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This document is a response to a letter to the editor that raised questions about the methodology used in a systematic literature review and meta-analysis comparing the effectiveness of two COVID-19 vaccines, mRNA-1273 and BNT162b2, among older adults. The authors of the response defend their methodology and conclusions, disagreeing with the claim that their analysis was based on inaccurate and out-of-date data. They also address concerns about the use of crude data in the meta-analysis, the exclusion of eligible studies, and errors in data extraction. The authors maintain the validity of their methods and affirm that they followed the appropriate analysis framework. This document is a response to criticisms made by Volkman and colleagues regarding a meta-analysis conducted by Kavikondala et al. The response addresses specific points raised by Volkman and provides clarification and evidence to support the original study's methodology and findings. The authors disagree with Volkman's opinion that there is no difference in effectiveness between the mRNA COVID-19 vaccines and argue that the literature supports their findings. The response also acknowledges the funding and contributions of Moderna, Inc. and ICON plc in conducting the study and providing medical writing assistance. [Extracted from the article]

Background/Objectives: This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus the BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19. Methods: In a linked electronic health record/claims dataset, US adults (≥18 years) with ≥1 underlying medical condition of interest who received either the bivalent vaccine between 31 August 2022 and 28 February 2023 were identified. The inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until 31 May 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions. Results: 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%–15.2%) against COVID-19-related hospitalization and 3.2% (1.7%–4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were as follows: diabetes 15.1% (8.7%–21.0%), cerebro- and cardiovascular disease 14.7% (9.0%–20.1%), chronic lung disease 11.9% (5.1%–18.2%), immunocompromised 15.0% (7.2%–22.2%), chronic kidney disease 8.4% (0.5%–15.7%). Conclusions: Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations. [ABSTRACT FROM AUTHOR]

Background Solid organ transplant recipients (SOTRs) are at high risk for severe COVID-19. Methods This open-label, phase 3b trial evaluated mRNA-1273 in 137 kidney and 77 liver SOTRs and 20 immunocompetent participants. In part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received 2 doses. In part B, an additional 100-µg dose was offered ≥4 months after the primary series. Here, we report interim trial results. Results mRNA-1273 was well-tolerated in SOTRs. Four serious adverse events were considered vaccine related by the investigator in 3 SOTRs with preexisting comorbidities. No vaccine-related biopsy-proven organ rejection events or deaths were reported. mRNA-1273 elicited modest neutralizing antibody responses after dose 2 and improved responses after dose 3 in SOTRs. Post–dose 3 responses among liver SOTRs were comparable to post–dose 2 responses in immunocompetent participants. Post-additional dose responses were increased in SOTRs, regardless of primary series vaccination. In liver SOTRs, post-additional dose responses were ∼3-fold higher versus post-dose 2 but lower than immunocompetent participant responses. Most kidney SOTRs received multiple immunosuppressants and had reduced antibody responses versus liver SOTRs. Conclusions mRNA-1273 was well-tolerated, and dose 3 and the additional dose improved antibody responses among SOTRs. Clinical Trials Registration NCT04860297. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsBNT162b2 and mRNA-1273 COVID-19 vaccines have been used for mass vaccinations in Curaçao, the Caribbean but information on adverse events (AEs)in this population is unavailable. This study describes the characteristics of vaccinees that incurred AEs, explores the associations between AEs by vaccine and doses, and estimates the rate of AEs.Vaccination and AEs data for all persons of age 5 years (range 5–105 years) and older who received two doses of COVID-19 vaccine at 71 centres in Curaçao between February 24, 2021, and April 5, 2023, were included in this retrospective observational study.The vaccines differed significantly in the frequency distribution of vaccinees by age, age groups, sex, AEs, and prior COVID-19 infection. Occurrence of AEs was strongly associated with mRNA vaccine brand, sex, number of doses, but not with age, age group, and prior COVID-19 infection. Of 209,720 doses, 84 persons (0.04%) incurred AEs following two doses of mRNA vaccines (overall rate of 40.1 per 100,000 persons (95% CI 32.4–49.6). AEs were also significantly higher in females compared to males.AE rates associated with BNT162b2, and mRNA-1273 vaccines were low, but BNT162b2 vaccinees incurred substantially significantly higher AE rates (58.3 per 100,000 persons, 95% CI 45.4–74.9) than mRNA-1273 vaccinees (21.9 per 100,000 persons, 95% CI 14.6–32.8). mRNA-1273 vaccine was associated with a significantly lower risk of AEs.AE reporting varied by age, sex, and vaccine used as well as the number of doses. Future studies with follow-up and longer-term reporting of AEs should be conducted. [ABSTRACT FROM AUTHOR]

Introduction Vaccination against SARS-CoV-2 is an integral pillar of the public health approach to COVID-19. With the emergence of variants of concern that increase transmissibility and escape from vaccine- or infection-induced protection, vaccines have been developed to more closely match the newly circulating SARS-CoV-2 strains to improve protection. The safety and immunogenicity of multiple authorized messenger RNA (mRNA)-based COVID-19 vaccines targeting the omicron sublineage (BA.1, BA.4/BA.5, and XBB.1.5) have been demonstrated in several clinical trials among adults and children.Areas covered This review will comprehensively detail the available evidence (published through July 2024) from ongoing clinical trials on omicron variant-containing mRNA-1273 vaccines administered as additional doses in previously vaccinated target demographics.Expert opinion Across three clinical trials, omicron variant-containing mRNA-1273 vaccines induced immune responses to vaccine-matched omicron strains as well as ancestral SARS-CoV-2, with a safety and reactogenicity profile comparable to the original mRNA-1273 vaccine. Combined with pivotal data demonstrating the safety, efficacy, and effectiveness of the original mRNA-1273 vaccine, these findings support the use of variant-containing mRNA-1273 vaccines and provide confidence that expeditious development of updated vaccines using this established mRNA platform can maintain protection against COVID-19.

Abstract Background Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. Methods We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. Results Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28–90, and IgG titers plateaued between day 90–360. During the BA.1/BA.2 wave (February–March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. Conclusions mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.

Abstract Introduction Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). Methods This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. Results In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506–0.887), 29.3% (0.707; 0.573–0.858), and 23.4% (0.766; 0.626–0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860–0.976), 6.4% (0.936; 0.895–0.978), and 2.4% (0.976; 0.935–1.017), respectively. Conclusions Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

Introduction: Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). Methods: This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. Results: In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506–0.887), 29.3% (0.707; 0.573–0.858), and 23.4% (0.766; 0.626–0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860–0.976), 6.4% (0.936; 0.895–0.978), and 2.4% (0.976; 0.935–1.017), respectively. Conclusions: Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. COVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. Methods: A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. Results: mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P < 0.0001; I2 = 66.8%] and higher total antibody titers [relative increase, 50.45% (95% CI, 34.63%, 66.28%); P < 0.0001; I2 = 89.5%] versus BNT162b2. mRNA-1273 elicited higher but statistically nonsignificant relative increases in neutralizing antibody titers and cellular immune responses versus BNT162b2. Conclusion: Higher-dose mRNA-1273 had increased immunogenicity versus BNT162b2 in IC patients. [ABSTRACT FROM AUTHOR]

Acquired hemophilia A (AHA) is a rare bleeding disorder (1.4 per million inhabitants per year) caused by neutralizing antibodies against factor VIII. Although uncommon, these autoantibodies can cause a high rate of morbidity and mortality. Several conditions are linked with AHA; based on an EACH2 study, 3.8% of AHA could be connected to infection. In the last four years, most humans have contracted the SARS-CoV-2 infection or have been vaccinated against it. Whether or not COVID-19 immunization might induce AHA remains controversial. This review aims to evaluate the evidence about this possible association. Overall, 18 manuscripts (2 case series and 16 case reports) were included. The anti-SARS-CoV-2 vaccination, as also happens with other vaccines, may stimulate an autoimmune response. However, older individuals with various comorbidities are both at risk of developing AHA and of COVID-19-related morbidity and mortality. Therefore, the COVID-19 vaccine must always be administered because the benefits still outweigh the risks. Yet, we should consider the rare possibility that the activation of an immunological response through vaccination may result in AHA. Detailed registries and prospective studies would be necessary to analyze this post-vaccine acquired bleeding disorder, looking for possible markers and underlying risk factors for developing the disease in association with vaccination. [ABSTRACT FROM AUTHOR]

Abstract Introduction Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. Methods A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. Results mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P

Leonidas D Panos,1,2 Panagiotis Bargiotas,2 Georgios Hadjigeorgiou,2 Georgios D Panos3,4 1Department of Neurology, Bern University Hospital « Inselspital », Bern, Switzerland; 2Department of Neurology, School of Medicine, University of Cyprus, Nicosia, Cyprus; 3Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals (NUH), Nottingham, U.K; 4Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, U.KCorrespondence: Leonidas D Panos, Department of Neurology, Bern University Hospital “Inselspital”, Freiburgstrasse 16, 3010, Bern, Switzerland, Tel +41 31 632 70 00, Email ldpanos@yahoo.gr Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, NUH, Derby Road, Lenton, Nottingham, NG7, 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comAbstract: The global deployment of SARS-CoV-2 vaccines has been pivotal in curbing the COVID-19 pandemic, reducing morbidity and mortality associated with the virus. While most of these vaccines have demonstrated high efficacy and overall safety, emerging reports have highlighted potential neurovascular adverse effects, albeit uncommon, associated with these vaccinations. This review aims to assess and summarize the current knowledge on the neurovascular complications arising post-SARS-CoV-2 vaccination. We conducted an extensive literature review, focusing on clinical studies and case reports to identify reported neurovascular events, such as ischemic stroke, cerebral sinus venous thrombosis, intracerebral hemorrhage, pituitary apoplexy and primary CNS angiitis Despite the relative rarity of these events, their impact on affected individuals underscores the importance of ongoing surveillance, early detection, and management strategies. We aim to provide healthcare professionals with the latest evidence on neurovascular adverse effects, facilitating informed decision-making in the context of SARS-CoV-2 vaccination programs. Furthermore, we highlight areas requiring further research to understand the pathophysiology of these adverse events better and to develop targeted prevention and treatment strategies.Keywords: neurovascular adverse effects, COVID-19, vaccines, SARS-CoV-2, coronavirus, pandemic, BNT162b2, mRNA-1273, ChAdOx1, NVX-CoV2373

Abstract The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID‐19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA‐1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti‐S‐IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti‐S‐IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti‐S‐IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non‐decompensation and 91.3% non‐liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non‐active HCC and 94.7% non‐HCC, p

Abstract Introduction The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. Methods We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19–related hospitalization, and COVID-19–related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. Results Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19–related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19–related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I 2 > 75%) except death (I 2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. Conclusion Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years.

The impact of pre-graft COVID-19 vaccinations in donor or recipient as well as pre-graft infection has been studied in 157 adults having received allogeneic stem cell transplantation (Allo-SCT) for various hematological diseases during the delta/omicron waves. We showed here that pre-Allo-SCT COVID-19 vaccination and/or infection do not provide more protection in patients receiving vaccine, immunotherapy or both after transplant. COVID-19 vaccination is and remains of crucial importance after Allo-SCT, reinforcing the recommendation to start COVID-19 vaccination as soon as the third month following the transplant.

ABSTRACTThe objective of the study was to assess the safety and immunogenicity of mRNA-1273 COVID-19 booster vaccination when co-administered with an egg-based standard dose seasonal quadrivalent influenza vaccine (QIV). This was a phase 3, randomized, open-label study. Eligible adults aged ≥ 18 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and QIV 2 weeks apart (Seq group) or concomitantly (Coad group). Primary objectives were non-inferiority of haemagglutinin inhibition (HI) and anti-Spike protein antibody responses in the Coad compared to Seq group. 497/498 participants were randomized and vaccinated in the Seq/Coad groups, respectively. The adjusted geometric mean titer/concentration ratios (95% confidence intervals) (Seq/Coad) for HI antibodies were 1.02 (0.89–1.18) for A/H1N1, 0.93 (0.82–1.05) for A/H3N2, 1.00 (0.89–1.14] for B/Victoria, and 1.04 (0.93–1.17) for B/Yamagata; and 0.98 (0.84–1.13) for anti-Spike antibodies, thus meeting the protocol-specified non-inferiority criteria. The most frequently reported adverse events in both groups were pain at the injection site and myalgia. The 2 groups were similar in terms of the overall frequency, intensity, and duration of adverse events. In conclusion, co-administration of mRNA-1273 booster vaccine with QIV in adults was immunologically non-inferior to sequential administration. Safety and reactogenicity profiles were similar in both groups (clinicaltrials.gov NCT05047770).

Immunological responses were investigated following immunization with two mRNA vaccines: BNT162b2 and mRNA-1273. Neutralizing antibody (NAb) was assayed before, 2–4 weeks after, and 3 and 6 months after the primary immunization, and the same time-points after booster dose with 6- or 8-months interval. Whole-blood culture was stimulated with spike antigen, and cytokine production was assayed. NAb was detected after primary immunization, NAb titers began to decrease three months after primary immunization with BNT162b2, lower than those after mRNA-1273, and elevated after booster immunization. The NAb level was 1/2 lower against δ variant, and 1/16 lower against omicron variant in comparison with that against α variant. Cytokine production following immunization with mRNA-1273 was maintained within three months at higher levels of Th1 (TNF-α), Th2 (IL-4 and IL-5), and inflammatory cytokines (IL-6 and IL-17) than that following immunization with BNT162b2, reflecting prominent levels of NAb following immunization with mRNA-1273. Cytokine production decreased six months after primary immunization in both vaccine recipients and was enhanced following booster doses. During the omicron outbreak, medical staff members in the outpatient office experienced asymptomatic infection, with a greater than 4-fold increase in NAb titers against omicron variant even after booster immunization. Asymptomatic infection enhanced the production of Th2 and inflammatory cytokines. mRNA-1273 induced stronger NAb responses with wide-range cross-reactive antibodies against δ and omicron variants. mRNA-1273 induced higher levels of Th1, Th2, and inflammatory cytokines than BNT162b2 did, reflecting higher levels of NAb against variant strains. [ABSTRACT FROM AUTHOR]

The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID‐19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA‐1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti‐S‐IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti‐S‐IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti‐S‐IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non‐decompensation and 91.3% non‐liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non‐active HCC and 94.7% non‐HCC, p < 0.001). Receiving the MMM booster regimen (OR = 10.67, 95% CI 5.20–21.91, p < 0.001) increased the odds of having significant antibody activity compared with the AZAZBNT booster regimen. Patients with active HCC had a reduced immune response to the third COVID‐19 vaccine booster. These findings underscore the importance of booster vaccinations, especially in immunocompromised patients, with superior efficacy observed with the homologous mRNA‐1273 regimen. [ABSTRACT FROM AUTHOR]

The article presents the case studies of a 84 year old male and a 27 year old female experiencing oral adverse events following immunization against SARS-CoV-2. It is reported that the patients developed symptoms such as extreme lower lip dryness, exfoliation, pruritus, burning of lips, swelling, vesicular eruptions, palatal lesions, xerostomia, and glossodynia after receiving COVID-19 vaccines. It discusses the clinical presentation, diagnostic evaluation, and management strategies.

Introduction: The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. Methods: We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19–related hospitalization, and COVID-19–related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. Results: Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19–related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19–related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2 > 75%) except death (I2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. Conclusion: Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years. [ABSTRACT FROM AUTHOR]

Background: Characterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines. Methods: This study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants. Results: Multiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster. Conclusion: Overall, these results identify key S-specific epitopes targeted by ant ibodies induced by mRNA-1273 primary and variant-updated booster vaccination. [ABSTRACT FROM AUTHOR]

• BNT162b2 or mRNA-1273 induced antibodies are not affected by 25(OH)D concentration. • BNT162b2 induced T cell responses are not associated with 25(OH)D concentration. • Our findings do not support vitamin D optimization preceding SARS-CoV-2 vaccination. To improve effectiveness of vaccination against SARS-CoV-2, it is important to identify factors that influence the immune response induced by vaccination. Evidence for the role of vitamin D in immune response against SARS-CoV-2 is contradictory. It is therefore of interest whether 25-hydroxyvitamin D (25[OH]D) concentrations affect the humoral and/or cellular response following SARS-CoV-2 vaccination. In this prospective cohort study, blood samples were collected from 98 SARS-CoV-2 naive health care workers (HCW) receiving the first two doses of either BNT162b2 or mRNA-1273 in 2021. Wild-type spike (S) protein binding and neutralizing antibodies were determined approximately three weeks after the first dose and four to five weeks after the second dose. Antigen specific T-cells and functionality (proliferative response and interferon gamma [IFN-γ] release) were determined in 18 participants four weeks after the second dose of BNT162b2. We studied the association between 25(OH)D concentrations, which were determined prior to vaccination, and humoral and cellular immune responses following vaccination. We found no association between 25(OH)D concentrations (median 55.9 nmol/L [IQR 40.5–69.8]) and binding or neutralizing antibody titers after complete vaccination (fold change of antibody titers per 10 nmol/L 25(OH)D increase: 0.98 [95% CI 0.93–1.04] and 1.03 [95% CI: 0.96–1.11], respectively), adjusted for age, sex and type of mRNA vaccine. Subsequently, continuous 25(OH)D concentrations were divided into commonly used clinical categories (<25 nmol/L [n = 6, 6%], 25–49 nmol/L [n = 33, 34%], 50–75 nmol/L [n = 37, 38%] and ≥75 nmol/L [n = 22, 22%]), but no association with the humoral immune response following vaccination was found. Also, 25(OH)D concentrations were not associated with the SARS-CoV-2 specific T cell response. No association was found between 25(OH)D concentrations and the humoral or cellular immune response following mRNA vaccination against SARS-CoV-2. Based on our findings there is no rationale to advise vitamin D optimization preceding SARS-CoV-2 vaccination in HCW with moderate vitamin D status. [ABSTRACT FROM AUTHOR]

Background Large-scale use of mRNA COVID-19 vaccines during the pandemic was associated with enhanced safety monitoring to ensure accurate and timely review of safety. We reviewed the mRNA-1273 (original strain) safety profile following 2 years of use (>772 million administered doses), primarily focusing on predefined safety topics (ie, adverse events of special interest [AESIs]) proposed in advance of COVID-19 vaccine use. Methods Cumulative mRNA-1273 safety data were included from spontaneous adverse event (AE) cases reported to Moderna's global safety database between 18 December 2020 and 17 December 2022. Reporting rates of AESIs were calculated per 1 million doses of mRNA-1273 administered. Observed-to-expected (OE) ratios were computed by comparing observed rates of AESIs with the background/expected rate for these events to evaluate potential associations with mRNA-1273. Results There were 658 759 identified case reports associated with 2 517 669 AEs. Most AEs were nonserious (83.4%; 2 098 954/2 517 669). Overall 0.7% (17 751/2 517 669) were fatal. AESIs represented 13.7% of all AEs (344 921/2 517 669), with reporting rates for most AESIs below the expected background incidence. Exceptions included anaphylaxis (OE ratio 3 days after vaccination, 2.09; 95% CI, 1.93–2.25) and, among individuals aged 12 to 40 years, myocarditis (OE ratio 7 days after any dose, 3.89 [3.50–4.32]; among men after dose 2, 8.57 [6.88–10.68]) and pericarditis (OE ratio 7 days after vaccination, 3.47; 2.89–4.16). Conclusions This safety analysis of mRNA-1273 identified evidence of increased risk for anaphylaxis, myocarditis, and pericarditis but not for other AESIs identified for enhanced monitoring ahead of COVID-19 vaccine use. [ABSTRACT FROM AUTHOR]

Introduction: Some studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable. Material and methods: Blood samples were obtained before the booster (third dose) and after 14, 90, and 180 days in two similar cohorts who received the original BNT162b2 or mRNA-1273 vaccine designed to target wild type SARS-CoV-2. The aim of our study is to compare their effectiveness by assessing the levels of binding and neutralizing antibodies specifically against each of the BA.1 variant, BA.5 variant, and the XBB.1.5 subvariant. Results: Once the peak was reached after two weeks, a drastic decline in binding and neutralizing antibodies was observed up to 6 months after the homologous booster administration. The humoral response was however more sustained with the mRNA-1273 booster, with half-lives of 167, 55, and 48 days for binding, BA.1, and BA.5 neutralizing antibodies compared to 144, 30, and 29 days for the BNT162b2 booster, respectively. Compared to the BA.1 variant, the neutralizing capacity was significantly decreased at 6 months with the BA.5 variant (fold-decrease: 1.67 to 3.20) and the XBB.1.5. subvariant (fold-decrease: 2.86 to 5.48). Conclusion: Although the decrease in the humoral response was observed with both mRNA vaccines over time, a more sustained response was observed with the mRNA-1273 vaccine. Moreover, the emergence of Omicron-based variants causes a reduced neutralizing capacity, notably with the XBB.1.5. subvariant. The administration of subsequent boosters would therefore be needed to restore a sufficiently high neutralizing response.

Summary: Background: Longitudinal changes in vaccination-induced immune response remain inadequately characterized in adolescents. We present long-term safety, immunogenicity, and COVID-19 incidence following a 2-dose mRNA-1273 100-μg primary series, and immunogenicity following a single dose of mRNA-1273 50 μg in vaccine-naïve adolescents. Methods: TeenCOVE (NCT04649151) Part 1 randomized adolescents (12–17 years) to 2-dose mRNA-1273 100 μg (n = 2490) or placebo (n = 1243) 28 days apart. Subsequently, placebo recipients (n = 91) could receive open-label mRNA-1273. Primary objectives included prespecified adverse events through 12 months; secondary objectives were COVID-19 incidence and neutralizing and spike-binding antibodies (nAbs/bAbs) against SARS-CoV-2 (ancestral/variants) through 12 months (study period: December 2020–January 2022). In Part 2, vaccine-naïve adolescents (n = 52) received up to 2 doses of mRNA-1273 50 μg; interim analysis included Day 28 (D28) nAbs post-injection 1 in SARS-CoV-2-baseline-positive participants (serologic/virologic evidence of prior infection). Findings: In SARS-CoV-2-baseline-negative adolescents (N = 369), mRNA-1273 induced robust nAb responses versus baseline (geometric mean concentration [GMC] = 11; 95% CI, 11–12) at D28 (1868 [1759–1985]), 6 months (625 [583–670]) and 12 months (550 [490–618]) post-injection 2. Similar bAb responses were observed to alpha/beta/delta/gamma variants; nAb/bAb responses were similar in SARS-CoV-2-baseline-positive adolescents. The 2-dose mRNA-1273 100-μg primary series was generally well-tolerated; one case of nonserious, moderate, probable acute myocarditis resolved by 8 days from symptom onset. A single dose of mRNA-1273 50 μg in SARS-CoV-2-baseline-positive adolescents induced higher D28 nAb GMCs against ancestral SARS-CoV-2 than 2-dose mRNA-1273 100 μg in young adults (geometric mean ratio = 4.322 [3.274-5.707]). Interpretation: The overall risk–benefit profile of mRNA-1273 remains favorable in adolescents, with durable 12-month immune responses against SARS-CoV-2 (ancestral/variants). A single mRNA-1273 50-μg injection in vaccine-naïve adolescents elicited robust immune responses against SARS-CoV-2. Funding: This project has been funded in whole or in part with federal funds by the Department of Health and Human Services, United States; Administration for Strategic Preparedness and Response, United States; Biomedical Advanced Research and Development Authority, United States, under Contract No. 75A50120C00034. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Department of Health and Human Services or its components.

Abstract Background The worldwide vaccination response to COVID-19 has been associated with rare thrombotic complications, including the case of postvaccination splanchnic venous thrombosis we report here. Case presentation An 80-year-old Japanese male with abdominal pain presented to our hospital six days after receiving a dose of the COVID-19 messenger ribonucleic acid vaccine. Abdominal computed tomography showed localized edema of the small intestine, increased density of the surrounding adipose tissue, and a thrombus in the superior mesenteric vein. Conservative inpatient treatment with unfractionated heparin relieved the thrombosis, and the patient is currently receiving oral apixaban as an outpatient. Conclusion Reported cases of thrombosis after COVID-19 vaccination typically have been associated with viral vector vaccines, with few reports of thrombosis induced by mRNA vaccines. The potential for venous thrombosis should be explored when patients present with abdominal pain soon after COVID-19 vaccination.

Abstract Although vaccination against COVID‐19 has been proven generally safe, rare but potentially serious adverse reactions do occur. Cutaneous leukocytoclastic vasculitis is the vasculitis of small vessels. We reported two patients with leukocytoclastic vasculitis who were vaccinated with the ChAdOx1‐S/nCoV‐19 and mRNA‐1273. Both cases were confirmed with a skin biopsy. There was a complete recovery with corticosteroids and both were followed up without any recurrence.

Objective This study aims to characterize the adverse events (AEs) following the administration of the mRNA-1273 COVID-19 vaccine from the Vaccine Adverse Event Reporting System (VAERS) data. Methods In this case/non-case analysis, reports between 1 January 2021, and 27 October 2022, were extracted from VAERS. AEs were defined as preferred terms (PTs) by Medical Dictionary for Regulatory Activities (MedDRA) terminology. Disproportionality analyses were conducted to calculate the reporting odds and proportional reporting ratios. The Bayesian approach was used to calculate information component (IC) values and Empirical Bayesian Geometric Mean scores for all the AEs detected. Results 186 MedDRA PTs compromising 702,495 AEs associated with the mRNA-1273 vaccine were identified. Three statistically significant signals were identified for general and systemic AEs, administration site conditions, and product issues. Cardiac disorders were rarely reported, the most common being; 489 reports for ‘myocarditis’ (19.44%), 475 for ‘acute myocardial infarction’ (18.88%), 457 for ‘myocardial infarction’ (18.16%), 290 for ‘bradycardia’ (11.53%) and 281 for ‘pericarditis’ (11.17%). Conclusions The most frequently identified AEs following mRNA-1273 vaccination agree with those listed within the Summary of Product Characteristics. In addition, disproportionality analysis did not find any statistically significant signals for myocarditis or pericarditis.

Introduction Current safety data from Phase 3 clinical trials have concluded that apart from transient local and systemic reactions, no safety concerns were identified for the Moderna COVID-19 vaccine (mRNA-1273). However, Phase 3 studies are insufficient to detect rare adverse events (AEs). A literature search of the two major electronic databases, Embase and PubMed, was performed to enable the identification and characterization of all relevant articles from December 2020 to November 2022. Areas Covered This narrative review summarizes the key safety outcomes associated with the mRNA-1273 vaccine to inform healthcare decisions and increase public awareness of mRNA-1273 vaccine safety. The primary adverse events (AEs) reported within a diverse population, receiving the mRNA-1273 vaccine, were; localized injection site pain, fatigue, headache, myalgia, and chills. In addition, the mRNA-1273 vaccine was also associated with; less than a 1-day change in the menstrual cycle, a 10-fold higher risk of myocarditis and pericarditis within young males aged 18–29 years and increased levels of anti-polyethylene glycol (PEG) antibodies. Expert Opinion The transient nature of commonly observed AEs and the rare occurrence of severe events within mRNA-1273 recipients show no significant safety concerns which should prevent vaccination. However, large-scale epidemiological studies with longer follow-up periods are required to surveillance rare safety outcomes.

Background Adverse events following mRNA COVID-19 vaccines, including herpes zoster (HZ), have been reported. We conducted a cohort study to evaluate the association between mRNA COVID-19 vaccination and subsequent HZ at Kaiser Permanente Southern California (KPSC). Research design and methods The vaccinated cohort consisted of KPSC members who received their first dose of mRNA COVID-19 vaccine (mRNA-1273 and BNT162b2) during 12/2020–05/2021 and were matched to unvaccinated individuals on age and sex. Incident HZ cases occurring within 90 days of follow-up were identified by diagnosis codes and antiviral medications. Cox proportional hazards models estimated adjusted hazard ratios (aHR), comparing HZ incidence between the vaccinated and unvaccinated cohorts. Results Cohort included 1,052,362 mRNA-1273 recipients, 1,055,461 BNT162b2 recipients, and 1,020,334 comparators. Compared to unvaccinated individuals, aHR for HZ up to 90 days after the second dose of mRNA-1273 and BNT162b2 was 1.14 (1.05–1.24) and 1.12 (1.03–1.22), respectively. In those aged ≥50 years not vaccinated with zoster vaccine, aHR was also increased after the second dose of mRNA-1273 (1.18 [1.06–1.33]) and BNT162b2 (1.15 [1.02–1.29]) vaccine vs. unvaccinated individuals. Conclusions Our findings suggest a potential increased risk of HZ after a second dose of mRNA vaccines, potentially driven by the increased risk in individuals aged ≥50 years without history of zoster vaccination.

Background/Objectives: This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus the BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19. Methods: In a linked electronic health record/claims dataset, US adults (≥18 years) with ≥1 underlying medical condition of interest who received either the bivalent vaccine between 31 August 2022 and 28 February 2023 were identified. The inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until 31 May 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions. Results: 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%–15.2%) against COVID-19-related hospitalization and 3.2% (1.7%–4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were as follows: diabetes 15.1% (8.7%–21.0%), cerebro- and cardiovascular disease 14.7% (9.0%–20.1%), chronic lung disease 11.9% (5.1%–18.2%), immunocompromised 15.0% (7.2%–22.2%), chronic kidney disease 8.4% (0.5%–15.7%). Conclusions: Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations.

Background and Purpose: To protect against SARS‐CoV‐2 infection, the first mRNA‐based vaccines, Spikevax (mRNA‐1273, Moderna) and Comirnaty (BNT162b2, Pfizer/Biontech), were approved in 2020. The structure and assembly of the immunogen—in both cases, the SARS‐CoV‐2 spike (S) glycoprotein—are determined by a messenger RNA sequence that is translated by endogenous ribosomes. Cardiac side‐effects, which for the most part can be classified by their clinical symptoms as myo‐ and/or pericarditis, can be caused by both mRNA‐1273 and BNT162b2. Experimental Approach: As persuasive theories for the underlying pathomechanisms have yet to be developed, this study investigated the effect of mRNA‐1273 and BNT162b2 on the function, structure, and viability of isolated adult rat cardiomyocytes over a 72 h period. Key Results: In the first 24 h after application, both mRNA‐1273 and BNT162b2 caused neither functional disturbances nor morphological abnormalities. After 48 h, expression of the encoded spike protein was detected in ventricular cardiomyocytes for both mRNAs. At this point in time, mRNA‐1273 induced arrhythmic as well as completely irregular contractions associated with irregular as well as localized calcium transients, which provide indications of significant dysfunction of the cardiac ryanodine receptor (RyR2). In contrast, BNT162b2 increased cardiomyocyte contraction via significantly increased protein kinase A (PKA) activity at the cellular level. Conclusion and Implications: Here, we demonstrated for the first time, that in isolated cardiomyocytes, both mRNA‐1273 and BNT162b2 induce specific dysfunctions that correlate pathophysiologically to cardiomyopathy. Both RyR2 impairment and sustained PKA activation may significantly increase the risk of acute cardiac events. [ABSTRACT FROM AUTHOR]

SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population. [ABSTRACT FROM AUTHOR]

Background: The worldwide vaccination response to COVID-19 has been associated with rare thrombotic complications, including the case of postvaccination splanchnic venous thrombosis we report here. Case presentation: An 80-year-old Japanese male with abdominal pain presented to our hospital six days after receiving a dose of the COVID-19 messenger ribonucleic acid vaccine. Abdominal computed tomography showed localized edema of the small intestine, increased density of the surrounding adipose tissue, and a thrombus in the superior mesenteric vein. Conservative inpatient treatment with unfractionated heparin relieved the thrombosis, and the patient is currently receiving oral apixaban as an outpatient. Conclusion: Reported cases of thrombosis after COVID-19 vaccination typically have been associated with viral vector vaccines, with few reports of thrombosis induced by mRNA vaccines. The potential for venous thrombosis should be explored when patients present with abdominal pain soon after COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 variants continue to emerge, vaccination remains a critical tool to reduce the COVID-19 burden. Vaccine reactogenicity and the impact on work productivity/daily activities are recognized as contributing factors to vaccine hesitancy. To encourage continued COVID-19 vaccination, a more complete understanding of the differences in reactogenicity and impairment due to vaccine-related side effects across currently available vaccines is necessary. The 2019nCoV-406 study (n = 1367) was a prospective observational study of reactogenicity and associated impairments in adults in the United States and Canada who received an approved/authorized COVID-19 vaccine. Compared with recipients of mRNA COVID-19 booster vaccines, a smaller percentage of NVX-CoV2373 booster recipients reported local and systemic reactogenicity. This study's primary endpoint (percentage of participants with ≥50% overall work impairment on ≥1 of the 6 days post-vaccination period) did not show significant differences. However, the data suggest that NVX-CoV2373 booster recipients trended toward being less impaired overall than recipients of an mRNA booster; further research is needed to confirm this observed trend. The results of this real-world study suggest that NVX-CoV2373 may be a beneficial vaccine option with limited impact on non-work activities, in part due to the few reactogenicity events after vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood. Methods: In this prospective observational study, we investigated the influence of sleep habits on immune acquisition induced by mRNA vaccines against SARSCoV- 2 in 48 healthy adults (BNT-162b2, n=34; mRNA-1273, n=14; female, n=30, 62.5%; male, n=18, 37.5%; median age, 39.5 years; interquartile range, 33.0–44.0 years) from June 2021 to January 2022. The study measured sleep duration using actigraphy and sleep diaries, which covered the periods of the initial and booster vaccinations. Results: Multivariable linear regression analysis showed that actigraphy-measured objective sleep duration 3 and 7 days after the booster vaccination was independently and significantly correlated with higher antibody titers (B=0.003; 95% confidence interval, 0.000–0.005; Beta=0.337; p=0.02), even after controlling for covariates, including age, sex, the type of vaccine, and reactogenicity to the vaccination. Associations between acquired antibody titer and average objective sleep duration before vaccination, and any period of subjective sleep duration measured by sleep diary were negligible. Discussion: Longer objective, but not subjective, sleep duration after booster vaccination enhances antibody response. Hence, encouraging citizens to sleep longer after mRNA vaccination, especially after a booster dose, may increase protection against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored. Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses. The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05–2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions. COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events. [ABSTRACT FROM AUTHOR]

Long-term analyses of the immune response following SARS-CoV-2 mRNA vaccines are essential to determining its characteristics and providing the basis for vaccination strategies. We conducted a prospective study in a cohort of 268 healthy adults followed for >2 years after two doses of BNT162b2. Antibodies targeting the receptor-binding domain of the S1 subunit of the spike of SARS-CoV-2 (anti-RBD) were measured at eight time points; T cell response was analyzed using an interferon-γ release assay. A total of 248 (93%) subjects received mRNA-1273 on month 9; 93 (35%) received the bivalent Omicron-adapted BNT162b2 vaccine between months 19 and 26. Breakthrough infections occurred in 215 (80%) participants, with frequencies unaffected by the additional vaccines. Anti-RBD declined over the initial 9 months, increased after mRNA-1273, and declined gradually thereafter. In 50 (17%) previously infected subjects, anti-RBD levels were significantly higher up to month 9 (p < 0.05) but subsequently declined below those of uninfected individuals. Anti-RBD titers protective against SARS-CoV-2 could not be defined. Most subjects developed a positive T cell response that remained after 26 months. Waning of protection against SARS-CoV-2 infection occurred over time, resulting in non-severe breakthrough infections in most participants. The evolution of anti-RBD suggests modulation of the immune response through immune imprinting. [ABSTRACT FROM AUTHOR]

A booster dose of a COVID-19 vaccine has been proven effective in restoring vaccine effectiveness and is currently recommended for use in some populations at risk of severe COVID-19 infection. Since sex differences in adverse events are significant in response to the vaccines, the safety of booster selection must be studied to avoid serious adverse events (SAE), such as life-threatening diseases. First, this study aimed to identify sex differences in SAE incidences using a prospective cohort design. Second, a nested unmatched case-control study was used to identify factors associated with reported SAE within 30 days after the booster shot. Multivariable logistic regression indicated the adjusted odds ratio by accounting for host and vaccine variables, thus, policy effects. The findings confirmed that SAE was rare and that age-sex-dominated disease classifications differed. Specific to SAE following the booster dose, we found that females aged 12–40 had a higher risk of being reported with SAE than males of the same age, while males over 50 had a higher risk than females. Other risk factors identified were the presence of metabolic syndrome and the use of certain vaccine brands. Mechanisms could be explained by individual host responses rather than the vaccines' direct effect. Therefore, SAE could be preventable by age-sex-specific vaccine selection, post-vaccination precautions, and early symptom detection. Future vaccine development should aim to limit host-specific reactogenicity for safety concerns. [ABSTRACT FROM AUTHOR]

BackgroundCharacterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines.MethodsThis study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants.ResultsMultiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster.ConclusionOverall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination.

Objective: To compare myocarditis/pericarditis risk after COVID-19 mRNA vaccination versus SARS-CoV-2 infection, and to assess if myocarditis/pericarditis risk varies by vaccine dosing interval. Methods: In this retrospective cohort study, we used linked databases in Quebec, Ontario, and British Columbia between January 26, 2020, and September 9, 2021. We included individuals aged 12 or above who received an mRNA vaccine as the second dose or were SARS-CoV-2-positive by RT-PCR. The outcome was hospitalization/emergency department visit for myocarditis/pericarditis within 21 days of exposure. We calculated age- and sex-stratified incidence ratios (IRs) of myocarditis/pericarditis following mRNA vaccination versus SARS-CoV-2 infection. We also calculated myocarditis/pericarditis incidence by vaccine type, homologous/heterologous schedule, and dosing interval. We pooled province-specific estimates using meta-analysis. Results: Following 18,860,817 mRNA vaccinations and 860,335 SARS-CoV-2 infections, we observed 686 and 160 myocarditis/pericarditis cases, respectively. Myocarditis/pericarditis incidence was lower after vaccination than infection (IR [BNT162b2/SARS-CoV-2], 0.14; 95%CI, 0.07–0.29; IR [mRNA-1273/SARS-CoV-2], 0.28; 95%CI, 0.20–0.39). Within the vaccinated cohort, myocarditis/pericarditis incidence was lower with longer dosing intervals; IR (56 or more days/15–30 days) was 0.28 (95%CI, 0.19–0.41) for BNT162b2 and 0.26 (95%CI, 0.18–0.38) for mRNA-1273. Conclusion: Myocarditis/pericarditis risk was lower after mRNA vaccination than SARS-CoV-2 infection, and with longer intervals between primary vaccine doses.

AbstractBackground This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored.Methods Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses.Results The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05–2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions.Conclusions COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events.

• This prospective study followed a cohort of BBIBP-CorV-vaccinated individuals. • Heterologous mRNA-based booster elevated NAb titre compared to homologous BBIBP-CorV. • NAb waning observed within 6 months following heterologous vaccination with BNT162b2. • NAb persist up to 9 months post-heterologous mRNA-1273 booster or COVID-19 infection. BBIBP-CorV inactivated vaccine is one of the most prevalent vaccines globally, but immune responses are far less studied than novel COVID-19 vaccine platforms. Longitudinal studies on BBIBP-CorV with homologous and heterologous booster doses are limited. This study follows a subset of participants from a national study comparing the immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody (NAb). Homologous and heterologous booster dose significantly increased NAb levels in BBIBP-CorV-vaccinated individuals. Similar NAb levels were observed 1 month following BNT162b2 or mRNA-1273 booster. Interestingly, NAb persisted following mRNA-1273 booster (n = 95), but waned significantly at 6 and 9 months following BNT162b2 booster (n = 50; P > 0.001). The persistence of NAb was also observed following breakthrough infection. This study provides evidence that not all mRNA vaccines are equal in the longer term and should provide valuable information for policy makers planning booster programmes for BBIBP-CorV vaccinated populations. [ABSTRACT FROM AUTHOR]

Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals =18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework. Results: Overall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75-0.97]; P=0.0151; I2 = 67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77-0.93]; P=0.0009; I2 = 0%), COVID-19-associated hospitalization (RR, 0.88 [95% CI, 0.79-0.97]; P<0.0001; I2 = 0%), and COVID-19-associated mortality (RR, 0.63 [95% CI, 0.44-0.90]; P=0.0119; I2 = 0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2. [ABSTRACT FROM AUTHOR]

Vaccines are an important tool in combating the COVID-19 pandemic. Two mRNA vaccines (mRNA-1273 and BNT-162b2) and an adenovirus vector vaccine (Ad26.COV2.S) were among the first vaccines to be approved by global regulatory authorities. The aim of this observational study was to characterize the levels and time course of the generation of anti-SARS-CoV-2 spike protein antibodies after vaccination with 3 different vaccines and the neutralizing activity of these antibodies. Seroconversion panels were generated from blood samples collected before and after vaccination with 3 COVID-19 vaccines: mRNA-1273, BNT-162b2, and Ad26.COV2.S. The seroconversion panels were tested for antibody activity by chemiluminescent immunoassay or enzyme-linked immunosorbent assay (ELISA), and 1 panel was tested for neutralization activity in a pseudovirus assay. Participants positive for anti-SARS-CoV-2 antibodies before vaccination (18.6%) had a higher response to the first dose than participants who tested negative. For 2-dose vaccines, older participants showed a lower response to the first dose than younger participants. All participants showed positive responses after the second vaccine. For the adenovirus vector vaccine, 2 participants did not generate antibody responses after vaccination. Four participants were negative at 2 weeks but positive at 2 months. Pseudovirus neutralization showed good correlation with antibody activity (correlation coefficient = 0.78, P <.0001). Antibody responses in participants over 45 years old tended to be less robust. Participants that had been infected with SARS-CoV-2 and had antibodies prior to vaccination showed a more robust response to initial vaccination. Older participants (>45 years) showed less robust responses to both types of vaccine. All participants receiving full mRNA vaccination showed positive antibody responses. Some participants receiving the adenovirus vaccine did not respond. Antibody responses correlated well with neutralization activity. Seroconversion panels can be useful in the development of antibody assays and in investigating their effectiveness against new SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Tujuan: Mengetahui prevalensi dan karakteristik responden breakthrough infection pada tenaga kesehatan di RSUD Arifin Achmad Provinsi Riau dalam 14 hari – 6 bulan pasca vaksinasi booster mRNA-1273. Metode: Metode penelitian cross sectional yang dilakukan pada Juli – September 2022 menggunakan sampel sebanyak 123 responden melalui wawancara. Hasil: 14 responden (11,4%) mengalami breakthrough infection. Mayoritas responden breakthrough infection berjenis kelamin perempuan (78,6%), rata-rata usia 44,1 tahun, pekerjaan dokter (42,9%), IMT obesitas (57,1%), mayoritas tidak ada komorbid (85,7%) dan bukan penyintas (85,7%). Simpulan: Terdapat kejadian breakthrough infection pada tenaga kesehatan di RSUD Arifin Ahmad pada 14 hari – 6 bulan pasca pemberian booster mRNA Heterolog (mRNA-1273). Kata kunci: breakthrough infection; vaksin booster; mRNA-1273; vaksin heterolog; COVID-19

Abstract This study reports the incidence of chronic graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplant (alloHCT) recipients who received SARS-CoV2 vaccination. The overall rates of new and worsening chronic GvHD combined were 14%, with median time from vaccination to GVHD being approximately three to four weeks. A majority of the cases were of mild to moderate severity and primarily localized to either the skin, mouth, or joints. Prior chronic GVHD and recent transplant were associated with higher GVHD rates following COVID-19 vaccination. More prospective studies are needed to provide a definitive mechanism for the impact of SARS-CoV2 vaccination on alloHCT patients.