ABSTRACT
The degree of immunity provided by standard vaccine regimens, boosted regimens, and immune responses elicited by the combination of vaccination and natural infection remain unknown for the immunocompromised population. The relative magnitude, quality, and durability of serological responses, and the likelihood of neutralizing protection against future SARS-CoV-2 variants following these modes of exposure are unknown but are critical to the future trajectory of the COVID-19 pandemic. This study aims to directly compare the humoral and cellular immune responses among heart transplant recipients (HTxRs) who received COVID-19 vaccines before or after naturally acquired SARS-CoV-2 infection. HTxRs were enrolled prospectively in the study belonging to three groups: vaccine-only (1-/2-/3-/4- doses vaccinated individuals with no history of COVID-19 or breakthrough infection), hybrid immunity (1-/2-/3-/4- doses vaccination after recovery from natural SARS-CoV-2 infection) and breakthrough infection (2-/3-/4- doses vaccinated individuals with PCR confirmed breakthrough infections). Vaccination protocol includes homologous primary/boosted BNT162b2 vaccine. Serum samples, collected longitudinally immediately before and 3 weeks after each dose or SARS-CoV-2 infection, were tested for SARS-CoV-2 anti-RBD IgG antibodies and for neutralizing antibodies (using live virus micro-neutralization assays) against wild-type sublineage B.1.1.50, the B.1.617.2 (delta) variant and four omicron variants (BA.1, BA.2, BA.4 and BA.5). SARS-CoV-2-specific-T-cell response were evaluated in a subset of patients by IFN-γ release of stimulated peripheral blood mononuclear cells. 1) Neutralizing antibody titers against wild-type virus and the variants of concern after breakthrough infection, hybrid immunity, and vaccination alone;2) T-cell response after breakthrough infection, hybrid immunity, and vaccination alone;and 3) Quality of the neutralizing antibody response [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Heart transplant (HT) recipients are at high risk for poor immunity after COVID-19 vaccination. A multidose vaccine strategy is thus recommended, but the clinical outcomes and immune correlates of clinical protection against SARS-CoV-2 are unknown. In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine between March 2020 and May 2022, patients were prospectively assessed for vaccine-induced neutralizing antibodies (nAbs) against the wild-type virus and Delta and Omicron variants (using live virus micro-neutralization assays), and for T-cell response. Clinical outcomes included COVID-19 infection and kidney function. Comparative analyses with controls were conducted to identify correlates of infection. We characterized 67 (43.8%) COVID-19 infections. Repeat vaccination decreased the risk of contracting COVID-19 (HR 0.05, p=0.02;HR 0.02, p=0.01;HR 0.01, p=0.004;for 1-2-, 3- and 4- doses, respectively) and of severe-critical disease (HR 0.003, p<0.001). Vaccine prevention of infectivity was lower for the Omicron. Vaccine-induced nAbs against the Delta and Omicron variants were associated with a reduced risk for COVID-19 (HR 0.36, p=0.01;HR 0.21, p=0.01, respectively), whereas a vaccine-induced T-cell response was not (p=0.6). The optimal nAbs titer thresholds for the prediction of COVID-19 were 48 (wild-type), 24 (Delta), and 4 (Omicron). COVID-19 was associated with an increased risk of long-term renal dysfunction (OR 17.4, p<0.001), with the extent of deterioration correlating with the severity of acute COVID-19. A repeat vaccination strategy provides protection from severe infection with SARS-CoV-2 and to a lesser extent from mild infection. BNT162b2-vaccine-induced nAbs conferred clinical immunity. Our findings could assist in rationally focusing improvements for future vaccines and immunotherapeutic for SARS-CoV-2 and population-tailored vaccination strategy. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
In 2022, omicron (BA.1) and omicron subvariants (BA.2, BA.4, and BA.5), the most antigenically divergent variants to date, outcompeted previous variants in the context of substantial preexisting population immunity from vaccination, infection, or both. Omicron variants continue to cause substantial numbers of illnesses and deaths. Booster immunization with mRNA vaccines improves neutralizing antibody responses against variants and vaccine effectiveness in heart transplant recipients (HTxRx). Nonetheless, the vaccine effectiveness against omicron is lower than that against other variants. The bivalent vaccine contains two mRNA components of SARS-CoV-2 virus, one of the original strain of SARS-CoV-2 and the other one in common between the BA.4 and BA.5 lineages of the omicron variant. This study aims to evaluate the immunogenicity, safety and reactogenicity of omicron-containing bivalent Pfizer-BioNTech COVID-19 booster in HTxRx. HTxRx who had received a homologous 2-doses primary/1-2 booster doses BNT162b2 vaccination schedule or 2-/3-/4- doses vaccinated HTxRx with breakthrough infections are prospectively enrolled to receive the bivalent Pfizer-BioNTech COVID-19 booster. Safety assessments include solicited local and systemic adverse reactions within 7 days after bivalent booster administration. Serum samples, collected longitudinally immediately before and 3 weeks after the bivalent booster dose, are tested for SARS-CoV-2 anti-RBD IgG antibodies and for neutralizing antibodies (using live virus micro-neutralization assays) against wild-type (B.1.1.50), the delta variant (B.1.617.2) and four omicron variants (BA.1, BA.2, BA.4 and BA.5). SARS-CoV-2-specific-T-cell response are evaluated in a subset of patients by IFN-γ release of stimulated peripheral blood mononuclear cells. 1) Tolerability and reactogenicity;2) bivalent booster-induced anti-RBD IgG antibodies;3) bivalent booster-induced variant-specific neutralizing antibodies;3) SARS-CoV-2-specific-T-cell response, and 4) post-bivalent booster vaccine infection and hospitalization. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Background: A reduction in acute myocardial infarction (AMI) hospitalizations during the coronavirus pandemic has been previously documented. We aimed to describe the characteristics and in-hospital outcomes of AMI patients during the Covid-19 era compared to a recent previous registry. Methods: We conducted a prospective, multicenter, observational study involving 13 intensive cardiac care units (ICCUs) to evaluate consecutive AMI patients admitted throughout an 8-week period during the Covid-19 outbreak. Data were compared to the corresponding period in 2018 using an acute coronary syndrome survey conducted in all ICCUs in Israel. The primary end-point was defined as a composite of sustained ventricular arrhythmia, pulmonary congestion, and/or in-hospital mortality. Results: The study cohort comprised 1466 patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with ST-elevation MI (STEMI): 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. No differences were detected in the admission rate of patients between the two study periods. STEMI patients admitted during the Covid-19 period tended to have fewer co-morbidities, but a higher Killip class (p value = 0.03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122-292) in 2018 to 290 minutes (IQR 161-1080, p<0.001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint of heart failure, malignant arrhythmia, or death in the multivariable logistic regression model (OR 1.63, 95% CI 1.02-2.65, p value = 0.05). Conclusion: While the admission rate of AMI and STEMI in Israel remained similar during both the Covid-19 era and the corresponding period in 2018, total ischemic time extended significantly during the Covid-19 period, which translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events.