Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan.

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19-2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19-3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Antibody and T-Cell Responses against SARS-CoV-2 after Booster Vaccination in Patients on Dialysis: A Prospective Observational Study.

Intensive vaccination is recommended for populations more vulnerable to COVID-19 infection, although data regarding the built of immunity after vaccination for dialysis patients are lacking. This prospective, observational cohort study of maintenance hemodialysis patients examined IgG antibody levels against the SARS-CoV-2 spike (S1) protein, neutralizing activity, and interferon gamma levels after the third dose of the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Humoral immunity was repeatedly measured for up to two months. The study includes 58 patients on hemodialysis. Median neutralizing antibodies reached a maximum at 56 and 9 days after booster vaccination with BNT162b2 and mRNA-1273, respectively. The median IgG antibody titer reached a maximum of 3104.38 and 7209.13 AU/mL after 16 days of booster dose, and cellular immunity was positive in 61.9% and 100% of patients with BNT162b2 and mRNA-1273 vaccination, respectively. By repeating the measurements over a period of two months, we clarified the chronological aspects of the acquisition of humoral immunity in dialysis patients after a booster COVID-19 vaccination; most dialysis patients acquired not only humoral immunity, but also cellular immunity against SARS-CoV-2. Future research should investigate the continued long-term dynamics of antibody titers and cellular immunity after the third or further vaccinations, evaluating the need for additional vaccinations for hemodialysis patients.

Waning of Humoral Immunity and the Influencing Factors after BNT162b2 Vaccination: A Cohort Study with a Latent Growth Curve Model in Fukushima.

Measuring long-term antibody titer kinetics and subsequent coronavirus disease 2019 (COVID-19) vaccinations are crucial for identifying vulnerable populations. Our aim was to determine the association between long-term antibody kinetics, including peak titers and factors, up to seven months post-second vaccination. A three-time antibody survey was conducted in 2021 among healthcare workers in Japan to investigate the changes in humoral immunity using chemiluminescence immunoassay. The study involved 205 participants who had received the second vaccine dose, completed the three-time survey, and were not infected with SARS-CoV-2. A latent growth curve model was used to identify factors affecting the peak titer and decreasing the antibody slope. Of the eligible participants, the mean titers of immunoglobulin G (IgG) against the spike (S) protein and the neutralizing activity 7 months after the second vaccination decreased to 154.3 (8.8% of the peak titer) and 62.1 AU/mL (9.5% of the peak titer), respectively. The IgG growth model showed that age significantly affected peak titers (p < 0.001); however, a significant difference was not found for the decreasing slope. Ultimately, aging adults had significantly low peak antibody titers; however, age was unrelated to the slope of log-transformed IgG against the S protein.

Effectiveness of the Booster of SARS-CoV-2 Vaccine among Japanese Adolescents: A Cohort Study.

Vaccination is effective in preventing COVID-19-related hospitalization among all age groups, but there is limited evidence on the effectiveness of the booster of the SARS-CoV-2 vaccine among adolescents. We analyzed the data on the status of SARS-CoV-2 infection and their vaccination profiles in adolescents aged 13-18 years in Soma city (Fukushima, Japan) (n = 1835) from 14 May to 15 June 2022. The crude incidence rate and 95% confidence interval were calculated with the negative-binomial regression model after classifying the immunization status. The crude effectiveness of a booster administration to prevent infections was estimated as 86.4% (95% confidence interval: 57.2-95.7) when compared with the primary vaccination alone. The results of this study support that the community-based mass vaccination campaign of a booster dose among adolescents has additional protection from COVID-19 during the period of the B.1.1.529 (omicron) variant wave.

Humoral response to SARS-CoV-2 vaccination in haemodialysis patients and a matched cohort.

OBJECTIVES: SARS-CoV-2 vaccination is a crucial intervention for infection control; however, the immune response to vaccination in dialysis patients has been reported to be moderate compared with healthy adults. There are few studies available on humoral response in immunised dialysis patients compared with well-matched control group, we conducted a prospective cohort study measuring SARS-CoV-2 antibody titres in Fukushima Prefecture, Japan since September 2021. PARTICIPANTS: We compared the titres of both anti-SARS-CoV-2 S1 IgG and neutralising antibodies of 65 haemodialysis patients (dialysis group) with 500 residents in Soma, Fukushima (control group). METHODS: Coarsened exact matching was used to balance sex, age and days from the second dose between dialysis and control groups. RESULTS: Significant differences in the titres of anti-SARS-CoV-2 S1 IgG and neutralising antibodies were observed between the dialysis and control groups; anti-SARS-CoV-2 S1 IgG: 168.35 (4.48-1074.29) AU/mL and 269.81 (4.72-945.96) AU/mL in dialysis and control groups, p=0.02, neutralising antibodies: 35.77 (2.94-826.06) AU/mL and 62.22 (0.00-535.57) AU/mL, p=0.007, respectively). CONCLUSIONS: We observed significantly reduced anti-SARS-CoV-2 S1 antibody and neutralising antibodies in haemodialysis patients compared with cohorts matched for duration after vaccination. Patients receiving haemodialysis should be carefully monitored for immunological responses to the vaccination and COVID-19 infection.

Humoral immunity after second dose of BNT162b2 vaccine in Japanese communities: an observational cross-sectional study, Fukushima Vaccination Community Survey.

To reveal waning humoral immunity after second dose BNT162b2 vaccinations in a rural Japanese community and determine factors affecting antibody titers. We aimed to report Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein levels and neutralizing activity in a large scale community based cohort. METHODS: Participants in the observational cross-sectional study received a second dose of vaccination with BNT162b2 (Pfizer/BioNTech) and were not previously infected with COVID-19. Questionnaire-collected data on sex, age, adverse vaccine reactions, and medical history was obtained. RESULTS: Data from 2496 participants revealed that older age groups reached a low antibody titer 90-120 days after the second vaccination. Neutralizing activity decreased with age; 35 (13.3%) of those aged ≥ 80 years had neutralizing activity under the cut-off value. Neutralizing activity > 179 days from the second vaccination was 11.6% compared to that at < 60 days from the second vaccination. Significantly lower IgG antibody titers and neutralizing activity were associated with age, male sex, increased time from second vaccination, smoking, steroids, immunosuppression, and comorbidities. CONCLUSIONS: Antibody titer decreased substantially over time. Susceptible populations, older people, men, smokers, steroid users, immunosuppression users, and people with three or more comorbidities may require a special protection strategy.

Factors Associated with COVID-19 Vaccine Booster Hesitancy: A Retrospective Cohort Study, Fukushima Vaccination Community Survey.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive a third dose of a coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. This study included participants who provided answers in the questionnaire about whether they had an intent to receive a third dose of a vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate over the booster vaccination were retrieved. Among the 2439 participants, with a mean (±SD) age of 52.6 ± 18.9 years, and a median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that participants of a younger age (OR = 0.98; 95% CI: 0.96-1.00) and with a higher antibody level (OR = 2.52; 95% CI: 1.27-4.99) were positively associated with hesitancy over the third vaccine. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had a significant impact on behavior regarding the third vaccination. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken with these groups that are likely to hesitate over the third vaccine, subsequently increasing booster contact rate.

Time-Dependent Changes in Death Reports and the Sex Ratio in the Safety Surveillance of SARS-CoV-2 Vaccination in Japan, the United States, and European Countries.

The national safety surveillance of vaccines is a fundamental measure to ensure vaccination safety and maintain transparency and public trust. Our previous study revealed an early increase in death reports after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in Japanese surveillance despite our hypothesis that no time-dependent variations in the number of death reports would be seen if the vaccination is not related to serious adverse events. This study is an extensive investigation to determine whether the number of death reports varied consistently over time after vaccination in the older population in Japan, the US, and European countries. We collected the death reports after BNT162b2 mRNA vaccination in individuals aged 65 years or older using the open databases in Japan, the US (Vaccine Adverse Event Reporting System, VAERS), and European countries (EudraVigilance). We observed an early increase of death reports on Day 2 after the vaccination in all three databases. The female-to-male ratio was also assessed and showed a certain degree of time-dependence (R2 of linear regression 0.54, p =0.01) in Japan but not in the US and European countries. The findings suggest the existence of unknown predictors of the adverse events of the SARS-CoV-2 vaccination, especially for the older Japanese population. The continuous and careful monitoring safety aspects of the vaccines are warranted.

A Case of Exacerbation of Subclinical Hyperthyroidism after First Administration of BNT162b2 mRNA COVID-19 Vaccine.

COVID-19 vaccines are the most critical measure for controlling the COVID-19 pandemic; however, we have little information on their complications. We experienced a case of a patient who developed hyperthyroidism complicated with atrial fibrillation and heart failure on the sixth day after the first dose of COVID-19 vaccination. This case report shows the importance of considering hyperthyroidism as a possible complication after COVID-19 vaccination.

Geographical Profiles of COVID-19 Outbreak in Tokyo: An Analysis of the Primary Care Clinic-Based Point-of-Care Antibody Testing.

Introduction: The primary care clinic plays a major role in triage for coronavirus disease 2019 (COVID-19), where seroprevalence in the setting of primary care clinic remains less clear. As a point-of-care immunodiagnostic test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the serosurvey represents an alternative to the polymerase chain reaction (PCR) test to measure the magnitude of COVID-19 outbreak in the communities lacking sufficient diagnostic capability for PCR testing. Methods: We assessed seropositivity for the SARS-CoV-2 IgG between April 21 and May 20, 2020, at 2 primary care clinics in Tokyo, Japan. Results: The overall positive percentage of SARS-CoV-2 IgG was 3.83% (95% confidence interval [CI]: 2.76-5.16) for the entire cohort (n = 1071). The 23 special wards of central Tokyo exhibited a significantly higher prevalence compared with the other areas of Tokyo after classification by residence (P = .02, 4.68% [3.08-6.79] vs 1.83 [0.68-3.95] in central and suburban Tokyo, respectively). In central Tokyo, the southern area showed the highest seroprevalence compared with the other areas (7.92% [3.48-15.01]), corresponding to the cumulative number of confirmed COVID-19 patients by PCR test reported by the Tokyo Metropolitan Government. Conclusion: The seroprevalence surveyed in this study was too low for herd immunity, suggesting the need for robust disease control and prevention. A regional-level approach, rather than state- or prefectural-level, could be of importance in ascertaining detailed profiles of the COVID-19 outbreak.