p = 0.003];(ii) malnutrition (MNA-SF: adjusted B –5.63, 95% CI –8.39 to –2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10–15.13, p = 0.003), impaired muscle performance (SPPB: B –3.47, 95% CI –6.33 to –0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52–619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37–813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87–1782.53, p = 0.009) at 1-month follow-up;(iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32–8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17–12.07, p = 0.005) at 3-month follow-up;and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44–1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009). Conclusion The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.

Post-COVID-19 Depressive Symptoms: Epidemiology, Pathophysiology, and Pharmacological Treatment.

The Coronavirus Disease 2019 (COVID-19) pandemic is still spreading worldwide over 2 years since its outbreak. The psychopathological implications in COVID-19 survivors such as depression, anxiety, and cognitive impairments are now recognized as primary symptoms of the "post-acute COVID-19 syndrome." Depressive psychopathology was reported in around 35% of patients at short, medium, and long-term follow-up after the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. Post-COVID-19 depressive symptoms are known to increase fatigue and affect neurocognitive functioning, sleep, quality of life, and global functioning in COVID-19 survivors. The psychopathological mechanisms underlying post-COVID-19 depressive symptoms are mainly related to the inflammation triggered by the peripheral immune-inflammatory response to the viral infection and to the persistent psychological burden during and after infection. The large number of SARS-CoV-2-infected patients and the high prevalence of post-COVID-19 depressive symptoms may significantly increase the pool of people suffering from depressive disorders. Therefore, it is essential to screen, diagnose, treat, and monitor COVID-19 survivors' psychopathology to counteract the depression disease burden and related years of life lived with disability. This paper reviews the current literature in order to synthesize the available evidence regarding epidemiology, clinical features, neurobiological underpinning, and pharmacological treatment of post-COVID-19 depressive symptoms.

Cognitive remediation therapy for post-acute persistent cognitive deficits in COVID-19 survivors: A proof-of-concept study.

ABSTRACTCognitive impairments figure prominently in COVID-19 survivors. Cognitive remediation therapy (CRT) improves functional outcomes reducing long-term cognitive deficits in several neurological and psychiatric conditions. Our case-control study investigates the efficacy of a CRT programme administered to COVID-19 survivors in the post-acute phase of the illness. Seventy-three COVID-19 survivors presenting cognitive impairments at one-month follow-up were enrolled. Among them, 15 patients were treated with a two-month CRT programme, and 30 non-treated patients were matched conditional to their baseline cognitive functioning. Cognitive functions were assessed before and after treatment. Depression and quality of life were also evaluated. Mixed model ANOVA revealed a significant effect over time of the CRT programme on global cognitive functioning (F = 4.56, p = 0.039), while no significant effect was observed in the untreated group. We observed a significant effect of the improvement in verbal fluency (χ2 = 7.20, p = 0.007) and executive functions (χ2 = 13.63, p < 0.001) on quality of life. A positive significant correlation was found between depressive symptomatology and verbal fluency (r = -0.35), working memory (r = -0.44), psychomotor coordination (r = -0.42), and executive functions (r = -0.33). Our results could pave the way to a plausible innovative treatment targeting cognitive impairments and ameliorating the quality of life of COVID-19 survivors.

Mood-congruent negative thinking styles and cognitive vulnerability in depressed COVID-19 survivors: A comparison with major depressive disorder.

BACKGROUND: COVID-19 is associated with depressive psychopathology in survivors. Negative thinking styles are a core feature of major depression, fostering the experience of negative emotions and affects and hampering recovery. This cognitive vulnerability has been observed in medical conditions associated with depression, but never explored in post-COVID depression. METHODS: We studied 729 participants: 362 COVID-19 survivors, 73 inpatients with Major Depressive Disorder (MDD), and 294 healthy participants (HC). Severity of depression was self-rated on the Zung Self-Rating Depression Scale (ZSDS). Neuropsychological bias toward negative emotional stimuli and the negative outlook on the self were tested in a self-description task, yielding latencies and frequencies of attribution of morally tuned elements. Dimensions of negative thinking and depressive cognitive style in evaluation of hypothetical events were measured on the Cognition Questionnaire (CQ). RESULTS: 22.4% COVID survivors self-rated depression above the clinical threshold. Frequencies and latencies of attribution of morally negative elements, and CQ scores, correlated between themselves and predicted ZSDS scores, with post-COVID depressed patients showing intermediate scores between the more severe MDD patients, and non-depressed post-COVID participants and HC. LIMITATIONS: Recruitment was in a single center, thus raising the possibility of population stratification. CONCLUSIONS: The breadth of self-reproach and depressive cognitive style in evaluating events showed the same association with severity of depression in MDD and in post-COVID depressed patients, distributing along a gradient of severity, thus suggesting that individual features of negative thinking styles are shared in these conditions, and should be addressed as treatment targets in depressed COVID-19 survivors.

A Nomogram-Based Model to Predict Respiratory Dysfunction at 6 Months in Non-Critical COVID-19 Survivors

Objective To assess the prevalence of respiratory sequelae of Coronavirus disease 2019 (COVID-19) survivors at 6 months after hospital discharge and develop a model to identify at-risk patients. Patients and Methods In this prospective cohort study, hospitalized, non-critical COVID-19 patients evaluated at 6-month follow-up between 26 August, 2020 and 16 December, 2020 were included. Primary outcome was respiratory dysfunction at 6 months, defined as at least one among tachypnea at rest, percent predicted 6-min walking distance at 6-min walking test (6MWT) ≤ 70%, pre-post 6MWT difference in Borg score ≥ 1 or a difference between pre- and post-6MWT oxygen saturation ≥ 5%. A nomogram-based multivariable logistic regression model was built to predict primary outcome. Validation relied on 2000-resample bootstrap. The model was compared to one based uniquely on degree of hypoxemia at admission. Results Overall, 316 patients were included, of whom 118 (37.3%) showed respiratory dysfunction at 6 months. The nomogram relied on sex, obesity, chronic obstructive pulmonary disease, degree of hypoxemia at admission, and non-invasive ventilation. It was 73.0% (95% confidence interval 67.3–78.4%) accurate in predicting primary outcome and exhibited minimal departure from ideal prediction. Compared to the model including only hypoxemia at admission, the nomogram showed higher accuracy (73.0 vs 59.1%, P < 0.001) and greater net-benefit in decision curve analyses. When the model included also respiratory data at 1 month, it yielded better accuracy (78.2 vs. 73.2%) and more favorable net-benefit than the original model. Conclusion The newly developed nomograms accurately identify patients at risk of persistent respiratory dysfunction and may help inform clinical priorities.

Brain correlates of depression, post-traumatic distress, and inflammatory biomarkers in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Psychiatric sequelae substantially contribute to the post-acute burden of disease associated with COVID-19, persisting months after clearance of the virus. Brain imaging shows white matter (WM) hypodensities/hyperintensities, and the involvement of grey matter (GM) in prefrontal, anterior cingulate (ACC) and insular cortex after COVID, but little is known about brain correlates of persistent psychopathology. With a multimodal approach, we studied whole brain voxel-based morphometry, diffusion-tensor imaging, and resting-state connectivity, to correlate MRI measures with depression and post-traumatic distress (PTSD) in 42 COVID-19 survivors without brain lesions, at 90.59 â€‹± â€‹54.66 days after COVID. Systemic immune-inflammation index (SII) measured in the emergency department, which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted worse self-rated depression and PTSD, widespread lower diffusivity along the main axis of WM tracts, and abnormal functional connectivity (FC) among resting state networks. Self-rated depression and PTSD inversely correlated with GM volumes in ACC and insula, axial diffusivity, and associated with FC. We observed overlapping associations between severity of inflammation during acute COVID-19, brain structure and function, and severity of depression and post-traumatic distress in survivors, thus warranting interest for further study of brain correlates of the post-acute COVID-19 syndrome. Beyond COVID-19, these findings support the hypothesis that regional GM, WM microstructure, and FC could mediate the relationship between a medical illness and its psychopathological sequelae, and are in agreement with current perspectives on the brain structural and functional underpinnings of depressive psychopathology.

One-year mental health outcomes in a cohort of COVID-19 survivors.

COVID-19 survivors are at increased risk of persistent psychopathology after the infection. Despite long-term sequelae are an increasing concern, long-term neuropsychiatric consequences remain largely unclear. This cohort study aimed at investigating the psychopathological impact of COVID-19 in Italy one year after infection, outlining the trajectory of symptomatology at one, six-, and twelve-months follow-up. We evaluated 402, 216, and 192 COVID-19 survivors respectively at one, six, and 12 months. A subgroup of 95 patients was evaluated longitudinally both at one, six, and 12 months. Validated self-report questionnaires were administered to assess depression, fatigue, anxiety, and post-traumatic distress. Socio-demographics and setting of care information were gathered for each participant. At six and twelve months, respectively 94 (44%) and 86 (45%) patients self-rated in the clinical range in at least one psychopathological dimension. Pathological fatigue at twelve months was detected in 63 patients (33%). Considering the longitudinal cohort an interaction effect of sex and time was observed for depression (F = 8.63, p < 0.001) and anxiety (F = 5.42, p = 0.005) with males showing a significant increasing trend of symptoms, whereas an opposite course was observed in females. High prevalence of psychiatric sequelae six and 12 months after COVID-19 was reported for the first time. These findings confirm the need to provide integrated multidisciplinary services to properly address long-lasting mental health sequelae of COVID-19 and to treat them with the aim of reducing the disease burden and related years of life lived with disability.

Long-term consequences of COVID-19 on cognitive functioning up to 6 months after discharge: role of depression and impact on quality of life.

Neurologic and psychiatric symptoms have been reported in the months following the infection with COVID-19. A low-grade inflammation has been associated both with depression and cognitive symptoms, suggesting a link between these disorders. The aim of the study is to investigate cognitive functioning 6 months following hospital discharge for COVID-19, the impact of depression, and the consequences on quality of life. Ninety-two COVID-19 survivors evaluated at 1-month follow-up, 122 evaluated at 3 months and 98 evaluated at 6 months performed neuropsychological and psychiatric evaluations and were compared with a healthy comparison group (HC) of 165 subjects and 165 patients with major depression (MDD). Cognitive performances were adjusted for age, sex, and education. Seventy-nine percent of COVID-19 survivors at 1 month and 75% at 3- and 6-month follow-up showed cognitive impairment in at least one cognitive function. No significant difference in cognitive performances was observed between 1-, 3-, and 6-months follow-up. COVID-19 patients performed worse than HC but better than MDD in psychomotor coordination and speed of information processing. No difference between COVID-19 survivors and MDD was observed for verbal fluency, and executive functions, which were lower than in HC. Finally, COVID-19 survivors performed the same as HC in working memory and verbal memory. The factor that most affected cognitive performance was depressive psychopathology which, in turn, interact with cognitive functions in determining quality of life. Our results confirm that COVID-19 sequelae include signs of cognitive impairment which persist up to 6 months after hospital discharge and affect quality of life.