Effects of inbound attendees of a mass gathering event on the COVID-19 epidemic using individual-based simulations (preprint)

Given that mass gathering events involve heterogeneous and time-varying contact between residents and visitors, we sought to identify possible measures to prevent the potential acceleration of the outbreak of an emerging infectious disease induced by such events. An individual-based simulator was built based on a description of the reproduction rate among people infected with the infectious disease in a hypothetical city. Three different scenarios were assessed using our simulator, in which controls aimed at reduced contact were assumed to be carried out only in the main event venue or at subsequent additional events, or in which behavior restrictions were carried out among the visitors to the main event. The simulation results indicated that the increase in the number of patients with COVID-19 could possibly be suppressed to a level equivalent to that if the event were not being held so long as the prevalence among visitors was only slightly higher than that among domestic residents and strict requirements were applied to the activities of visitors.

What Proportion of Population has achieved Cellular Immunity against SARS-CoV-2 after Booster Vaccination: A Cross-sectional Study (preprint)

Background Booster vaccination reduces the incidence of severe cases and mortality of COVID-19, with cellular immunity playing an important role. However, little is known about what proportion of population has achieved cellular immunity after booster vaccination. Methods We conducted a Fukushima cohort database and assessed the humoral and cellular immunity in 2526 residents and HCWs in Fukushima Prefecture in Japan by continuous blood collection every 3 months since September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination, using T-SPOT.COVID test, and analyzed their background characteristics. Results Among 1089 participants, 64.3 % (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following as 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. Conclusion This is the first study to evaluate cellular immunity at the population level after booster vaccination using T-SPOT.COVID test, however, with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

Time course of adverse reactions after BNT162b2 vaccination in healthy and allergic disease individuals aged 5–11 years: an observational and historical cohort study (preprint)

Purpose: We aimed to assess whether BNT162b2 vaccination in children meets high safety standards by surveying adverse reactions in healthy and allergic disease individuals aged 5–11 years in Japan throughout seven days following their first and second BNT162b2 vaccination. Methods This was an observational and historical cohort study. The eligibility criteria of study participants included those aged 5–11 years, who received two doses of BNT162b2, with consent by the children and their guardians. We collected data on sex, age, height, weight, blood type, history of BCG vaccination, allergic disease, medication, history of COVID-19 infection and adverse reactions seven days following the first and second BNT162b2 vaccination using a questionnaire. We used previous reports to compare our result with individuals aged 12–15years. Results A total of 421 participants were eligible for this study. Among the 216 patients with allergic disease, 48 (22.2%) had experienced worsening of their chronic diseases, and the frequency of fatigue and dizziness after the second dose was higher than that of healthy individuals. The experience of systemic adverse reactions was associated with asthma. The frequency of headache, diarrhea, fatigue, muscle/joint pain, and fever after the second BNT162b2 vaccination was lower in the individuals aged 5–11 years than in those aged 12–15 years. Fever was the only systemic adverse reaction that lasted longer than five days (1.0% of participants). Conclusions Individuals with allergic diseases, who are potentially susceptible to COVID-19, may experience worsening of their chronic diseases and more frequent adverse reactions after BNT162b2 vaccination than healthy individuals. To ensure that children with allergic diseases receive the vaccine safely, further information needs to be collected.

Waning of humoral immunity and affecting factors after BNT162b2 vaccination: a cohort study with latent growth curve model in Fukushima (preprint)

Measuring long-term antibody titer kinetics and subsequent COVID-19 vaccinations are crucial for identifying vulnerable populations. Our aim was to determine the association between long-term antibody kinetics up to seven months post second vaccination, including peak titers and factors. A three-time survey was performed in 2021 on healthcare workers in Japan to investigate the changes in humoral immunity using chemiluminescence immunoassay. We included participants who completed the second-dose vaccination, the antibody survey for all three terms, and those who were not infected with COVID-19. A latent growth curve model was used to identify the factors affecting the peak titer and decreasing the antibody slope. Overall, 205 eligible participants were included in the final analysis. Of these, the mean titers of immunoglobulin G (IgG) against the spike (S) protein and the neutralizing activity at seven months after the second vaccination decreased to 154.3 AU/ml (8.8% of the peak titer) and 62.1 AU/ml (9.5% of the peak titer), respectively. The growth model of IgG showed that age significantly affected peak titers (p < 0.001); however, a significant difference was not found for the decreasing slope. In conclusion, aging adults had significantly lower peak antibody titers, however age did not relate to decreasing slope.

A personalized antibody score for predicting individual COVID-19 vaccine-elicited antibody levels from basic demographic and health information (preprint)

Antibody titers wane after two-dose COVID-19 vaccinations, but individual variation in vaccine-elicited antibody dynamics remains to be explored. Here, we created a personalized antibody score that enables individuals to infer their antibody status by use of a simple calculation. We recently developed a mathematical model of B cell differentiation to accurately interpolate the longitudinal data from a community-based cohort in Fukushima, Japan, which consists of 2,159 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time course of the vaccine- elicited antibody response, we first elucidated individual background factors that contributed to the main features of antibody dynamics, i.e., the peak, the duration, and the area under the curve. We found that increasing age was a negative factor and a longer interval between the two doses was a positive factor for individual antibody level. We also found that the presence of underlying disease and the use of medication affected antibody levels negatively, whereas the presence of adverse reactions upon vaccination affected antibody levels positively. We then applied to these factors a recently proposed computational method to optimally fit clinical scores, which resulted in an integer-based score that can be used to evaluate the antibody status of individuals from their basic demographic and health information. This score can be easily calculated by individuals themselves or by medical practitioners. There is a potential usefulness of this score for identifying vulnerable populations and encouraging them to get booster vaccinations.

Stratifying elicited antibody dynamics after two doses of SARS-CoV-2 vaccine in a community-based cohort in Fukushima, Japan (preprint)

Recent studies have provided insights into the effect of vaccine boosters on recall immunity. Given the limited global supply of COVID-19 vaccines, identifying vulnerable populations with lower sustained vaccine-elicited antibody titers is important for targeting individuals for booster vaccinations. Here we investigated longitudinal data in a cohort of 2,526 people in Fukushima, Japan, from April 2021 to December 2021. Antibody titers following two doses of a COVID-19 vaccine were repeatedly monitored and information on lifestyle habits, comorbidities, adverse reactions, and medication use was collected. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers and identified vulnerable populations with low sustained antibody titers. Moreover, we showed that only 5.7% of the participants in our cohort were part of the "durable" population with high sustained antibody titers, which suggests that this durable population might be overlooked in small cohorts. We also found large variation in antibody waning within our cohort. There is a potential usefulness of our approach for identifying the neglected vulnerable population.

Factors Associated with COVID-19 Vaccine Booster Hesitancy: a Retrospective Cohort Study, Fukushima Vaccination Community Survey (preprint)

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of 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 booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and 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 younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

Possible Association of Typhoon Hagibis and the COVID-19 Pandemic on Patient Delay in Breast Cancer Patients: a case report (preprint)

Little is known on how disasters interact in their impacts on patient care. We experienced a breast cancer patient whose initial presentation was delayed for two years due to the COVID-19 pandemic and Typhoon Hagibis. Increasing awareness is needed on the combined impacts of disasters on breast cancer management.

Shortcomings of telemedicine and importance of uninterrupted cancer care during the COVID-19 pandemic: A case report of advanced breast cancer in Fukushima, Japan (preprint)

We experienced an advanced breast cancer patient who failed to receive diagnostic imaging despite regular video conferences with her physician during the COVID-19 pandemic, resulting in delayed liver metastasis detection. Recognizing shortcomings of telemedicine and collaboration among medical institutions for uninterrupted cancer care is imperative during the pandemic.

Stay with Your Community: Bridges between Clusters Trigger Expansion of COVID-19 (preprint)

The spreading of virus infection is here simulated over artificial human networks. The real-space urban life of people is modeled as a modified scale-free network with constraints. A scale-free network has been adopted in several studies for modeling on-line communities so far but is modified here for the aim to represent peoples' social behaviors where the generated communities are restricted reflecting the spatiotemporal constraints in the real life. Furthermore, the networks have been extended by introducing multiple cliques in the initial step of network construction and enabling people to zero-degree people as well as popular (large degree) people. As a result, four findings and a policy proposal have been obtained. First, the "second waves" occur without external influence or constraints on contacts or the releasing of the constraints. These second waves, mostly lower than the first wave, implies the bridges between infected and fresh clusters may trigger new expansions of spreading. Second, if the network changes the structure on the way of infection spreading or after its suppression, the peak of the second wave can be larger than the first. Third, the peak height in the time series depends on the difference between the upper bound of the number of people each member accepts to meet and the number of people one chooses to meet. This tendency is observed for two kinds of artificial networks and implies the impact of the bridges between communities on the virus spreading. Fourth, the release of once given constraint may trigger a second wave higher than the peak of the time series without introducing any constraint from the beginning, if the release is introduced at a time close to the peak. Thus, both governments and individuals should be careful in returning to human society with inter-community contacts.