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

Mazza, Mario Gennaro; Palladini, Mariagrazia; Poletti, Sara; Benedetti, Francesco

doi:10.1007/s40263-022-00931-3

Cited by 124 publications

(146 citation statements)

References 194 publications

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“…Fatigue is also an important component of MDD and it has been shown that SARS-CoV-2 infection is able to elicit episodes of major depression. 49, 50 Indeed, also in our series we found a prevalence of 23% (HADS-D) and 37% (BDI-12) of depression in the group of long COVID patients with disabling fatigue. Our long COVID patients show monocyte gene expression abnormalities similar as those found in “regular” MDD patients with severe and recurrent depression.…”

Section: Discussionsupporting

confidence: 75%

Severe fatigue as symptom of long COVID is characterized by increased expression of inflammatory genes in monocytes, increased serum pro-inflammatory cytokines, and increased CD8+ T-lymphocytes: A putative dysregulation of the immune-brain axis, the coagulation process, and auto-inflammation to explain the diversity of long COVID symptoms

Berentschot

Drexhage

Mersha

et al. 2022

Preprint

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BackgroundA significant proportion of patients with SARS-CoV-2 infection develops long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immunologic profiling of fatigued and non-fatigued long COVID patients and age and gender matched healthy controls (HCs).MethodsWe included 37 long COVID patients with and 36 without severe fatigue and assessed inflammation-related monocyte gene expression, serum levels of inflammatory cytokines, and leukocyte and lymphocyte subsets 3-6 months after hospital discharge, and followed clinical symptoms up to one year.ResultsLong COVID with fatigue represented a severe variant with many symptoms (median 9 [IQR 5.0-10.0] symptoms) and signs of cognitive failure (41%) and depression (>24%). Symptoms persisted up to one year follow-up. Fatigued patients showed increased expression of inflammatory genes in monocytes, increased serum IL-6, TNF-α, galectin-9, and CXCL10, and increased CD8+ T-lymphocytes compared to HCs.Non-fatigued long COVID patients were arbitrarily divided in those with moderately severe disease (4 [2.5-5.0] symptoms, primarily impaired fitness, n=25) and those with mild disease (1 [1.0-2.0] symptom, n=11). Symptoms in non-fatigued long COVID patients persisted up to one year follow-up. Moderately severe patients showed reduced CD45RO- naïve CD4+ T-lymphocytes and CD25+FOXP3+ regulatory CD4+ T-lymphocytes and limited monocyte and serum (galectin-9) inflammation. Mild patients showed monocyte and serum (IL-6, galectin-9) inflammation and decreased CD4+ T-lymphocyte subsets (T-helper 1 cells).ConclusionLong COVID with fatigue is associated with many concurrent and persistent symptoms up to one year after hospitalization and with clear signs of low grade inflammation and increased CD8+ T-lymphocytes. We showed that long COVID is a clinical and immunologic heterogeneous disorder. Diagnostic tools and personalized therapies combatting the diverse immune abnormalities might be required to alleviate the persisting disabling complaints of the patients.

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Section: Discussionsupporting

confidence: 75%

Severe fatigue as symptom of long COVID is characterized by increased expression of inflammatory genes in monocytes, increased serum pro-inflammatory cytokines, and increased CD8+ T-lymphocytes: A putative dysregulation of the immune-brain axis, the coagulation process, and auto-inflammation to explain the diversity of long COVID symptoms

Berentschot

Drexhage

Mersha

et al. 2022

Preprint

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“…The relevance of depression as a factor associated with chronic pain is supported in the literature [ 48 ]. Additionally, the relevance of depressive symptoms in people with the post-COVID-19 condition is also clear in the literature [ 49 ]. The presence of depressive symptoms has been associated to higher risk of other post-COVID-19 symptoms such as fatigue [ 50 ] or dyspnea [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…This interaction between physical and emotional post-COVID-19 symptoms would explain a worse HRQoL experienced by the patients. Potential psychopathological mechanisms underlying depressive symptoms in subjects with the post-COVID-19 condition are mainly related to the inflammation triggered by an exaggerated immune response to the viral acute infection (i.e., cytokine storm) and to the persistent psychological burden during (e.g., severity of the disease, or hospitalization) and after (e.g., isolation, post-traumatic stress, or uncertainty about prognosis) the acute infection [ 49 ]. Since anxiety and depressive symptoms can be present up to several years after the infection [ 51 ], continuous monitoring of this symptom will be important for determining the evolution of HRQoL in these patients.…”

Section: Discussionmentioning

confidence: 99%

Sleep Quality Mediates the Effect of Sensitization-Associated Symptoms, Anxiety, and Depression on Quality of Life in Individuals with Post-COVID-19 Pain

Hernández

Fernández‐de‐las‐Peñas

Fuensalida‐Novo

et al. 2022

Brain Sciences

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A better understanding of biological and emotional variables associated with health-related quality of life in people with long-COVID is needed. Our aim was to identify potential direct and indirect effects on the relationships between sensitization-associated symptoms, mood disorders such as anxiety/depressive levels, and sleep quality on health-related quality of life in people suffering from post-COVID-19 pain. One hundred and forty-six individuals who were hospitalized due to COVID-19 during the first wave of the pandemic and suffering from long-term post-COVID-19 pain completed different patient-reported outcome measures (PROMs), including clinical features, symptoms associated with sensitization of the central nervous system (Central Sensitization Inventory), mood disorders (Hospital Anxiety and Depressive Scale), sleep quality (Pittsburgh Sleep Quality Index), and health-related quality of life (paper-based five-level version of EuroQol-5D) in a face-to-face interview conducted at 18.8 (SD 1.8) months after hospitalization. Different mediation models were conducted to assess the direct and indirect effects of the associations among the different variables. The mediation models revealed that sensitization-associated symptoms and depressive levels directly affected health-related quality of life; however, these effects were not statistically significant when sleep quality was included. In fact, the effect of sensitization-associated symptomatology on quality of life (β = −0.10, 95% CI −0.1736, −0.0373), the effect of depressive levels on quality of life (β= −0.09, 95% CI −0.1789, −0.0314), and the effect of anxiety levels on quality of life (β = −0.09, 95% CI −0.1648, −0.0337) were all indirectly mediated by sleep quality. This study revealed that sleep quality mediates the relationship between sensitization-associated symptoms and mood disorders (depressive/anxiety levels) with health-related quality of life in individuals who were hospitalized with COVID-19 at the first wave of the pandemic and reporting post-COVID-19 pain. Longitudinal studies will help to determine the clinical implications of these findings.

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“…The use of nutraceuticals in post-COVID syndrome is currently under study. Several reports are described in adults [ 66 , 67 ], older people [ 68 ], and children [ 69 , 70 ] for different symptoms including olfactory loss [ 71 ], telogen effluvium [ 72 ], and depression and anxiety [ 73 ].…”

Section: Nutraceuticals and Dietary Supplements Against Covid-19 Dise...mentioning

confidence: 99%

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

Catalano

Iacopetta

Ceramella

et al. 2022

Foods

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The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.

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

Cited by 124 publications

References 194 publications

Sleep Quality Mediates the Effect of Sensitization-Associated Symptoms, Anxiety, and Depression on Quality of Life in Individuals with Post-COVID-19 Pain

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

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