Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity.

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, the mechanisms underlying this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identified several factors that are associated with COVID-19 vaccine-induced adaptive immune responses. BNT162b2-induced T cell response is positively associated with late monocyte responses and inversely associated with baseline mRNA expression of activation protein 1 (AP-1) transcription factors. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with mRNA expression of AP-1, as well as a gene encoding an enzyme producing prostaglandin E2 (PGE2), which promotes AP-1 expression, and inversely correlated with BNT162b2-induced T-cell responses. These results suggest that baseline AP-1 expression, which is affected by commensal microbial activity, is a negative correlate of BNT162b2-induced T-cell responses.

Narratives on the Current Medical Situation in Japan According to Highly Specialized Foreign Professionals.

In order to understand the difficulties faced by highly skilled foreign professionals when dealing with the Japanese healthcare system and to identify the support they require therein, university health center staff members of the Okinawa Institute of Science and Technology Graduate University conducted semi-structured interviews with faculty, staff, and students from the Institute. Data from the interviews were analyzed by subject matter analysis using a narrative-oriented approach. In total, 13 participants were interviewed, and five themes and 15 subthemes were generated from the 40 codes extracted. Although participants considered themselves to be accepting of other cultures and made little mention of the need for cultural and religious considerations that previous studies have identified as important, they reported that their experiences receiving healthcare in Japan were fraught with many difficulties. They felt that the capacity to communicate in Japanese was a prerequisite for receiving appropriate healthcare and that hospitals should assume the responsibility of providing language support. While they reported satisfaction with the easy and inexpensive access to advanced medical equipment and specialists in Japan, they also noted challenges in selecting medical institutions and departments, the flow and procedures in the hospital, and building open and direct relationships with doctors. In addition, based on the present study, people with chronic illnesses felt isolated from the community, worried about a lack of privacy, and wanted a primary care physician they could trust. In order to provide appropriate healthcare to foreigners, we require an accurate understanding of their needs, how to address these comprehensively and in a multifaceted manner, and how the communication responsibilities should be shared among the involved parties (i.e., foreign care recipients and Japanese medical professionals).

Altered pre-existing SARS-CoV-2-specific T cell responses in elderly individuals.

Pre-existing SARS-CoV-2-specific T cells, but not antibodies, have been detected in some unexposed individuals. This may account for some of the diversity in clinical outcomes ranging from asymptomatic infection to severe COVID-19. Although age is a risk factor for COVID-19, how age affects SARS-CoV-2-specific T cell responses remains unknown. We found that pre-existing T cell responses to specific SARS-CoV-2 proteins, Spike (S) and Nucleoprotein (N), were significantly lower in elderly donors (>70 years old) than in young donors. However, substantial pre-existing T cell responses to the viral membrane (M) protein were detected in both young and elderly donors. In contrast, young and elderly donors exhibited comparable T cell responses to S, N, and M proteins after infection with SARS-CoV-2. These data suggest that although SARS-CoV-2 infection can induce T cell responses specific to various viral antigens regardless of age, diversity of target antigen repertoire for long-lived memory T cells specific for SARS-CoV-2 may decline with age; however, memory T cell responses can be maintained by T cells reactive to specific viral proteins such as M. A better understanding of the role of pre-existing SARS-CoV-2-specific T cells that are less susceptible to age-related loss may contribute to development of more effective vaccines for elderly people.

COVID-19 serological survey using micro blood sampling.

During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.

Characterizing patients issued DNR orders who are ultimately discharged alive: a retrospective observational study in Japan.

BACKGROUND: The present study aimed to characterize factors associated with patients issued DNR orders during hospitalization who are discharged alive without any instruction orders by physicians regarding end-of-life treatment, with a focus on the timing of DNR order issuance. METHODS: In total, 2997 DNR cases from all 61,037 patients aged ≥20 years admitted to a representative general hospital in Tokyo were extracted and divided into two groups by patient hospital release status (discharged alive/deceased). Study items included age, sex, disease type (non-cancer/cancer), hospital department (internal medicine/others), timing of DNR order issuance, implementation (or not) of life-sustaining treatment (LST) or the presence of any restrictions on LST and hospital length of stay. We conducted multiple logistic regression analysis, setting hospital release status as the dependent variable and each above study item as explanatory variables. RESULTS: DNR orders were issued at a rate of 4.9%. The analysis revealed that patients with a DNR who were ultimately discharged alive were statistically more likely to be those for whom DNR orders are issued early after admission (adjusted odds ratio: AOR, 13.7), non-cancer patients (AOR, 3.4), internal medicine department patients (AOR, 1.63), females (AOR, 1.34), and elderly (aged ≥85 years; AOR, 1.02); these patients were also less likely to be receiving LST (AOR, 0.36). CONCLUSIONS: By focusing on those with DNR orders who were ultimately discharged alive, we discovered that these patients were likely to have DNR orders issued early after admission, and that they were more likely to be elderly, female, non-cancer patients, or those in internal medicine departments. Further examination of these data may help to elucidate why these particular DNR-related characteristics (including socio-economic and cultural factors) are evident in patients who end up being discharged alive.

Autonomous Continuation of Community Health Workers' Activities in Thegon Township, Bago Region, Myanmar.

Background: Few studies have reported on the autonomous continuation of Community Health Worker (CHW) activities after external supervision and support have ended. Objective: The study reports CHW activity continuation in Thegon Township, Bago Region, Myanmar, observed after the supervision by the external organization is completed. Method: Following the completion of a child nutrition program in Thegon Township, CHWs were left unsupervised and uninformed of a follow-up at 10, 23, and 40 months from the end of the program survey due to unforeseen circumstances. In a follow-up survey in 2014, data on the activity implementation status from CHWs and activity attendance from caregivers of the target children were collected. Focus group discussions were held with caregivers concerning their information sources on child nutrition and health. Results: On average, CHWs were found to have continued with 2.6 of the four core activities, often with modifications, irrespective of the time since completion of the non-profit-organization-led program. Meanwhile, caregiver attendance decreased over time. Caregivers recognized CHWs as information sources. Discussion: Although unsupervised, CHWs ambitiously continued with their activities, but sorted through and modified them, which may have been unrelated to the local acceptance of the program, as caregiver attendance decreased even as CHWs continued the activities. The observation may highlight the importance of proactive engagement and thus, the autonomy of CHWs in their activity continuation.