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ABSTRACT: Background: Cardiovascular magnetic resonance (CMR) cine imaging is still limited by long acquisition times. This study evaluated the clinical utility of an accelerated two-dimensional (2D) cine sequence with deep learning reconstruction (Sonic DL) to decrease acquisition time without compromising quantitative volumetry or image quality. Methods: A sub-study using 16 participants was performed using Sonic DL at two different acceleration factors (8× and 12×). Quantitative left-ventricular volumetry, function, and mass measurements were compared between the two acceleration factors against a standard cine method. Following this sub-study, 108 participants were prospectively recruited and imaged using a standard cine method and the Sonic DL method with the acceleration factor that more closely matched the reference method. Two experienced clinical readers rated images based on their diagnostic utility and performed all image contouring. Quantitative contrast difference and endocardial border sharpness were also assessed. Left- and right-ventricular volumetry, left-ventricular mass, and myocardial strain measurements were compared between cine methods using Bland-Altman plots, Pearson’s correlation, and paired t-tests. Comparative analysis of image quality was measured using Wilcoxon-signed-rank tests and visualized using bar graphs. Results: Sonic DL at an acceleration factor of 8 more closely matched the reference cine method. There were no significant differences found across left ventricular volumetry, function, or mass measurements. In contrast, an acceleration factor of 12 resulted in a 6% (5.51/90.16) reduction of measured ejection fraction when compared to the standard cine method and a 4% (4.32/88.98) reduction of measured ejection fraction when compared to Sonic DL at an acceleration factor of 8. Thus, Sonic DL at an acceleration factor of 8 was chosen for downstream analysis. In the larger cohort, this accelerated cine sequence was successfully performed in all participants and significantly reduced the acquisition time of cine images compared to the standard 2D method (reduction of 37% (5.98/16) p 0.05). Left- and right-ventricular volumetry and circumferential and radial strain were also similar between methods (p > 0.05) but left-ventricular mass and longitudinal strain were over-estimated using the proposed accelerated cine method (mass over-estimated by 3.36 g/m2, p

SARS-CoV-2 vaccines and infection induce antibody responses but the evolution of subsequent variants has resulted in the development of escape mutants. Here the authors characterise, at single cell level, the antibody response in donors after a third dose of SARS-CoV-2 mRNA vaccination and show difference in breadth, neutralisation and molecular signature according to the vaccination regimen used.

Antibodies elicited by a triple homologous or heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1.

IntroductionIn early to mid-2022, an unexpected outbreak of Monkeypox virus infections occurred outside the African endemic regions. Vaccines originally developed in the past to protect against smallpox are one of the available countermeasures to prevent and protect against Orthopoxvirus infections. To date, there are few studies on the cross-reactivity of neutralizing antibodies elicited by previous vaccinia virus-based vaccination and/or Monkeypox virus infection. The aim of this study was to evaluate a possible approach to performing Monkeypox and vaccinia live-virus microneutralization assays in which the read-out is based on the production of cytopathic effect in the cell monolayer.MethodsGiven the complexity of Orthopoxviruses, the microneutralization assay was performed in such a way as to uncover a potential role of complement, with and without the addition of an external source of Baby Rabbit Complement. A set of human serum samples from individuals who had been naturally infected with Monkeypox virus and individuals who may have and not have undergone vaccinia virus vaccinations, was used to evaluate the performance, sensitivity, and specificity of the assay.Results and conclusionsThe results of the present study confirm the presence and cross-reactivity of antibodies elicited by vaccinia-based vaccines, which proved able to neutralize the Monkeypox virus in the presence of an external source of complement.

Here, Andreano and Paciello et al. show, at single cell level, the functional and genetic characteristics underlying the Omicron BA.1 and BA.2 cross-protective antibody response in naïve and previously infected COVID-19 vaccinees.

Monoclonal antibodies (mAbs) are a potential therapeutic option for treatment of COVID-19. Here, the authors report safety and pharmacokinetics of an intramuscularly injected mAb (MAD0004J08) during the first 30 days of a phase 1 clinical study.

The SARS-CoV-2 pandemic has posed a challenge for correctional facilities worldwide. People in such settings are more vulnerable to severe forms of infection and it is impossible to completely isolate inmates from the outside world. This study aimed to assess the antibody-mediated immune response in terms of neutralizing antibodies against Alpha, Beta, Gamma and Omicron (sub-lineage BA.1) variants of concern after two doses of mRNA vaccine in correctional officers and inmates from an Italian correctional facility. Most of the correctional officers (56.5%) and inmates (52.3% and 63.6%) retained their neutralizing activity toward the Alpha and Gamma variants, respectively. By contrast, the most striking reduction in comparison with the ancestral virus was found in the antibody response toward the Beta and Omicron variants, in both correctional officers (91.2% and 93.9%) and inmates (85.1% and 92.8%). In addition, subjects who had undergone primary vaccination and had previously been naturally infected had higher neutralizing antibody titers toward the 4 variants than negative subjects. Overall, our findings indicate that primary mRNA vaccination is able to induce neutralizing antibodies toward the ancestral virus, while titers toward variants may vary, depending on the mutations harboring by the variants. Although the correctional setting is often considered distinct or isolated from the wider society and sanitary system, the health of correctional workers and prisoners is inexorably linked to the public health of the country as a whole and it is of paramount importance to monitor the antibody response in these settings.

The rapid replacement of Omicron BA.1 by BA.2 sublineage is very alarming, raising the question of whether BA.2 can escape the immunity acquired after BA.1 infection. We compared the neutralizing activity toward the Omicron BA.1 and BA.2 sub-lineages in five groups: COVID-19 patients; subjects who had received two doses of mRNA vaccine; subjects naturally infected with SARS-CoV-2 who had received two doses of mRNA; and subjects who had received three doses of homologous or heterologous vaccine. The results obtained highlight the importance of vaccine boosters in eliciting neutralizing antibody responses against Omicron sub-lineages, and suggest that the adenovirus vectored vaccine elicits a lower response against BA.1 than against BA.2 sub-lineage.

Background. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods. Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results. In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions. Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.