Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo.

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Safety of heterologous ChAdOx1-S/BNT162b2 primary schedule versus homologous BNT162b2 vaccination: Insights from an Italian post-marketing study, 2021.

During COVID-19 vaccination campaign, possible ChAdOx1-S-associated risks of thrombosis with thrombocytopenia syndrome led to implement ChAdOx1-S/BNT162b2 heterologous vaccination, despite the limited information on its reactogenicity and safety. We conducted a prospective observational post-marketing surveillance study to assess the safety of this heterologous schedule. A casually selected sample of recipients (n: 85; age: 18-60 years) of ChAdOx1-S/BNT162b2 at the vaccination hub of the Foggia Hospital, Italy, was matched with an equal sample of recipients of homologous BNT162b2. Safety was evaluated 7 days, 1 month and 14 weeks after the primary vaccination series using an adapted version of the "V-safe active surveillance for COVID-19 vaccine safety" CDC standardized questionnaire. After 7 days, local reactions were highly frequent (>80%) in both groups, and systemic reactions were less common (<70%). Moderate or severe pain at the injection site (OR = 3.62; 95%CI, 1.45-9.33), moderate/severe fatigue (OR = 3.40; 95%CI, 1.22-9.49), moderate/severe headache (OR = 4.72; 95%CI, 1.37-16.23), intake of antipyretics (OR = 3.05; 95 CI%, 1.35-6.88), inability to perform daily activities and work (OR = 2.64; 95%CI, 1.24-5.62) were significantly more common with heterologous than homologous vaccination. No significant difference in self-reported health status was recorded 1 month or 14 weeks after the second dose with BNT162b2 or ChAdOx1-S/BNT162b2. Our study confirms the safety of both heterologous and homologous vaccination, with a slight increase in some short-term adverse events for the heterologous regimen. Therefore, administering a second dose of a mRNA vaccine to the recipients of a previous dose of viral vector vaccine may have represented an advantageous strategy to improve flexibility and to accelerate the vaccination campaign.

Humoral and cellular immune response to SARS-CoV-2 mRNA BNT162b2 vaccine in pediatric kidney transplant recipients compared with dialysis patients and healthy children.

BACKGROUND: Compared with the general population, the immune response to COVID-19 mRNA vaccines is lower in adult kidney transplant recipients (KTRs). However, data is limited for pediatric KTRs. In this study, we aimed to assess humoral and cellular immune responses to the COVID-19 mRNA vaccine in pediatric KTRs. METHODS: This multicenter, prospective, case-control study included 63 KTRs (37 male, aged 12-21 years), 19 dialysis patients, and 19 controls. Humoral (anti-SARS-CoV2 IgG, neutralizing Ab (nAb)) and cellular (interferon-gamma release assay (IGRA)) immune responses were assessed at least one month after two doses of BNT162b2 mRNA vaccine. RESULTS: Among COVID-19 naïve KTRs (n = 46), 76.1% tested positive for anti-SARS-CoV-2 IgG, 54.3% for nAb, and 63% for IGRA. Serum levels of anti-SARS-CoV-2 IgG and nAb activity were significantly lower in KTRs compared to dialysis and control groups (p < 0.05 for all). Seropositivity in KTRs was independently associated with shorter transplant duration (p = 0.005), and higher eGFR (p = 0.007). IGRA titer was significantly lower than dialysis patients (p = 0.009). Twenty (43.4%) KTRs were positive for all immune parameters. Only four of 11 seronegative KTRs were IGRA-positive. COVID-19 recovered KTRs had significantly higher anti-SARS-CoV-2 IgG and nAb activity levels than COVID-19 naïve KTRs (p = 0.018 and p = 0.007, respectively). CONCLUSIONS: The humoral and cellular immune responses to SARS-CoV-2 mRNA BNT162b2 vaccine are lower in pediatric KTRs compared to dialysis patients. Further prospective studies are required to demonstrate the clinical efficacy of the mRNA vaccine in KTRs. This prospective study was registered in ClinicalTrials.gov (NCT05465863, registered retrospectively at 20.07.2022). A higher resolution version of the Graphical abstract is available as Supplementary information.

Post Covid-19 Vaccination Inflammatory Syndrome: A Case Report.

A previously healthy 24-year-old male patient was referred to our clinic with bilateral lower extremity pain and dark urine, which developed two weeks after receiving the second dose of BNT162b2 vaccine against SARS-CoV-2. Laboratory tests indicated rhabdomyolysis. Lower extremity magnetic resonance imaging was compatible with myositis. Myositis-related antibodies were negative. Biopsy taken from gastrocnemius muscle revealed muscle necrosis and striking expression of major histocompatibility complex class I antigen. He was successfully treated, and his complaints resolved. One week later at follow-up, he reported new-onset exertional dyspnea with palpitations. ST-segment depressions were spotted on electrocardiography. Troponin T was found elevated as 0.595 ng/mL (normal <0.014 ng/mL). Echocardiography showed hypokinetic left ventricle with ejection fraction of 40%, and pericardial effusion of 2mm. An appropriate treatment plan was formulated for the diagnosis of myocarditis, eventually the patient recovered within ten days. BNT162b2 mRNA vaccine was felt to cause the aforementioned condition since no other etiology could be identified. Although it is known that BNT162b2 may induce myocarditis, myositis concomitant myocarditis appears to be a very rare adverse effect of this vaccine.

Tozinameran (Pfizer, BioNTech) and Elasomeran (Moderna) Efficacy in COVID-19-A Systematic Review of Randomised Controlled Trial Studies.

Background: The objective of this research was to test the efficacy and safety profile of tozinameran (30 µg, BNT162b2, Pfizer, BioNTech) and elasomeran (100 µg, mRNA-1273, Moderna) in COVID-19 prevention in ≥16-year-old patients vaccinated with two doses. Methods: A meta-analysis of the literature was conducted using the MEDLINE and EMBASE databases, following inclusion and exclusion criteria. Eight RCTs have been selected. The results were presented using the risk ratio (RR) with a 95% confidence interval (CI). A fixed-effect model or random-effect model was applied based on the heterogeneity of the results. Results: BNT162b2 and mRNA-1273 vaccines are efficient in preventing COVID-19 in comparison to a placebo (MH, RR 0.08 [0.07, 0.09] p < 0.00001 (95% CI)). It was found that administering the vaccines BNT162b2 and mRNA-1273 was associated with a higher proportion of adverse events in comparison to the placebo (IV, RR 2.14 [1.99, 2.29] p < 0.00001 (95% CI)). Administering the vaccines BNT162b2 and mRNA-1273 was associated with a higher proportion of serious adverse events in comparison to the placebo (MH, RR 0.98 [0.89, 1.08] p = 0.68 (95% CI)). Conclusions: Tozinameran and elasomeran are effective and safe in preventing the occurrence of COVID-19.

Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters.

Introduction: Assessing the response to vaccinations is one of the diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered the unique opportunity to analyze the immune response to a novel antigen. We identify four CVIDs phenotype clusters by the integration of immune parameters after BTN162b2 boosters. Methods: We performed a longitudinal study on 47 CVIDs patients who received the 3rd and 4th vaccine dose of the BNT162b2 vaccine measuring the generation of immunological memory. We analyzed specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells. Results: We found that, depending on the readout of vaccine efficacy, the frequency of responders changes. Although 63.8% of the patients have specific antibodies in the serum, only 30% have high-affinity specific memory B cells and generate recall responses. Discussion: Thanks to the integration of our data, we identified four functional groups of CVIDs patients with different B cell phenotypes, T cell functions, and clinical diseases. The presence of antibodies alone is not sufficient to demonstrate the establishment of immune memory and the measurement of the in-vivo response to vaccination distinguishes patients with different immunological defects and clinical diseases.

Age, Sex and BMI Relations with Anti-SARS-CoV-2-Spike IgG Antibodies after BNT162b2 COVID-19 Vaccine in Health Care Workers in Northern Greece.

The aim of this work was to study age, sex, and BMI (Body Mass Index)-related differences in the development of anti-SARS-CoV-2-Spike IgG antibodies, after vaccination with the BNT162b2 COVID-19 vaccine, in health care workers of a General Hospital in a city in Northern Greece. Blood sampling was drawn two to four weeks following the second dose of the vaccine, and six months after the first blood sample collection. Measurement of serum IgG antibodies against the spike domain of SARS-CoV-2 was performed using the SARS-CoV-2 IgG II Quant assay. All participants had sufficient serum IgG titers in the first measurement. Women developed higher IgG titers than men. The IgG titers were inversely related to age in both sexes; there was also a small, insignificant tendency to be inversely related to BMI. Six months after the first measurement, the IgG titers decreased dramatically to values less than 5% of the initial. This decrease was observed in both men and women and was inversely related to age. Multivariate regression analysis showed that age and sex explained with statistical significance 9% of the variance in SARS-CoV-2 IgG titers in our study population; the role of BMI was limited and insignificant.

Impact of Health Workers' Choice of COVID-19 Vaccine Booster on Immunization Levels in Istanbul, Turkey.

BACKGROUND: There are limited data regarding short- and medium-term IgG antibody levels after the CoronaVac and BNT162b2 vaccines. This study aimed to investigate the antibody responses of health workers who initially received two doses of CoronaVac one month apart followed by a booster dose of either CoronaVac or BNT162b2, as well as determine whether either vaccine provided superior results. METHODS: This research represents the second phase of a mixed-methods vaccine cohort study and was conducted between July 2021 and February 2022. The participants (n = 117) were interviewed in person and blood samples were collected before and at 1 and 6 months after the booster vaccination. RESULTS: BNT162b2 was found to have greater immunogenic potential than CoronaVac (p < 0.001). Health workers without chronic disease exhibited statistically significant increases in antibody levels after both vaccines (p < 0.001), whereas only BNT162b2 caused a significant increase in antibody levels in participants with chronic disease (p < 0.001). Samples obtained before and at 1 and 6 months after the booster vaccination revealed no age- or sex-based differences in IgG-inducing potential for either vaccine (p > 0.05). Antibody levels were comparable in both vaccine groups before the booster regardless of COVID-19 history (p > 0.05); however, antibody levels were significantly higher after the BNT162b2 booster at 1 month (<0.001) and at 6 months, except among participants who had a positive history of COVID-19 infection (p < 0.001). CONCLUSIONS: Our results suggest that even a single booster dose of BNT162b2 after initial vaccination with CoronaVac provides a protective advantage against COVID-19, especially for risk groups such as health workers and those with chronic diseases.

Three to four mRNA COVID-19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization.

BACKGROUND AND PURPOSE: An enhanced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated by anti-CD20. The aim was to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti-CD20 receiving a primary vaccine regimen enhanced with three injections. METHODS: In this prospective longitudinal cohort study of 90 patients (47 on anti-CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G antibodies were quantified and their neutralization capacity was evaluated by enzyme-linked immunosorbent assay (GenScript) and a virus neutralization test against B.1 historical strain, Delta and Omicron variants, before and after three to four BNT162b2 injections. RESULTS: After the primary vaccination scheme, the anti-RBD positivity rate was strongly decreased in patients on anti-CD20 (28% [15%; 44%] after two shots, 45% [29%; 62%] after three shots) and fingolimod (50% [16%; 84%]) compared to other treatments (100% [90%; 100%]). Neutralization activity was also decreased in patients on anti-CD20 and fingolimod, and notably low for the Omicron variant in all patients (0%-22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti-RBD seropositivity in patients on anti-CD20 although it was still lower compared to other treatments (65% [43%; 84%] vs. 100% [87%; 100%] respectively). After a booster, Omicron neutralization activity remained low on anti-CD20 and fingolimod treated patients but was strongly increased in patients on other treatments (91% [72%; 99%]). DISCUSSION: In MS patients on anti-CD20, an enhanced primary vaccination scheme moderately increased anti-RBD seropositivity and anti-RBD antibody titre, but neutralization activity remained modest even after a fourth booster injection. TRIAL REGISTRATION INFORMATION: COVIVAC-ID, NCT04844489, first patient included on 20 April 2021.

Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand.

This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron variant. We enrolled 97 children and 57 adolescents. At 3 months, 30 children (31%) and 34 adolescents (60%) reported at least one long COVID symptom, with respiratory symptoms prevailing (25% children and 32% adolescents). The median time from infection to vaccination was 3 months in adolescents and 7 months in children. At 1 month following vaccination, in children who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 86.2% inhibition (71.1-91.8) and 79.2% inhibition (61.5-88.9), respectively (p = 0.26). Among adolescents who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 64.4% inhibition (46.8-88.8) and 68.8% inhibition (65.0-91.2) (p = 0.64). Adolescents had a higher prevalence of long COVID than children. Immunogenicity against the Omicron variant after vaccination was high and did not vary between one or two doses of the vaccine in either children or adolescents.

Efficacy of BNT162b2 and CoronaVac in patients diagnosed with COVID-19.

This retrospective observational study is aimed to determine the efficacy of BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines against symptomatic or severe disease in COVID-19-diagnosed patients. The secondary aim was to define the differences between vaccinated and un-vaccinated patients in terms of age, comorbidities and course of the disease, and to determine the survival rates. Of the 1463 PCR-positive patients, 55.3 % were vaccinated, and 44.7 % were unvaccinated. While 959 patients had mild-moderate symptoms, 504 patients had severe-critical symptoms and were treated in the intensive care unit. There was a statistically significant difference in the distribution of the type and doses of vaccines between the patient groups (p = 0.021). The rate of receiving 2 doses of Biontech was 18.9 % in the mild-moderate patient group but lower in the severe patient group (12.6 %). The rate of two doses of Sinovac and two doses of Biontech vaccine (four doses of vaccine) was 5 % in the mild-moderate patient group and 1.9 % in the severe patient group. The mortality rates were statistically significantly different (p < 0.001) between the patient groups: 65.3 % in the severe patient group and 1 % in the mild-moderate patient group. The multivariate model showed that the mortality risk of the unvaccinated patients was 1.5 times higher than the vaccinated ones (p = 0.042). In addition to being unvaccinated, advanced age, coronary artery disease (CAD), diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and obesity were found to be associated with higher mortality risk. Besides, the reduction in mortality rate was more evident in individuals vaccinated with at least 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine than in CoronaVac group.

A Saliva-Based Serological and Behavioral Analysis of SARS-CoV-2 Antibody Prevalence in Howard County, Maryland.

The objective of the study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the Howard County, Maryland, general population and demographic subpopulations attributable to natural infection or coronavirus disease 2019 (COVID-19) vaccination and to identify self-reported social behaviors that may affect the likelihood of recent or past SARS-CoV-2 infection. A cross-sectional, saliva-based serological study of 2,880 residents of Howard County, Maryland, was carried out from July through September 2021. Natural SARS-CoV-2 infection prevalence was estimated by inferring infections among individuals according to anti-nucleocapsid immunoglobin G levels and calculating averages weighted by sample proportions of various demographics. Antibody levels between BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) recipients were compared. Antibody decay rate was calculated by fitting exponential decay curves to cross-sectional indirect immunoassay data. Regression analysis was carried out to identify demographic factors, social behaviors, and attitudes that may be linked to an increased likelihood of natural infection. The estimated overall prevalence of natural infection in Howard County, Maryland, was 11.9% (95% confidence interval, 9.2% to 15.1%), compared with 7% reported COVID-19 cases. Antibody prevalence indicating natural infection was highest among Hispanic and non-Hispanic Black participants and lowest among non-Hispanic White and non-Hispanic Asian participants. Participants from census tracts with lower average household income also had higher natural infection rates. After accounting for multiple comparisons and correlations between participants, none of the behavior or attitude factors had significant effects on natural infection. At the same time, recipients of the mRNA-1273 vaccine had higher antibody levels than those of BNT162b2 vaccine recipients. Older study participants had overall lower antibody levels compared with younger study participants. The true prevalence of SARS-CoV-2 infection is higher than the number of reported COVID-19 cases in Howard County, Maryland. A disproportionate impact of infection-induced SARS-CoV-2 positivity was observed across different ethnic/racial subpopulations and incomes, and differences in antibody levels across different demographics were identified. Taken together, this information may inform public health policy to protect vulnerable populations. IMPORTANCE We employed a highly innovative noninvasive multiplex oral fluid SARS-CoV-2 IgG assay to ascertain our seroprevalence estimates. This laboratory-developed test has been applied in NCI's SeroNet consortium, possesses high sensitivity and specificity according to FDA Emergency Use Authorization guidelines, correlates strongly with SARS-CoV-2 neutralizing antibody responses, and is Clinical Laboratory Improvement Amendments-approved by the Johns Hopkins Hospital Department of Pathology. It represents a broadly scalable public health tool to improve understanding of recent and past SARS-CoV-2 exposure and infection without drawing any blood. To our knowledge, this is the first application of a high-performance salivary SARS-CoV-2 IgG assay to estimate population-level seroprevalence, including identifying COVID-19 disparities. We also are the first to report differences in SARS-CoV-2 IgG responses by COVID-19 vaccine manufacturers (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]). Our findings demonstrate remarkable consistency with those of blood-based SARS-CoV-2 IgG assays in terms of differences in the magnitude of SARS-CoV-2 IgG responses between COVID-19 vaccines.

Selection Effects and COVID-19 Mortality Risk after Pfizer vs. Moderna Vaccination: Evidence from Linked Mortality and Vaccination Records.

Prior research generally finds that the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA1273) COVID-19 vaccines provide similar protection against mortality, sometimes with a Moderna advantage due to slower waning. However, most comparisons do not address selection effects for those who are vaccinated and with which vaccine. We report evidence on large selection effects, and use a novel method to control for these effects. Instead of directly studying COVID-19 mortality, we study the COVID-19 excess mortality percentage (CEMP), defined as the COVID-19 deaths divided by non-COVID-19 natural deaths for the same population, converted to a percentage. The CEMP measure uses non-COVID-19 natural deaths to proxy for population health and control for selection effects. We report the relative mortality risk (RMR) for each vaccine relative to the unvaccinated population and to the other vaccine, using linked mortality and vaccination records for all adults in Milwaukee County, Wisconsin, from 1 April 2021 through 30 June 2022. For two-dose vaccinees aged 60+, RMRs for Pfizer vaccinees were consistently over twice those for Moderna, and averaged 248% of Moderna (95% CI = 175%,353%). In the Omicron period, Pfizer RMR was 57% versus 23% for Moderna. Both vaccines demonstrated waning of two-dose effectiveness over time, especially for ages 60+. For booster recipients, the Pfizer-Moderna gap is much smaller and statistically insignificant. A possible explanation for the Moderna advantage for older persons is the higher Moderna dose of 100 µg, versus 30 µg for Pfizer. Younger persons (aged 18-59) were well-protected against death by two doses of either vaccine, and highly protected by three doses (no deaths among over 100,000 vaccinees). These results support the importance of a booster dose for ages 60+, especially for Pfizer recipients. They suggest, but do not prove, that a larger vaccine dose may be appropriate for older persons than for younger persons.

Key Lessons from COVID-19: A Narrative Review Describing Qatar's Multifactorial Approach in Executing a Vaccination Campaign.

Widespread vaccination programs have been implemented in many countries to curtail the COVID-19 pandemic, with varying success and challenges. To better understand the successes and challenges of the global COVID-19 response in the face of emerging new variants and epidemiologic data, we discuss how Qatar engaged the healthcare sector, governmental bodies, and the populace to combat COVID-19, with a focus on the country's vaccination strategy. This narrative provides the history and timeline of the Qatar COVID-19 vaccination campaign; factors that helped the vaccination campaign and the transferable lessons learned are discussed. Details regarding how Qatar responded to challenges, such as vaccine hesitancy and mitigation of misinformation, are highlighted. Qatar was one of the first countries to procure the BNT162b2 (Comirnaty®; Pfizer-BioNTech, Pfizer Inc., New York, NY, USA) and mRNA-1273 (Spikevax®; Moderna, Cambridge, MA, USA) COVID-19 vaccines. A relatively high vaccination rate and low case mortality rate (0.14% as of 4 January 2023) was observed in Qatar compared with other countries (global case mortality rate, 1.02%). Learnings will be carried forward as a basis for addressing this evolving pandemic and any future national emergencies in Qatar.

Effectiveness of mRNA and inactivated COVID-19 vaccines: A test-negative study in an infection-naïve Hong Kong population.

OBJECTIVE: Assess real-world effectiveness of vaccines against COVID-19. METHODS: A test-negative study was conducted in January-May 2022 during an Omicron BA.2 wave in Hong Kong. COVID-19 was identified by RT-PCR. 1-1 case-control matching was based on propensity score with vaccine effectiveness adjusted for confounders. RESULTS: Altogether, 1781 cases and 1737 controls aged 3-105 years were analysed. The mean lag time from the last dose of vaccination to testing for SARS-CoV-2 was 133.9 (SD: 84.4) days. Two doses of either vaccine within 180 days offered a low effectiveness against COVID-19 of all severity combined (VEadj [95% CI] for BNT162b2: 27.0% [4.2-44.5], CoronaVac: 22.9% [1.3-39.7]), and further decreased after 180 days. Two doses of CoronaVac were poorly protective 39.5% [4.9-62.5] against severe diseases for age ≥ 60 years, but the effectiveness increased substantially after the third dose (79.1% [25.7-96.7]). Two doses of BNT162b2 protected age ≥ 60 years against severe diseases (79.3% [47.2, 93.9]); however, the uptake was not high enough to assess three doses. CONCLUSIONS: The current real-world analysis indicates a high vaccine effectiveness of three doses of inactivated virus (CoronaVac) vaccines against Omicron variant, whereas the effectiveness of two doses is suboptimal.

Guillain-Barré Syndrome Following the BNT162b2 mRNA COVID-19 Vaccine

PURPOSE: The onset of the COVID-19 (SARS-CoV-2) pandemic in December 2019 created the need for multiple scientific research activities and clinical trials in an attempt to find solutions to mitigate the impact of the virus. One of the important tools to combat the virus is the development of vaccination programs. All types of vaccines have been associated with a mild to severe risk of neurological adverse events. One of these severe adverse events is Guillain-Barré syndrome. CASE REPORT: Here, we describe a case of Guillain-Barré syndrome after the first dose of the BNT162b2 mRNA COVID-19 vaccine and review the literature to increase the current knowledge regarding this complication. CONCLUSION: Guillain-Barré syndrome after COVID-19 vaccination is responsive to treatment. The benefits of administering the vaccine outweigh the risks. Due to the negative impact of COVID-19, it is essential to recognize the development of neurological complications that are potentially associated with vaccination, including Guillain-Barré syndrome.

Characteristics and outcomes of adverse events after COVID-19 vaccination.

OBJECTIVES: BNT-162b2, mRNA-1273, and Ad26.COV2.S vaccines data regarding adverse events (AEs) are scarce. In this report, we aimed to describe fatal and non-fatal possible AEs after COVID-19 vaccine administration. METHODS: An observational multicenter study investigating the causes of emergency department visits and hospital admissions within 10 days of COVID-19 vaccination. Patients who received first or second doses of COVID-19 vaccines and presented to the emergency department (ED), as well as those admitted to the hospitals or intensive care units (ICUs) were included. Causes of ED, hospital, and ICU admissions and discharges were collected based on the International Classification of Diseases, Tenth Revision (ICD-10) coding system. RESULTS: Between December 2020 and March 2021, 1842 patients visited the ED within 10 days of COVID-19 vaccine administration. The mean age was 70.3 years. Overall, 1221 patients presented after the first dose of the vaccine and 653 after the second dose. Trauma (14.9%), hypertensive emergency/urgency (7.8%), generalized pain and arthralgia (5.7%), and chest pain (4.4%) were the most common causes of presentation to the ED. Of all ED presentations, mortality rate was at 2.2% (41 patients) with a median follow-up time of 68.0 days, versus 2.6% in unvaccinated ED patients. Postvaccination acute hypoxemic respiratory failure (46.3%), septic shock (24.4%), and cardiogenic shock (12.2%) were the most common causes of death. CONCLUSION: Although reported AEs are not necessarily caused by the vaccination, this study provides further information about possible AEs after COVID-19 immunization, especially those requiring hospital admission. This study also supports prior data that serious AEs post vaccination are much lower than primary COVID-19 infections. Further studies are needed to investigate causalities between vaccines and reported AEs across all age groups.

Variation in antibody titers determined by Abbott and Roche Elecsys SARS-CoV-2 assays in vaccinated healthcare workers.

SARS-CoV-2-specific antibody measurement is important for evaluating COVID-19 vaccine efficacy. We quantified and compared anti-spike (S) antibodies using different commercial immunoassays. We tested serum samples from 70 SARS-CoV-2-naive health care workers 2 weeks after vaccination with a single dose of BNT162b2, 2 and 4 weeks, and 3 months after the second dose of BNT162b2. The following quantitative assays were used: Roche Elecsys Anti-SARS-CoV-2 S (Roche-S), Abbott SARS-CoV-2 IgG II Quant [Abbott-IgG(S)], and Abbott SARS-CoV-2 IgM (Abbott-IgM). All samples tested positive for Roche-S and Abbott-IgG antibodies after the second dose, with 83.6% Abbott-IgM positive rate. Roche-S and Abbott-IgG(S) correlated significantly in all samples (r = 0.920, p < 0.0001), and the Roche-S and Abbott-IgG(S) assay showed a strong correlation with each other at each time point after vaccination. Roche-S and Abbott-IgG(S) antibody titers were correlated with age; their rate of decline was age-dependent in males but not in females. Abbott-IgG(S) antibody titers decreased from 2 weeks after the second dose. Roche-S antibody titers peaked 2 weeks after the second dose in 76.2% of the participants; the titers recovered 3 months post-vaccination after declining at week 4 in 40.7% of the participants. The concordance between Roche-S and Abbott-IgG(S) antibody titers over time was 47.5%. Most participants presented significantly high Roche-S and Abbott-IgG(S) antibody titers after immunization. Some measurements were inconsistent with titer changes between these assays, possibly because of differences in the immunoglobulin-specificity of the kits.

B-cell lymphoblastic lymphoma following intravenous BNT162b2 mRNA booster in a BALB/c mouse: A case report.

Unprecedented immunization campaigns have been rolled out worldwide in an attempt to contain the ongoing COVID-19 pandemic. Multiple vaccines were brought to the market, among two utilizing novel messenger ribonucleic acid technology. Despite their undisputed success in decreasing COVID-19-associated hospitalizations and mortality, various adverse events have been reported. The emergence of malignant lymphoma is one of such rare adverse events that has raised concern, although an understanding of the mechanisms potentially involved remains lacking. Herein, we present the first case of B-cell lymphoblastic lymphoma following intravenous high-dose mRNA COVID-19 vaccination (BNT162b2) in a BALB/c mouse. Two days following booster vaccination (i.e., 16 days after prime), at only 14 weeks of age, our animal suffered spontaneous death with marked organomegaly and diffuse malignant infiltration of multiple extranodal organs (heart, lung, liver, kidney, spleen) by lymphoid neoplasm. Immunohistochemical examination revealed organ sections positive for CD19, terminal deoxynucleotidyl transferase, and c-MYC, compatible with a B-cell lymphoblastic lymphoma immunophenotype. Our murine case adds to previous clinical reports on malignant lymphoma development following novel mRNA COVID-19 vaccination, although a demonstration of direct causality remains difficult. Extra vigilance is required, with conscientious reporting of similar cases and a further investigation of the mechanisms of action explaining the aforementioned association.