Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection.

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.

The spectrum of side effects associated with COVID-19 vaccines in patients with inborn errors of immunity.

OBJECTIVE: COVID-19 immunization was implemented with emergency-use authorization. We had concerns/lack of information on mRNA vaccine side effects in different inborn errors of immunity (IEI) types. METHODS: We enrolled 141 patients (IEIP) and 151 healthy controls(HC) who received SARS-CoV-2 vaccine/s(Sinovac and/or Pfizer-BioNTech(mRNA vaccine), one to five doses), questioned them for side-effects, evaluated in three groups according to the vaccine/s they received; only Sinovac, only Pfizer-BioNTech, and both vaccines. RESULTS: Arm pain, generalized weakness, myalgia, and fever were common side effects in IEI-P and HC groups. Generalized weakness/fatigue, fever, and palpitation were significantly frequent in IEI-P who experienced COVID-19 compared to those who did not (p = 0.021, p = 0.047, and p = 0.024, respectively). Severe symptoms after vaccination, new-onset splenomegaly and pancytopenia, urticaria, herpes simplex virus (HSV), and varicella zoster virus (VZV) reactivation were seen in four IEI-P (2.8%). CONCLUSION: IEI-P mRNA vaccination is relatively safe compared to the conventional vaccine. Individuals who experience uncommon side effects should undergo immunological screening.

HLA binding-groove motifs are associated with myocarditis induction after Pfizer-BioNTech BNT162b2 vaccination.

BACKGROUND AND AIMS: We found a higher incidence of myocarditis in young males who had received at least two Pfizer-BioNTech BNT162b2 vaccinations. The human leukocyte antigens (HLA) are known to play an important role in infectious and autoinflammatory diseases. We hypothesized that certain HLA alleles might be associated with vaccination-induced myocarditis. METHODS: HLA typing was performed using next-generation sequencing technology with the Illumina Iseq100 platform. HLA class I and II loci were genotyped in 29 patients with post-vaccination myocarditis and compared with HLA data from 300 healthy controls. RESULTS: We demonstrate that the DRB1*14:01, DRB1*15:03 alleles and the motifs in HLA-A - Leu62 and Gln63, which are part of binding pocket B and HLA-DR Tyr47, His60, Arg70 and Glu74, which are part of binding pockets P4, P7 and P9, were significantly associated with disease susceptibility. CONCLUSIONS: Our findings suggest that immunogenetic fingerprints in HLA peptide-binding grooves may affect the presentation of peptides derived from the Pfizer-BioNTech BNT162b2 vaccination to T cells and induce an inflammatory process that results in myocarditis.

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.

A study on the side effects caused by the Pfizer/BioNTech COVID-19 vaccine: Focus on IgG antibodies and serological biomarkers.

Introduction: The SARS-CoV-2 pandemic that spread swiftly is now a major global public health issue. Vaccines are currently being distributed in an effort to limit the viral transmission and mortality. The aim of the study was monitoring of both safety and efficacy in determining the overall effectiveness of the vaccine and identifying any potential safety concerns. Material and methods: A retrospective, cross-sectional study employing a validated 13-item structured questionnaire divided into two sections was performed between March 2022 and September 2022. Different post-vaccination side effects (SE) according to symptoms severity in terms of age and sex for participants were reported. Additionally, some pertinent serological assays for participants' post-vaccinations were investigated. Results: A total of 502 participants (male: 262, female: 240) with comorbidity (healthy: 258, morbid: 244) who received two Pfizer/BioNTech mRNA vaccine doses were included. Importantly, second dose (D2) vaccination was associated with significantly more SE than single dose (D1) vaccination (p < 0.0001). In D1 vaccination injection site pain (ISP) (45%), followed by equal proportions of headache and fever (40%) were the most common vaccine SE, while in D2 vaccination, ISP (66%) and nausea (57%) were reported. In all, 97% (p < 0.0001) of participants were IgG antibody positive at D2 vaccination. Similarly, serum CR protein level was elevated significantly (p < 0.0001) corresponding to the severity of SE between D1 and D2. Significant differences in IgG concentration were found between D1 and D2 vaccination in different gender and age groups (p < 0.0001). Conclusions: In light of the extensive data from this study, it is evident that mRNA vaccines, particularly the Pfizer/BioNTech vaccine, have proven to be highly safe and effective in mitigating the impact of the SARS-CoV-2 pandemic.

Effectiveness of Heterologous Coronavirus Disease 2019 (COVID-19) Vaccine Booster Dosing in Brazilian Healthcare Workers, 2021.

BACKGROUND: Little is currently known about vaccine effectiveness (VE) for either 2 doses of Oxford-AstraZeneca (ChAdOx1) viral vector vaccine or CoronaVac (Instituto Butantan) inactivated viral vaccine followed by a third dose of mRNA vaccine (Pfizer/BioNTech) among healthcare workers (HCWs). METHODS: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil from January to December 2021. VE was defined as 1 - incidence rate ratio (IRR), with IRR determined using Poisson models with the occurrence of laboratory-confirmed coronavirus disease 2019 (COVID-19) infection as the outcome, adjusting for age, sex, and job type. We compared those receiving viral vector or inactivated viral primary series (2 doses) with those who received an mRNA booster. RESULTS: A total of 11 427 HCWs met the inclusion criteria. COVID-19 was confirmed in 31.5% of HCWs receiving 2 doses of CoronaVac vaccine versus 0.9% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001) and 9.8% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 1% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). In the adjusted analyses, the estimated VE was 92.0% for 2 CoronaVac vaccines plus mRNA booster and 60.2% for 2 ChAdOx1 vaccines plus mRNA booster, when compared with those with no mRNA booster. Of 246 samples screened for mutations, 191 (77.6%) were Delta variants. CONCLUSIONS: While 2 doses of ChAdOx1 or CoronaVac vaccines prevent COVID-19, the addition of a Pfizer/BioNTech booster provided significantly more protection.

BNT162b2 mRNA Vaccination Against Coronavirus Disease 2019 is Associated With a Decreased Likelihood of Multisystem Inflammatory Syndrome in Children Aged 5-18 Years-United States, July 2021 - April 2022.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. METHODS: In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. RESULTS: We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. CONCLUSIONS: Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.

Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses against the SARS-CoV-2 Omicron Variant in Adolescents and Adults.

Emerging variants, especially the recent Omicron variant, and gaps in vaccine coverage threaten mRNA vaccine mediated protection against SARS-CoV-2. While children have been relatively spared by the ongoing pandemic, increasing case numbers and hospitalizations are now evident among children. Thus, it is essential to better understand the magnitude and breadth of vaccine-induced immunity in children against circulating viral variant of concerns (VOCs). Here, we compared the magnitude and breadth of humoral immune responses in adolescents and adults 1 month after the two-dose Pfizer (BNT162b2) vaccination. We found that adolescents (aged 11 to 16) demonstrated more robust binding antibody and neutralization responses against the wild-type SARS-CoV-2 virus spike protein contained in the vaccine compared to adults (aged 27 to 55). The quality of the antibody responses against VOCs in adolescents were very similar to adults, with modest changes in binding and neutralization of Beta, Gamma, and Delta variants. In comparison, a significant reduction of binding titers and a striking lack of neutralization was observed against the newly emerging Omicron variant for both adolescents and adults. Overall, our data show that a two-dose BNT162b2 vaccine series may be insufficient to protect against the Omicron variant. IMPORTANCE While plasma binding and neutralizing antibody responses have been reported for cohorts of infected and vaccinated adults, much less is known about the vaccine-induced antibody responses to variants including Omicron in children. This illustrates the need to characterize vaccine efficacy in key vulnerable populations. A third (booster) dose of BNTb162b was approved for children 12 to 15 years of age by the Food and Drug Administration (FDA) on January 1, 2022, and pediatric clinical trials are under way to evaluate the safety, immunogenicity, and effectiveness of a third dose in younger children. Similarly, variant-specific booster doses and pan-coronavirus vaccines are areas of active research. Our data show adolescents mounted stronger humoral immune responses after vaccination than adults. It also highlights the need for future studies of antibody durability in adolescents and children as well as the need for future studies of booster vaccination and their efficacy against the Omicron variant.

Evaluation of retinal and optic disc vascular structures in individuals before and after Pfizer-BioNTech vaccination.

INTRODUCTION: We conducted this study to detect possible changes in posterior segment structures using the optical coherence tomography angiography (OCTA) in individuals vaccinated with the Pfizer-BioNTech vaccine. MATERIALS AND METHODS: The study included healthcare professionals who presented to the Ophthalmology Clinic of Health Sciences University Antalya Training and Research Hospital, who were scheduled to receive the first dose of the Pfizer-BioNTech vaccine. The exclusion criteria were any eye pathology (e.g., glaucoma, uveitis, diabetic retinopathy, amblyopia), myopia with the absolute value of refractive error >6, axial length >26 mm, history of eye surgery, and presence of systemic disease.OCTA was performed to 40 healthcare professionals before vaccination and on the third day after vaccination. RESULTS: After Pfizer-BioNTech vaccination, there was a statistically significant decrease in the total vascular, foveal vascular, parafoveal vascular and perifoveal vascular density of the superficial capillary plexus and the perifoveal vascular density of the deep capillary plexus and a statistically significant increase in the retinal foveal thickness and total retinal parafoveal thickness compared to the pre-vaccination values (p < 0.0001, p = 0.009, p < 0.0001, p = 0.001, p = 0.04, p = 0.03, and p = 0.05, respectively). CONCLUSION: We consider that the decrease in the retinal vascular density may be due to vascular endothelial damage and inflammation in vaccinated people. It can be suggested that increased inflammation plays a role in the retinal thickness in vaccinated people similar to patients with a history of COVID-19. We also consider that spike protein may be effective in these processes.

Prolonged headache with vaccine- and dose-specific headache pattern associated with vaccine against SARS-CoV-2 in patients with migraine.

OBJECTIVE: To examine SARS-CoV-2 vaccine-related headache characteristics and risk factors in migraine patients. METHODS: This retrospective cohort study included 732 migraine patients who had AstraZeneca Vaxzevria, Pfizer-BioNTech Comirnaty, or Moderna Spikevax vaccines. Participants provided information through questionnaires and headache diaries. Headache frequency before and after vaccination and factors associated with headache risk were examined. RESULTS: Approximately a third of patients reported increased headache the day after having primary and booster doses, with mean increase ± SD of 1.9 ± 1.2 and 1.8 ± 1.1 days/week, respectively. Proportions of migraine patients with headache (after vaccination vs. before vaccination) increased after having primary-dose Vaxzevria (35.3% vs. 22.8%, p < 0.001) but not Spikevax (23.8% vs. 26.7%, p = 0.700) or Comirnaty (33.2% vs. 25.8%, p = 0.058). Headache proportion increased after having all three boosters (Vaxzevria 27.1% vs. 17.9% p = 0.003; Comirnaty 34.1% vs. 24.5% p = 0.009; Spikevax 35.2% vs. 24.8% p = 0.031). For primary dose with Vaxzevria and Comirnaty, headache risk increased on the vaccination day, peaked on the day after vaccination, and subsided within a week, while for Spikevax headache risk rose gradually after vaccination, peaked on the seventh post-vaccination day and subsided subsequently. For booster dose, headache risk generally increased on the vaccination day, peaked on the day after vaccination, and subsided gradually with fluctuating pattern within a month. Our study also showed that headache increased on the day before primary dose but not booster dose vaccination and it may be attributable to stress associated with having to undertake new vaccines. Multivariable analyses showed that depression was associated with headache. CONCLUSION: Prolonged headache with vaccine- and dose-specific headache pattern was found. Patients with higher risks of vaccine-related headache must be informed of the potential worsening headache.

Association between COVID-19 vaccination and myasthenia gravis: A population-based, nested case-control study.

BACKGROUND: Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with both new-onset MG and MG exacerbation. METHODS: For the first aim, we conducted a nested case-control study in a cohort of 3,052,467 adults, without a diagnosis of MG, from the largest healthcare provider in Israel. Subjects were followed from January 1, 2021 until June 30, 2022 for the occurrence of MG. Ten randomly selected controls were matched to each case of new-onset MG on age and sex. For the second aim, a nested case-control study was conducted in a cohort of 1446 MG patients. Four randomly selected MG patients (controls) were matched to each case of MG exacerbation. Exposure to COVID-19 vaccine in the prior 4 weeks was assessed in cases and controls. RESULTS: Overall, 332 patients had new-onset MG and were matched with 3320 controls. Multivariable conditional logistic regression models showed that the odds ratio (OR) for new-onset MG, associated with COVID-19 vaccine, was 1.14 (95% CI 0.73-1.78). The results were consistent in sensitivity analysis that used more stringent criteria to define MG. Overall, 62 patients with MG exacerbation were matched to 248 MG controls. The multivariable OR for MG exacerbation, associated with COVID-19 vaccine, was 1.35 (95% CI 0.37-4.89). All results were similar when the prior exposure to COVID-19 vaccine was extended to 8 weeks. CONCLUSION: This study suggests that Pfizer-BioNTech vaccine is not associated with increased risk of new-onset nor exacerbation of MG.

Side effects of Pfizer/BioNTech (BNT162b2) COVID-19 vaccine reported by the Birzeit University community.

BACKGROUND: The Pfizer BioNTech COVID-19 vaccine was the first to receive emergency authorization and approval from the FDA. Therefore, it is preferred by most recipients; however, many people are concerned about the vaccine's side effects. At the time of the study, December 2021, Palestine lacked a national reporting system for monitoring adverse vaccine effects. Therefore, this study investigates the post-vaccine adverse events following the Pfizer/BioNTech COVID-19 Vaccine administration in Palestine and identifies the occurrence, extent, and severity among university staff, employees, and students at Birzeit University. METHOD: A questionnaire-based retrospective cross-sectional study was conducted using a university website (Ritaj), social media platforms (e.g., Facebook and Telegram), and in-person interviews. The Chi-square, Fisher's exact, and McNemar's tests were used to investigate significant relationships. Data were analyzed using SPSS version 22. RESULTS: In total, 1137 participants completed the questionnaire, 33.2% were males, and the mean age was 21.163 years. All participants received at least one dose of the Pfizer-BioNTech COVID-19 vaccine. Approximately one-third of participants reported no adverse effects after receiving the first, second, or third doses (34%, 33.6%, and 32.5%, respectively). The most commonly reported adverse events were fever, chills, headache, fatigue, pain and swelling at the injection site, muscle pain, and joint pain. Allergic reactions were reported by 12.7% of the participants; furthermore, participants with a history of allergy or anaphylaxis before vaccination had a significantly higher tendency for post-vaccination allergic reactions. Eight participants reported rare side effects, including 7 (0.6%) cases of thrombocytopenia and one (0.1%) case of myocarditis. Males aged less than 20 years and smokers were significantly less likely to complain of adverse events. The number of reported side effects was significantly higher after the second vaccine dose than after the first dose. Finally, participants infected with COVID-19 before vaccination was significantly associated with side effects such as fever, chills, shortness of breath, and persistent cough. CONCLUSION: In this study, the most common post- BNT162b2 Vaccination reported self-limiting side effects similar to those reported by Pfizer/BioNTech Company. However, higher rates of allergic reactions were reported in this sample. Rare side effects, such as thrombocytopenia and myocarditis, were reported by 8 participants. COVID vaccines have been developed at an accelerated pace, and vaccine safety is a top priority; therefore, standard monitoring through a national adverse event reporting system is necessary for safety assurance. Continuous monitoring and long-term studies are required to ensure vaccine safety.

The association between COVID-19 vaccination and idiopathic sudden sensorineural hearing loss, clinical manifestation and outcomes.

PURPOSE: Previous data demonstrated an increased incidence of Idiopathic Sensorineural Hearing Loss (ISSNHL) in 2021 compared to 2019-2020, suggesting an association with the anti-COVID-19 vaccine. We aimed to assess our center's incidence and compare the clinical manifestations and outcomes of vaccinated vs. unvaccinated patients. METHODS: A retrospective chart review of all patients diagnosed with ISSNHL during 2021 was conducted and compared to patients who presented in 2018-2020. Patient demographics, audiometry features, vaccination status, and prognosis were evaluated. RESULTS: Throughout 2021, 51 patients were diagnosed with ISSNHL, compared with 31 during 2020, 38 in 2019, and 41 in 2018, demonstrating a 64%, 34%, and 24% increase, respectively. Among patients who presented in 2021, 13 (25.4%) received the anti-COVID-19 vaccine within 30 days before their presentation, and 4 received it within 96 h. Most presented after receiving the second or third dose. Patient characteristics, audiometry features, and prognosis did not significantly differ between vaccinated and unvaccinated patients. CONCLUSIONS: A marked incline was seen in the 2021 ISSNHL incidence at our medical center, of which 25% of cases were within a month post-anti-COVID-19 vaccination. No significant difference was found in clinical manifestations and outcomes between vaccinated and nonvaccinated patients. While other justifications could be sought, an association cannot be ruled out, and further research is needed.

Axillary lymph nodes enlargement after Sars-CoV-2 vaccine in patients undergoing breast examination: a single-centre experience in 285 women.

PURPOSE: To assess the incidence of axillary lymphadenopathy over established time ranges after COVID-19 vaccination and lymph node pathologic features (i.e. size increase and qualitative characteristics) in subjects undergoing axillary evaluation during a breast imaging examination. METHODS AND MATERIALS: The institutional review board approved this prospective study. INCLUSION CRITERIA: women undergoing mammography and breast ultrasound between July and October 2021; information about the COVID-19 vaccine and infection, if any. EXCLUSION CRITERIA: known metastatic lymphadenopathy. Participants were divided into 5 subgroups according to time between vaccine and imaging: < 6 weeks; 7-8 weeks; 9-10 weeks; 11-12 weeks; > 12 weeks. Evaluation of axillary lymph nodes was performed with ultrasound. Descriptive statistical analysis was performed. p < 0.05 was considered significant. RESULTS: A total of 285 women were included. Most of the patients underwent Moderna vaccine (n = 175, 61.4%). 63/285 patients had a previous history of breast cancer (22.1%). 13/17 (76.5%) patients with previous COVID-19 infection had no previous history of cancer, whereas 4/17 had a previous history of cancer (p < .001). 41/285 (14.4%) women showed lymphadenopathy, and they were significantly younger (46.9 ± 11.6 years) than women with borderline (54.0 ± 11.9 years) or no lymphadenopathy (57.3 ± 11.9 years) (p < .001). Lymphadenopathy and borderline lymphadenopathy were more frequently observed in the Moderna-vaccinated women and in the subgroup of patients evaluated < 6 weeks after vaccination (p < 0.001). The most common pathologic feature was cortical thickening, followed by complete or partial effacement of fatty hilum. CONCLUSION: A lymphadenopathy within 12 weeks after vaccination is a common finding particularly in younger women and after Moderna vaccine and no further assessment should be required.

Is the Effect of the COVID-19 Vaccine on Heart Rate Variability Permanent?

Background and Objectives: The risk of autonomic dysfunction with COVID-19 vaccines used worldwide in the COVID-19 pandemic remains a topic of debate. Heart rate variability has a number of parameters that can be used to assess autonomic nervous system dynamics. The aim of this study was to investigate the effect of a COVID-19 vaccine (Pfizer-BioNTech) on heart rate variability and autonomic nervous system parameters, and the duration of the effect. Materials and Methods: A total of 75 healthy individuals who visited an outpatient clinic to receive the COVID-19 vaccination were included in this prospective observational study. Heart rate variability parameters were measured before vaccination and on days 2 and 10 after vaccination. SDNN, rMSSD and pNN50 values were evaluated for time series analyses, and LF, HF, and LF/HV values for frequency-dependent analyses. Results: The SDNN and rMSDD values declined significantly on day 2 after vaccination, while the pNN50 and LF/HF values increased significantly on day 10. The values at pre-vaccination and at day 10 were comparable. The pNN50 and LF/HF values declined significantly on day 2 and increased significantly on day 10. The values at pre-vaccination and at day 10 were comparable. Conclusions: This study showed that the decline in HRV observed with COVID-19 vaccination was temporary, and that the Pfizer-BioNTech COVID-19 vaccination did not cause permanent autonomic dysfunction.

Effectiveness of a Third Dose of BNT162b2 mRNA Vaccine.

A retrospective cohort study was carried out in a large Israeli health maintenance organization to determine vaccine effectiveness (VE) of a third dose of BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Of nearly 1 million members receiving 2 doses of BNT162b2 in January-February 2021, infection rates (based on polymerase chain reaction results) were compared between those who received a third dose with those who did not during August-October 2021 (maximum, 70 days). Crude VE was 92.9% (95% confidence interval [CI], 92.6%-93.2%) and adjusted VE was 89.1% (95% CI, 87.5%-90.5%). We conclude that the third dose provides added protection against SARS-CoV-2 infection for those vaccinated 6 months ago.

Effectiveness of BNT162b2 Vaccine Booster against SARS-CoV-2 Infection and Breakthrough Complications, Israel.

We estimated vaccine effectiveness (VE) of the BNT162b2 (Pfizer-BioNTech, https://www.pfizer.com) booster dose against SARS-CoV-2 infection and reduction of complications (hospitalization, severe disease, and death) among breakthrough cases in persons in Israel >16 years of age for <20 weeks. VE estimates reached 96.8% (95% CI 96.0%-97.5%) for persons 16-59 years of age and 93.1% (95% CI 91.8%-94.2%) for persons >60 years of age on week 3. VE estimates remained at these levels for 8 weeks in the 16-59 age group and 11 weeks in those >60. A slow decline followed, becoming more pronounced in the last 2-3 weeks of evaluation. Estimates in the last week of evaluation were 77.6% (95% CI 68.4%-84.2%) and 61.3% (52.5%-68.4%) for persons 16-59 years and >60 years, respectively. The more pronounced VE decline coincided with rapid increase in Omicron variant activity. Rate reduction of breakthrough complications remained moderate to high throughout the evaluation.

Elevated CD21low B Cell Frequency Is a Marker of Poor Immunity to Pfizer-BioNTech BNT162b2 mRNA Vaccine Against SARS-CoV-2 in Patients with Common Variable Immunodeficiency.

PURPOSE: Limited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the results from vaccinating a single-center cohort of patients with common variable immunodeficiency (CVID). METHODS: In a prospective, open-label clinical trial, 50 patients with CVID and 90 age-matched healthy controls (HC) were analyzed for SARS-CoV-2 spike antibody (Ab) production after one or two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Additionally, in selected patients, SARS-CoV-2 spike-specific T-cells were assessed. RESULTS: A potent vaccine-induced anti-spike-specific IgG Ab response was observed in all the HC. In contrast, only 68.3% of the CVID patients seroconverted, with median titers of specific Ab being 83-fold lower than in HC. In fact, only 4/46 patients (8.6%) of patients who were seronegative at baseline reached the threshold for an optimal response (250 U/mL). Using the EUROclass definition, patients with either a reduced proportion, but not absolute counts, of switched memory B-cells or having an increased frequency of CD21low B-cells generally generated poor vaccine responses. Overall, CVID-patients had reduced spike-specific IFN-γ positive CD4+ T cell responses 2 weeks after the second dose, compared to HC. The total CD4 and CD4 central memory cell counts correlated with humoral immunity to the vaccine. CONCLUSIONS: CVID patients with low frequency of switched memory B-cells or an increased frequency of CD21low B-cells according to the EUROclass definition demonstrated poor responses to Pfizer-BioNTech BNT162b2 mRNA vaccination. Cellular immune responses were significantly affected, affirming that the defect in CVID is not limited to humoral immunity.

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4+ T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs). Anti-S IgG, IgA, and IgG subclasses 1 and 3 increased after vaccination and correlated with neutralization activity in HCs and patients with oPADs. However, 42% of CVID patients developed such responses after the 2nd dose. A similar pattern was also observed with S-specific CD4+ T-cells as determined by OX40 and 4-1BB expression. Patients with poor anti-S IgG response had significantly lower levels of baseline IgG, IgA, CD19+ B-cells, switched memory B-cells, naïve CD8+ T-cells, and a higher frequency of EM CD8+ T-cells and autoimmunity compared to patients with adequate anti-S IgG responses. Patients with oPADs can develop humoral and cellular immune responses to vaccines similar to HCs. However, a subset of CVID patients exhibit impairment in developing such responses, which can be predicted by the baseline immune profile and history of autoimmunity.

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review.

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90-180 days and 55%-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.