Third Dose Of Vaccine Research Articles

Third dose of COVID-19 mRNA vaccine appears to overcome vaccine hyporesponsiveness in patients with cirrhosis.

Background & AimsCirrhosis is associated with immune dysregulation and hyporesponsiveness to several vaccines including those against COVID-19. Our aim was to compare outcomes between patients with cirrhosis who received 3 doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines to a propensity-matched control group of patients at similar risk of infection who received 2 doses.MethodsThis was a retrospective cohort study of patients with cirrhosis who received 2 or 3 doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received 3 doses of the vaccine (n = 13,041) were propensity score matched with 13,041 controls who received 2 doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (delta) and B.1.1.529 (omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19.ResultsReceipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction in COVID-19 (95% CI 39.2-89.1, p <0.001), an 80.4% reduction in symptomatic COVID-19, an 80% reduction in moderate, severe or critical COVID-19, (95% CI 34.5-87.6%, p = 0.005), a 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p = 0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p = 0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated rather than decompensated cirrhosis.ConclusionsAdministration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in patients with cirrhosis than in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population.Lay summaryCirrhosis is associated with decreased responsiveness to several vaccines, including those against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with an 80% reduction in COVID-19, a 100% reduction in severe/critical COVID-19, and a 100% reduction in COVID-19-related death. These findings support the importance of a third dose of mRNA vaccine among patients with cirrhosis.

Quantitative Analysis of SARS-CoV-2 Antibody Levels in Cancer Patients Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections.

(1) Background: COVID-19 vaccine effectiveness should be carefully evaluated and explicitly defined. To our knowledge, this is the first report to quantitatively evaluate humoral responses post 3 doses of SARS-CoV-2 immunization and prior to breakthrough COVID-19 infection in Canadian cancer patients. (2) Methods: In a prospective cohort study, we enrolled 185 cancer participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor–binding domain were quantified by immunoassay post three doses of immunization. With the COVID-19 rapid antigen test and polymerase chain reaction (PCR), 16 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccination (including BNT162b2, AZD1222, and mRNA-1273), the mean serum anti-spike protein antibody level was 197.2 BAU/mL (binding antibody unit, SD ± 393.9), 1335.9 BAU/mL (±3337.8), and 3164.8 BAU/mL (±6500.9) post the first, second, and third dose of vaccination. Observed differences were significant (p ≤ 0.001). The average antibody level of 3164.8 BAU/mL post the third dose was 89.9 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In 11 breakthrough cases confirmed by PCR, prior to infection, the average antibody concentration was 3675.6 BAU/mL with the highest concentration being 9107.4 BAU/mL. Compared with this average antibody concentration of 3675.6 BAU/mL (104.4 times that of the seroconversion concentration), 0% of single dosed, 9.6% of double vaccinated, and 29.5% of triple vaccinated cancer patients had higher SARS-CoV-2 antibody levels. When patients were split into hematological and solid cancer, the hematological cancer group demonstrated lower serological responses than the solid cancer group in the first and second doses (first dose, average concentration 11.1 vs. 201.4 BAU/mL, respectively, p < 0.05; second dose, average concentration 441.5 vs. 1725.9 BAU/mL, respectively, p < 0.05). There was no difference in the third dose level (1756.3 vs. 2548.0 BAU/mL, p = 0.21). (4) Conclusions: Most vaccines were effective in producing robust antibody responses when more than one dose was given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants had SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.

CLL-461 Humoral Response to COVID-19 Vaccine: A Challenge in CLL

Chronic lymphocytic leukaemia (CLL) is associated with some degree of immune dysfunction as a result of the disease itself and/or treatment. COVID-19 has a major impact on patients with CLL who are at increased risk for severe disease and death. In this study, we aimed to understand the efficacy of anti-SARS-CoV-2 vaccines in patients with CLL. From January 2021, we collected data on 166 vaccinated patients with CLL followed at our site. Median age was 68 years (range 41-92); 43 (26%) were treatment-naïve (TN), 25 (15%) were previously treated, 95 (57%) were on active therapy, and 3 (2%) were experiencing relapse. Most patients received BNT162b2 (87%), followed by mRNA-1273 (4%) and ChAdOx1-S (3%); data is missing in 6%. Serology testing was performed with the SARS-CoV-2 S1/S2 IgG assay (Elecsys® Anti-SARS-CoV-2) 2 to 3 weeks after second and third vaccine doses and considered negative for antibody titers below 0.4 U/ml. Vaccine response was evaluated post-dose 2 in 119 patients and post-dose 3 in 74 patients. Post second dose, a higher seroconversion rate was observed in TN patients and those with sustained clinical response after therapy discontinuation (42% and 46% respectively) compared with actively treated patients (20.5%; [p=0.024; p=0.048]). Antibody response rate in patients receiving BTKi was considerably lower 19.7% (12/61). Three (42.9%) out of 7 patients who received venetoclax monotherapy seroconverted. None of the patients exposed to anti-CD20 antibodies (3/8 with targeted therapy, 2/8 with chemotherapy, 3/8 as single agent) <12 months before vaccination responded. Among patients actively treated who failed to achieve a humoral response after two-dose, 25.6% responded to the third dose of vaccine, although with a weak antibody level (median 8.64 U/ml, range 0.55-175). Overall, post third dose a higher median (IQR) antibody titer (127.9 U/mL; 0.55-2500) was observed compared to one post second dose (19.2 U/ml; 0.86-2500) in patients on therapy. Notably, all patients in clinical remission after treatment present titers above the upper limit of quantification (>2500 U/mL) post third dose. Conclusions: Humoral immune response to the COVID-19 vaccine is impaired in most patients with CLL and correlates with treatment status.

COVID-19, Vaccination, and Female Fertility in the Czech Republic.

The fast-track process to approve vaccines against COVID-19 has raised questions about their safety, especially in relation to fertility. Over the last 2 years, studies have appeared monitoring female fertility, especially from assisted reproduction centers or in animal experiments. However, studies monitoring healthy populations are still limited. The aim of our study was to monitor the relevant parameters of female fertility (sex and other steroids, LH, FSH, SHBG, Antimüllerian hormone and antral follicle count) before and then 2–4 months after the third dose of vaccination against COVID-19 in a group of 25 healthy fertile woman. In addition, anti-SARS-CoV-2 and anti-SARS-CoV-2S antibodies were determined. We did not observe significant changes in the measured parameters before and after the third dose of vaccination. By comparing levels of the analytes with antibodies indicating a prior COVID-19 infection, we found that women who had experienced the disease had statistically lower levels of estrone, estradiol, SHBG and 5α-dihydroprogesterone, and conversely, higher levels of androgen active dehydroepiandrosterone and dihydrotestosterone. Our results confirm that vaccination does not affect female fertility, and that what fertile women should be worried about is not vaccination, but rather COVID-19 infection itself.

The importance of booster vaccination in the context of Omicron wave.

Omicron (B.1.1.529) was first detected in a sample collected in Botswana on November 11, 2021, and has rapidly replaced Delta as the dominant global variant given the robust transmissibility. Moreover, it displays a lower virulence than other variants. However, the pathogenicity of Omicron appears to be underestimated in view of the increasing levels of herd immunity through natural infection or vaccination. Additionally, the volume of hospitalizations and deaths increase in proportion to the number of cases due to the high transmissibility of Omicron. Therefore, vaccination remains an important public health priority. Notably, a series of important mutations in the Omicron spike protein, especially in the receptor-binding domain and N-terminal domain, appears to be associated with immune escape capacity, reducing the willingness of people to receive vaccines. Herein, we provide an in-depth discussion to assess the effectiveness of the second and third vaccination against Omicron variant. On the one hand, the two-dose vaccination program adopted by many countries is insufficient to prevent Omicron infection given the mutations correlated with immune escape and the decline in vaccine efficacy over time. On the other hand, booster dose significantly increases the protective efficacy against Omicron infection. Most importantly, heterologous third dose vaccination induces a more robust immune response than homologous booster dose. Therefore, under the special background of this pandemic, there is an urgent need to accelerate the third dose of vaccination, especially providing better booster vaccination strategies, to combat emerging Omicron variant.

P16.39: Immunogenicity of the Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV; Sinopharm) And Short Term Clinical Outcomes in Vaccinated Solid Organ Transplant Recipients: A Prospective Cohort Study

Introduction: Immunocompromised patients have lower seroconversion rate to Coronavirus disease 2019 (COVID-19) vaccination due to immune system dysfunction. So far, the majority of studies in this area are conducted on messenger ribonucleic acid (mRNA) based vaccines. The aim of this study is evaluation of humoral immune response and in transplant patients and short term clinical outcomes in transplant patients vaccinated with SARS-CoV-2 Vaccine (BBIBP-CorV). Methods: All patients older than 18 years old who had been transplanted more than six months prior to recruitment were included in this prospective cohort conducted in Shiraz transplant center as the largest transplant center in Asia from March to December, 2021. The patients received two doses of Sinopopharm 4 weeks apart. The immunogenicity was evaluated through assessment of antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 by enzyme-linked immunosorbent assay (ELISA) method 4 weeks after the first and second dose of vaccine. The patients were followed up weekly up to six months after the second dose monthly up to six months after second dose and were evaluated for occurrence of vaccine adverse events, or getting COVID-19, hospitalization and laboratory parameters. The clinical and laboratoty data of patients was recorded and analyzed by statistical tests. Results: Totally, 921 transplant patients (665 kidney transplantation, 221 liver transplantation, 28 simultaneous pancreas kidney (SPK) and 7 heart transplant recipients). 115 (12.5%) and 239 (26%) patients had acceptable anti S-RBD IgG levels 4 weeks after the first and second dose, respectively. After omitting COVID19 cases with positive PCR test within 6 months before vaccination, 104 (12.6%) and 211 (25.5%) patients had acceptable anti S-RBD level 4 weeks after the first and second dose. Totally, 80 patients (8.68%) got infected with COVID-19 after vaccination.45 (4.9%) patients were admitted in the hospital due to COVID-19 after receiving the second dose of vaccine. None of the patients died during 6 months follow up period. 24 (10.9%) ones developed liver enzyme elevation Also, rise in serum creatinine was observed in 86 (13.5%) kidney transplant patients. Two of SOT recipients experienced biopsy proven rejection which managed by high dose of corticosteroid without any graft loss episodes. Conclusion: The results of our study showed that humoral response rate to Sinopharm vaccine was low in transplant patients. Short time from transplant was only effective factor on low seroconversion rate in transplant patients due to the high dose of immunosuppressive medications in this time frame. It is recommended that the third dose of vaccine, particularly from a different vaccine platform from the inactivated vaccine be administered in transplant patients.

P16.36: Effectiveness of SARS-Cov 2 Vaccination in Kidney Transplant Patients in Chile

Introduction: The humoral response to COVID-19 vaccines in transplant recipients has been reported to be lower than the obtained in the general population. For the Pfizer vaccine, an antibody response in 5-59% of those vaccinated is described, depending on the immunosuppressive maintenance therapy implemented, with a 56% of cellular response after the 2nd dose of the vaccine. The clinical significance of this poorer immune reaction is unclear. On the other hand, the degree of response to the Sinovac vaccine, the most used early in Chile, is unknown. Taking into account that the lethality of SARS-CoV-2 infection in transplanted patients was 6 times higher than the general population during the first wave of the pandemic (renal FUTAC data), we carried out this study with the aim of knowing the clinical effectiveness of the first two vaccines implemented in Chile in kidney transplant patients. Methods: Prospective, observational, multicenter study. The FUTAC database was available with a periodic report from all transplant centers in the country with 98% coverage and information available from 3/27/2020 to 7/7/2021. The data of transplanted patients who were infected with SARS-COV-2 were recorded comparing between those who had been fully vaccinated or not, with the Sinovac or Pfizer vaccine, evaluating the incidence of hospitalization and lethality. The group with complete vaccination was defined if the infection occurred 15 days after the second dose and the unvaccinated group corresponded to those without vaccination, with incomplete vaccination or in a period < 15 days after the second dose. Results: Of a total of 424 cases, 16 were discarded due to incomplete data, analysing 408 patients, of which 336 (82%) suffered the infection without being effectively vaccinated and 72 (18%) who were fully vaccinated. Of the total patients fully vaccinated, 57% (40/70) received Sinovac vaccine and 43% (30/70) Pfizer. No differences were found between COVID-19 infection rates between 2020 and 2021. Of the fully vaccinated patients, 42/72 (58%) were hospitalized, and 14/72. (19%) died; in this group, there are 7 patients who are alive but seriously ill at the time of closing the registry. In the unvaccinated group, 53% (179/336) were hospitalized and 15% (50/336) died, without significant differences in hospitalization or fatality rates. No differences were found in hospitalization or fatality rates between those vaccinated with Pfizer or Sinovac. Conclusions: The transplanted population, although fully vaccinated, maintains a high fatality rate, which is still 6 times higher than the general population. Although these data could be biased by the patients who did not consult, they were an input to decide a third dose of vaccination just applied to this highly vulnerable population, whose results are waiting to be evaluated. In Chile, the third booster dose was started in September 2021 and a 4th booster dose is currently being delivered starting in January 2022. Marion Alarcon; Loreto Oliva; Silvana Morales.

Third dose of anti-SARS-CoV-2 inactivated vaccine for patients with RA: Focusing on immunogenicity and effects of RA drugs.

ObjectivesTo evaluate the immunogenicity of the third dose of inactivated SARS-CoV-2 vaccine in rheumatoid arthritis (RA) patients and explore the effect of RA drugs on vaccine immunogenicity.MethodsWe recruited RA patients (n = 222) and healthy controls (HC, n = 177) who had been injected with a third dose of inactivated SARS-CoV-2 vaccine, and their neutralizing antibody (NAb) titer levels were assessed.ResultsRA patients and HC were age- and gender-matched, and the mean interval between 3rd vaccination and sampling was comparable. The NAb titers were significantly lower in RA patients after the third immunization compared with HC. The positive rate of NAb in HC group was 90.4%, while that in RA patients was 80.18%, and the difference was significant. Furthermore, comparison of NAb titers between RA treatment subgroups and HC showed that the patients in the conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) group exhibited no significant change in NAb titers, while in those receiving the treatment of biological DMARDs (bDMARDs), Janus Kinase (JAK) inhibitors, and prednisone, the NAb titers were significantly lower. Spearman correlation analysis revealed that NAb responses to SARS-CoV-2 in HC did differ significantly according to the interval between 3rd vaccination and sampling, but this finding was not observed in RA patients. In addition, NAb titers were not significantly correlated with RA-related laboratory indicators, including RF-IgA, RF-IgG, RF-IgM, anti-CCP antibody; C-RP; ESR; NEUT% and LYMPH%.ConclusionSerum antibody responses to the third dose of vaccine in RA patients were weaker than HC. Our study will help to evaluate the efficacy and safety of booster vaccination in RA patients and provide further guidance for adjusting vaccination strategies.

Early Adverse Events and Immune Response Following Second and Third COVID-19 Vaccination in Pregnancy.

(1) Background: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women. (2) Objective: To determine the vaccine-induced immunity and adverse events associated with the third (booster) dose of the BNT162b2 vaccine compared to the first and second dose of the vaccine among pregnant women. (3) Study design: A prospective cohort study in a tertiary referral center comparing pregnant women who were vaccinated by the first and second dose of the BNT162b2 (Pfizer/BioNTech) vaccine to pregnant women vaccinated by a third (booster) dose, between January and November 2021. A digital questionnaire regarding adverse events was filled by both groups 2–4 weeks after vaccination. Blood samples were collected and tested for SARS-COV-2 IgG antibodies 28–32 days after the administration of the second or third BNT162b2 dose. (4) Results: Seventy-eight pregnant women who received the first and second doses of the vaccine were compared to eighty-four pregnant women who received the third dose of the vaccine. In terms of adverse events following vaccination, local rash/pain/swelling (93.6% vs. 72.6%, p < 0.001) was significantly less common after the third vaccination compared to after the second vaccination. Other adverse events, including early obstetric complications, did not differ between the two groups. SARS-CoV-2 IgG serum levels 28–32 days after the vaccination were significantly higher after the third vaccination compared to the second vaccination (1333.75 vs. 2177.93, respectively, p < 0.001). (5) Conclusion: This study confirms the safety regarding early adverse events and immunogenicity, and the lack of early obstetric complications of the BNT162b2 second- and third-dose vaccine in pregnant women. The third (booster) dose is effective in generating a stronger humoral immune response in pregnant women compared with the second dose.

Effectiveness of third vaccine dose for coronavirus disease 2019 during the Omicron variant pandemic: a prospective observational study in Japan

The administration of a third booster dose of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 2019 (COVID-19) has progressed worldwide. Since January 2022, Japan has faced a nationwide outbreak caused by the Omicron variant, which occurred simultaneously with the progression of mass vaccination with the third booster dose. Therefore, this study evaluated the effectiveness of the third dose of vaccine by reverse transcription-polymerase chain reaction (RT-PCR) test using nasopharyngeal swab samples from adults aged ≥ 18 years tested after having close contact with COVID-19 cases between January and May 2022. Participants who completed only one dose were excluded from the study. Among the 928 enrolled participants, 139 had never been vaccinated, 609 had completed two doses, 180 had completed three doses before the swab test, and the overall RT-PCR test positivity rate in each group was 48.9%, 46.0%, and 32.2%, respectively. The vaccine effectiveness of the third dose to prevent infection after close contact was approximately 40% (95% confidence interval: 20–60%), which was the highest at 10–70 days after receiving the third dose. In conclusion, the effectiveness of the three-dose mRNA COVID-19 vaccine after close contact during the Omicron outbreak is approximately 40%.

Factors associated with severe or fatal clinical manifestations of SARS-CoV-2 infection after receiving the third dose of vaccine.

BackgroundLittle is known about vulnerability to severe COVID‐19 illness after vaccination completion with three doses of vaccine against COVID‐19.ObjectivesTo identify individual features associated with increased risk of severe clinical manifestation of SARS‐CoV‐2 infections after receiving the third dose of vaccine against COVID‐19.MethodsWe performed a nested case‐control study based on 3,360,116 citizens from Lombardy, Italy, aged 12 years or older who received the third dose of vaccine against COVID‐19 from 20 September through 31 December 2021. Individuals were followed from 14 days after vaccination completion until the occurrence of severe COVID‐19 illness, death unrelated to COVID‐19, emigration or 15 March 2022. For each case, controls were randomly selected to be 1:10 matched for the date of vaccination completion and municipality of residence. The association between candidate predictors and outcome was assessed through multivariable conditional logistic regression models.ResultsDuring 12,538,330 person‐months of follow‐up, 5171 cases of severe illness occurred. As age increased, a trend towards increasing odds of severe illness was observed. Male gender was a significant risk factor. As the number of contacts with the Regional Health Service increased, a trend towards increasing odds of severe illness was observed. Having had a previous SARS‐CoV‐2 infection was a significant protective factor. Having received the Moderna vaccine significantly decreased the odds of severe illness. Significant higher odds were associated with 42 diseases/conditions. Odds ratios ranged from 1.23 (diseases of the musculoskeletal system) to 5.00 (autoimmune disease).ConclusionsThis study provides useful insights for establishing priority in fourth‐dose vaccination programs.

New onset of acute uveitis following COVID-19 vaccination.

PurposeThis study reported 11 cases of new-onset acute uveitis following coronavirus disease 2019 (COVID-19) vaccination.MethodsThis retrospective observational case study included 11 eyes of 11 patients with acute uveitis after the COVID-19 vaccination. We only included patients with new-onset uveitis. The medical records of the patients from January 2021 to January 2022 were reviewed.ResultsThe mean age of the participants was 51.81 years, and all patients demonstrated anterior chamber reaction with keratic precipitates in the affected eye. The mean duration between vaccination and uveitis was 8.27 days. Seven patients developed uveitis after receiving the second dose of vaccination, and four developed uveitis after receiving the third dose of vaccination. Five patients showed posterior synechiae, and three patients showed hypopyon. After treatment with topical 1% prednisolone acetate eye drops and systemic prednisolone, inflammation was adequately controlled and quickly resolved.ConclusionsCOVID-19 vaccination with messenger RNA and viral vector vaccines may cause acute anterior uveitis. Although initially severe, uveitis responded well to steroid therapy with no visual impairment.

Six-month humoral and cellular immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors: a longitudinal cohort study with a focus on the variants of concern

BackgroundThe role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated.Patients and methodsWe have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA).ResultsSix months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy.ConclusionsOur work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed.

Analysis of the Specific Immune Response after the Third Dose of mRNA COVID-19 Vaccines in Organ Transplant Recipients: Possible Spike-S1 Reactive IgA Signature in Protection from SARS-CoV-2 Infection.

Background: Several studies have indicated that anti-SARS-CoV-2 mRNA vaccinations are less effective in inducing robust immune responses among solid organ transplant recipients (SOTRs) compared with the immunocompetent. The third dose of vaccine in SOTRs showed promising results of immunogenicity, even though clinical studies have suggested that immunocompromised subjects are less likely to build a protective immune response against SARS-CoV-2 resulting in lower vaccine efficacy for the prevention of severe COVID-19. Methods: Serological IgG and IgA were analyzed through CLIA or ELISA, respectively, while Spike-specific T cells were detected by ELISpot assay after the second and third dose of vaccine in 43 SOTRs. Results: The third dose induced an improvement in antibody response against SARS-CoV-2. We also reported a strong correlation between specific humoral and cellular responses after the third dose, even though we did not see significant changes in the magnitude of the SARS-CoV-2-specific T cell response. SOTRs who contracted the SARS-CoV-2 infection after the third dose, despite eliciting a positive IgG response, failed to mount an anti-Spike-S1 IgA response, both after the third dose and after SARS-CoV-2 infection. Conclusions: We can conclude that serum IgA detection can be helpful, along with IgG detection, for the evaluation of vaccine efficacy, principally in fragile subjects at high risk of infection.

Three-month follow-up of durability of response to the third dose of the SARS-CoV-2 BNT162b2 vaccine in adults aged 60 years and older: a prospective cohort study

ObjectiveTo evaluate the durability of response 3 months after the third BNT162b2 vaccine in adults aged 60 years and older.DesignProspective cohort study.SettingSingle tertiary centre.ParticipantsHealthcare workers/family members aged ≥60 years old...

Investigation of Humoral and Cellular Immunity in TOBB ETÜ Hospital Workers After Three Doses of CoronaVac Vaccination and after One Dose of Comirnaty Vaccination Following Two Doses of CoronaVac

The Coronavirus disease 2019 (COVID-19) pandemic still continues around the world by making peaks with different variants. In the fight against COVID-19, vaccination is currently the only protective measure. In Turkey, vaccination started firstly in healthcare workers on 13 January 2021 with the CoronaVac (Sinovac Biotech, Chinese) vaccine, and booster doses were administered with the CoronaVac and Comirnaty vaccines in July 2021. In this cross-sectional study, it was aimed to determine the humoral and cellular immunity levels of the employees of the TOBB ETU Hospital 2.5-3.5 months after three doses of vaccination and identify the effective factors. With the power analysis that was conducted with the G*Power software, it was determined to be suitable to include 40 TOBB ETU Hospital workers who had their third dose with the CoronaVac vaccine and 60 workers of the same hospital who had their third dose with the Comirnaty (Pfizer Biontech, Germany) vaccine, and age- and sex-matching was considered by selecting 60 workers randomly from among 223 workers who had Comirnaty as their third dose. The study excluded individuals who had a previous COVID-19 infection or had a positive PCR test result. After collecting blood samples on 18-22 October 2021, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immunoglobulin G levels were studied with the chemiluminescence immunoassay method using a Beckman-Access device (Beckman Coulter Inc., CA, USA) for humoral immunity, and T-SPOT test (T-SPOT. COVID SARS-CoV-2 test-Oxford Immunotec, Singapur) was carried out for cellular immunity. Additionally, demographic data, habits, personal information such as weight and height, reasons for choosing the vaccine and post-vaccine side effects were obtained through the data collection form. Data collection was completed on 29 November 2021. As a result, among the healthcare workers who had received their third dose of vaccine with Comirnaty and CoronaVac; while 25% of those who received three doses of CoronaVac had humoral immunity, 93.3% humoral immunity was determined in the heterogeneous vaccine group with two doses of CoronaVac and one dose of Comirnaty vaccine (p<0.05). Cellular immunity was found to be higher (88.3%, 70%) in those who received the heterologous vaccine than those who completed three doses of the same vaccine (p<0.05). In the heterogeneous vaccination group consisting of the healthcare workers who had their third vaccine dose with Comirnaty and those who had it with CoronaVac, humoral and cellular immunity levels were found high. Among the participants whose humoral immunity was found negative, cellular immunity was present in 75% of those who had Comirnaty as their third dose and 63.3% of those who had CoronaVac. While no significant relationship was found between immunity levels and age, sex or body mass index (BMI), the levels of both forms of immunity were lower in those who had chronic diseases. Among the participants, physicians preferred the third dose of Comirnaty vaccine at a rate of 71.4% and laboratory workers preferred this vaccine at a rate of 80% according to the workplace. In the third dose vaccine preference reasons, it was stated that 55% would continue with the same vaccine, experience fewer side effects, 44% provide more immunity and 9% do not prevent going abroad. The incidence of side effects after the third dose of vaccine was 53% higher in those who received the Comirnaty vaccine than in those who received CoronaVac (35%). Based on these data, it was concluded that heterologous vaccination should be preferred in vaccination strategies, and knowing cellular immunity levels is important for the decision. There is a need for more comprehensive and follow-up studies on how long humoral and especially cellular immunity lasts.

Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.

Acute myocarditis following a third dose of COVID-19 mRNA vaccination in adults

IntroductionMyocarditis has been reported following the second dose of COVID-19 mRNA vaccination. Whether administration of additional doses of COVID-19 vaccines further increases the risk of myocarditis is unknown. MethodsWe included individuals who received one to three doses of BNT162b2 or mRNA-1273 mRNA vaccine between 12/14/2020 and 2/18/2022. Myocarditis within 21 days of vaccine administration was identified using electronic medical records. Incidence rate ratios were calculated by comparing the observed incidence with the expected incidence from the same population during a 365-day baseline period. ResultsOf 3,076,660 KPSC members who received at least one dose of COVID-19 mRNA vaccines, 2,916,739 (94.5%) received at least two doses, and 1,146,254 (47.0%) received three doses. The incidence rate ratio for myocarditis was 0.86 (95% CI 0.31–1.93) for the first dose, 4.22 (95% CI 2.63–6.53) for the second dose, and 2.61 (1.13–5.29) for the third dose. Most myocarditis cases following the second and third dose occurred within seven days of vaccination. ConclusionMyocarditis was a rare event observed after the second or third dose of vaccination. Most cases presented within seven days of vaccination. The incidence of myocarditis following the third dose was not significantly higher than that observed after the second dose.

Impaired serological response to COVID-19 vaccination following anticancer therapy: A systematic review and meta-analysis.

Owing to the high coronavirus disease 2019 (COVID‐19)‐related morbidity and fatality rate among patients with cancer, the introduction of COVID‐19 vaccines is of profound significance in this fragile population. Accumulating data suggested that oncologic patients, especially those with anticancer therapy have an impaired immune response to COVID‐19 vaccination. However, the exact effect of anticancer treatments on postvaccination response has not been elucidated yet. We, therefore, conducted a meta‐analysis to evaluate the impact of treatments on response to COVID‐19 vaccination in patients with cancer. A total of 39 studies were finally included comprising 11 075 oncologic patients. Overall, we found the humoral response was significantly decreased in patients undergoing anticancer treatments (odds ratio [OR] = 2.55, 95% confidence interval [CI]: 2.04–3.18) compared with those without active treatment. The seroconversion rates were significantly lower in patients with chemotherapy (OR = 3.04, 95% CI: 2.28–4.05), targeted therapy (OR = 4.72, 95% CI: 3.18–7.01) and steroid usage (OR = 2.19, 95% CI: 1.57–3.07), while there was no significant association between immunotherapy or hormonal therapy and seroconversion after vaccination. Subgroup analyses showed therapies with anti‐CD20 antibody (OR = 11.28, 95% CI: 6.40–19.90), B‐cell lymphoma 2 inhibitor (OR = 5.76, 95% CI: 3.64–9.10), and Bruton tyrosine kinase inhibitor (OR = 6.86, 95% CI: 4.23–11.15) were significantly correlated with the risk of negative humoral response to vaccination. In conclusion, our results demonstrated that specific oncologic therapies may significantly affect serological response to COVID‐19 vaccines in patients with cancer. Thus, an adapted vaccination strategy taking the influence of active treatment into account is in need, and further research on the effect of the third dose of vaccine and the role of postvaccination cellular response in oncologic patients is also needed.

Third Dose of the BNT162b2 Vaccine Results in Sustained High Levels of Neutralizing Antibodies Against SARS-CoV-2 at 6 Months Following Vaccination in Healthy Individuals.

Third Dose of the BNT162b2 Vaccine Results in Sustained High Levels of Neutralizing Antibodies Against SARS-CoV-2 at 6 Months Following Vaccination in Healthy Individuals.