New‑onset neuropsychiatric sequelae and ‘long‑COVID’ syndrome (Review)

Abstract:

The ongoing coronavirus disease 2019 (COVID‑19) pandemic has had a widespread impact on individuals’ mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability.
The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post‑acute ‘long‑COVID’ phase. In addition to the COVID‑19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID‑19, there is accumulating evidence that a diagnosis of COVID‑19 may also be associated with new‑onset neuropsychiatric morbidity among survivors without pre‑existing mental health disorders.
In particular, studies investigating the incidence of post‑acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new‑onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID‑19 survivors were compared with SARS‑CoV‑2‑negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies.
While there is evidence of an association between SARS‑CoV‑2 infection and the subsequent occurrence of new‑onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.
Source: Efstathiou, V., Stefanou, M., Demetriou, M., Siafakas, N., Katsantoni, E., Makris, M., Tsivgoulis, G., Zoumpourlis, V., Kympouropoulos, S. P., Tsoporis, J. N., Spandidos, D. A., Ferentinos, P., Smyrnis, N., Rizos, E.”New‑onset neuropsychiatric sequelae and ‘long‑COVID’ syndrome (Review)”. Experimental and Therapeutic Medicine 24.5 (2022): 705. https://www.spandidos-publications.com/10.3892/etm.2022.11641 (Full text available as PDF file)

Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19

Abstract:

The incidence of infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalated following the initial outbreak in China in late 2019, resulting in a global pandemic with millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment of vaccines have afforded increased immunity against SARS-CoV-2, long term sequelae of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological dysfunction that may lead to psychological and neurocognitive impairment. A major component of cognitive dysfunction is operationally categorized as “brain fog” which comprises difficulty with concentration, forgetfulness, confusion, depression, and fatigue.

Multiple parameters associated with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of COVID-19 are by nature complex, but broad based working models have focused on mitochondrial dysregulation leading to systemic reductions of metabolic activity and cellular bioenergetics within CNS structures. Multiple factors underlying the expression of brain fog may facilitate future pathogenic insults leading to repetitive cycles of viral and bacterial propagation. Interestingly, diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed in other historical pandemics, thereby providing a broad and integrative perspective on potential common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection by diverse pathogens.

By extrapolation, we contend that COVID-19 may potentiate the severity of neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Accordingly, the prevention, diagnosis, and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal health care directives and provide a compelling rationale for careful monitoring of infected patients, as early mitigation efforts may reduce short- and long-term complications.

Source: Stefano GB, Büttiker P, Weissenberger S, Ptacek R, Wang F, Esch T, Bilfinger TV, Kream RM. Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19. Curr Neuropharmacol. 2021 Dec 23. doi: 10.2174/1570159X20666211223130228. Epub ahead of print. PMID: 34951387. https://pubmed.ncbi.nlm.nih.gov/34951387/

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma

Abstract:

The aim of this article is to provide a comprehensive and updated review of the key neuropsychiatric and neuropsychological complaints associated with chronic fatigue syndrome (CFS). Neuropsychiatric and neuropsychological difficulties are common in CFS and are linked primarily to disorders of mood, affect and behaviour.

The neuropsychiatric complaint most frequently encountered amongst CFS patients is depression and in particular major depressive disorder (MDD). Despite decades of research, the precise aetiological relationship between CFS and MDD remains poorly understood. This has resulted in the development of a number of interesting and polarised hypotheses regarding the aetiological nature of CFS. Recent scientific advances have however begun to unravel a number of interesting inflammatory and immunological explanations that suggest CFS and MDD are distinct yet interrelated conditions.

The possibility that the overlap between CFS and MDD might be explained in terms of shared oxidative and nitrosative (IO&NS) pathways is an area of intense research interest and is reviewed in detail in this article. The overlap between CFS and MDD is further differentiated by variations in HPA axis activity between the two disorders. Important immunological differences between MDD and CFS are also reviewed with particular emphasis on antiviral RNase L pathways in CFS.

In addition to the presence of neuropsychiatric complaints, CFS is also associated with neuropsychological symptoms such as impaired attention, memory and reaction time. The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS.

 

Source: Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013 Apr;15(4):353. doi: 10.1007/s11920-013-0353-8. https://www.ncbi.nlm.nih.gov/pubmed/23440559