Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

Abstract

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome. Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up.

Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection

“…Despite our humanized hACE2ki mouse line not displaying severe disease progression when inoculated with various SARS‐CoV‐2 variants at a young adult age, we aimed to assess its suitability for investigating long‐COVID or post‐acute sequelae of SARS‐CoV‐2 infection pathogenesis and potential interventions. A key focus was to determine if SARS‐CoV‐2 infection in this model leads to tau pathologies, a known indicator for neurological disorders and a suggested long‐term consequence of SARS‐CoV‐2 infection 8–13 …”

“…suggested long-term consequence of SARS-CoV-2 infection. [8][9][10][11][12][13] Recent investigations have revealed increased hyperphosphorylated tau181 (p-tau181) in individuals afflicted with SARS-CoV-2 infection 14 and during the convalescence phase following COVID-19 infection. 15 This particular variant of hyperphosphorylated tau 181 has been identified as a specific biomarker associated with AD.…”

Microgliosis, astrogliosis and loss of aquaporin-4 polarity in frontal cortex of COVID-19 patients

“…Several studies reported signs of neuroinflammation in tissue from COVID-19 patients (reviewed by (Almutairi et al, 2021; Brown et al, 2023; Gonçalves de Andrade et al, 2021; Hernández-Parra et al, 2023; Iadecola et al, 2020; Natale, Lukens, & Petri, 2022; Tremblay et al, 2020; Vanderheiden & Klein, 2022; A. C. Yang et al, 2021)). SARS-CoV-2 not only infects the respiratory tract but also other organs, including the brain and its cerebrovasculature (Y.…”

“…Among the cytokines are interleukin 2R, interleukin 6, interleukin 8, tumor necrosis factor (TNF, also known as TNF-alpha) and, interestingly, also the anti-inflammatory interleukin-10 (Devlin & Gombolay, 2023; Liu et al, 2020). Macrophages and lymphocytes penetrate the blood-brain barrier, activate microglial cells and astrocytes and finally determine neuroinflammation (Almutairi et al, 2021; Brown et al, 2023; Gonçalves de Andrade et al, 2021; Hernández-Parra et al, 2023; Iadecola et al, 2020; Tremblay et al, 2020; Vanderheiden & Klein, 2022). In our study, both microglial cells and astrocytes showed an activated phenotype in COVID-19 patients, confirming neuroinflammation.…”

“…Both neurological as well as non-neurological symptoms persist after subsidence of the infection in a considerable number of patients, a syndrome known as post acute sequelae of COVID-19 (PASC), or simply post-COVID or long-COVID (Goldstein, 2024; Nalbandian et al, 2021; Song et al, 2021; Steardo, Steardo, Verkhratsky, & Scuderi, 2021). Recent investigations found an increased risk of incident neurological sequelae such as stroke, migraine, seizures, mental health disorders, Guillain-Barre syndrome and encephalitis in long-COVID patients and late effects of COVID-19 may become a major health issue in the future (Aghajani Mir, 2023; Brown et al, 2023). Therefore, understanding the molecular and cellular consequences of the viral infection within the central nervous system is inevitable to develop treatment of long-COVID.…”