Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19

Abstract

The dysfunctional effects of the coronavirus disease 2019 (COVID-19) infection on the nervous system are established. The manifestation of neuropsychiatric symptoms during and after infection is influenced by the neuroinvasive and neurotrophic properties of SARS-CoV-2 as well as strong inflammation characterised by a specific "cytokine storm". Research suggests that a strong immune response to a SARS-CoV-2 infection and psychological stressors related to the pandemic may cause chronic inflammatory processes in the body with elevated levels of inflammatory markers contributing to the intensification of neurodegenerative processes. It is suggested that neuroinflammation and associated central nervous system changes may significantly contribute to the etiopathogenesis of depressive disorders. In addition, symptoms after a COVID-19 infection may persist for up to several weeks after an acute infection as a post-COVID-19 syndrome. Moreover, previous knowledge indicates that among SSRI (selective serotonin reuptake inhibitor) group antidepressants, fluoxetine is a promising drug against COVID-19. In conclusion, further research, observation and broadening of the knowledge of the pathomechanism of a SARS-CoV-2 infection and the impact on potential complications are necessary. It is essential to continue research in order to assess the long-term neuropsychiatric effects in COVID-19 patients and to find new therapeutic strategies.

Keywords: COVID-19; SARS-CoV-2; complications; depression; depressive disorders; long-term; neurocognitive disorders; neuroinflammation; post-covid.

Figure 1

Multifactorial aetiology of depression.

Figure 2

Pathophysiology of SARS-CoV-2 infection. SARS-CoV-2 first infects alveolar epithelial cells, replicates and then induces cell death via a pyrocytosis mechanism causing the release of damage-associated molecular structures (DAMPs) and pathogen-associated molecular patterns (PAMPs) that are recognised by receptors (Toll-like receptors-TLR-s) of neighbouring epithelial cells, endothelial cells and macrophages. The activation of the innate and adaptive inflammatory response results in the release of inflammatory cytokines and chemokines, including IL1-β, IL-6, IL-18, IFN-γ, IP-10, CCL-2, TNF-α, IL -2, IL-7, G-CSF and MIP1α, in addition to IL4, IL-10 and IL-1RA with anti-inflammatory properties. In addition, the level of CRP, SAA, fibrinogen, antitrypsin, hepcidin and complement components that worsen inflammatory reactions and activate the coagulation pathway leading to coagulation disorders increases. As a result of a cytokine storm, systemic inflammation occurs and, as a consequence, organ damage and failure can lead to death. Abbreviations: IL1-β, interleukin 1 beta; IL-6, interleukin 6; IL-18, interleukin 18; IFN-γ, interferon gamma; IP-10, interferon gamma-induced protein 10; CCL-2, the chemokine ligand 2; TNF-α, tumour necrosis factor alpha; IL-2, interleukin 2; IL-7, interleukin 7; G-CSF, granulocyte colony-stimulating factor; MIP1α, macrophage inflammatory protein 1α; IL4, interleukin 4; IL-10, interleukin 10; IL-1RA, interleukin-1 receptor antagonist; CRP, C-reactive protein; SAA, serum amyloid A.

Figure 3

Changes in laboratory parameters in a SARS-CoV-2 infection. COVID-19 infection may be manifested by elevated levels of interleukins (IL-1, IL-6, IL10, IL-2R) and other inflammatory markers (CRP, PCT, ESR, ferritin, SAA) and by liver (AST, ALT) and kidney (creatinine) parameters, as well as by CK, LDH, NLR, D-dimers, correlating with inflammation and decreased levels of lymphocytes, thrombocytes, eosinophils and albumin, depending on the course of infection. Abbreviations: IL-1, interleukin-1; IL-6, interleukin-6; IL-10, interleukin-10; IL-2R, the interleukin-2 receptor; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; NLR, neutrophil-to-lymphocyte ratio.

Figure 4

Symptoms of Post-COVID syndrome.