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.

Intracranial Hemorrhage After Pfizer-BioNTech (BNT162b2) mRNA COVID-19 Vaccination: A Case Report.

The Coronavirus 2019 (COVID-19) pandemic has affected over 700 million people worldwide and caused nearly 7 million deaths. Vaccines currently developed or in development are the most effective tools for curbing the pandemic and mitigating its impacts. In Turkey, inoculation with the Pfizer-BioNTech COVID-19 vaccine (BNT162b2, also known as tozinameran) has been approved. We report a 56-year-old female patient with underlying essential hypertension who experienced intracranial hemorrhage after receiving her first dose of tozinameran. The patient underwent immediate surgical evacuation of the hematoma, during which a left middle cerebral artery bifurcation aneurysm was macroscopically identified and clipped. The patient was pronounced deceased on the second postoperative day. This is the second case of intracranial hemorrhage following tozinameran administration caused by a ruptured middle cerebral artery bifurcation aneurysm. Upon analyzing the case, there might be a connection between the vaccine's potential immune-triggering effect on hemodynamic patterns and the rupture of the previously unknown cerebral aneurysm. However, these severe complications do not justify avoiding vaccines; further studies are needed. This study emphasizes the need for increased vigilance in patients with underlying systemic comorbidities who have recently been vaccinated and to share our insights into the potential relationship between tozinameran and intracranial hemorrhage.

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes.

Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types. Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer-BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations. Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r 2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r 2 = 0.789; p = 0.0001) and 91-190 days (T2) after vaccination (r 2 = 0.764; p = 0.0001) for both vaccine types (r 2 = 0.842; p = 0.0001 and r 2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age (p < 0.01), sex (p = 0.03), and type of vaccine (p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated (TP53, rs1042522; APOE, rs7412/rs429358; ABO, rs657152; ACE2, rs2285666; HLA-A rs2571381/rs2499; CRP, rs2808635/rs876538; LZTFL1, rs35044562; OAS3, rs10735079; SLC6A20, rs11385942; CFH, rs1061170; and ACE1, ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P1 and P2, respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53, rs1042522 (P1 = 0.03; P2 = 0.04); ABO, rs657152 (P1 = 0.01; P2 = 0.03); APOE, rs7412/rs429358 (P1 = 0.0018; P2 = 0.0002); ACE2, rs2285666 (P1 = 0.014; P2 = 0.009); HLA-A, rs2571381/rs2499 (P1 = 0.02; P2 = 0.03); and CRP, rs2808635/rs876538 (P1 = 0.01 and P2 = 0.09). Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations.

ZnO-Based Electrochemical Immunosensor to Assess Vaccine-Induced Antibody-Mediated Immunity against Wild-Type and Gamma SARS-CoV-2 Strains.

The evaluation of serological responses to COVID-19 is crucial for population-level surveillance, developing new vaccines, and evaluating the efficacy of different immunization programs. Research and development of point-of-care test technologies remain essential to improving immunity assessment, especially for SARS-CoV-2 variants that partially evade vaccine-induced immune responses. In this work, an impedimetric biosensor based on the immobilization of the recombinant trimeric wild-type spike protein (S protein) on zinc oxide nanorods (ZnONRs) was employed for serological evaluation. We successfully assessed its applicability using serum samples from spike-based COVID-19 vaccines: ChAdOx1-S (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech). Overall, the ZnONRs/ spike-modified electrode displayed accurate results for both vaccines, showing excellent potential as a tool for assessing and monitoring seroprevalence in the population. A refined outcome of this technology was achieved when the ZnO immunosensor was functionalized with the S protein from the P.1 linage (Gamma variant). Serological responses against samples from vaccinated individuals were acquired with excellent performance. Following studies based on traditional serological tests, the ZnONRs/spike immunosensor data reveal that ChAdOx1-S vaccinated individuals present significantly less antibody-mediated immunity against the Gamma variant than the BNT162b2 vaccine, highlighting the great potential of this point-of-care technology for evaluating vaccine-induced humoral immunity against different SARS-CoV-2 strains.

Progression of hemolysis in a patient with hereditary spherocytosis after the second dose of COVID-19 mRNA vaccine.

Herein, we report the case of a 22-year-old woman with hereditary spherocytosis (HS) whose condition worsened after administration of the coronavirus disease 2019 (COVID-19), mRNA vaccine 'BNT162b2 Pfizer-BioNTech.' The woman had been diagnosed with HS in 2005, and her condition remained stable until February 2021. In March 2021, she received the first dose of the above vaccine and experienced pain at the injection site. After the second dose in April 2021, she developed fever and general malaise. Investigations revealed progression of hemolysis, which improved after a few days. To the best of our knowledge, this is the first report of progression of hemolysis in a patient with HS after administration of the mRNA vaccine COVID-19, BNT162b2 'Pfizer-BioNTech.'

Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial.

Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8-34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1-58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.

Bimodal antibody-titer decline following BNT162b2 mRNA anti-SARS-CoV-2 vaccination in healthcare workers of the INT - IRCCS "Fondazione Pascale" Cancer Center (Naples, Italy).

BACKGROUND: Both SARS-CoV-2 mRNA-based vaccines [BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)] have shown high efficacy, with very modest side effects in limiting transmission of SARS-CoV-2 and in preventing the severe COVID-19 disease, characterized by a worrying high occupation of intensive care units (ICU), high frequency of intubation and ultimately high mortality rate. At the INT, in Naples, only the BNT162b2/Pfizer vaccine has been administered to cancer patients and healthcare professionals aged 16 and over. In the present study, the antibody response levels and their decline were monitored in an interval of 6-9 months after vaccine administration in the two different cohorts of workers of the INT - IRCCS "Fondazione Pascale" Cancer Center (Naples, Italy): the group of individuals previously infected with SARS-CoV-2 and vaccinated with a single dose; and that of individuals negative for previous exposure to SARS-CoV-2 vaccinated with two doses 21 days apart. METHODS: Specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S ECLIA immunoassay were determined in serum samples of 27 healthcare workers with a previously documented history of SARS-CoV-2 infection and 123 healthcare workers without, during antibody titers' monitoring. Moreover, geometric mean titers (GMT) and relative fold changes (FC) were calculated. RESULTS: Bimodal titer decline was observed in both previously infected and uninfected SARS-CoV-2 subjects. A first rapid decline was followed by a progressive slow decline in the 6/9 month-period before the further vaccine boost. The trend was explained by 2 different mathematical models, exponential and power function, the latter revealing as predictive of antibody titer decline either in infected or in not previously infected ones. The value of the prolonged lower vaccine titer was about 1 log below in the 6/9-month interval after the single dose for previously infected individuals with SARS-CoV-2 and the two doses for those not previously infected. The titer change, after the boost dose administration, on the other hand, was ≥ 1.5 FC higher than the titers at the 6/9-month time-points in both cohorts. A similar quantitative immune titer was observed in both cohorts 8 days after the last boost dose. The subsequent immunoresponse trend remains to be verified. DISCUSSION: The results show that a very rapid first decline, from the highest antibody peak, was followed by a very slow decline which ensured immune protection lasting more than 6 months. The apparent absence of adverse effects of the rapid decline on the vaccine's immune protective role has been related to a large majority of low avidity antibodies induced by current vaccines. High avidity antibodies with prolonged anti-transmission efficacy show a longer half-life and are lost over a longer interval period. The cellular immunity, capable of preventing severe clinical diseases, lasts much longer. The unbalanced dual activity (cellular vs humoral) while effective in limiting ICU pressure and overall mortality, does not protect against transmission of SARS-CoV-2, resulting in high circulation of the virus among unvaccinated subjects, including the younger population, and the continuous production of variants characterized by changes in transmissibility and pathogenicity. The high mutation rate, peculiar to the RNA virus, can however lead to a dual opposite results: selection of defective and less efficient viruses up to extinction; risk of more efficiently transmitted variants as the current omicron pandemic. CONCLUSIONS: In conclusion the current bimodal antibody-titer decline, following BNT162b2 mRNA anti-SARS-CoV-2 vaccination, needs a further extended analysis to verify the protective borderline levels of immunity and the optimal administration schedule of vaccine boosters. Our current results can contribute to such goal, besides a direct comparison of other FDA-approved and candidate vaccines.

COVID-19 Vaccine-Related Myocarditis: A Descriptive Study of 40 Case Reports.

After the surging rise in the Coronavirus disease 2019 (COVID-19) pandemic, the Food and Drug Administration (FDA) approved emergency approval of vaccinations to prevent life-threatening complications of COVID-19 infection. These vaccines are BNT162b2, mRNA-1273. Later, the FDA also approved JNJ-78436735. COVID-19 vaccination does not have major side effects, but there are some concerning adverse events reported right after vaccination. Myocarditis is one of them. Based on our analysis of 40 case reports, we are presenting the epidemiology and clinical picture of myocarditis related to the COVID-19 vaccine. Based on our analysis, we found that the majority of cases were seen in males with 90% predominance, and these cases were seen in the age group of 29.13 years old (mean, SD of 14.39 years). In 65% of cases, patients took the BNT162b2 vaccine; 30% of cases were reported with the mRNA-1273 vaccine; and 5% of cases with JNJ-78436735. Of all the cases, 80% of them are reported after the second dose of the vaccine with either Moderna or Pfizer. The characteristics of COVID-19 vaccine-related myocarditis were analyzed in this study. We identified several findings, ranging from age, gender, type of vaccination, presentation of symptoms, and diagnosis modality. This depicts the picture of COVID-19 vaccine-related myocarditis and what physicians should expect when dealing with the disease. Our analysis showed that more cases were reported after receiving the BNT162b2 vaccine compared to mRNA-1273 and JNJ-78436735 vaccines. Further research needs to be conducted to analyze the underlying cause of this association.

Evaluation of circulating leucocyte populations both in subjects with previous SARS-COV-2 infection and in healthy subjects after vaccination.

Innate immune mechanisms are central players in response to the binding of pathogens to pattern-recognition receptors providing a crucial initial block on viral replication. Moreover, innate immune response mobilizes cells of the cellular-mediated immune system, which develop into effector cells that promote viral clearance. Here, we observed circulating leukocyte T cell response in healthy subjects, COVID-19 infected, and in healthy vaccinated subjects. We found a significant CD8+ T cells (p < 0,05) decrease and an augmented CD4+/CD8+ ratio (p < 0,05) in COVID-19 infected group compared with vaccinated subjects. In addition, healthy vaccinated subjects have a significant increased expression of CD8+ T cells, and a reduction of CD4+/CD8+ ratio with respect to subjects previously COVID-19 infected. Central Memory and Terminal Effector Memory cells (TEMRA) increased after vaccine but not among groups.

Humoral response to BNT162b2 mRNA COVID-19 vaccine in peritoneal and hemodialysis patients: A comparative study.

INTRODUCTION: Maintenance dialysis patients (MDP) are at higher risk of exposure with increased mortality from COVID-19 with generalized immunization becoming the cornerstone in prevention. This study aims to compare humoral response between hemodialysis (HD) and peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Observational prospective study following HD and PD programs from a Portuguese Center receiving BNT162b2 vaccine. Specific anti-Spike IgG quantification to compare both for absolute value and non-responders (NR) between modalities and against risk factors. RESULTS: Of 67 MDP, 42 were HD and 25 PD patients. PD developed higher antibody titers after both first (median 5.44 vs. 0.99 AU/ml, p < 0.01) and second dose (median 170.43 vs. 65.81 AU/ml; p < 0.01). HD associated with NR after the first dose (p < 0.01). CONCLUSION: This study demonstrated improved humoral immunogenicity with BNT162b2 in PD compared to HD patients. These differences are attributed to comorbidity burden and age differences, rather than dialysis modality.

Antibody response after one and two jabs of the BNT162b2 vaccine in nursing home residents: The CONsort-19 study.

BACKGROUND: The humoral immune response following COVID-19 vaccination in nursing home residents is poorly known. A longitudinal study compared levels of IgG antibodies against the spike protein (S-RBD IgG) (S-RDB protein IgG) after one and two BNT162b2/Pfizer jabs in residents with and without prior COVID-19. METHODS: In 22 French nursing homes, COVID-19 was diagnosed with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2. Blood S-RDB-protein IgG and nucleocapsid (N) IgG protein (N-protein IgG) were measured 21-24 days after the first jab (1,004 residents) and 6 weeks after the second (820 residents). RESULTS: In 735 residents without prior COVID-19, 41.7% remained seronegative for S-RDB-protein IgG after the first jab vs. 2.1% of the 270 RT-PCR-positive residents (p < 0.001). After the second jab, 3% of the 586 residents without prior COVID-19 remained seronegative. However, 26.5% had low S-RDB-protein IgG levels (50-1050 UA/ml) vs. 6.4% of the 222 residents with prior COVID-19. Residents with an older infection (first wave), or with N-protein IgG at the time of vaccination, had the highest S-RDB-protein IgG levels. Residents with a prior COVID-19 infection had higher S-RDB-protein IgG levels after one jab than those without after two jabs. INTERPRETATION: A single vaccine jab is sufficient to reach a high humoral immune response in residents with prior COVID-19. Most residents without prior COVID-19 are seropositive for S-RDB-protein IgG after the second jab, but around 30% have low levels. Whether residents with no or low post-vaccine S-RDB protein IgG are at higher risk of symptomatic COVID-19 requires further analysis.