Temporal changes in spike IgG levels after two doses of BNT162b2 vaccine in Japanese healthcare workers: Do spike IgG levels at 3 months predict levels 6 or 8 months after vaccination?

BACKGROUND: Accurate timing of BNT162b2 boosters to prevent breakthrough infections of coronavirus disease 2019 (COVID-19) requires reliable estimates of immune status. We hypothesized that spike IgG levels at 3 months after two doses of the BNT162b2 vaccine might predict subsequent spike IgG levels. METHODS AND RESULTS: Spike IgG levels were tested at 3, 6, and 8 months after the second dose of the BNT162b2 vaccine in 251 Japanese health care workers (median age: 39 years, female: 187). The median level of spike IgG was 2,882 AU/mL at 3 months. This decreased to 875 AU/mL at 6 months and 579 AU/mL at 8 months. There were good correlations of log-transformed spike IgG levels between 3 and 6 months (r = 0.86) and between 3 and 8 months (r = 0.82). The correlation further improved after excluding three subjects who had possible COVID-19 infections (r = 0.91, r = 0.86). Log-transformed spike IgG levels at 6 or 8 months yields the following equation: log spike IgG at 6 (8) months = 0.92 (0.86) X log spike IgG at 3 months- 0.23 (0.18). Predicted spike IgG at 6 months of ≥ 300 or < 300 AU/mL had 98% sensitivity, 47% specificity, and 94% accuracy for discriminating subjects whose actual spike IgG titers at 6 months were above or below 300 AU/mL. Corresponding values of predicted spike IgG at 8 months were 97%, 70%, and 93%, respectively. CONCLUSIONS: We conclude that predictive formulae using spike IgG levels at 3 months after two-dose vaccination with BNT162b2 reliably estimate subsequent spike IgG levels up to 8 months and provide useful information in terms of vaccination booster timing.

Brain natriuretic peptide measurements using standard biochemical equipment: Comparisons with conventional immunoassays.

BACKGROUND: Brain natriuretic peptide (BNP) is an essential cardiac biomarker for diagnosing heart failure and for prognoses in patients with various cardiac diseases. However, measurement requires immunological assays that are not available in every hospital. Recently, a novel BNP kit (Nanopia BNP-A, Sekisui Inc.; BNPn) that uses general-purpose, automated, biochemical analyzers has become commercially available. We assessed how its accuracy and utility compare with those of conventional immunological tests. METHODS AND RESULTS: We retrospectively collected 1491 conventional BNP measurements (BNPc), which had been clinically indicated for BNP testing and for which residual samples were still stored in the laboratory. We measured BNP using the novel kit and determined the correlation of BNP levels between the two methods. We also assessed the predictive value of both BNP measurements for major cardiac events (MACEs). The analytical performance of both measuring methods was similar. Log-transformed BNP measured by both methods showed strong correlation (r = 0.92); however, log-transformed BNPn was significantly higher than log-transformed BNPc (p<0.001). BNPc of 200 ng/L was used to stratify patients into two groups. According to the regression formula between the two methods, we determined a cut-off value of BNPn as 250 ng/L. During a median of 15 months of follow-up, 43 MACEs developed. Both BNPc and BNPn were associated with MACEs. Kaplan-Meier survival analysis indicated that both BNPc and BNPn cut-off values stratified the high-risk group for prognostication. The diagnostic and prognostic utilities were proven even if the lower cut-off values (BNPc = 100 ng/L, BNPn = 130 ng/L) were employed. CONCLUSIONS: A new BNP measurement using biochemical equipment provides prognostic value similar to that of conventional BNP analysis; thus, it should prove useful in hospitals in which conventional immunological examinations are not available.

Does reactogenicity after a second injection of the BNT162b2 vaccine predict spike IgG antibody levels in healthy Japanese subjects?

BACKGROUND: Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech's BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). METHODS AND RESULTS: Blood samples were obtained from 67 Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% confidence interval (95% CI): 855-1282 AU/mL) after the first injection to 17,378 AU/mL (95% CI: 14,622-20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, AE score after the first injection, and log-transformed spike IgG after the first injection. CONCLUSIONS: Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.

Impact of image quality on reliability of the measurements of left ventricular systolic function and global longitudinal strain in 2D echocardiography.

BACKGROUND: Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) play important roles in diagnosis and management of cardiac diseases. However, the issue of the accuracy and reliability of LVEF and GLS remains to be solved. Image quality is one of the most important factors affecting measurement variability. The aim of this study was to investigate whether improved image quality could reduce observer variability. METHODS: Two sets of three apical images were acquired using relatively old- and new-generation ultrasound imaging systems (Vivid 7 and Vivid E95) in 308 subjects. Image quality was assessed by endocardial border delineation index (EBDI) using a 3-point scoring system. Three observers measured the LVEF and GLS, and these values and inter-observer variability were investigated. RESULTS: Image quality was significantly better with Vivid E95 (EBDI: 26.8 ± 5.9) than that with Vivid 7 (22.8 ± 6.3, P < 0.0001). Regarding the inter-observer variability of LVEF, the r-value, bias, 95% limit of agreement and intra-class correlation coefficient for Vivid 7 were comparable to those for Vivid E95. The % variabilities were significantly lower for Vivid E95 (5.3-6.5%) than those for Vivid 7 (6.5-7.5%). Regarding GLS, all observer variability parameters were better for Vivid E95 than for Vivid 7. Improvements in image quality yielded benefits to both LVEF and GLS measurement reliability. Multivariate analysis showed that image quality was indeed an important factor of observer variability in the measurement of LVEF and GLS. CONCLUSIONS: The new-generation ultrasound imaging system offers improved image quality and reduces inter-observer variability in the measurement of LVEF and GLS.

Three-Dimensional Echocardiographic Assessment of Left Heart Chamber Size and Function with Fully Automated Quantification Software in Patients with Atrial Fibrillation.

BACKGROUND: Echocardiographic determination of left heart chamber volumetric parameters by using manual tracings during multiple beats is tedious in atrial fibrillation (AF). The aim of this study was to determine the usefulness of fully automated left chamber quantification software with single-beat three-dimensional transthoracic echocardiographic data sets in patients with AF. METHODS: Single-beat full-volume three-dimensional transthoracic echocardiographic data sets were prospectively acquired during consecutive multiple cardiac beats (≥10 beats) in 88 patients with AF. In protocol 1, left ventricular volumes, left ventricular ejection fraction, and maximal left atrial volume were validated using automated quantification against the manual tracing method in identical beats in 10 patients. In protocol 2, automated quantification-derived averaged values from multiple beats were compared with the corresponding values obtained from the indexed beat in all patients. RESULTS: Excellent correlations of left chamber parameters between automated quantification and the manual method were observed (r = 0.88-0.98) in protocol 1. The time required for the analysis with the automated quantification method (5 min) was significantly less compared with the manual method (27 min) (P < .0001). In protocol 2, there were excellent linear correlations between the averaged left chamber parameters and the corresponding values obtained from the indexed beat (r = 0.94-0.99), and test-retest variability of left chamber parameters was low (3.5%-4.8%). CONCLUSIONS: Three-dimensional transthoracic echocardiography with fully automated quantification software is a rapid and reliable way to measure averaged values of left heart chamber parameters during multiple consecutive beats. Thus, it is a potential new approach for left chamber quantification in patients with AF in daily routine practice.

Coronary Artery Imaging with Transthoracic Doppler Echocardiography.

Coronary artery imaging with transthoracic Doppler echocardiography is a simple and useful technique to diagnose significant coronary artery stenosis. The visualization of mosaic flow in the proximal left coronary artery provides a direct indication of the presence of significant stenosis at the corresponding site during routine echocardiography. Coronary flow velocity reserve (CFVR) has a high diagnostic accuracy and feasibility in detecting the presence of functionally significant coronary stenosis in the left anterior descending coronary artery (LAD) and in the right coronary artery. The measurement of CFVR in the LAD also provides prognostic information in patients with intermediate coronary stenosis. This review summarizes the utility of transthoracic coronary artery imaging.

Mitral stenosis reversed by medical treatment for heart failure.

It is reported that functional mitral stenosis frequently develops after ring annuloplasty for ischemic mitral regurgitation. The mechanism is a combination of annular size reduction by surgery and diastolic mitral valve tethering, restricting the anterior leaflet opening due to posteriorly displaced papillary muscles with left ventricular dilatation. We report the case of a 57-year-old man who had a history of successful mitral valve plasty for degenerative mitral regurgitation. Four years later he developed heart failure, severe hypertension, mild mitral regurgitation, and significant mitral stenosis, which were reversed by aggressive medical treatment for heart failure.