Early CD4+ T cell responses induced by the BNT162b2 SARS-CoV-2 mRNA vaccine predict immunological memory.

Longitudinal studies have revealed large interindividual differences in antibody responses induced by SARS-CoV-2 mRNA vaccines. Thus, we performed a comprehensive analysis of adaptive immune responses induced by three doses of the BNT162b2 SARS-CoV-2 mRNA vaccines. The responses of spike-specific CD4+ T cells, CD8+ T cells and serum IgG, and the serum neutralization capacities induced by the two vaccines declined 6 months later. The 3rd dose increased serum spike IgG and neutralizing capacities against the wild-type and Omicron spikes to higher levels than the 2nd dose, and this was supported by memory B cell responses, which gradually increased after the 2nd dose and were further enhanced by the 3rd dose. The 3rd dose moderately increased the frequencies of spike-specific CD4+ T cells, but the frequencies of spike-specific CD8+ T cells remained unchanged. T cells reactive against the Omicron spike were 1.3-fold fewer than those against the wild-type spike. The early responsiveness of spike-specific CD4+ T, circulating T follicular helper cells and circulating T peripheral helper cells correlated with memory B cell responses to the booster vaccination, and early spike-specific CD4+ T cell responses were also associated with spike-specific CD8+ T cell responses. These findings highlight the importance of evaluating cellular responses to optimize future vaccine strategies.

Sex, Age, and Ethnic Background Shape Adaptive Immune Responses Induced by the SARS-CoV-2 mRNA Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced adaptive responses have been well investigated. However, the effects of sex, age, and ethnic background on the immune responses elicited by the mRNA vaccine remain unclear. Here, we performed comprehensive analyses of adaptive immune responses elicited by the SARS-CoV-2 mRNA vaccine. Vaccine-induced antibody and T cell responses declined over time but persisted after 3 months, and switched memory B cells were even increased. Spike-specific CD4+ T and CD8+ T cell responses were decreased against the B.1.351 variant, but not against B.1.1.7. Interestingly, T cell reactivity against B.1.617.1 and B.1.617.2 variants was decreased in individuals carrying HLA-A24, suggesting adaptive immune responses against variants are influenced by different HLA haplotypes. T follicular helper cell responses declined with increasing age in both sexes, but age-related decreases in antibody levels were observed only in males, and this was associated with the decline of T peripheral helper cell responses. In contrast, vaccine-induced CD8+ T cell responses were enhanced in older males. Taken together, these findings highlight that significant differences in the reactogenicity of the adaptive immune system elicited by mRNA vaccine were related to factors including sex, age, and ethnic background.

Modeling the effects of contact-tracing apps on the spread of the coronavirus disease: Mechanisms, conditions, and efficiency.

This study simulates the spread of the coronavirus disease (COVID-19) using a detailed agent-based model and the census data of Japan to provide a comprehensive analysis of the effects of contact-tracing apps. The model assumes two types of response to the app notification: the notified individuals quarantine themselves (type-Q response) or they get tested (type-T response). The results reveal some crucial characteristics of the apps. First, type-Q response is successful in achieving containment; however, type-T response has a limited curve-flattening effect. Second, type-Q response performs better than type-T response because it involves quarantine of those who are infected but have not become infectious yet, and the current testing technology cannot detect the virus in these individuals. Third, if the download rate of the apps is extremely high, type-Q response can achieve virus containment with a small number of quarantined people and thereby high efficiency. Finally, given a fixed download rate, increasing the number of tests per day enhances the effectiveness of the apps, although the degree of improved effectiveness is not proportional to the change in the number of tests.

Resolution of One-Year Persisting COVID-19 Pneumonia and Development of Immune Thrombocytopenia in a Follicular Lymphoma Patient With Preceding Rituximab Maintenance Therapy: A follow-up Report and Literature Review of Cases With Prolonged Infections.

BACKGROUND: We previously reported elsewhere of a follicular lymphoma patient suffering from persistent COVID-19 pneumonia that was still ongoing at 2 months after onset. MATERIALS AND METHODS: We provide a follow-up report of the case along with a literature review of immunocompromised lymphoma patients experiencing prolonged COVID-19 infections. RESULTS: Although requiring a full 1 year, the presented case eventually achieved spontaneous resolution of COVID-19 pneumonia. Anti-SARS-CoV-2 antibodies could not be detected throughout the disease course, but COVID-19-directed T-cell response was found to be intact. The patient also developed secondary immune thrombocytopenia subsequent to COVID-19 pneumonia. We found 19 case reports of immunocompromised lymphoma patients with prolonged COVID-19 infections in the literature. All 5 patients who died did not receive convalescent plasma therapy, whereas resolution of COVID-19 infection was achieved in 8 out of 9 patients who received convalescent plasma therapy. CONCLUSIONS: We demonstrate through the presented case that while time-consuming, resolution of COVID-19 infections may be achieved without aid from humoral immunity if cellular immunity is intact. Immunocompromised lymphoma patients are at risk of a prolonged disease course of COVID-19, and convalescent plasma therapy may be a promising approach in such patients.

The effectiveness of mobility control, shortening of restaurants' opening hours, and working from home on control of COVID-19 spread in Japan.

Since the first outbreak of COVID-19, various interventions have been implemented to prevent the global spread of the virus. Using an agent-based model that describes the attributes and mobility of the Japanese population, the present research evaluates the effectiveness of mobility control, shortening of restaurants' opening hours, and working from home. Results show that early and severe mobility control that restricts 90% of domestic travel decreases the peak cases by 40%, compared to no intervention implementation. Mobility control that only limits movement to and from highly populated regions is as effective as nationwide travel restrictions. Furthermore, shortening of restaurants' opening hours is the most effective intervention in a state of emergency; it should be utilized even after the emergency. However, working from home has comparatively limited effects.