Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.

Atypical diarrhoeagenic Escherichia coli in milk related to a large foodborne outbreak.

A foodborne outbreak related to milk cartons served in school lunches occurred in June 2021, which involved more than 1,800 cases from 25 schools. The major symptoms were abdominal pain, diarrhoea, vomiting, and fever. Although major foodborne toxins and pathogens were not detected, a specific Escherichia coli strain, serotype OUT (OgGp9):H18, was predominantly isolated from milk samples related to the outbreak and most patients tested. The strains from milk and patient stool samples were identified as the same clone by core genome multilocus sequence typing and single-nucleotide polymorphism analysis. The strain was detected in milk samples served for two days related to the foodborne outbreak at a rate of 69.6% and levels of less than ten most probable number/100 mL but not on days unrelated to the outbreak. The acid tolerance of the strain for survival in the stomach was similar to that of enterohaemorrhagic E. coli O157:H7, and the same inserts in the chu gene cluster in the acid fitness island were genetically revealed. The pathogenicity of the strain was not clear; however, it was indicated that the causative pathogen was atypical diarrhoeagenic E. coli OUT (OgGp9):H18.

Trends in CD4+ Cell Counts, Viral Load, Treatment, Testing History, and Sociodemographic Characteristics of Newly Diagnosed HIV Patients in Osaka, Japan, From 2003 through 2017: A Descriptive Study.

BACKGROUND: The CD4 cell count of patients during diagnosis and distribution of CD4 cell counts in the patient population are important to understand infection-diagnosis interval and incidence rate of human immunodeficiency virus (HIV) infection, respectively. However, this information has not been published in Japan. This study aimed to describe the change in CD4 cell count trends and clarify the change in patients' characteristics in association with the CD4 cell count information. METHODS: A descriptive study was conducted to analyze the medical records of patients with HIV who visited one of the largest acquired immunodeficiency syndrome (AIDS) core hospitals in western Japan. The basic characteristics, CD4 cell counts, viral loads, and diagnosis-treatment intervals between the first (2003-2010) and second (2011-2017) halves of the study duration were compared. RESULTS: The distribution of CD4 cell counts significantly changed between 2003-2010 and 2011-2017 (χ2 = 20.42, P < 0.001). The proportion of CD4 cell count <200 cells/mm3 increased (38.8% in 2003 to 45.9% in 2017), whereas CD4 cell count ≥500 cells/mm3 decreased (19.4% in 2003 to 12.2% in 2017). Moreover, the distributions of age groups, history of HIV screening test, patient outcomes, HIV viral load, and diagnosis-treatment interval also significantly changed (χ2 = 25.55, P < 0.001; χ2 = 8.37, P = 0.015; χ2 = 6.07, P = 0.014; χ2 = 13.36, P = 0.020; χ2 = 173.76, P < 0.001, respectively). CONCLUSION: This study demonstrated the fundamental trends of the HIV epidemic in Osaka, Japan between 2003-2010 and 2011-2017 and indicated that the incidence rate of HIV was decreasing in Japan.

Association of severe COVID-19 outcomes with radiological scoring and cardiomegaly: findings from the COVID-19 inpatients database, Japan.

PURPOSE: We aimed to characterize novel coronavirus infections based on imaging [chest X-ray and chest computed tomography (CT)] at the time of admission. MATERIALS AND METHODS: We extracted data from 396 patients with laboratory-confirmed COVID-19 who were managed at 68 hospitals in Japan from January 25 to September 2, 2020. Case patients were categorized as severe (death or treatment with invasive ventilation during hospitalization) and non-severe groups. The imaging findings of the groups were compared by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for sex, age, and hospital size (and radiographic patient positioning for cardiomegaly). Chest X-ray and CT scores ranged from 0 to 72 and 0 to 20, respectively. Optimal cut-off values for these scores were determined by a receiver-operating characteristic (ROC) curve analysis. RESULTS: The median age of the 396 patients was 48 years (interquartile range 28-65) and 211 (53.3%) patients were male. Thirty-two severe cases were compared to 364 non-severe cases. At the time of admission, abnormal lesions on chest X-ray and CT were mainly observed in the lower zone/lobe. Among severe cases, abnormal lesions were also seen in the upper zone/lobe. After adjustment, the total chest X-ray and CT score values showed a dose-dependent association with severe disease. For chest X-ray scores, the area under the ROC curve (AUC) was 0.91 (95% CI = 0.86-0.97) and an optimal cut-off value of 9 points predicted severe disease with 83.3% sensitivity and 84.7% specificity. For chest CT scores, the AUC was 0.94 (95% CI = 0.89-0.98) and an optimal cut-off value of 11 points predicted severe disease with 90.9% sensitivity and 82.2% specificity. Cardiomegaly was strongly associated with severe disease [adjusted OR = 24.6 (95% CI = 3.7-166.0)]. CONCLUSION: Chest CT and X-ray scores and the identification of cardiomegaly could be useful for classifying severe COVID-19 on admission.

Causal Effect of the Tokyo 2020 Olympic and Paralympic Games on the Number of COVID-19 Cases under COVID-19 Pandemic: An Ecological Study Using the Synthetic Control Method.

Previous studies have not assessed the causal effect of the Olympic Games on the spread of pandemics. Using the synthetic control method and the national public city data in Japan recorded from February to September 2021, we estimated the causal effects of the Tokyo 2020 Olympic and Paralympic Games on the number of coronavirus disease 2019 (COVID-19) cases. The difference between the number of COVID-19 cases in Tokyo and a counterfactual "synthetic Tokyo" (created using synthetic control method) after the opening of the Tokyo 2020 Games (23 July 2021) widened gradually and then considerably over time. It was predicted that the Tokyo 2020 Games increased the number of COVID-19 cases in Tokyo by approximately 469.4 per 100,000 population from the opening of the event to 30 September. However, sensitivity analysis of the ratio of the pre- and post-game root mean square prediction errors using regression weights did not suggest robustness. Our results showed that the Tokyo 2020 Games probably increased the number of COVID-19 cases even under preventive regulations; however, the extent of this increase was difficult to estimate clearly due to an overlap with the fifth wave associated with the Delta variant.

Reduced mortality during the COVID-19 outbreak in Japan, 2020: a two-stage interrupted time-series design.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group. METHODS: Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level. RESULTS: In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years. CONCLUSIONS: All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted.

Replacement of SARS-CoV-2 strains with variants carrying N501Y and L452R mutations in Japan: an epidemiological surveillance assessment.

Objective: Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important due to concerns regarding infectivity, transmissibility, immune evasion and disease severity. We evaluated the temporal and regional replacement of previous SARS-CoV-2 variants by the emergent strains, Alpha and Delta. Methods: We obtained the results of polymerase chain reaction screening tests for variants conducted in multiple commercial laboratories. Assuming that all previous strains would be replaced by one variant, the new variant detection rate was estimated by fitting a logistic growth model. We estimated the transmission advantage of each new variant over the pre-existing virus strains. Results: The variant with the N501Y mutation was first identified in the Kinki region in early February 2021, and by early May, it had replaced more than 90% of the previous strains. The variant with the L452R mutation was first detected in the Kanto-Koshin region in mid-May, and by early August, it comprised more than 90% of the circulating strains. Compared with pre-existing strains, the variant with the N501Y mutation showed transmission advantages of 48.2% and 40.3% in the Kanto-Koshin and Kinki regions, respectively, while the variant with the L452R mutation showed transmission advantages of 60.1% and 71.9%, respectively. Discussion: In Japan, Alpha and Delta variants displayed regional differences in the replacement timing and their relative transmission advantages. Our method is efficient in monitoring and estimating changes in the proportion of variant strains in a timely manner in each region.

Epidemiology of Coronavirus Disease 2019 in Japan: Descriptive Findings and Lessons Learned through Surveillance during the First Three Waves.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has caused unprecedented global morbidity and mortality. Japan has faced three epidemic "waves" of COVID-19 from early 2020 through early 2021. Here we narratively review the three waves in Japan, describe the key epidemiologic features of COVID-19, and discuss lessons learned. METHODS: We assessed publicly available surveillance data, routine surveillance reports, and other relevant sources-multiple indicators were monitored to improve interpretation of surveillance data. Weekly trends for each wave were described based on the number of case notifications; number of tests performed; proportion of those tests that were positive for the novel coronavirus; the prevalent number of COVID-19 hospitalizations (total hospitalizations and those categorized as severe); and number of COVID-19 deaths. For each indicator and wave, we recorded the first calendar week to show an increase over two consecutive previous weeks, along with the peak week. RESULTS: The spring wave was characterized by detection of cases imported from China, followed by notifications of sporadic cases without travel history, clusters, and mild/asymptomatic cases. The summer wave saw a large increase in notifications and a younger age distribution, but in the context of increased testing with lower test positivity. The winter wave brought considerable morbidity and mortality, surpassing the cumulative case counts and fatalities from the earlier waves, with high peak values. Overall, relative to the first wave, the burden of severe outcomes was lower in the second and higher in the third wave, but varied by prefecture. In all three waves, severe outcomes peaked after notification counts and test positivity peaked; severe outcomes were also consistently skewed toward the elderly. CONCLUSIONS: Important lessons were learned from each wave and across waves-some aspects remained constant, while others changed over time. In order to rapidly detect an increase in incidence, continuous, timely, and sensitive surveillance-using multiple information sources with careful interpretations-will be key in COVID-19 control.

Clinical Characteristics and Risk Factors for Severe Outcomes of Novel Coronavirus Infection, January-March 2020, Japan.

BACKGROUND: Notifications of novel coronavirus infections increased in early 2020 in Japan. We described characteristics of novel coronavirus infection cases and analyzed risk factors for severe outcomes. METHODS: Cases were persons with laboratory-confirmed novel coronavirus infection reported under national surveillance between January and March 2020. Clinical characteristics were described, and risk factors of (1) intensive care unit [ICU] admission and (2) invasive ventilation/death were analyzed using Poisson regression. RESULTS: Among the 516 cases analyzed, median age was 60 years (range: 1-97 years) and 285 (55%) were male. Common symptoms/signs were fever (375/475, 79%), cough (353/465, 76%), and pneumonia (245/387, 63%). Ten (2%) cases died. Of the 348 cases with data, 50 (14%) required invasive ventilation. Adjusted for each other, male gender and 1-year increase in age were associated with ICU admission (risk ratio [RR] 4.18; 95% confidence interval [CI], 1.69-10.32 and RR 1.05; 95% CI, 1.03-1.08, respectively) and invasive ventilation/death (RR 2.79; 95% CI, 1.49-5.21 and RR 1.06; 95% CI, 1.04-1.08, respectively). Diabetes, dyslipidemia, hyperuricemia, and lung diseases were also associated with severe outcomes. Of the 80 cases asymptomatic at hospitalization, 40 developed symptoms and five of them >70 years of age required invasive ventilation. CONCLUSIONS: The early stage of the novel coronavirus epidemic in Japan disproportionately affected the elderly. Older age, male gender, and underlying conditions were associated with severe outcomes. Notably, some elderly case-patients who were asymptomatic at diagnosis and promptly hospitalized still went on to develop severe disease, indicating the importance of careful monitoring of certain populations.

Knowledge, Attitudes, and Practices Associated with Pertussis Vaccination during Pregnancy: Japan, 2016-2017.

Neonatal pertussis can potentially cause severe complications and even death. Mothers have been most frequently identified as the source of neonatal pertussis. Approximately a dozen countries have implemented pertussis vaccination programs for pregnant women to protect neonates; however, in Japan, this has not been implemented. The aim of this questionnaire-based study was to ascertain the willingness of women to be vaccinated during pregnancy and the factors associated with willingness. The subjects were 977 pregnant women who visited either of the two selected hospitals for maternity health checks. Most of the women were in their first pregnancy (96%), and approximately half of them considered a physician to be the most reliable source of information about vaccination (481/977, 49%). "Willingness to receive pertussis vaccination" was significantly associated with the factors "no fear of receiving vaccination" (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 2.21-4.34), "necessary to prevent pertussis" (OR = 8.70, 95% CI: 6.17-12.28), "effective in pregnancy" (OR = 5.46, 95% CI: 3.94-7.56), and "no concern about the side effects after vaccination" (OR = 3.03, 95% CI: 1.66-5.55). Pregnant women are likely to consider vaccination if they have a good understanding of the disease and its outcomes. Physicians are well positioned to improve knowledge and attitudes toward pertussis vaccination during pregnancy.

Excess All-Cause Deaths during Coronavirus Disease Pandemic, Japan, January-May 20201.

To provide insight into the mortality burden of coronavirus disease (COVID-19) in Japan, we estimated the excess all-cause deaths for each week during the pandemic, January-May 2020, by prefecture and age group. We applied quasi-Poisson regression models to vital statistics data. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the 1-sided prediction interval. A total of 208-4,322 all-cause excess deaths at the national level indicated a 0.03%-0.72% excess in the observed number of deaths. Prefecture and age structure consistency between the reported COVID-19 deaths and our estimates was weak, suggesting the need to use cause-specific analyses to distinguish between direct and indirect consequences of COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020.

In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly.

[An outbreak of Streptococcus pneumoniae serotype 11A pneumonia at a nursing home, Tokyo, 2009].

This is a report of an outbreak of Pneumococcal pneumonia among nursing home residents in Tokyo, 2009. A total of 15 cases were identified, and their sputum culture grew Streptococcus pneumoniae, all of which were confirmed as serotype 11A and ST116. This outbreak ended through the implementation of strict contact precautions, education regarding the standard precautions among the staff, administration of prophylactic antibiotics to other asymptomatic residents, and vaccination. The fact that many cases were unvaccinated in this outbreak implies the importance of vaccination against S. pneumoniae among nursing home residents.

Association between seasonal influenza vaccination in 2008-2009 and pandemic influenza A (H1N1) 2009 infection among school students from Kobe, Japan, April-June 2009.

We assessed the effect of seasonal trivalent inactivated influenza vaccination (TIV) on pandemic influenza 2009 (pH1N1)-related illness from April to June 2009 among 2849 students (aged 12-18 years). TIV was associated with an increase in the frequency of pH1N1-related illness among subjects (adjusted odds ratio, 1.47; 95% confidence interval, 1.14-1.89). TIV during the 2008-2009 season increased the risk of pH1N1-related illness from April to June 2009.

Seroprevalence of antibodies to pandemic (H1N1) 2009 influenza virus among health care workers in two general hospitals after first outbreak in Kobe, Japan.

OBJECTIVE: To assess the prevalence including asymptomatic infection, infection risk of exposure to patients, and effectiveness of personal protective equipment (PPE) among health care workers (HCWs) during the first pandemic (H1N1) 2009 (pH1N1) outbreak in Kobe, Japan in May 2009. METHODS: A cross-sectional seroepidemiological study was conducted on 268 HCWs in the two hospitals in Kobe to which all pH1N1 inpatients were directed. Participating HCWs completed a self-administrated questionnaire and provided a single serum sample which was analyzed using a hemagglutination-inhibition (HI) antibody test. RESULTS: Of 268 subjects, 14 (5.2%) were found to have positive antibodies to the pH1N1 by HI assay; only 1 reported a febrile episode. Among the 14 seropositive cases, 8 received chemoprophylaxis. 162 HCWs (60.4%) had been exposed to patients. The seropositive rate (SPR) for pH1N1 of the exposed group was higher than that of the unexposed group, however not statistically significant (6.8% vs. 3.1%, p = 0.197). There were no statistically significant differences in SPR for any PPE. CONCLUSION: The SPR for pH1N1 in the exposed group was higher than that of the unexposed group in HCWs; however, most of these individuals were asymptomatic. There was no statistically significant association between PPE implementation and pH1N1 seropositivity.

Environmental factors and seasonal influenza onset in Okayama city, Japan: case-crossover study.

Seasonal influenza infection is a major challenge in public health. The term "seasonal influenza" refers to the typical increase in the number of influenza patients in the winter season in temperature zones. However, it is not clear how environmental factors within a single flu season affect influenza infection in a human population. Therefore, we evaluated the effects of temperature and humidity in the 2006-7 flu season on the onset of seasonal influenza using a case-crossover study. We targeted patients who attended one pediatric clinic in Okayama city, Japan and who were diagnosed as being infected with the seasonal influenza virus. Using 2 references (time-stratified and symmetric bidirectional design), we estimated the effects of average temperature and relative humidity from the onset day (lag0) to 10 days before (lag10). The total number of subjects was 419, and their onset days ranged from 26 December 2006 to 30 April 2007. While the onset was significantly associated with lower temperature, relative humidity was not related. In particular, temperatures before the 3-day incubation period had higher-magnitude odds ratios. For example, the odds ratio and 95% confidence interval for average temperature at time lag 8 was 1.12 (1.08-1.17) per 1.0℃ decrease. Low environmental temperature significantly increased the risk of seasonal influenza onset within the 2006-7 winter season.