Project description:Abstract Messenger RNA vaccines are the main COVID-19 vaccines authorized for use in the United States. Side effects are typically minor and transient. We report a case series of four subjects with an acute myocarditis-like illness following mRNA COVID-19 vaccination who were hospitalized at our hospital in Lubbock, Texas. Three patients were young men who presented with acute chest pain after the second dose of the mRNA-1273 vaccine. Another patient was a 53-year-old white woman who presented with acute left arm pain 3 days after the first dose of the mRNA-1273 vaccine. She was later found to have acute decompensated heart failure, and endomyocardial biopsy revealed eosinophilic injury–mediated myocarditis.
Project description:BackgroundClinical trials of the BNT162b2 vaccine, revealed efficacy and safety. We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination.MethodsPatients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort. In all study patients, we excluded past and current COVID-19. Routine clinical and laboratory investigations for common etiologies of myocarditis were performed. Laboratory tests also included troponin and C-reactive protein levels. The diagnosis of myocarditis was established after cardiac MRI.FindingsFive patients presented after the second and one after the first dose of the vaccine. All patients were males with a median age of 23 years. Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection. Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely. All patients responded to the BNT162b2 vaccine. The clinical course was mild in all six patients.InterpretationOur report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization. We believe our information should be interpreted with caution and further surveillance is warranted.
Project description:It is urgently needed to evaluate the necessity and benefits of booster vaccination to facilitate clinical decision-making for recovered COVID-19 patients. In this study, we conducted a multicentre, prospective clinical trial of the earliest COVID-19 patients with a definitive history of direct or indirect exposure to SARS-CoV-2 through Hubei Province from three Chinese hospitals to evaluate the efficiency, safety and immune response of CoronaVac (an inactivated COVID-19 vaccine). Convalescent patients with high titres (≥ 1:96) or non-severe also exhibited higher frequency of long COVID-19 symptoms. One booster dose in convalescent patients with antibody titres below 1:96 significantly induced neutralizing antibodies against prototypic SARS-CoV-2 and the Delta variant by 13.03- and 9.27-fold, respectively. Transient adverse events occurred in three out of the twenty-eight immunized participants (10.71%). In addition, the ratio of naïve T cells increased dramatically, and TEMRA and TEM cells gradually decreased post vaccination. The expression levels of activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes in convalescent patients. Our results indicate that vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.
Project description:BackgroundWe studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.MethodsSera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.ResultsAfter completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19 + individuals (132-fold increase). Age >65 years (β=-0.94, p = 0.001) and malignancy (β=-0.88, p = 0.002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p = 0.004); (β=-0.66, p = 0.014)], diabetes mellitus [(β=-0.57, p = 0.032); (β=-0.44, p = 0.028)], and systemic steroid use [(β=-0.066, p = 0.032); (β=-0.55, p = 0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2. Post-booster neutralization increased with prior COVID-19 (β = 2.9, p-value < 0.0001), and malignancy reduced neutralization response (β=-0.68, p = 0.03), regardless of infection status.ConclusionMultiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.
Project description:BackgroundPublic health measures to stem the coronavirus disease 2019 (COVID-19) pandemic are challenged by social, economic, health status, and cultural disparities that facilitate disease transmission and amplify its severity. Prior pre-clinical biomedical technologic advances in nucleic acid-based vaccination enabled unprecedented speed of conceptualization, development, production, and widespread distribution of mRNA vaccines that target SARS-CoV-2's Spike (S) protein.DesignTwenty-five female and male volunteer fulltime employees at the Providence VA Medical Center participated in this study to examine longitudinal antibody responses to the Moderna mRNA-1273 vaccine. IgM-S and IgG-S were measured in serum using the Abbott IgM-S-Qualitative and IgG2-S-Quantitative chemiluminescent assays.ResultsPeak IgM responses after Vaccine Dose #1 were delayed in 6 (24%) and absent in 7 (28%) participants. IgG2-S peak responses primarily occurred 40 to 44 days after Vaccine Dose #1, which was also 11 to 14 days after Vaccine Dose #2. However, subgroups exhibited Strong (n = 6; 24%), Normal (n = 13; 52%), or Weak (n = 6; 24%) peak level responses that differed significantly from each other (P < .005 or better). The post-peak IgG2-S levels declined progressively, and within 6 months reached the mean level measured 1 month after Vaccine Dose #1. Weak responders exhibited persistently low levels of IgG2-S. Variability in vaccine responsiveness was unrelated to age or gender.ConclusionHost responses to SARS-CoV-2-Spike mRNA vaccines vary in magnitude, duration and occurrence. This study raises concern about the lack of vaccine protection in as many as 8% of otherwise normal people, and the need for open dialog about future re-boosting requirements to ensure long-lasting immunity via mRNA vaccination versus natural infection.
Project description:BackgroundPost-marketing surveillance studies have raised concerns of increased myocarditis rates following coronavirus disease-19 (Covid-19) mRNA vaccines. The present study aims to accumulate the published mRNA Covid-19 vaccine-associated myocarditis cases, describe their clinical characteristics and determine the factors predisposing to critical illness.MethodsMedline, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched from inception. Studies reporting adult myocarditis cases following BNT162b2 or mRNA-1273 vaccination were included. Individual participant data coming from case reports/series were pooled. Proportional random-effects meta-analysis was conducted by combining the pooled cohort and observational studies with aggregated data.ResultsOverall, 39 studies were included with a total of 129 patients. Most cases occurred in young males after the second vaccine dose. Myocarditis after the first dose was significantly associated with prior Covid-19 (p-value: 0.025). The most common electrocardiographic finding was ST-segment elevation, while late gadolinium enhancement was invariably observed in cardiac magnetic reasoning. Logistic regression analysis demonstrated that signs of heart failure were predictive of subsequent critical illness (Odds ratio: 19.22, 95% confidence intervals-CI: 5.57-275.84). Proportion meta-analysis indicated that complete resolution of symptoms is achieved in 80.5% of patients (95% CI: 59.3-92.1), while the proportion of participants necessitating intensive care unit admission is 7.0% (95% CI: 3.8-12.9).ConclusionsMyocarditis following mRNA Covid-19 vaccination is typically mild, following an uncomplicated clinical course with rapid improvement of symptoms. Future research is needed to define its exact incidence, clarify its pathophysiology and determine the optimal management plan depending on its severity. Protocol registration: dx.https://doi.org/10.17504/protocols.io.bxwtppen.
Project description:BackgroundOmicron variants with immune evasion have emerged, and they continue to mutate rapidly, raising concerns about the weakening of vaccine efficacy, and the very elderly populations are vulnerable to Coronavirus Disease 2019 (COVID-19). Therefore, to investigate the effect of multiple doses of mRNA vaccine for the newly emerged variants on these populations, cross-neutralizing antibody titers were examined against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, including BQ.1.1 and XBB.MethodsBlood samples were taken from residents at four long-term care facilities in Hyogo prefecture, Japan (median age, 91 years), after 3rd (n = 67) and 4th (n = 48) mRNA vaccinations, from April to October 2022. A live virus microneutralization assay was performed to determine the neutralizing antibody titers in participants' sera.ResultsAfter 3rd vaccination, cross-neutralizing antibody prevalence against conventional (D614G) virus, Delta, Omicron BA.2, BA.5, BA.2.75, BQ.1.1, and XBB were 100%, 97%, 81%, 51%, 67%, 4%, and 21%, respectively. After 4th vaccination, the antibody positivity rates increased to 100%, 100%, 98%, 79%, 92%, 31%, and 52%, respectively. The 4th vaccination significantly increased cross-neutralizing antibody titers against all tested variants.ConclusionThe positivity rates for BQ.1.1 and XBB increased after 4th vaccination, although the titer value was lower than those of BA.5 and BA.2.75. Considering the rapid mutation of viruses and the efficacy of vaccines, it may be necessary to create a system that can develop vaccines suitable for each epidemic in consideration of the epidemic of the virus.