Neuropsychiatric Manifestations and Neuroimmune Correlates of COVID-19

Respiratory epithelial cells and alveolar macrophages seem to be primary targets for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nevertheless, coronaviruses affect diverse organ systems, including the central nervous system (CNS). Indeed, there is an increasing number of reports pointing to neuropsychiatric symptoms in SARS-CoV-2 infected patients and in those with coronavirus disease 2019 (COVID-19) manifested infection. Neuropsychiatric manifestations can be attributed to an individual psychological response to changed reality in pandemic circumstances, to the viral infection per se, due to the host immune response, and much more rarely as an adverse effect of therapy. Although the exact route of entry of SARS-CoV-2 into the CNS is yet to be elaborated, it has been suggested that SARS-CoV-2 might be transmitted to the CNS via retrograde axonal transport from the olfactory nerve. Invasion of neurons directly follows colonization in the respiratory tract and could induce neurodegenerative processes in the brain. In addition to its direct neuroinvasive potential, enhanced inflammatory response and immune-mediated processes activated by SARS-CoV-2 might imitate the molecular architecture of self-directed immunity in the CNS and may trigger cytokine release in the CNS. In line with all this, it has also been hypothesized that the viral binding to angiotensin-converting enzyme-2 (ACE-2) receptors expressed in glia and neurons may be involved in neuromodulation. The ACE-2 receptor has recently been regarded as having a key role in the stress response system and in psychiatric illness pathophysiology. Further, one of the hypotheses has suggested that potential neurodegeneration may result from the penetration of peripheral cytokines into the CNS due to the damaged blood-brain barrier. In the light of the knowledge summarized above, it has been thought that investigating the neuropsychiatric manifestations and neuroimmune correlates of COVID-19, will be valuable for a thorough understanding of the much wider damage potential of this ongoing pandemic.

Despite burgeoning evidence suggesting the possible deteriorating impact of SARS-CoV-2 on the CNS, there still exists a gap in clarifying the short- and long-term clinical manifestations of the impact on the CNS of SARS-CoV-2. Neurobiological evidence is needed to validate the theories regarding the etiopathogenesis of neuropsychiatric presentations of COVID-19. Because of the unprecedented breadth and unforeseen duration of the current SARS-CoV-2 pandemic, in this Research Topic, we aim to offer a closer examination of the neuroimmunological and other related biological mechanisms underlying extensive and heterogenous neuropsychiatric complications, which have a substantial burden on the prognosis and morbidity of the illness. We believe that such an examination from both clinical and preclinical perspectives will be invaluable to fully appreciate the etiopathogenesis and ultimately guide the clinicians to prioritize and individualize therapeutic protocols especially focused on neuropsychiatric complications, along with the proposed treatment strategies.

We welcome manuscripts with a conceptual or methodological focus with the formats of original research, brief research report, review (mini, narrative, or systematic), case report and series, hypothesis and theory, perspective, commentary, or opinion. Studies addressing the following themes are encouraged:

• Clinical manifestations of the central and peripheral nervous system involvement of acute SARS-CoV-2 infection
• Overall clinical characteristics of COVID-19 patients with coexisting neuropsychiatric symptomatology
• Psychological and social implications of the pandemic
• Neuroimmune correlates and psychoneuroimmunological characteristics of COVID-19
• Systemic inflammatory processes in COVID-19 affecting the nervous system
• Immune biomarker’s deviations and possible specific complications in patients with psychiatric disorders who suffered from COVID-19
• Potential biomarkers related to neuropsychiatric manifestations and sequelae of COVID-19
• Neurological and psychiatric symptoms induced by COVID-19 treatments
• Potential therapeutical approaches for neuropsychiatric presentations of COVID-19
• Preclinical models mimicking the COVID-19 infections in in vitro and in vivo conditions
• The clinical picture of long covid including what it might imply for other disorders like chronic fatigue syndrome