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.

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.

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.

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.

Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors.

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.