PET Imaging of Innate Immune Activation Using 11C Radiotracers Targeting GPR84.

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11Svia carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713-an existing radiotracer used to image innate immune activation in clinical research studies-11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology.

Atrial Fibrillation and Cardiovascular Risk Assessment among COVID-19 Patients Using Different Scores.

Since the advent of severe acute respiratory syndrome-coronavirus-2 in December 2019, millions of people have been infected and succumbed to death because of this deadly virus. Cardiovascular complications such as thromboembolism and arrhythmia are predominant causes of morbidity and mortality. Different scores previously used for atrial fibrillation (AF) identification or prediction of its complications were investigated by physicians to understand whether those scores can predict in-hospital mortality or AF among patients infected with the severe acute respiratory syndromecoronavirus-2 virus. Using such scores gives hope for early prediction of atrial arrhythmia and in-hospital mortality among coronavirus disease 2019-infected patients. We have discussed the mechanisms of AF and cardiovascular damage in coronavirus disease 2019 patients, different methods of AF prediction, and compared different scores for prediction of in-hospital mortality after this viral infection.

Exacerbation of Pre-existing Neurological Symptoms With COVID-19 in Patients With Chronic Neurological Diseases: An Updated Systematic Review.

The neurotropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can potentially explain the worsening of symptoms in patients with a history of neurological conditions such as stroke, Parkinson's disease, Alzheimer's, and epilepsy. Several studies have reported that these pre-existing conditions may worsen with a higher frequency of flare-ups, thus resulting in a more significant risk of patient mortality. In this review, we sought to provide an overview of the relationship between pre-existing neurological disorders and COVID-19, focusing on whether the initial infection directly influenced the severity of symptoms. We systematically searched the electronic database PubMed (MEDLINE) and used specific keywords related to our aims from January 2020 to July 2022. All articles published on COVID-19 with keywords pertaining to pre-existing neurological diseases were retrieved and subsequently analyzed. After independent review, the data from 107 articles were selected and evaluated. After analyzing the data from selected articles reviewing the effect of COVID-19 on neurological conditions, we have documented the relationship between said pre-existing neurological diseases, showing an increased risk of hospitalization, admission length, worsening of symptoms, and even mortality in COVID-19 patients.