Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

BACKGROUND AND OBJECTIVES: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. METHODS: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. RESULTS: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. CONCLUSIONS: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

Micronized/ultramicronized palmitoylethanolamide improves depression and fatigue in coronavirus disease 2019 (COVID-19) survivors.

Coronavirus disease 2019 (COVID-19) may lead to neuropsychiatric sequelae. Palmitoylethanolamide (PEA) is an anti-inflammatory and neuroprotective amide used in depressive syndromes. Here we investigate whether micronized/ultramicronized (m/um) PEA improves neuropsychiatric sequelae in COVID-19 survivors. Patients evaluated at our post-COVID-19 outpatient clinic between February and August 2021 and presenting neuropsychiatric manifestations (n = 98) were offered treatment with m/umPEA 600 mg twice daily for 3 months. Those accepting m/umPEA therapy (n = 57) were compared with those who did not (n = 41), in terms of depression, fatigue, chronic pain and subjective well-being, through validated scales administered pre- and posttreatment. The two groups did not differ in terms of demographics, comorbidities, psychiatric history, antidepressant therapy, acute COVID-19 severity and baseline neuropsychiatric status. Patients receiving m/umPEA showed a greater improvement in depression and fatigue (both P < 0.05). Conversely, no association was found with changes in chronic pain or subjective well-being. At multivariable logistic regression, m/umPEA predicted neuropsychiatric improvement independently of age, sex and baseline neuropsychiatric status. Worse pretreatment fatigue and subjective well-being identified those who most likely benefited from treatment. In conclusion, despite its retrospective nature, our study suggests that m/umPEA may improve depression and fatigue in COVID-19 survivors, justifying future research in this setting.

Choroid plexus volume is increased in mood disorders and associates with circulating inflammatory cytokines.

Depressed patients exhibit altered levels of immune-inflammatory markers both in the peripheral blood and in the cerebrospinal fluid (CSF) and inflammatory processes have been widely implicated in the pathophysiology of mood disorders. The Choroid Plexus (ChP), located at the base of each of the four brain ventricles, regulates the exchange of substances between the blood and CSF and several evidence supported a key role for ChP as a neuro-immunological interface between the brain and circulating immune cells. Given the role of ChP as a regulatory gate between periphery, CSF spaces and the brain, we compared ChP volumes in patients with bipolar disorder (BP) or major depressive disorder (MDD) and healthy controls, exploring their association with history of illness and levels of circulating cytokines. Plasma levels of inflammatory markers and MRI scans were acquired for 73 MDD, 79 BD and 72 age- and sex-matched healthy controls (HC). Patients with either BD or MDD had higher ChP volumes than HC. With increasing age, the bilateral ChP volume was larger in patients, an effect driven by the duration of illness; while only minor effects were observed in HC. Right ChP volumes were proportional to higher levels of circulating cytokines in the clinical groups, including IFN-γ, IL-13 and IL-17. Specific effects in the two diagnostic groups were observed when considering the left ChP, with positive association with IL-1ra, IL-13, IL-17, and CCL3 in BD, and negative associations with IL-2, IL-4, IL-1ra, and IFN-γ in MDD. These results suggest that ChP could represent a reliable and easy-to-assess biomarker to evaluate the brain effects of inflammatory status in mood disorders, contributing to personalized diagnosis and tailored treatment strategies.

In Between the Psychological and Physiological Self - The Impact of Covid-19 Pandemic on the Neuro-Socio-Ecological and Inflammatory Mind-Body-Brain System.

The COVID-19 pandemic has had a profound impact on individuals' sense of self perturbating the sense of connectedness with the others, touching upon deep existential fears and deep intersubjective and cultural layers, emphasizing the importance of a neuro-socio-ecological alignment for the sense of security of psychological self. We can still observe after years how social distancing measures, quarantines, and lockdowns have disrupted social connections and routines, leading to feelings of isolation, anxiety and depressive symptomatology. Furthermore, from a physiological perspective, some people continue to experience health problems long after having COVID-19, and these ongoing health problems are sometimes called post-COVID-19 syndrome or post-COVID conditions (PASC). In this complex scenario, through the operationalization of the sense of self and its psychological and physiological baseline, our aim is to try to shed some new light on elements of resilience vs. vulnerability. Here we intend the self and its baseline as the crossroads between psychology and physiology and we show how COVID-19 pandemic, especially in post-COVID-19 syndrome (PACS), left traces in the mind-body-brain system at a neuro-socio-ecological and inflammatory level.

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.

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.

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.

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

Cognitive 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.

Interleukin 6 associates with reduced grey matter volume and resting-state connectivity in the anterior cingulate cortex in bipolar patients.

High levels of peripheral IL-6, a pro-inflammatory cytokine, have been indicated as a key element of the bipolar disorder (BD), allowing to differentiate BD from major depression with high accuracy and to early detect poor responders to antidepressant treatments. IL-6 may contribute to BD pathophysiology through its effects on the neurobiological underpinnings of the disorder, such as grey matter (GM) volumes and resting state functional connectivity (rs-FC) abnormalities. In this study, we primary investigate the relationship between the peripheral plasmatic level of IL-6 and GM volumes, obtained with Voxel-Based Morphometry, in 84 BD inpatients. As secondary aims, we explored if IL-6 levels may be related to self-reported psychopathological dimensions of depression (i.e. symptoms severity and cognitive biases) and seed based rs-FC of brain regions structurally associated with the cytokine. Results showed that higher level of peripheral IL-6 was associated to lower GM volumes in supragenual anterior cingulate cortex, and reduced rs-FC between this area and medial orbito-frontal cortex in BD. Furthermore, in depressed patients IL-6 positively correlated to cognitive biases typically associated to depressive episodes, such as the perceived uncontrollability of negative events, or their generalization across future and situations. Our data provide additional evidence of detrimental effect of systemic inflammation on brain structure in BD and confirm the crucial role of anterior cingulate cortex as neural underpinning of the disorder. However, future studies are needed to replicate our findings in larger samples.

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.

Lower levels of glutathione in the anterior cingulate cortex associate with depressive symptoms and white matter hyperintensities in COVID-19 survivors.

SARS-CoV-2 is a novel coronavirus that mainly affects the respiratory system. However, clinical manifestations such as neurological symptoms, psychopathological outcomes and brain alterations suggest brain involvement during SARS-CoV-2 infection. Depressive symptoms and cerebral white matter hypodensities/hyperintensities (WMH) have been widely reported in COVID-19 survivors and have been shown to persist after recovery from infection. At the same time viral Infections, including COVID-19, have been shown to lead to oxidative stress. Glutathione (GSH) is the main antioxidant in the brain and reduced GSH levels have been implicated both in COVID-19 and depression. We therefore hypothesise that reduced GSH levels may be associated with depressive symptoms and WMH in COVID-19 survivors. Forty-nine participants (age 18-70) surviving COVID-19 underwent magnetic resonance imaging to measure WMH and brain GSH levels in the ACC, blood sampling to measure systemic inflammation and psychopathological assessment for depressive symptoms. ACC concentrations of GSH inversely associated with both depression scores and the number and volume of WMH. The volume of WMH also positively associated with depressive symptomatology. Finally, systemic inflammation negatively predicted GSH concentration in ACC. In conclusion, we observed overlapping associations of GSH levels in ACC, WMH and severity of depression in COVID-19 survivors, and confirmed the central role of systemic inflammation, thus warranting interest for further study of oxidative stress and antioxidants in the post-acute COVID-19 syndrome.

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.

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.

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.

Rapid response to selective serotonin reuptake inhibitors in post-COVID depression.

The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. After COVID-19, depression was reported in 40% of patients at one-, three-, and six-months follow-up. Emerging literature suggests anti-inflammatory and antiviral properties of antidepressants in the treatment of SARS-CoV-2. We aim to investigate the efficacy of Selective Serotonin Reuptake Inhibitor (SSRI) in treating post-COVID depression. We included 60 patients affected by a major depressive episode and treated with SSRI in the six months following recovery from COVID. The severity of depression was rated at baseline and after four weeks on the Hamilton Depression Rating Scale (HDRS). Response to treatment was considered when the patients achieved a 50% HDRS reduction. To investigate changes of depressive symptomatology over time, repeated measures ANOVAs according to clinical variables were performed. We found that 55 (92%) patients showed a clinical response to antidepressant. Patients showed a significant decrease over time of HDRS score (baseline HDRS = 23.37 ± 3.94, post-treatment HDRS = 6.71±4.41, F = 618.90, p < 0.001), irrespectively of sex, previous psychiatric history, previous history of mood disorder, and SSRI type. This is the first study to explore the SSRI efficacy in post-COVID depression, suggesting rapid antidepressant effects in most patients. SSRIs treatment could contribute to the rapid antidepressant response by directly targeting the neuroinflammation triggered by SARS-CoV-2. We suggest screening psychopathology of COVID-19 survivors to diagnose emergent depression and pharmacologically treat it to reduce the disease burden and related years of life lived with disability.

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.

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.

Persistent psychopathology and neurocognitive impairment in COVID-19 survivors: Effect of inflammatory biomarkers at three-month follow-up.

COVID-19 outbreak is associated with mental health implications during viral infection and at short-term follow-up. Data on psychiatric and cognitive sequelae at medium-term follow-up are still lacking. During an ongoing prospective cohort study, the psychopathological and cognitive status of 226 COVID-19 pneumonia survivors (149 male, mean age 58) were prospectively evaluated one and three months after hospital discharge. Psychiatric clinical interview, self-report questionnaires, and neuropsychological profiling of verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency were performed. Three months after discharge from the hospital, 35.8% still self-rated symptoms in the clinical range in at least one psychopathological dimension. We observed persistent depressive symptomatology, while PTSD, anxiety, and insomnia decreased during follow-up. Sex, previous psychiatric history, and the presence of depression at one month affected the depressive symptomatology at three months. Regardless of clinical physical severity, 78% of the sample showed poor performances in at least one cognitive domain, with executive functions and psychomotor coordination being impaired in 50% and 57% of the sample. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted self-rated depressive symptomatology and cognitive impairment at three-months follow-up; and changes of SII predicted changes of depression during follow-up. Neurocognitive impairments associated with severity of depressive psychopathology, and processing speed, verbal memory and fluency, and psychomotor coordination were predicted by baseline SII. We hypothesize that COVID-19 could result in prolonged systemic inflammation that predisposes patients to persistent depression and associated neurocognitive dysfunction. The linkage between inflammation, depression, and neurocognition in patients with COVID-19 should be investigated in long-term longitudinal studies, to better personalize treatment options for COVID-19 survivors.