Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Cross-cultural Study about Cancer and Palliative Care in the Okinawa, Tohoku, and Tokyo Metropolitan Area

Background: Consideration of cultural aspects is important in medical care. We explored regional differences in cancer and palliative care among Okinawa, Tohoku, and Tokyo metropolitan area. Methods: We conducted a questionnaire survey of physicians involved in cancer medicine from September to November 2020. A total of 11 items related to physician experiences were rated using a 5-point Likert-type scale. Results: Responses were received from 553 physicians (187 in Okinawa, 219 in Tohoku, 147 in the Tokyo metropolitan area). In Okinawa, “When patients die, it is important that all family members are present at the last moment,” “Patients/family members primarily consult the elders of the family about the medical treatments,” “Family members hope the patients die at home, because the soul will not return when they die at the hospital,” “Patients/family members get advice from religious advisors about the medical treatments,” and “Family members wish to take the patient home when he/she is about to die and to confirm death at home” were significantly more frequently observed. In Tohoku, “Patients wish to be hospitalized at a specific season” was significantly more frequently reported. In Tohoku and Okinawa, “Patients hide cancer from neighbors and relatives” and “Elderly patients do not want treatment, because they cover the living expenses and education expenses for their children and grandchildren.” were significantly more frequently experienced. Conclusion: There are regional differences in cancer and palliative care in Japan. Being sensitive to the culture of the region is needed.

Effect of 100 Hz electroacupuncture on salivary immunoglobulin A and the autonomic nervous system.

BACKGROUND: A previous study has reported that low-frequency (LF) electroacupuncture (EA) influences salivary secretory immunoglobulin A (sIgA) and the autonomic nervous system (ANS). The ANS is known to control the secretion volume of sIgA; however, the effect of high-frequency (HF) EA on salivary sIgA has not been determined. We investigated whether HF EA affects salivary sIgA levels and the ANS. METHOD: Sixteen healthy subjects were randomly classified into two groups: a control group and an EA group. After a 5 min rest, subjects in the EA group received EA at 100 Hz bilaterally at LI4 and LI11 for 15 min before resting for a further 40 min post-stimulation. Subjects in the control group rested for a total of 60 min. Measurements of the ANS and sIgA levels in both groups were made before, immediately after, 20 min after, and 40 min after rest or 15 min EA treatment. HF and LF components of heart rate variability were analysed as markers of ANS function. LF/HF ratio and HF were taken as indices of sympathetic and parasympathetic nerve activity, respectively. Salivary protein concentrations and sIgA levels were determined by Bradford protein assay and ELISA, respectively. RESULTS: LF/HF ratio was significantly increased immediately after EA. HF was significantly increased at 20 min after EA and sIgA level was significantly increased at 40 min after EA. In addition, HF and salivary sIgA level were positively correlated with each another. CONCLUSIONS: HF EA exerted sequential positive effects on sympathetic nerve activity, parasympathetic nerve activity, and salivary sIgA level (immediately and after 20 and 40 min, respectively). HF EA may increase salivary sIgA levels by influencing parasympathetic nerve activity.

Preoperative comorbidity correlates inversely with survival after intestinal and multivisceral transplantation in adults.

We investigated the relationship between preoperative comorbidity and postoperative survival after intestinal transplantation. Each patient received a score for preoperative comorbidity. Each comorbidity was given a score based on the degree it impaired function (score range 0-3). A total score was derived from the summation of individual comorbidity scores. Patients (72 adults (M : F, 33 : 39)) received an isolated intestinal graft (27) or a cluster graft (45). Mean (standard deviation) survival was 1501 (1444) days. The Kaplan-Meier analysis revealed a significant inverse association between survival and comorbidity score (logrank test for trend, P < 0.0001). Patients grouped into comorbidity scores of 0 and 1, 2 and 3, 4 and 5, 6, and above had hazard ratios (95% confidence intervals) for death (compared to group 0 + 1), which increased with comorbidity scores: 1.945 (0.7622-5.816), 5.075 (3.314-36.17), and 13.77 (463.3-120100), respectively, (P < 0.0001). Receiver-operator curves at 1, 3, 5, and 10 years postoperative had "C" statistics of 0.88, 0.85, 0.88, and 0.92, respectively. When evaluating patients for transplantation, the degree of comorbidity should be considered as a major factor influencing postoperative survival.

Two Patients with Ophthalmic Symptoms due to Post Herpetic Infection Dramatically Improved with Chotosan / 日本東洋医学雑誌

We successfully treated 2 patients with ophthalmic symptoms due to post herpetic infection using chotosan. Case1was a 78-year-old woman who had been suffering from ophthalmic symptoms such as foreign body sensation and irritation pain due to post herpetic infection for almost 20 years, and had a history of hypertension. We treated her with stellate ganglion block every week and orally administered keishikajutsubuto, amitriptyline, and later mexiletine. Initially, stellate ganglion block was very effective, but its effect gradually decreased over about one month. Considering the same action of stellate ganglion block and chotosan, both of which might increase intracranial blood flow, we administered chotosan instead of keishikajutsubuto. Her ophthalmic symptoms subsided for 5 days, and had completely disappeared almost two and half months after initiating chotosan. Case 2 was a 65-year-old man who had also complained of foreign body sensation due to post herpetic infection for 11 months. He also had a history of hypertension. Initial stellate ganglion block was also effective for relieving his symptom, but the effect was transient as in Case 1. Taking into consideration of our experience in Case 1,we administered chotosan. His foreign body sensation gradually subsided for 2 weeks, and had almost disappeared 2 months after initiating chotosan. Our experiences suggest that chotosan may be an optimal formulation for the patients suffering from ophthalmic disorders due to post herpetic inflammation and hypertension.