A longitudinal study of anti-SARS-CoV-2 antibody seroprevalence in a random sample of the general population in Hiroshima in 2020.

BACKGROUND: This longitudinal study aimed to determine chronological changes in the seroprevalence of prior SARS-CoV-2 infection, including asymptomatic infections in Hiroshima Prefecture, Japan. METHODS: A stratified random sample of 7,500 residents from five cities of Hiroshima Prefecture was selected to participate in a three-round survey from late 2020 to early 2021, before the introduction of the COVID-19 vaccine. The seroprevalence of anti-SARS-CoV-2 antibodies was calculated if at least two of four commercially available immunoassays were positive. Then, the ratio between seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was calculated and compared to the results from other prefectures where the Ministry of Health, Labour and Welfare conducted a survey by using the same reagents at almost the same period. RESULTS: The numbers of participants in the first, second, and third rounds of the survey were 3025, 2396, and 2351, respectively and their anti-SARS-CoV-2 antibodies seroprevalences were 0.03% (95% confidence interval: 0.00-0.10%), 0.08% (0.00-0.20%), and 0.30% (0.08-0.52%), respectively. The ratio between the seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was 1.2, which was smaller than that in similar studies in other prefectures. CONCLUSIONS: The seroprevalence of anti-SARS-CoV-2 antibodies in Hiroshima increased tenfold in a half year. The difference between seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was smaller than that in other prefectures, suggesting that asymptomatic patients were more actively detected in Hiroshima.

Absence of neonatal intensive care units in secondary medical care zones is an independent risk factor of high perinatal mortality in Japan.

AIM: National medical projects are carried out according to medical care plans directed by the Medical Care Act of Japan. In order to improve Japanese perinatal medical care, it is necessary to determine the factors that might influence perinatal outcome. METHODS: Statistical data of births and perinatal deaths were obtained for all municipalities in Japan from 2008 to 2012 from the Portal Site of Official Statistics of Japan (e-Stat). The perinatal mortality of all 349 Japanese secondary medical care zones was calculated. The number of neonatal intensive care units (NICUs), maternal-fetal intensive care units (MFICUs), pediatricians and obstetricians in 2011 were also obtained from e-Stat. Nine secondary medical care zones in two prefectures, Fukushima (7) and Miyagi (2) were excluded to eliminate the influence of the 2011 Great East Japan Earthquake. RESULTS: The 340 secondary medical care zones were divided into three groups according to population size and density: metropolis, provincial city, and depopulation. The number of secondary medical care zones in each group were 52, 168, and 120, respectively. The secondary medical care zones in the depopulation group had fewer pediatricians and significantly fewer NICUs and MFICUs than the metropolis group, but there was no significant difference in perinatal mortality. The only independent risk factor for high perinatal mortality, determined by multivariable analysis, was the absence of an NICU (P = 0.011). CONCLUSIONS: To consider directions in perinatal medical care, planned arrangement and appropriate access to NICUs is indispensable.

Effectiveness of COVID-19 mRNA vaccine in preventing infection against Omicron strain: Findings from the Hiroshima Prefecture COVID-19 version J-SPEED for PCR center.

BACKGROUND AND PURPOSE: Despite the widespread adoption of various preventive measures since the spread of COVID-19, there remains a lack of consensus on universally acknowledged best practices. However, the significance of vaccination has risen to prominence as a paramount preventive strategy. Numerous investigations have demonstrated vaccine effectiveness against the omicron strain in severe disease and symptomatic disease, however, the scope of research pertaining to vaccine effectiveness in preventing infection is presently limited. Therefore, the current study aimed to evaluate COVID-19 mRNA (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) vaccine effectiveness in preventing infection. METHODS: We conducted a test-negative case-control study using a dataset of 117,335 individuals. These data were collected through the COVID-19 J-SPEED form in the PCR center at Hiroshima Prefecture, Japan from 1 February to 17 March 2022. We estimated propensity score matching for vaccine status based on participants' demographic characteristics. Subsequently, odds ratio was calculated from logistic regression to determine the association between vaccination status and test positivity rate adjusting for symptoms, exposure to close contact, and previous infection history. Vaccine effectiveness was defined as (1 -aORs) ×100%. RESULTS: The PCR test positivity rates were 7.9%, 4.5%, and 2.8% for the non-vaccinated (non-vaccinated, vaccinated with a single dose, and vaccinated with two doses less than 14 days ago), vaccinated with two doses (vaccinated over 14 days ago), and three doses, respectively. In unadjusted and adjusted analyses, vaccine effectiveness of two doses against infection were 38.5% (95% confidence interval [CI]: 32.8%-43.8%) and 34.7% (95%CI: 28.4%-40.4%), respectively, compared to non-vaccinated group. Vaccine effectiveness of three doses were 33.8% (95%CI: 25.0%-41.5%) and 26.4% (95%CI: 16.4%-35.2%), respectively, compared to those vaccinated with two doses. CONCLUSIONS: These results illustrate the protective effect of mRNA vaccines against Omicron strain infections and emphasize the significance of completing the suggested vaccination schedule.

Potential Risk Factors to COVID-19 Severity: Comparison of SARS-CoV-2 Delta- and Omicron-Dominant Periods.

BACKGROUND: Continued study of risk factors can inform future pandemic preparedness and response. We aimed to determine the potential risk factors of COVID-19 severity among patients admitted to the hospital during the Delta- and Omicron-dominant periods. METHODS: We utilized the J-SPEED-style COVID-19 Hospital version, a pre-administered questionnaire, to collect data from hospitals in Hiroshima Prefecture between 8 August 2021 and 19 April 2022. RESULTS: During the Delta-dominant period, patients aged over 65 (OR = 2.59, 95% CI = 1.75-3.84), males (OR = 1.42, 95% CI = 1.12-1.81) and with BMI exceeding 25 (OR = 1.99, 95% CI = 1.57-2.52), diabetes (OR = 2.03, 95% CI = 1.40-2.95), and those with fewer than two doses of vaccine (OR = 2.39, 95% CI = 1.46-3.91) were at a greater risk of severe COVID-19 compared to those without these risk factors. During the Omicron-dominant period, significantly greater severity was observed among patients over 65 years old (OR = 3.89, 95% CI = 2.95-5.12), males (OR = 1.76, 95% CI = 1.40-2.21), those with high blood pressure (OR = 1.30, 95% CI = 1.02-1.65), and mental disorder (OR = 2.22, 95% CI = 1.69-2.92) compared to patients without these risks. CONCLUSIONS: Our findings indicate that risk factors vary across different SARS-CoV-2 variants. Examining variant-specific risk factors for COVID-19 severity can aid policymakers, public health specialists, and clinicians in prioritizing screening, treatment, and vaccination efforts, especially during potential healthcare resource shortages.

Natural course of post-COVID symptoms in adults and children.

More than 200 million COVID-19 survivors have lasting symptoms after recovering, but the duration and related risk factors remain uncertain. This study focused on all 6551 patients diagnosed with COVID-19 at a medical institution in Hiroshima from March 2020 to July 2022. In November 2022, a questionnaire survey was conducted regarding post-COVID symptoms and their duration. The prevalence and duration of post-COVID symptoms were illustrated using the Kaplan-Meier method. Risk factors for symptoms lasting over 3 months and interfering with daily life were assessed via multivariate logistic regression. A total of 2421 survivors responded: 1391 adults, 1030 children, median age 34 years (IQR 9-55), 51·2% male, 36·7% hospitalized, median time from infection to the survey was 295 days (IQR 201-538). Upon their initial recovery, the prevalence of post-COVID symptoms was 78·4% in adults and 34·6% in children. Three months later, the rates were 47·6% and 10·8%. After over one year, they were 31·0% and 6·8%. Regarding symptoms interfere with daily life, 304 people (12.6%) experienced symptoms lasting for over three months, with independent risk factors including age, being female, diabetes mellitus, infection during the Delta period, and current smoking. There was no significant association between vaccination history and post-COVID symptoms.

Relationship between clinical symptom profiles and COVID-19 infection status during Delta-dominant period versus Omicron-dominant period-analysis of real-world data collected in Hiroshima Prefecture, Japan.

OBJECTIVES: The present study investigates the diagnosis and prediction of COVID-19 based on clinical symptoms, and corresponding difference between the Delta- and Omicron-dominant periods, using data collected at polymerase chain reaction (PCR) centers in Hiroshima Prefecture, Japan. METHODS: Data was collected using a J-SPEED-style COVID-19 standard data collection form. The analysis was done in two directions: calculating the likelihood ratio that clinical symptoms will manifest in "infected" versus "non-infected" individuals and calculating the diagnostic odds ratio (OR) of infection for those who have symptoms compared to those without symptoms. RESULTS: COVID-19 was more strongly associated with smell and taste disorders during the Delta-dominant period, and muscle pain during the Omicron-dominant period. An age-specific analysis of likelihood and diagnostic ORs found cold-like symptoms had the lowest ability to diagnose COVID-19, and the lowest predictability of COVID-19 with children during both periods. The likelihood and diagnostic ORs of other symptoms for COVID-19 were highest in adults and lowest in those over 65. CONCLUSION: Symptoms are an important indicator of COVID-19, but the association between specific symptoms and COVID-19 is dependent on the dominant variant of the virus.

Emergency Medical Teams' Responses during the West Japan Heavy Rain 2018: J-SPEED Data Analysis.

INTRODUCTION: Rainfall-induced floods and landslides accounted for 20.7% of all disaster events in Japan from 1985 through 2018 and caused a variety of health problems, both directly and indirectly, including injuries, infectious diseases, exacerbation of pre-existing medical conditions, and psychological issues. More evidence of health problems caused by floods or heavy rain is needed to improve preparedness and preventive measures; however, collecting health data surrounding disaster events is a major challenge due to environmental hazards, logistical constraints, political and economic issues, difficulties in communication among stakeholders, and cultural barriers. In response to the West Japan Heavy Rain in July 2018, Emergency Medical Teams (EMTs) used Japan - Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED) as a daily reporting template, collecting data on the number and type of patients they treated and sending it to an EMT coordination cell (EMTCC) during the response. STUDY OBJECTIVE: The aim of the study was to conduct a descriptive epidemiology study using J-SPEED data to better understand the health problems during floods and heavy rain disasters. METHODS: The number and types of health problems treated by EMTs in accordance with the J-SPEED (Ver 1.0) form were reported daily by 85 EMTs to an EMTCC, where data were compiled during the West Japan Heavy Rain from July 8 through September 11, 2018. Reported items in the J-SPEED form were analyzed by age, gender, area (prefecture), and time period. RESULTS: The analysis of J-SPEED data from the West Japan Heavy Rain 2018 revealed the characteristics of a total of 3,617 consultations with the highest number of consultations (2,579; 71.3%) occurring between Day 5 and Day 12 of the 65-day EMT response. During the response period, skin disease was the most frequently reported health event (17.3%), followed by wounds (14.3%), disaster stress-related symptoms (10.0%), conjunctivitis (6.3%), and acute respiratory infections (ARI; 5.4%). CONCLUSION: During the response period, skin disease was the most frequently reported health event, followed by wounds, stress, conjunctivitis, and ARIs. The health impacts of a natural disaster are determined by a variety of factors, and the current study's findings are highly context dependent; however, it is expected that as more data are gathered, the consistency of finding will increase.

Incidence of Acute Respiratory Infections during Disasters in the Absence and Presence of COVID-19 Pandemic.

INTRODUCTION: Japan recently experienced two major heavy rain disasters: the West Japan heavy rain disaster in July 2018 and the Kumamoto heavy rain disaster in July 2020. Between the occurrences of these two disasters, Japan began experiencing the wave of the coronavirus disease 2019 (COVID-19) pandemic, providing a unique opportunity to compare the incidence of acute respiratory infection (ARI) between the two disaster responses under distinct conditions. SOURCES FOR INFORMATION: The data were collected by using the standard disaster medical reporting system used in Japan, so-called the Japan-Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED), which reports number and types of patients treated by Emergency Medical Teams (EMTs). Data for ARI were extracted from daily aggregated data on the J-SPEED form and the frequency of ARI in two disasters was compared. OBSERVATION: Acute respiratory infection in the West Japan heavy rain that occurred in the absence of COVID-19 and in the Kumamoto heavy rain that occurred in the presence of COVID-19 were responsible for 5.4% and 1.2% of the total consultation, respectively (P <.001). ANALYSIS OF OBSERVATION AND CONCLUSION: Between the occurrence of these two disasters, Japan implemented COVID-19 preventive measures on a personal and organizational level, such as wearing masks, disinfecting hands, maintaining social distance, improving room ventilation, and screening people who entered evacuation centers by using hygiene management checklists. By following the basic prevention measures stated above, ARI can be significantly reduced during a disaster.

Exercising the Sanger Sequencing Strategy for Variants Screening and Full-Length Genome of SARS-CoV-2 Virus during Alpha, Delta, and Omicron Outbreaks in Hiroshima.

This study aimed to exercise the Sanger sequencing strategy for screening of variants among confirmed COVID-19 cases and validate our strategy against NGS strains in Hiroshima retrieved from GISAID. A total of 660 samples from confirmed COVID-19 cases underwent screening for variants by Sanger-based partial sequencing to the targeted spike gene (nt22,735~nt23,532) using an in-house-developed primer set. The identification of variants was done by unique checkpoints of base nucleotide changes in the targeted spike gene. Moreover, we amplified one full-length genome using Sanger method and an in-house-developed primer library. Using NGS strains of the same sampling period from GISAID, a phylogenetic tree was constructed to examine the distribution pattern of variants in Hiroshima and to validate our Sanger method. The modified primer set provided 100% validation and 99.2% amplification. PANGO Lineage R.1 was detected in late in the third wave, followed by Alpha (B.1.1.7) domination in the fourth wave, Delta (B.1.617.2) domination in the fifth wave, and Omicron (B.1.1.529) domination in the sixth wave, and there was no significant difference in viral copies between variants (p = 0.09). The variants showed different transmission patterns, but the distribution of variants is consistent to that shown by the phylogenetic tree. The Sanger method also provided successful amplification of the full-length genome of the SARS-CoV-2 virus. Our Sanger sequencing strategy was useful for the screening of SASR-CoV-2 variants without the need for full-genome amplification. The modified primer set was validated to use universally, which allows an understanding of the variants' distribution in real time and provides the evidence for policy-making and the formulation or modification of preventive strategies.

Prevalence of Mental Health Problems among Patients Treated by Emergency Medical Teams: Findings from J-SPEED Data Regarding the West Japan Heavy Rain 2018.

It is crucial to provide mental health care following a disaster because the victims tend to experience symptoms such as anxiety and insomnia during the acute phase. However, little research on mental health during the acute phase has been conducted, and reported only in terms of the temporal transition of the number of consultations and symptoms. Thus, the aim of the study was to examine how mental health care needs are accounted for in the overall picture of disaster relief and how they change over time. Using data from the Japanese version of Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED), we assessed the mental health of injured and ill patients to whom Emergency Medical Teams (EMTs) were providing care during the acute period of a disaster. Approximately 10% of all medical consultations were for mental health issues, 83% of which took place within the first 2 weeks after the disaster. The findings showed that, from the start of the response period to the 19th response day, the daily proportion of mental health problems declined substantially, and then gradually increased. Such a V-shaped pattern might be helpful for identifying phase changes and supporting the development of EMT exit strategies.

Mass Screening of SARS-CoV-2 Variants using Sanger Sequencing Strategy in Hiroshima, Japan.

This study aimed to develop the feasible and effective universal screening strategy of the notable SARS-CoV-2 variants by Sanger Sequencing Strategy and then practically applied it for mass screening in Hiroshima, Japan. A total of 734 samples from COVID-19 confirmed cases in Hiroshima were screened for the notable SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.1, C.37, B.1.1.529, etc.). The targeted spike region is amplified by nested RT-PCR using in-house designed primer set hCoV-Spike-A and standard amplification protocol. Additionally, randomly selected 96 samples were also amplified using primer sets hCoV-Spike-B and hCoV-Spike-C. The negative amplified samples were repeated for second attempt of amplification by volume-up protocol. Thereafter, the amplified products were assigned for Sanger sequencing using corresponding primers. The positive amplification rate of primer set hCoV-Spike-A, hCoV-Spike-B and hCoV-Spike-C were 87.3%, 83.3% and 93.8% respectively for standard protocol and increased to 99.6%, 95.8% and 96.9% after second attempt by volume-up protocol. The readiness of genome sequences was 96.9%, 100% and 100% respectively. Among 48 mutant isolates, 26 were B.1.1.7 (Alpha), 7 were E484K single mutation and the rest were other types of mutation. Moreover, 5 cluster cases with single mutation at N501S were firstly reported in Hiroshima. This study indicates the reliability and effectiveness of Sanger sequencing to screen large number of samples for the notable SARS-CoV-2 variants. Compared to the Next Generation Sequencing (NGS), our method introduces the feasible, universally applicable, and practically useful tool for identification of the emerging variants with less expensive and time consuming especially in those countries where the NGS is not practically available. Our method allows not only to identify the pre-existing variants but also to examine other rare type of mutation or newly emerged variants and is crucial for prevention and control of pandemic.

The Association between Wearing a Mask and COVID-19.

With the widespread and increasing number of cases of Coronavirus Disease (2019) globally, countries have been taking preventive measures against this pandemic. However, there is no universal agreement across cultures on whether wearing face masks are an effective physical intervention against disease transmission. We investigated the relationship between mask wearing and COVID-19 among close contacts of COVID-19 patients in the Hiroshima Prefecture, Japan. In the Hiroshima Prefecture, a COVID-19 form adapted from the reporting form, "Japanese Surveillance in Post-Extreme Emergencies and Disasters", was developed to collect data from COVID-19 patients' close contacts under active epidemiological surveillance at Public Health Centers. The relative risk of COVID-19 for mask users versus non-mask users was calculated. A total of 820 interviewees were included in the analysis and 53.3% of them responded that they wore masks. Non-mask users were infected at a rate of 16.4%, while mask users were infected at a rate of 7.1%. Those who wore masks were infected at a rate of 0.4 times that of those who did not wear masks. (RR = 0.4, 95%CI = 0.3-0.6; Adjusted RR = 0.6, 95%CI = 0.3-0.9). These findings implied that COVID-19 could be avoided to a certain degree by wearing a mask.

Molecular characterization and the mutation pattern of SARS-CoV-2 during first and second wave outbreaks in Hiroshima, Japan.

BACKGROUND: In this study, we performed molecular characterization of SARS-CoV-2 strains in Hiroshima and its mutation pattern between the first and second waves of the outbreak. METHOD: A total of 55 nasal swab samples from the first wave in Hiroshima and 13 from the second wave were examined quantitatively by RT-qPCR and qualitatively by nested PCR using specific primers. Four samples from each wave underwent next-generation sequencing and phylogenetic tree analysis including controls and all sequences retrieved in Japan from GISAID and GenBank. Subsequently, mutations were examined. RESULTS: Viral load ranged 7.85 × 101-1.42 × 108 copies/ml. Of 68 samples, one was Asian type-O, 65 were European type-GR, and 2 were undetectable. Phylogenetic tree analysis indicated that Japan was infected with various Asian strains (L, S, V, O) from January through April. By second week of March, European strains (G, GH, GR) had appeared, and GR strains became predominant after mid-March. The first case in Hiroshima was classified as Asian strain O, and the rest were GR strains. Then, second wave of GR strains appeared independently with 11-15 base mutations. Comparing the first- and second-wave GR strains, mutation rate was 1.17-1.36 × 10-3 base substitutions per site per year; in addition, amino acid changes occurred at S1361P and P3371S in ORF1a, A314V in ORF1b, and P151L in N. All seven GR strains were D614G variants with R202K and G203R mutations in N. A single-nucleotide insertion in ORF8 that causes a defect in ORF8 protein was found in one isolate (S66) from the second wave. CONCLUSION: Our findings reveal the evolutionary hierarchy of SARS-CoV-2 in Japan. The predominant D614G variants and a new form of ORF8 deletion in Hiroshima provide the clue for role of viral factor in local outbreaks of SARS-CoV-2.