Immunogenicity and safety of Sinovac-CoronaVac booster vaccinations in 12-17- year-olds with clinically significant reactions from Pfizer-BNT162b2 vaccination.

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.

Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults.

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine. Design, Setting, and Participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023. Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary). Main Outcomes and Measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window. Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]). Conclusions and Relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

The Impact of the Emotional Disposition of Healthcare Workers on the Expression of Adverse Events after Primary Vaccination against SARS-CoV-2.

Background and Objectives: Vaccination is one means of SARS-CoV-2 prevention and control. However, despite the effectiveness of vaccination, adverse reactions continue to require vigilance and monitoring. The researchers emphasize the possibility that some of the reported side effects may be psychological in origin. Based on this hypothesis, the main goal of this study was to evaluate the emotional dispositions of healthcare workers who experienced emotions before vaccination and adverse reactions after vaccination. Materials and Methods: This study was conducted between February and May 2021 in the Kaunas Clinics of the University of Health Sciences. A total of 2117 employees of the clinic departments who were vaccinated with two doses of the Pfizer-BioNTech vaccine participated in this study. Statistical analysis was performed on the data using IBM SPSS Statistics®. Results: Most participants (74.5%) experienced systemic (including local) adverse events; 16.5% experienced only local adverse events, and 9.1% experienced no adverse events. The frequency of systemic (including local) adverse events reduced with increasing age (p < 0.05). The main emotions that participants experienced before vaccination were anxiety (37.88%) and happiness (39.02%). Systemic (including local) adverse events occurred 1.26 times more frequently in women than men (77.44% vs. 61.6%, p < 0.05), while local adverse events occurred 1.4 times more often in male participants than in female participants (21.39% vs. 15.27%, p < 0.05). Among the respondents who did not experience adverse events, the most common emotion felt was happiness (25.5%), and most of the participants who experienced systemic (including local) adverse events felt anxiety (42.6%). Conclusions: The information about vaccination and potential adverse events should be targeted at younger persons. It is recommended that women, more than men, should receive professional counseling from psychologists or psychotherapists. The public dissemination of positive messages about the benefits and safety of vaccines prior to a vaccination campaign may alleviate the tension or anxiety felt regarding potential adverse events. Healthcare specialists-both those who work directly with vaccines and those who do not-should maintain a positive psychological attitude towards vaccination, as this can increase patient satisfaction with the benefits of vaccines.

Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis.

INTRODUCTION: Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received. METHODS: Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria. RESULTS: Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization. CONCLUSIONS: COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

BioNTech COVID-19 (BNT162b2) Vaccination and Varicella Zoster Reactivation: A Comprehensive Cross-sectional Study.

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Recent observations have suggested that HZ is associated with vaccination against COVID-19. To investigate the association between the vaccine and HZ severity, a single-centre, cross-sectional study of all patients diagnosed with HZ and 2 control diagnoses (cellulitis and bone fractures), between 2017 and 2021, was performed. Hospital visits and hospitalization rates were compared. All medical records of patients diagnosed with HZ in the first year after the COVID-19 vaccination campaign began were reviewed, in order to generate a retrospective cohort comparing vaccinated and unvaccinated patients with HZ. All participants had received the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. During the study period, 2,413 patients were diagnosed with HZ, and when normalized to control diagnoses the number of cases remained stable. The retrospective cohort included 365 patients. A multivariate analysis controlling for sex, age, autoimmune diseases, malignancies, and immunosuppressive therapy showed higher admission rates in vaccinated compared with unvaccinated individuals (odds ratio (OR) 2.75, 95% CI 1.27-5.96, p = 0.01). However, matching techniques and stratification by age, used to better control for confounders, invalidated these findings. No differences were observed in other variables indicative of disease severity (hospital stay length and complications). In conclusion, COVID-19 vaccination was not found to be associated with an increased risk of HZ-related admission and complications.

Incidence rates of myocarditis and pericarditis within 30 days following homologous and heterologous BNT162b2 vaccinations in individuals 5-40 years of age.

INTRODUCTION: Due to the data scarcity in low- and middle-income countries, we aimed to examine the incidence rate of myocarditis and pericarditis within 30 days after each dose of homologous (3 × BNT162b2) and heterologous prime-boost (2 × BBIBP-CorV/BNT162b2) vaccine regimen among individuals younger than 40 years. METHODS: We conducted a historical control cohort using routinely recorded data from Thai national vaccine and insurance claims databases. Sex-specific incidence rate ratios (IRRs) for myocarditis and pericarditis were calculated for each vaccination strategy and contrasted with incidence rates among the non-immunised population in the pre-COVID-19 period. From August 2021 to September 2022, we tracked the incidence of myocarditis and pericarditis within 30 days after vaccinations using < 40-year-old national population databases. Our reference was the average monthly incidence of these conditions in the non-immunised population from August to October 2019. The exposure of interest was immunisation against the SARS-CoV-2 virus, incorporating the following vaccination strategies: three-dose 3 × BNT162b2 regimen, three-dose 2 × BBIBP-CorV/BNT162b2 regimen, and non-immunisation. RESULTS: For myocarditis, a total of 215 cases were identified among 7,594,965 individuals in the 3 × BNT162b2 cohort, 5 cases among 2,914,643 individuals in the 2 × BBIBP-CorV/BNT162b2 cohort, and 115 cases among 32,424,780 non-immunised individuals. The sex-specific IRRs (95 % confidence intervals) of myocarditis and pericarditis after the homologous vaccination were 3.09 (1.61, 5.93) and 1.84 (0.72, 4.73) for females and 7.43 (3.11, 17.73) and 10.48 (3.90, 28.15) for males, respectively. Conversely, the IRRs of myocarditis after the heterologous vaccination were not significant (females: 2.24 (0.70, 7.17); males: 1.99 (0.48, 8.21)). IRRs could not be obtained for pericarditis after the heterologous vaccination because of the small number of observed events. CONCLUSIONS: The study observed a significantly increased risk of myocarditis and pericarditis following homologous 3 × BNT162b2 vaccination but had insufficient power to confirm an increased risk for myocarditis following the heterologous prime-boost 2 × BBIBP-CorV/BNT162b2 vaccination. The incidence of pericarditis following the heterologous vaccination was too rare to evaluate.

Echocardiographic function evaluation in adolescents following BNT162b2 Pfizer-BioNTech mRNA vaccination: A preliminary prospective study.

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) is crucial for preventing and minimizing illness. Myocarditis and pericarditis after messenger RNA (mRNA) COVID-19 vaccination in adolescents and young adult males have been reported. Most of the studies in this area rely on retrospective symptom reporting, especially for adolescents experiencing myocarditis as a potential side effect. However, prospective postvaccination echocardiographic evaluation is rare. METHODS: The study enrolled adolescents aged 12 to 15 years who received the second dose of the BNT162b2 Pfizer-BioNTech mRNA (BNT) vaccine. Serial echocardiographic examinations were conducted at baseline before vaccination, followed by subsequent assessments on days 2, 7, 14, and 28 to identify any notable differences or abnormal changes in cardiac function. Clinical symptom assessments were also recorded during each follow-up. RESULTS: The study included 25 adolescents, comprising 14 males and 11 females, who completed the four follow-ups. Their mean age was 14 ± 1 years. The average interval between the first and second BNT vaccine doses was 90 ± 7 days. Ejection fraction values were 73.8% ± 5.2% at baseline, followed by 75.7% ± 5.3%, 75.5% ± 4.6%, 75.7% ± 4.5%, and 77.8% ± 5.8% at day 2, 7, 14, and 28, respectively. The cardiac function remained stable across all time points, with no significant differences observed between male and female participants. Within postvaccination 48 hours, 18 (72%) of the enrolled adolescents experienced temporary discomfort symptoms, which completely resolved by the final follow-up on the 28th day after vaccination. CONCLUSION: Although adolescents vaccinated with the second dose of BNT vaccine commonly experienced transient postvaccination discomfort, the serial echocardiographic examinations did not reveal any significant deterioration of cardiac function within 28 days. Further studies are required to investigate the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination-associated myocarditis in adolescents and the related mechanisms.

N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3-5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization.

Vestibular disorders following BNT162b2 mRNA COVID-19 vaccination: A retrospective case series.

BACKGROUND: There are few publications regarding manifestations of vestibular disorders (VDs) following BNT162b2 mRNA COVID-19 vaccination. PURPOSE: We describe cases of VD potentially related to BNT162b2 vaccination and calculate its reporting rate, in order to enlarge knowledge about this adverse effect. METHODS: A retrospective analysis of cases of VD following BNT162b2 vaccination reported to the pharmacovigilance centre of Georges-Pompidou European Hospital (France), in 2021 was performed. In order to identify these cases from the pharmacovigilance database containing all our registered cases, we used the Standardised MedDRA Query (SMQ) 'vestibular disorders'. Then we analysed cases with vestibular symptoms, based on the association of typical manifestations. The reporting rate was calculated based on the number of VD cases and the number of vaccinated patients. RESULTS: Among 6608 cases reported to our centre related to COVID-19 vaccines during 2021, 34 VDs associated with BNT162b2 administration were included. They were mainly reported in females (79%), 62% occurred after the first dose and 32% were serious. Symptoms had completely resolved in 13 cases (38%). Vertigo was the most common symptom followed by balance disorders. Three patients received second dose without reappearance of VD. The final diagnosis was reported in 10 patients (six cases of vestibular neuritis, two cases of central VD, two cases of benign paroxysmal positional vertigo). The regional reporting rate was 26 [95% CI: 17-34] cases of VD per 1 million persons vaccinated. CONCLUSION: Although the relationship between vaccination and VD cannot be established, clinicians should be aware of this rare adverse effect.

Possible association between vaccination against SARS-CoV-2 and recurrence of macular edema due to branch retinal vein occlusion: a case report.

We herein describe a patient who developed recurrence of macular edema (ME) due to branch retinal vein occlusion (BRVO) 3 days after administration of the BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A man in his early 50s visited our hospital because of vision loss in his right eye. His logarithmic best-corrected visual acuity (BCVA) was -0.79 in both eyes. ME due to superior temporal BRVO was observed in his right eye, and the central foveal thickness (CFT) was 486 µm. The patient was treated with an intravitreal aflibercept injection with logarithmic BCVA of -0.79, leading to resolution of the ME with a CFT of 299 µm. Three months after the initial visit, he received a fourth dose of an mRNA vaccine. Three days later, he developed vision loss in his right eye. Although the logarithmic BCVA was maintained at -0.79, ME recurred with a CFT of 507 µm. The patient was treated with an additional dose of intravitreal aflibercept injection. The ME resolved and the logarithmic BCVA in the right eye was maintained at -0.79. This case indicates a possible association between vaccination against SARS-CoV-2 and recurrence of ME due to BRVO.

Risk of lymphadenopathy from SARS-CoV-2 vaccination in Korea: a self-controlled case series analysis.

OBJECTIVES: To assess the risk of lymphadenopathy following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1-day to 42-day risk interval after coronavirus disease 2019 (COVID-19) vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval. RESULTS: The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% confidence interval [CI], 1.17 to 1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44 to 1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson's comorbidity index <5, and those who received mRNA vaccines (mRNA-1273>BNT162b2). Within the 1-day to 42-day post-dose risk period, the relative risk was highest during the 1-day to 7-day post-dose period (1.59; 95% CI, 1.57 to 1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI. CONCLUSIONS: SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.

Intraneural ganglion cyst of the peroneal nerve occurring after coronavirus disease-19 vaccination: A case report.

Ganglion cysts are relatively common, but intraneural ganglion cysts (INGCs) within peripheral nerves are rare and poorly understood. We present the case of a 58-year-old woman who presented with acute right-foot drop. She experienced acute knee pain radiating from the lateral leg to the dorsal foot two days after the first coronavirus disease-19 (COVID-19) vaccination (BNT162b2, Pfizer-BioNTech). She had no history of trauma or medication use. Two weeks after the onset of symptoms, she developed a dorsiflexor weakness of the right foot (Medical Research Council grade, poor). The weakness worsened to a "trace" grade despite providing conservative management for one month. Ultrasonography revealed a fusiform echolucent structure within the course of the right common peroneal nerve around the fibular head. Magnetic resonance imaging revealed multiple intraneural cysts within the right common peroneal nerve. Nerve conduction and electromyographic studies revealed multiphasic motor unit action potentials accompanied by abnormal spontaneous activities in the innervated muscles, along with axonal degeneration of the deep peroneal nerves. Surgical removal of the cyst was performed, and the patient's symptoms gradually improved. Pathological examination revealed a cystic structure containing mucinous or gelatinous fluid and lined with flattened or cuboidal cells. The clinical course and sequential electromyographic findings relevant to this symptomatic cyst were temporally related to the vaccination date. The present case suggests that INGC-induced peroneal palsy is a possible complication after COVID-19 vaccination.

Safety of BNT162b2 and CoronaVac during pregnancy on birth outcomes and neonatal mortality: a cohort study from Brazil.

BACKGROUND: COVID-19 vaccines have been shown to protect pregnant individuals against mild and severe COVID-19 outcomes. However, limited safety data are available for inactivated (CoronaVac) and mRNA (BNT162b2) vaccines during pregnancy regarding their effect on birth outcomes and neonatal mortality, especially in low- and middle-income countries. METHODS: We conducted a retrospective population-based cohort study in Rio de Janeiro, Brazil, with 17 513 singleton live births conceived between 15 May 2021 and 23 October 2021. The primary exposure was maternal vaccination with CoronaVac or mRNA BNT162b2 vaccines and sub-analyses were performed by the gestational trimester of the first dose and the number of doses given during pregnancy. The outcomes were pre-term birth (PTB), small for gestational age (SGA), low birthweight (LBW), low Apgar 5 and neonatal death. We used the Cox model to estimate the hazard ratio (HR) with a 95% CI and applied the inverse probability of treatment weights to generate adjusted HRs. RESULTS: We found no significant increase in the risk of PTB (HR: 0.98; 95% CI 0.88, 1.10), SGA (HR: 1.09; 95% CI 0.96, 1.27), LBW (HR: 1.00; 95% CI 0.88, 1.14), low Apgar 5 (HR: 0.81; 95% CI 0.55, 1.22) or neonatal death (HR: 0.88; 95% CI 0.56, 1.48) in women vaccinated with CoronaVac or BNT162b2 vaccines. These findings were consistent across sub-analyses stratified by the gestational trimester of the first dose and the number of doses given during pregnancy. We found mild yet consistent protection against PTB in women who received different vaccine platforms during the third trimester of pregnancy (any vaccines, HR: 0.78; 95% CI 0.63, 0.98; BNT162b2, HR: 0.75; 95% CI 0.59, 0.99). CONCLUSIONS: This study provides evidence that COVID-19 vaccination in all trimesters of pregnancy, irrespective of the vaccine type, is safe and does not increase the risk of adverse birth outcomes or neonatal deaths.

Aseptic Meningitis after BNT-162b2 COVID-19 Vaccination: Case Report and Literature Review.

We encountered a-27-year-old female patient who developed refractory severe headache and photophobia after the first dose of COVID-19 vaccine. Despite her prior history of migraine, we diagnosed COVID-19 vaccine-induced aseptic meningitis. Symptoms were significantly resolved after methylprednisolone therapy. On reviewing the literature, we could find only nine similar cases, with over half of them affecting women aged 20-40 years. Although uncommon, aseptic meningitis should be suspected in patients with persistent or delayed onset of headache following COVID-19 vaccination.

Acute Interstitial Nephritis with Glomerular Capillary IgA Deposition Following SARS-CoV-2 mRNA Vaccination.

We herein report a case of acute kidney injury (AKI) presenting as acute interstitial nephritis (AIN) after the first dose of the BNT162b2 mRNA vaccine against coronavirus disease 2019 (COVID-19). A 69-year-old man with a history of diabetes and hypertension presented with AKI 4 days after receiving the vaccine. Despite the administration of methylprednisolone pulse treatment, his renal function worsened, which prompted us to initiate temporal hemodialysis. His renal function subsequently improved, and a renal biopsy confirmed AIN and glomerular capillary IgA deposition without apparent crescents. The clinical history and histological findings suggest a relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and AIN as a rare side effect.