Alteration of type I interferon response is associated with subclinical atherosclerosis in virologically suppressed HIV‐1‐infected male patients

Abstract

Given human immunodeficiency virus‐1 (HIV‐1)‐infected patients have alterations in the type I interferon (IFN‐I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN‐I response and subclinical cardiovascular disease (CVD) association in HIV‐1‐infected patients. Transcript levels of IFN‐α/β and IFN‐stimulated gene 56 (ISG56) were evaluated by RT/real‐time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV‐1‐positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or <50%), calcium volume score, calcium Agatston score, and myocardial extracellular volume were examined by coronary computerized tomography scan. Carotid intima‐media thickness (cIMT), Framingham risk score, atherosclerotic cardiovascular disease (ASCVD) score, and risk score developed by data collection on adverse effects of anti‐HIV drugs (D:A:D) were also measured. Increased IFN‐α, IFN‐β, and ISG56 levels were observed in all HIV‐1‐infected males compared to healthy controls (p < .001 for all genes analyzed). HIV‐1‐infected patients with a stenosis degree ≥50% showed a higher Framingham risk score (p = .019), which was correlated with IFN‐β and ISG56 levels. HIV‐1‐infected males with enhanced IFN‐I levels and stenosis displayed a higher ASCVD calculated risk (p = .011) and D:A:D score (p = .004). Also, there was a trend toward higher IFN‐α and ISG56 mRNA levels in HIV‐1‐positive patients with an increased cIMT (p > .05). Dysregulation of IFN‐I response might participate in the pathogenesis of HIV‐1‐associated CVD.

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission

“…2 , Panel D). Patients with COVID-19 received broad-spectrum antibiotics more frequently than patients with FLU (92.7% vs 63.1%, p = 0.0048); in detail, teicoplanin and piperacillin/tazobactam were commonly used in COVID-19 critically ill patients (81.8% vs 0% and 67.2% vs 17%, p < 0.0001 and p = 0.003, respectively) due to a predefined protocol [ 31 – 33 ]. Patients with COVID-19 and FLU had the same length of hospitalization in the ICU [21 (12–37) vs 23 (17.5–36.5) days, p = 0.672, respectively].…”

Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity

“…The mRNAs levels of IFN‐I‐related genes were measured in PBMC and respiratory samples by quantitative RT/real time PCR assay as previously reported [ 39 , 40 ]. The following primers and probes targeting IFN‐I genes were purchased from Integrated DNA Technologies (Coralville, IA, USA): IFN‐α2 (Hs.PT.58.24294810.g), IFN‐β1 (Hs.PT.58.39481063.g), IFNW1 (Hs.PT.5820160308.g).…”

“…The following primers and probes targeting IFN‐I genes were purchased from Integrated DNA Technologies (Coralville, IA, USA): IFN‐α2 (Hs.PT.58.24294810.g), IFN‐β1 (Hs.PT.58.39481063.g), IFNW1 (Hs.PT.5820160308.g). Primers and probes sequences for ISG15 and ISG56 were previously reported [ 39 , 40 ]. The housekeeping gene β‐glucuronidase was used as an internal control to normalize the amount of total RNA of target genes.…”

The immune response as a double‐edged sword: The lesson learnt during the COVID‐19 pandemic

“…Accordingly, several studies showed that patients with mild to moderate COVID‐19 show an effective type‐I IFN response both in the lung and in the peripheral blood. In contrast, patients with severe/critical COVID‐19 manifestations showed a suppressed expression of IFNs and a parallel increase in tissue and systemic inflammation [ 16 , 17 ].…”