Time-series transcriptome analysis of peripheral blood mononuclear cells obtained from individuals who received the SARS-CoV-2 mRNA vaccine.

Messenger ribonucleic acid (mRNA) vaccination against coronavirus disease 2019 (COVID-19) is an effective prevention strategy, despite a limited understanding of the molecular mechanisms underlying the host immune system and individual heterogeneity of the variable effects of mRNA vaccination. We assessed the time-series changes in the comprehensive gene expression profiles of 200 vaccinated healthcare workers by performing bulk transcriptome and bioinformatics analyses, including dimensionality reduction utilizing the uniform manifold approximation and projection (UMAP) technique. For these analyses, blood samples, including peripheral blood mononuclear cells (PBMCs), were collected from 214 vaccine recipients before vaccination (T1) and on Days 22 (T2, after second dose), 90, 180 (T3, before a booster dose), and 360 (T4, after a booster dose) after receiving the first dose of BNT162b2 vaccine (UMIN000043851). UMAP successfully visualized the main cluster of gene expression at each time point in PBMC samples (T1-T4). Through differentially expressed gene (DEG) analysis, we identified genes that showed fluctuating expression levels and gradual increases in expression levels from T1 to T4, as well as genes with increased expression levels at T4 alone. We also succeeded in dividing these cases into five types based on the changes in gene expression levels. High-throughput and temporal bulk RNA-based transcriptome analysis is a useful approach for inclusive, diverse, and cost-effective large-scale clinical studies.

Heterogeneity assessment of vaccine-induced effects using point-of-care surrogate neutralization test for severe acute respiratory syndrome coronavirus 2.

INTRODUCTION: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests. METHODS: Serum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS-CoV-2 S-RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851). RESULTS: The NAb (SARS-CoV-2 S-RBD IgG) titer peaked on day 90 after vaccination (30,808.0 µg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 µg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT-sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA). CONCLUSIONS: Neutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT-sVNT is rapid and user-friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.

[Intervention for COPD Exacerbation - How To Prevent and Treat COPD Exacerbation ?]

COPD exacerbation is associated with a high mortality rate and severe decrease in the QOL.Most medical expenses associated with COPD involve treatment costs related to exacerbation.However, the identification of pre-exacerbation changes in respiratory conditions from self controlled range, risk assessment, and multidisciplinary integrated respiratory care intervention could truly stabilize the condition of a patient with COPD and thus decrease the frequency of exacerbation.Such a decrease would be expected to lead to a high QOL, better COPD survival rate, and medical economic benefits.In addition, a reduced frequency of exacerbation would increase the stability of a patient's condition, allowing the continuation of effective pulmonary rehabilitation and maintenance of beneficial physical activity.

[Responding to patients with home mechanical ventilation after the Great East Japan Earthquake and during the planned power outages. How should we be prepared for a future disaster ?].

The unprecedented earthquake(magnitude-9 in the Japanese seismic intensity scale)hit off the east coast of Japan on March 11, 2011. Consequently, there were planned power outages in the area nearby Tokyo to avoid massive blackouts caused by a stoppage of Fukushima nuclear plants.Our clinic located in Kawasaki city was also hit by the earthquake(magnitude- 5).During the period of two months(March and April 2011), we had a total of 52 patients with home respiratory care (5-TPPV, 11-NPPV and 36-HOT)at that time.Two out of three 24 hour-TPPV users had no external battery.After the earthquake, there was a 7-hour electricity failure in some areas, and a patient with ASV(adaptive servo ventilator)was living there.Moreover, 3-hour/day power outages were carried out from March 14 to March 28, affecting people's everyday lives. However, the patient had no harmful influences from the power failure because a ventilation company lent us an external battery(4-9 hour life capacity)for the patients, and we were able to avoid an emergency situation caused by the power failure.In conclusion, we ought to be prepared for patients with home mechanical ventilation in the future toward unforeseen large scale power outages.

[Domiciliary non-invasive positive pressure ventilation (NPPV) care].

A breakdown of 28 patients on domiciliary NPPV from September. 3, 2007 through July 31, 2009 includes 11 patients with chronic obstructive pulmonary disease, 7 patients with neuro-muscular disease, 4 patients with pulmonary tuberculosis sequela, 4 patients with conjestive heart failure, a patient with bronchiectasis and a patient with pulmonary interstitial pneumonia. Sixteen patients of them started NPPV at home. All of domiciliary NPPV patients had very severe conditions and frequent exacerbations. An avoidance of exacerbation led to improve a prognosis. Actually, a domiciliary pulmonary care team should do a pulmonary rehabilitation for them. It needs a special knowledge and artistic skills for their stable and high quality of life at home. Not only all of the team members should be an expert, but also the patient and family members who belong to the team should be an expert as well. We should educate them how to assess their symptoms and act patho-physiologically.