Immune recall improves antibody durability and breadth to SARS-CoV-2 variants.

Key features of immune memory are greater and faster antigen-specific antibody responses to repeat infection. In the setting of immune-evading viral evolution, it is important to understand how far antibody memory recognition stretches across viral variants when memory cells are recalled to action by repeat invasions. It is also important to understand how immune recall influences longevity of secreted antibody responses. We analyzed SARS-CoV-2 variant recognition; dynamics of memory B cells; and secreted antibody over time after infection, vaccination, and boosting. We find that a two-dose SARS-CoV-2 vaccination regimen given after natural infection generated greater longitudinal antibody stability and induced maximal antibody magnitudes with enhanced breadth across Beta, Gamma, Delta and Omicron variants. A homologous third messenger RNA vaccine dose in COVID-naïve individuals conferred greater cross-variant evenness of neutralization potency with stability that was equal to the hybrid immunity conferred by infection plus vaccination. Within unvaccinated individuals who recovered from COVID, enhanced antibody stability over time was observed within a subgroup of individuals who recovered more quickly from COVID and harbored significantly more memory B cells cross-reactive to endemic coronaviruses early after infection. These cross-reactive clones map to the conserved S2 region of SARS-CoV-2 spike with higher somatic hypermutation levels and greater target affinity. We conclude that SARS-CoV-2 antigen challenge histories in humans influence not only the speed and magnitude of antibody responses but also functional cross-variant antibody repertoire composition and longevity.

Ghrelin and ghrelin/total cholesterol ratio as independent predictors for coronary artery disease: a systematic review and meta-analysis.

The present meta-analysis aimed to summarize the available data regarding the circulating levels of ghrelin in patients with cardiovascular diseases (CVDs). A comprehensive search was performed in electronic databases including PubMed, Scopus, EMBASE, and Web of Science up to January 20, 2021. Since the circulating levels of ghrelin were measured in different units across the included studies, they were expressed as the standardized mean difference (SMD) and 95% CI (summary effect size). A random-effects model comprising the DerSimonian and Laird method was used to pool SMDs. Sixteen articles (20 studies) comprised of 1087 cases and 437 controls were included. The pooled results showed that there were no significant differences between cases and controls in terms of ghrelin levels (SMD=-0.61, 95% CI -1.38 to 0.16; p=0.120; I2=96.9%, p<0.001). The ghrelin concentrations in the CAD stratum were significantly lower than in controls, whereas they increased in other disease strata. New combined biomarkers demonstrated a significant decrease in the SMD of the ghrelin/total cholesterol (TC) ratio (-1.02; 95% CI -1.74 to -0.29, p=0.000; I2=94.5%). However, no significant differences were found in the SMD of the ghrelin/high-density lipoprotein cholesterol ratio, ghrelin/low-density lipoprotein cholesterol ratio, and ghrelin/triglyceride (TG) ratio in cases with CVDs compared with the control group. Ghrelin was associated with CAD; therefore, it may be considered a biomarker for distinguishing between patients with and without CAD. Furthermore, the ghrelin/TC ratio could be proposed as a diagnostic marker for CVD.

Association of renin-angiotensin-aldosterone system gene polymorphisms with left ventricular hypertrophy in patients with heart failure with preserved ejection fraction: A case-control study.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has close ties with hypertension, though risk factors to the development of HFpEF in hypertensive patients are not fully understood. Left ventricular hypertrophy (LVH) signifies the susceptibility toward diastolic heart dysfunction, and genetic determinants of LVH as a result may serve as risk predictors for HFpEF in hypertension. We investigated the role of three renin-angiotensin-aldosterone system (RAAS) gene polymorphisms in the development of LVH in hypertensive patients with a diagnosis of HFpEF. METHODS: A total of 176 hypertensive patients with a diagnosis of HFpEF were divided to cases with LVH and controls without. rs4343 and rs4291 of angiotensin-converting enzyme (ACE) and rs5186 of angiotensin receptor type 1 were genotyped using PCR-RFLP method. RESULTS: Genotypes and allele frequencies were significantly different between the case and control groups for rs4343 and rs4291, whereas no difference was observed for rs5186. CONCLUSION: Increased ACE activity explains the significant association of rs4343 and rs4291 polymorphisms with LVH in the carriers. Furthermore, findings support the pathophysiologic links between RAAS and increased LV mass in hypertension and suggest a genetic susceptibility to HFpEF. Such polymorphisms may serve as risk predictors of HFpEF in hypertensive patients.

Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study.

OBJECTIVES: To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. DESIGN: Case control study. SETTING: An Iranian referral university hospital. PARTICIPANTS: 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. RESULTS: The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. CONCLUSIONS: In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease.