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.

Designing isolation guidelines for COVID-19 patients utilizing rapid antigen tests: a simulation study using viral dynamics models (preprint)

Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adapted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation (thus they are redundantly isolated), whereas others may still be infectious. Utilizing viral test results to determine ending isolation would minimize both the risk of ending isolation of infectious patients and the burden due to redundant isolation of noninfectious patients. In our previous study, we proposed a computational framework using SARS-CoV-2 viral dynamics models to compute the risk and the burden of different isolation guidelines with PCR tests. In this study, we extend the computational framework to design isolation guidelines for COVID-19 patients utilizing rapid antigen tests. Time interval of tests and number of consecutive negative tests to minimize the risk and the burden of isolation were explored. Furthermore, the approach was extended for asymptomatic cases. We found the guideline should be designed considering various factors: the infectiousness threshold values, the detection limit of antigen tests, symptom presence, and an acceptable level of releasing infectious patients. Especially, when detection limit is higher than the infectiousness threshold values, more consecutive negative results are needed to ascertain loss of infectiousness. To control the risk of releasing of infectious individuals under certain levels, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation, and the length of prolonged isolation increases when the detection limit is higher than the infectiousness threshold values, even though the guidelines are optimized for given conditions.

Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment (preprint)

Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.