SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence.

A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals. Methods: A longitudinal cohort of healthcare workers (HCW, N = 46; 30.4% men; 69.6% women; mean age 36.05 ± 2.2 years) with no SARS-CoV-2 infection as documented by negative polymerase chain reaction was immunophenotyped in PBMC once a week for 4 weeks from the prime immunization (Pfizer mRNA BNT162b2) and had received 2 doses, to study the kinetic response. Results: We identified three risk groups to develop SARS-CoV-2 infection IgG+-based (late responders, R-; early responders, R+; pauci responders, PR). In all receipts, amplification of B cells and NK cells, including IL4-producing B cells and IL4-producing CD8+ T cells, is early stimulated by the vaccine. After the boost, we observed a growing increase of NK cells but a resistance of T cells, IFNγ-producing CD4+T cells, and IFNγ-producing NK cells. Also, hematologic parameters decline until the boost. The positive association of IFNγ-producing NK with IFNγ-producing CD4+T cells by the multiple mixed-effect model, adjusted for confounders (p = 0.036) as well as the correlation matrix (r = 0.6, p < 0.01), suggests a relationship between these two subsets of lymphocytes. Conclusions: These findings introduce several concerns about policy delay in vaccination: based on immunological protection, B cells and the persistent increase of NK cells during 2 doses of the mRNA-based vaccine could provide further immune protection against the virus, while CD8+ T cells increased slightly only in the R+ and PR groups.

Occupational Exposure in the Lombardy Region (Italy) to SARS-CoV-2 Infection: Results from the MUSTANG-OCCUPATION-COVID-19 Study.

Sero-epidemiological surveys are valuable attempts to estimate the circulation of SARS-CoV-2 in general or selected populations. Within this context, a prospective observational study was conducted to estimate the prevalence and persistence of SARS-CoV-2 antibodies in different categories of workers and factors associated with positivity, through the detection of virus-specific immunoglobulin G and M (IgG/IgM) in serum samples. Enrollees were divided in low exposure and medium-high groups on the basis of their work activity. Antibody responders were re-contacted after 3 months for the follow-up. Of 2255 sampled workers, 4.8% tested positive for SARS-CoV-2 IgG/IgM antibodies, with 81.7% to IgG only. Workers who continued to go to their place of work, were healthcare workers, or experienced at least one COVID-19-related symptom were more likely to test positive for SARS-CoV-2 antibodies. SARS-CoV-2 antibodies prevalence was significantly higher in the medium-high risk vs. low-risk group (7.2% vs. 3.0%, p < 0.0001). At 3-month follow-up, 81.3% of subjects still had antibody response. This study provided important information of SARS-CoV-2 infection prevalence among workers in northern Italy, where the impact of COVID-19 was particularly intense. The presented surveillance data give a contribution to refine current estimates of the disease burden expected from the SARS-CoV-2.

AnatoMy and physIopathoLogy of the heArt in a ceNtenarian cOhort (MILANO study).

Background: Centenarians are increasingly being encountered in clinical practice. The aim of the study was to characterize centenarians' clinical features and cardiovascular system. Methods: A prospective, observational, cross-sectional, case-control study included 118 hospitalized >100-year-old patients compared to 50 octogenarians, selected in Milan (Italy) from December 2010 to December 2017, to assess their clinical and echocardiographic characteristics. Results: Centenarians were mostly women with small body surface area; long history of hypertension; chronic renal failure; and low incidence of smoking, diabetes, dyslipidemia, hyperuricemia, coronary artery disease, atrial fibrillation, and cerebrovascular disease. They showed high prevalence of severe cognitive impairment and disability. Almost half of patients (46%) were hospitalized for congestive heart failure (HF), mostly diastolic (80% of cases). Centenarians' hearts had reduced left ventricular end-diastolic dimensions (25.3 ± 3.8 mm/m^2), increased septal thickness (13.3 ± 1.9 mm), and higher relative wall thickness (0.58 ± 0.1). The ejection fraction was usually normal and rarely depressed (57.1% ± 11.7%), whereas the E/e' ratio was considerably increased (17.0 ± 6.0). Noninvasive evaluation of ventricular-arterial coupling parameters revealed significantly higher values of LV end-diastolic elastance in all centenarians versus octogenarians (0.4 ± 01 mm Hg/mL/m^2 vs 0.18 ± 0.2 mm Hg/mL/m^2, P < .0001) and in centenarians with HF versus those without HF (0.5 ± 0.1 mm Hg/mL/m^2 vs 0.34 ± 0.1 mm Hg/mL/m^2, P < .0001). Conclusions: The centenarians' cardiovascular system manifested a significant increase in LV diastolic stiffness with consequent susceptibility to diastolic HF. A progressive afterload increase and a passive load independent mechanism could have contributed to such changes.

Ventricular-arterial coupling in centenarians without cardiovascular diseases.

BACKGROUND: Ventricular-arterial (VA) coupling is a central determinant of cardiovascular system performance and cardiac energetics. This index is expressed by the Ea/Ees ratio, where the effective arterial elastance (Ea) indicates the net arterial load exerted on the left ventricle and the left ventricular end-systolic elastance (Ees) is a load-independent measure of left ventricular chamber performance. METHODS: Thirty-three centenarians (100.6 ± 1.2 years, range 99-105 years, 10 M) without cardiovascular diseases underwent a complete echocardiographic evaluation and an instantaneous arterial blood pressure measurement, to characterize the Ea/Ees ratio and its two determinants indexed to body surface area. RESULTS: VA coupling was markedly reduced (Ea/Ees ratio 0.40 ± 0.1), reflecting a disproportionate increase in Ees index (8.5 ± 2.2 mmHg/ml/m2) compared with Ea index (3.2 ± 0.8 mmHg/ml/m2). Notably, the coupling ratio was significantly lower in women (0.37 ± 0.1) than in men (0.45 ± 0.1, p = 0.0003), due to an increase in Ees index significantly greater in women (9.4 ± 1.9 mmHg/ml/m2) than in men (6.5 ± 1.5 mmHg/ml/m2, p = 0.0002). Using multivariate regression analysis, only female gender (ß coefficient -0.04, p = 0.01) and relative wall thickness (ß coefficient -0.49, p < 0.0001) showed a significant inverse correlation to VA coupling. CONCLUSIONS: Our analysis in a population of centenarians without overt cardiovascular disease revealed very low values of VA coupling, especially in women. Both a LV structural remodeling as well as a high aortic elastance might have contributed to a secondary disproportionate increase in myocardial stiffness.

Exercise stress echocardiography with tissue Doppler imaging in risk stratification of mild to moderate aortic stenosis.

BACKGROUND: Patients with mild to moderate aortic stenosis (AS) seem to have a worse outcome than commonly expected. Early identification of subjects who may develop a rapid disease progression or cardiovascular events is critical in order to apply adequate risk management. STUDY DESIGN: Observational prospective single-centre study. OBJECTIVE: To determine the prognostic role of exercise stress echocardiography (ESE) in patients with mild and moderate asymptomatic AS. PATIENTS: Ninety consecutive patients (mean age 74 ± 12 years) with isolated mild and moderate AS were enrolled into the study protocol over a 20 months period. Follow-up time was 12 months. METHODS: A complete echocardiographic study with tissue Doppler imaging (TDI) was performed at baseline and during semi-supine symptom-limited exercise test to evaluate: (1) the occurrence of symptoms, (2) ST segment changes, (3) transaortic pressure gradient, (4) the E/A ratio, (5) the E/e' ratio and (6) the systolic pulmonary artery pressure. MAIN OUTCOME MEASURES: During the 1 year follow-up time, we evaluated the occurrence of adverse cardiac events, defined as any of the following: (1) cardio-vascular hospitalization; (2) requirement for aortic valve replacement; (3) cardiac death. RESULTS: During follow-up, three patients died, 11 underwent aortic valve replacement and 26 had cardiovascular hospitalizations. On univariate analysis, patients who exhibited symptoms during exercise (HR 2.93, p = 0.003); the occurrence of a ≥ 2 mm exercise-induced ST segment depression (HR 3.12, p = 0.001); a ≥ 15 mmHg increase in mean transaortic pressure gradient during exercise (HR 2.77, p = 0.001); a ≥ 50 mmHg exercise-induced increase in systolic pulmonary artery pressure (HR 2.90, p = 0.009); an exercise-induced pseudo-normalization of the E/A ratio (E/A ≥ 1) (HR 7.50, p = 0.0001) and, particularly, a ≥ 15 exercise-induced increase in the E/e' ratio (HR 7.69, p = 0.0001) had a significantly higher risk of cardiac events during the follow-up time. On multivariate analysis, only the latter covariate (HR 6.04, p = 0.009) was independently associated with adverse cardiac events. CONCLUSIONS: A ≥ 15 stress-induced increase in E/e' ratio is highly predictive of cardiac events in patients with mild to moderate AS. Assessment of diastolic function using TDI during ESE provides additional prognostic information in such patients.