Different clinical characteristics and outcomes of adult hospitalized SARS-CoV-2 pneumonia patients complicated by cardiovascular events during the first, delta and omicron waves of COVID-19.

Background: The effects of SARS-CoV-2 have varied between significant waves of hospitalization. Research question: Are cardiovascular complications different among the first, delta and omicron waves of hospitalized COVID-19 pneumonia patients? Study design and methods: This was a multi-centre retrospective study of patients hospitalized with SARS-CoV-2 pneumonia: 632 were hospitalized during the first wave (March-July 2020), 1013 during the delta wave (September 2020-March 2021), and 323 during the omicron wave (January 2022-July 2022). Patients were stratified by wave and occurrence of cardiovascular events. Results: Among all hospitalized patients with cardiovascular events, patients in the omicron wave were younger (62.4 ± 14 years) than patients in the first wave (67.4 ± 7.8 years) and the delta wave (66.9 ± 12.6 years) and had a higher proportion of non-Hispanic White people than in the first wave (78.6% vs. 61.7%). For COVID-19 patients who suffered from cardiovascular events, the omicron wave patients had significantly higher neutrophil/lymphocyte ratio, white blood cell and platelet counts when compared to the first wave. Omicron wave patients had significantly lower albumin and B-type natriuretic peptide levels (only 5.8% of the first wave and 14.6% of the delta wave) when compared to either the first wave or delta wave patients. In COVID-19 patients who suffered cardiovascular events during hospitalization, mortality rate in the omicron wave (26.8%) was significantly lower than the first wave (48.3%), time to mortality for non-survivors of COVID-19 patients who suffered cardiovascular events was significantly longer in the omicron wave (median 16 days) than in the first wave (median 10 days). Conclusions: Younger and white patients were affected with cardiovascular complications more often by the omicron variant. Despite higher neutrophil/lymphocyte ratio and WBC counts, the omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves.

Differences in regional and subcellular localization of G(q/11) and RGS4 protein levels in Alzheimer's disease: correlation with muscarinic M1 receptor binding parameters.

Deficits in M1 muscarinic receptor system signaling in Alzheimer's disease (AD) prompted an analysis of components of these systems, namely, the G(q/11) protein and the regulator of G-protein signaling (RGS) 4 protein. In AD parietal cortex, total levels of G(q/11) and RGS4 proteins were significantly lower than age-matched control cases by 40% and 53%, respectively. However, the levels of membrane-bound G(q/11) and RGS4 protein in AD parietal cortex were maintained at levels comparable to controls. Furthermore, in the frontal cortex and cerebellum both the total and membrane levels of G(q/11) and RGS4 protein were not altered in AD cases compared to control cases. To our knowledge, this is the first report to examine RGS proteins in AD. Using receptor binding assays on the parietal cortex membrane fractions from AD cases, we found the muscarinic agonist carbachol still bound to high- and low-affinity sites (two-site fit) and the potency of 5-guanylylimidodiphosphate (GppNHp) to shift receptors from the high- to low-affinity state (based on the ternary complex model) was greater in AD cases compared to controls. In contrast, we previously reported a lack of high-affinity agonist binding sites in the frontal cortex in AD cases even in the absence of GppNHp. The data suggest that the equilibrium dynamics between the cytosolic and membrane levels of G(q/11) and RGS4 may contribute to the regional differences in the coupling of muscarinic M1 receptors in AD and have implications for the variability in effects of cholingeric treatment strategies currently in place.