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.

A Case of Sigmoid Colon Perforation by a Toothpick Treated by Laparoscopic-Assisted Surgery / 日本農村医学会雑誌

Laparoscopy is useful for minimally invasive detailed examination of patients with suspected gastrointestinal perforation. Here we report a case of gastrointestinal perforation of unknown cause that was diagnosed laparoscopically as perforation of the sigmoid colon by a toothpick. The patient was a 41-year-old woman. She presented with a chief complaint of left lower abdominal pain and CT showed a small amount of free air in the peritoneal cavity, so emergency surgery was performed. Laparoscopy revealed a foreign body penetrating the sigmoid colon. After mobilization of the sigmoid colon, the surgical technique was switched to minilaparotomy and partial sigmoid colectomy was performed. The foreign body that had penetrated the intestine was identified as a toothpick. We later learned that the patient had become intoxicated while eating at a yakiniku barbecue restaurant 7 days prior to the operation, and she guessed that she had accidentally consumed a toothpick stuck in an onion. Gastrointestinal perforation by a toothpick is rare and is difficult to diagnose preoperatively because toothpicks appear transparent on X-ray imaging. In this case, laparoscopy was useful for identifying the site and cause of perforation as well as the extent of leakage into the peritoneal cavity.

A Case of Severe Respiratory Failure in a Patient with Sepsis From a Pressure Ulcer in Which Cooperation Among Many Professions Was Useful for Discharge From the Intensive Care Unit / 日本農村医学会雑誌

A woman in her 60s was being treated for diabetes and hypertension but had impaired activities of daily living (ADL) due to severe obesity (150 kg). She was transported to the emergency department because of disturbance of consciousness in August 201X. Imaging findings showed decreased permeability of the whole right lung field. She was intubated and started on ceftriaxone plus levofloxacin for severe infection with respiratory failure. Erysipelothrix rhusiopathiae was detected in blood cultures, leading to a diagnosis of sepsis due to a large pressure ulcer on the posterior aspect of the thigh. We switched levofloxacin to clindamycin and continued medical treatment, and she was extubated on the 10th day of illness. However, type 2 respiratory failure was prolonged because of alveolar hypoventilation due to obesity and she required noninvasive positive pressure ventilation. Also, she had difficulty getting out of bed due to obesity, disuse syndrome, and pressure ulcer. Cooperation among staff from many professions, including respiratory nursing, intensive care nursing, wound, ostomy and continence nursing, physical therapy, and nutrition management, led to improvement of ADL and weight loss (to 109 kg), allowing her to be transferred out of the intensive care unit.

Clinical Study of 67 Cases of Japanese Mamushi Viper (Gloydius blomhoffii) Bite / 日本農村医学会雑誌

We treated a total of 67 patients for mamushi viper (Gloydius blomhoffii) bite during a 10-year period between 2007 and 2016. The mean age of the patients was 68 years, with those aged ≥ 60 years accounting for about 80％ of all patients. Most injuries occurred between July and September in rice fields and other cropland, or in the patients’ homes. Except for 1 severe case who developed a marked thrombocytopenia immediately after the incident, the remaining 66 patients were included in the analysis. All patients received inpatient care, with a mean hospital stay of 6.8 days. There was a significant positive correlation between the size of the swelling at the bite site and the length of hospital stay. Kidney dysfunction occurred in 3 patients, 1 of whom died. The mean time to the largest swelling was 21.8 h while the mean time to the highest creatine phosphokinase level was 2.6 days. The more severe cases were more likely to be have been treated with mamushi antitoxin while 2 of the 3 patients with kidney dysfunction, including the 1 fatality, were not, suggesting that the use of mamushi antitoxin is essential in severe cases. We also report a very rare case of mamushi viper bite complicated by thrombocytopenia.

Relationship between dietary habits and urinary concentrations of 3-phenoxybonzoic acid in a middle-aged and elderly general population in Japan

<p><b>OBJECTIVES</b>The ingestion of pesticides in the daily diet is assumed to be the main modality of pesticide exposure for most people. A widely used class of pesticides in agricultural or residential settings is pyrethroid. We have examined the relationship between the intake frequency of selected items of vegetables and fruits and urinary metabolites of pyrethroid pesticides in a healthy general population.</p><p><b>METHODS</b>A total of 535 residents (184 men and 351 women) who attended a healthcare checkup program conducted in a rural area of Hokkaido, Japan, in August 2005 provided informed consent for their spot urine samples to be used for the determination of 3-phenoxybenzoic acid (3-PBA) levels. They also completed a self-administered questionnaire regarding the intake frequency of 12 food items. The concentrations of creatinine-corrected 3-PBA were predicted by the intake frequency of each item, using analysis-of-covariance models to adjust for age, sex, body mass index, and drinking and smoking status.</p><p><b>RESULTS</b>Both a significant association between the 3-PBA concentration and the frequency of tomato consumption and a significant positive linear trend was found in female subjects. In contrast, no such association was found in the male subjects.</p><p><b>CONCLUSIONS</b>The frequency of tomato consumption was confirmed to strongly predict the urinary pyrethroid metabolite levels in the general population-presumably because tomatoes are most often consumed raw and unpeeled (more so than all other vegetables and fruits analyzed in the current study). However, it should be noted that the 3-PBA levels, even among those subjects with the highest consumption of tomatoes, were far below the levels of toxicological significance, although the health consequences from long-term low-level exposure to pyrethroid requires further exploration.</p>

Association of serum NO( x ) level with clustering of metabolic syndrome components in middle-aged and elderly general populations in Japan

<p><b>OBJECTIVES</b>The aim of this study was to determine whether the serum nitrite plus nitrate (NO( x )) level correlates with biomarkers that are known components of the metabolic syndrome (MetS).</p><p><b>METHODS</b>Serum NO( x ) levels were measured using a commercial kit in 608 Japanese men and women between the ages of 39 and 85 years. Multivariate adjustments for age, smoking status, alcohol consumption and exercise were made in the analysis of covariance (ANCOVA). The components of the metabolic syndrome were defined based on the following criteria: body mass index (BMI) >/=25.0 kg/m(2), glycated hemoglobin (HbA1c) >/=5.6%, systolic blood pressure >/=130 mmHg or diastolic blood pressure >/=85 mmHg, high-density lipoprotein-cholesterol (HDL-C) </=1.03 mmol/l for men and </=1.29 mmol/l for women and triglyceride >/=1.69 mmol/l.</p><p><b>RESULTS</b>The logarithmically transformed age-adjusted serum NO( x ) (lnNO( x )) value was significantly higher in the low HDL-C group (1.76 +/- 0.05 mumol/l; p < 0.05) than MetS component groups (1.65 +/- 0.01 mumol/l) in men, but no difference was found in women. The means of serum lnNO( x ) after multivariate adjustment were 1.64, 1.65, 1.64, 1.66, and 1.81 mumol/l for 0, 1, 2, 3, and 4-5 MetS components for all subjects, respectively. The results of ANCOVA confirmed that the serum lnNO( x ) level was significantly correlated with the clustering of MetS components in both men and women (p < 0.0001 for trend).</p><p><b>CONCLUSION</b>Our results suggest that an increase in the clustering of MetS components was associated with the increase in serum NO levels in our general population.</p>