Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events.

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.

Evaluation of SARS-CoV-2 antibody levels on hospital admission as a correlate of protection against mortality.

BACKGROUND: Millions of people have now been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is still unclear which antibody levels provide protection against mortality. It is further unknown whether measuring antibody concentrations on hospital admission allows for identifying patients with a high risk of mortality. OBJECTIVES: To evaluate whether anti-SARS-CoV2-spike antibodies on hospital admission predict in-hospital mortality in patients with coronavirus disease 2019. METHODS: We conducted a prospective, multicentre cohort study on 1152 hospitalized patients who tested positive for SARS-CoV-2 with a polymerase chain reaction-based assay. Patients were classified by vaccination status. Anti-SARS-CoV-2 spike antibodies were determined on hospital admission. The investigated end point was in-hospital mortality for any cause. RESULTS: Spike antibodies on hospital admission were significantly lower in non-survivors in both non-vaccinated (73 U/ml, 95%CI 0-164 vs. 175 U/ml, 95%CI 124-235, p = 0.002) and vaccinated patients (1056 U/ml, 95%CI 701-1411 vs. 1668 U/ml, 95%CI 1580-1757, p < 0.001). Further, spike antibodies were significantly lower in fully vaccinated and boostered patients who died compared to those who survived (mean 883 U/ml, 95%CI 406-1359 vs. 1292 U/ml, 95%CI 1152-1431, p = 0.017 and 1485 U/ml, 95%CI 836-2133 vs. 2050 U/ml, 95%CI 1952-2149, p = 0.036). Patients infected with the currently prevailing Omicron variant were three times more likely to die if spike antibodies were <1200 U/ml (OR 3.458, 95%CI 1.562-7.656, p = 0.001). After adjusting for potential confounders, this value increased to an aOR of 4.079 (95%CI 1.809-9.198, p < 0.001). CONCLUSION: Anti-SARS-CoV2 spike-antibody levels on hospital admission are inversely associated with in-hospital mortality. Hospitalized patients with lower antibody levels have a higher risk of mortality.

Idiopathic Multicentric Castleman Disease Occurring Shortly after mRNA SARS-CoV-2 Vaccine.

Idiopathic Multicentric Castleman Disease (iMCD) is a potentially life-threatening systemic disease whose complex symptomatology is due to cytokine dysregulation. We, herein, present a case of severe iMCD occurring in a previously healthy young man shortly after mRNA SARS-CoV-2 vaccination, responding to interleukin-6 blockade with siltuximab. Six months after the completion of siltuximab, the patient remained without any signs of iMCD or inflammation, indicating a temporal trigger of the disease. This case not only adds to the potential pathogenetic spectrum of MCD, but also extends the clinical picture of potential but rare adverse events following COVID-19 immunization.

SARS-CoV-2 RBD-specific and NP-specific antibody response of healthcare workers in the westernmost Austrian state Vorarlberg: a prospective cohort study.

OBJECTIVES: Austria, and particularly its westernmost federal state Vorarlberg, developed an extremely high incidence rate during the COVID-19 pandemic. Healthcare workers (HCWs) worldwide are known to have an increased risk of contracting the disease within the working environment and, therefore, the seroprevalence in this population is of particular interest. We thus aimed to analyse SARS-CoV-2-specific antibody dynamics in Vorarlberg HCWs. DESIGN: Prospective cohort study of HCWs including testing at three different time points for the prevalence of anti-SARS-CoV-2 IgG antibodies specific for nucleocapsid protein (NP) and receptor-binding domain (RBD). SETTING: All five state hospitals of Vorarlberg. PARTICIPANTS: A total of 395 HCWs, enrolled in June 2020 (time point 1 (t1)), 2 months after the end of the first wave, retested between October and November at the beginning of the second wave (time point 2 (t2)) and again at the downturn of the second wave in January 2021 (time point 3 (t3)). MAIN OUTCOMES: We assessed weak and strong seropositivity and associated factors, including demographic and clinical characteristics, symptoms consistent with COVID-19 infection, infections verified by reverse transcription PCR (RT-PCR) and vaccinations. RESULTS: At t1, 3% of HCWs showed strong IgG-specific responses to either NP or RBD. At t2, the rate had increased to 4%, and at t3 to 14%. A strong response was found to be stable for up to 10 months. Overall, only 55% of seropositive specimen had antibodies against both antigens RBD and NP; 29% had only RBD-specific and 16% only NP-specific antibodies. Compared with the number of infections found by RT-PCR, the number of HCWs being seropositive was 38% higher. CONCLUSION AND RELEVANCE: Serological testing based on only one antigen implicates the risk of missing infections; thus, the set of antigens should be broadened in the future. The seroprevalence among participating HCWs was comparable to the general population in Austria. Nevertheless, in view of undetected infections, monitoring and surveillance should be reconsidered.