Catching hold of COVID‐19‐related encephalitis by tracking ANGPTL4 signature in blood

Abstract

Infection by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in humans is characterized by a plethora of symptoms varying in intensity, such as non‐specific febrile illness, dry cough, dyspnea, hypoxemia to severe lung damage, and even death. In addition to pulmonary complications associated with coronavirus disease‐19 (COVID‐19), perturbations in the physiology of multiple other organ systems have been reported, resulting in multiorgan failure (MoF) that is frequently observed in severe COVID‐19 cases. Central nervous system (CNS) infection by SARS‐CoV‐2 is characterized by neurological impairments in patients with COVID‐19, with the development of encephalopathy at the severe end of the spectrum. While mechanistic investigations of SARS‐CoV‐2‐related encephalitis may reveal promising therapeutic candidates for reducing COVID‐19‐associated disease morbidity, the discovery of biomarkers capable of diagnosing and predicting prognosis in patients with encephalitis upon SARS‐CoV‐2 infection will afford significant value for the rapid detection of encephalitis and predicting disease outcomes. This will ultimately enable appropriate modifications of therapeutic regimens aimed at reducing disease morbidity and mortality. In this editorial, we highlight a study by Le Guennec and colleagues, entitled “Endothelial cell biomarkers in critically ill COVID‐19‐patients with encephalitis”, reporting the association of increased serum angiopoietin‐like 4 (ANGPTL4) abundance with COVID‐19‐related encephalitis. The study highlights ANGPTL4 as a potential molecular marker for this disease. These novel findings may catalyze developments in the field of COVID‐19‐associated encephalitis by facilitating accurate and rapid diagnosis of encephalitis and timely treatment initiation, thus improving patient outcomes by ameliorating disease burden.

SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids

“…There is increasing evidence for brain abnormalities in COVID-19 patients (Douaud et al, 2022;Graham et al, 2022;Karpiel et al, 2022;Ledford, 2022;Pelizzari et al, 2022;Sanabria-Diaz et al, 2022). Encephalitis is well documented, usually in hospitalized COVID-19 patients with severe disease, with encephalitis predisposing to poor outcomes and a higher risk of mortality (Siow et al, 2021;Altmayer et al, 2022;Chakraborty and Basu, 2022;Islam et al, 2022;Ong et al, 2023). The mechanism(s) whereby brain pathology/immunopathology and/or neuropathology might manifest in COVID-19 patients remains to be fully characterized, with the systemic cytokine storm likely involved, but direct brain infection also implicated in some COVID-19 and long-COVID patients (Zhang et al, 2020;Burks et al, 2021;Andrews et al, 2022;Aschman et al, 2022;Douaud et al, 2022;Fernandez-Castaneda et al, 2022;Rutkai et al, 2022;Samudyata Oliveira et al, 2022;Bauer et al, 2022a;Proal et al, 2023;Shuai et al, 2023;Silva et al, 2023).…”

Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids

“…4B,C,D). Multiple sclerosis-like features, myelitis, demyelination (Bellucci et al, 2021; Ismail and Salama, 2022) and encephalitis (Altmayer et al, 2022; Chakraborty and Basu, 2022; Islam et al, 2022; Siow et al, 2021) are also features described for COVID-19 patients. Apoptosis of neurons was reported in the NHP model (Rutkai et al, 2022), with pyroptosis in the CNS of COVID-19 patients also proposed (Sepehrinezhad et al, 2021).…”

“…There is increasing evidence for brain abnormalities in COVID-19 patients (Douaud et al, 2022; Graham et al, 2022; Karpiel et al, 2022; Ledford, 2022; Pelizzari et al, 2022; Sanabria-Diaz et al, 2022). Encephalitis is well documented, usually in hospitalized COVID-19 patients with severe disease, with encephalitis predisposing to poor outcomes and a higher risk of mortality (Altmayer et al, 2022; Chakraborty and Basu, 2022; Islam et al, 2022; Ong et al, 2023; Siow et al, 2021). The mechanism(s) whereby brain pathology/immunopathology and/or neuropathology might manifest in COVID-19 patients remains debatable, with the systemic cytokine storm and/or direct brain infection likely involved (Andrews et al, 2022; Aschman et al, 2022; Bauer et al, 2022a; Burks et al, 2021; Douaud et al, 2022; Fernandez-Castaneda et al, 2022; Rutkai et al, 2022; Samudyata et al, 2022; Silva et al, 2023; Zhang et al, 2020).…”