ABSTRACT
Purpose: While SARS-CoV-2 vaccination has dramatically reduced COVID-19 severity in the general population, fully vaccinated solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates. Furthermore, a third vaccine dose only increases antibody and T cell responses in a proportion of SOTRs. We sought to investigate the underlying mechanisms resulting in varied humoral responses in SOTRs. Method(s): Within a longitudinal prospective cohort of SOTRs, anti-spike IgG, total and spike-specific B cells were evaluated in 44 SOTR participants before and after a third vaccine dose using high dimensional flow cytometry to assess immunologic and metabolic phenotypes. B cell phenotypes were compared to those of 10 healthy controls who received a standard two-dose mRNA series. Result(s): Notably, even in the absence anti-spike antibody after two doses, spikespecific B cells were detectable in most SOTRs (76%). While 15% of participants were seropositive before the third dose, 72% were seropositive afterward. B cells, however, were differentially skewed towards non-class switched B cells in SOTRs as compared to healthy control B cells. Expansion of spike-specific class-switched B cells in SOTRs following a third vaccine dose correlated with increased classswitched (IgG) antibody titers. Antibody response to a third vaccine dose was associated with expanded populations of germinal center-like (CD10+CD27+) B cells, as well as CD11c+ alternative lineage B cells with specific upregulation of CPT1a, the rate limiting enzyme of fatty acid oxidation and a preferred energy source of germinal center B cells. Conclusion(s): This analysis defines a distinct B cell phenotype in SOTRs who respond to a third SARS-CoV-2 vaccine dose, specifically identifying fatty acid oxidation as pathway that could be targeted to improve vaccine response such as through targeted immunosuppressive modulation. (Figure Presented).
ABSTRACT
Background The COVID pandemic has been a major disruptor of preventive health programs. We set out to establish the burden and control rates of hypertension(HTN) at the dawn of this pandemic, providing baseline reference measures for which the impact of the pandemic on HTN prevalence and control rates can be assessed in future. Methods HTN was classified as mean systolic blood pressure (mSBP) ≥130 mmHg or mean diastolic blood pressure (mDBP) ≥80 mmHg or self-reported current use of antihypertensive medications. Hypertensives on medications with mSBP <130 mmHg and mDBP <80 mmHg were considered as well-controlled. Chi-square test was used in subgroup comparisons of HTN prevalence and p-values <0.05 were considered statistically significant. Results The age-adjusted pre-pandemic prevalence of HTN in the US was 52.3% (50.2-54.3). The prevalence was significantly higher in men: 54.7% (51.6-57.8), Non Hispanic Blacks: 64.8%(62.8-66.9), obese: 62.8%(60.8-64.8) and persons aged ≥ 60years: 77.1%(74.3-79.8). The control rate of HTN was 44.2% (42.0-46.5). There was a statistically significant difference in the rate of control across socioeconomic and racial groups. Conclusion About 52% of individuals ≥20 years in the USA were hypertensives and less than half of them on medications were well-controlled. Significant discrepancies exist in the burden and control rates in different subpopulation categories. Our study calls for more screening for HTN during and especially post COVID pandemic. [Formula presented]