Stress levels, psychological symptoms, and C-reactive protein levels in COVID-19: A cross-sectional study.

BACKGROUND: Although many studies have pointed out a possible relationship between COVID-19 and the presence of psychiatric disorders, the majority of the studies have significant limitations. This study investigates the influence of COVID-19 infection on mental health. METHODS: This cross-sectional study included an age- and sex-matched sample of adult individuals positive (cases) or negative (controls) for COVID-19. We evaluated the presence of psychiatric conditions and C-reactive protein (CRP). RESULTS: Findings showed greater severity of depressive symptoms, higher levels of stress, and greater CRP in cases. The severity of depressive and insomnia symptoms, as well as the CRP were more remarkable in individuals with moderate/severe COVID-19. We found a positive correlation between stress and severity of anxiety, depression, and insomnia in individuals with or without COVID-19. There was a positive correlation between CRP levels and severity of depressive symptoms in cases and controls, and a positive correlation between CRP levels and the severity of anxiety symptoms and stress levels only in individuals with COVID-19. Individuals with COVID-19 and depression had greater CRP than those with COVID-19 without current major depressive disorder. LIMITATIONS: We cannot infer causality because this is a cross-sectional study, and the majority of COVID-19 sample was asymptomatic or had mild symptoms, which may limit the generalizability of our findings for moderate/severe cases. CONCLUSIONS: Individuals with COVID-19 showed greater severity of psychological symptoms, which may impact on the development of psychiatric disorders in the future. CPR seem to be a promising biomarker for earlier detection of post-COVID depression.

Impact of COVID-19 on anxiety and depression - biopsychosocial factors.

Anxiety and depression are prevalent mental disorders around the world. The etiology of both diseases is multifactorial, involving biological and psychological issues. The COVID-19 pandemic settled in 2020 and culminated in several changes in the routine of individuals around the world, affecting mental health. People infected with COVID-19 are at greater risk of developing anxiety and depression, and individuals previously affected by these disorders have worsened the condition. In addition, individuals diagnosed with anxiety or depression before being affected by COVID-19 developed the severe illness at higher rates than individuals without mental disorders. This harmful cycle involves several mechanisms, including systemic hyper-inflammation and neuroinflammation. Furthermore, the context of the pandemic and some previous psychosocial factors can aggravate or trigger anxiety and depression. Disorders are also risks for a more severe picture of COVID-19. This review discusses research on a scientific basis, which brings evidence on biopsychosocial factors from COVID-19 and the context of the pandemic involved in anxiety and depression disorders.

Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19.

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.

COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route.

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.

Impact of COVID-19 in the Mental Health in Elderly: Psychological and Biological Updates.

Since December 2019, the world has been experiencing the challenge of facing coronavirus disease-19 (COVID-19), a severe infectious disease caused by the new coronavirus, SARS-CoV-2. The individuals with the most severe symptoms and the highest risk of death are the elderly and those with chronic illness. Among chronic conditions, those with a certain degree of chronic inflammation may predispose to a more severe evolution of COVID-19. Elderly with psychiatric disorders can present a persistent inflammatory state, a characteristic of the age's immunological senescence, but the disorder can accentuate that. Social isolation is still the safest way to avoid contamination. However, isolated older people may have or worsen mental health conditions due to isolation and health concerns. In this scenario, a SARS-CoV-2 infection may progress to more severe disease. Conversely, COVID-19 can predispose or aggravate psychiatric disorders, as it induces a cytokine storm, causing systemic hyper inflammation. It may damage the blood-brain barrier, resulting in inflammation in the central nervous system. Besides, SARS-CoV-2 is likely to reach and trigger an inflammatory process directly in the nervous system. This review makes an update about research on the mental health of the elderly during the pandemic. Also, it discusses the vulnerability of these individuals in the face of stress and in the case of contracting COVID-19, considering mainly the stress's hormonal and inflammatory mechanisms. Finally, the review points out possible care and attention strategies and entertainment and activities that can reduce the damage to mental and physical health and improve the elderly's quality of life. Graphical abstract Isolation and concerns about COVID-19 may harm elderly mental health. Immunosenescence and pandemic stress increase the risk of psychiatric disorders. Stress and disorders may potentiate the elderly's inflammation and COVID-19 symptoms. SARS-CoV-2 hyperinflammation is a risk factor for elderly psychiatric disorders.