Effects of inbound attendees of a mass gathering event on the COVID-19 epidemic using individual-based simulations

Given that mass gathering events involve heterogeneous and time-varying contact between residents and visitors, we sought to identify possible measures to prevent the potential acceleration of the outbreak of an emerging infectious disease induced by such events. An individual-based simulator was built based on a description of the reproduction rate among people infected with the infectious disease in a hypothetical city. Three different scenarios were assessed using our simulator, in which controls aimed at reduced contact were assumed to be carried out only in the main event venue or at subsequent additional events, or in which behavior restrictions were carried out among the visitors to the main event. The simulation results indicated that the increase in the number of patients with COVID-19 could possibly be suppressed to a level equivalent to that if the event were not being held so long as the prevalence among visitors was only slightly higher than that among domestic residents and strict requirements were applied to the activities of visitors.

Sensitivity of rapid antigen tests for COVID-19 during the Omicron variant outbreak

BackgroundRapid antigen tests have been used to prevent the spread of the coronavirus disease 2019 (COVID-19); however, there have been concerns about their decreased sensitivity to the Omicron variant. AimsIn this study, we compared the sensitivity and specificity of the rapid antigen and the polymerase chain reaction (PCR) tests among the players and staff members of the Japan Professional Football League and clubs. Furthermore, we evaluated the relationship between the sensitivity and the duration from the onset of the symptoms to testing, the manufacturer of the rapid antigen test kits, and the PCR test analyte. Design and methodsThis was a retrospective observational study. We used 656 results from both the rapid antigen and PCR tests for COVID-19 using the analytes collected on the same day from January 12 to March 2, 2022, during the Omicron variant outbreak in Japan. ResultsThe sensitivity of the rapid antigen test compared with the PCR test was 0.63 (95% confidence interval: 0.54-0.72) and the specificity was 0.998 (95% confidence interval: 0.995-1.000). There were no significant associations between the sensitivity and the duration from the onset of the symptoms to testing (including asymptomatic cases in the category), vaccination status, manufacturer of the rapid antigen test kit or PCR analyte (P > 0.05) with small effect sizes (Cramers V or {varphi}: [≤] 0.22). ConclusionsEven during the Omicron outbreak, the sensitivity of the rapid antigen tests did not depend on the duration from the onset of the symptoms to testing.

Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights. Author SummaryCOVID-19 clinical outcomes vary immensely, but a patients genetic make-up is an important determinant of how they will fare against the virus. While many genetic variants commonly found in the populations were previously found to be contributing to more severe disease by the COVID-19 Host Genetics Initiative, it isnt clear if more rare variants found in less individuals could also play a role. This is important because genetic variants with the largest impact on COVID-19 severity are expected to be rarely found in the population, and these rare variants require different technologies to be studies (usually whole-exome or whole-genome sequencing). Here, we combined sequencing results from 21 cohorts across 12 countries to perform a rare variant association study. In an analysis comprising 5,085 participants with severe COVID-19 and 571,737 controls, we found that the gene for toll-like receptor 7 (TLR7) on chromosome X was an important determinant of severe COVID-19. Importantly, despite being found on a sex chromosome, this observation was consistent across both sexes.

Development of a COVID-19 risk-assessment model for participants at an outdoor music festival: Evaluation of the validity and control measure effectiveness

We developed an environmental exposure model to estimate the Coronavirus Disease 2019 (COVID-19) risk among participants at an outdoor music festival and validated the model using a real cluster outbreak case. Furthermore, we evaluated the extent to which the risk could be reduced by additional infection control measures such as negative proofs of antigen tests on the day of the event, wearing masks, disinfection of environmental surfaces, and vaccination. The total number of already- and newly-infected individuals who participated in the event according to the new model was 47.0 (95% uncertainty interval: 12.5-185.5), which is in good agreement with the reported value (45). Among the additional control measures, vaccination, mask-wearing, and disinfection of surfaces were determined to be effective. Based on the combination of all measures, a 94% risk reduction could be achieved. In addition to setting a benchmark for an acceptable number of newly-infected individuals at the time of an event, the application of this model will enable us to determine whether it is necessary to implement additional measures, limit the number of participants, or refrain from holding an event.

Quantifying the effect of isolation and negative certification on COVID-19 transmission

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSIsolation of close contact people and negative test certification are used to manage the spread of new coronavirus infections worldwide. These effectively prevent the spread of infection in advance, but they can lead to a decline in socio-economic activity. Thus, the present study quantified the extent to which isolation and negative test certification respectively reduce the risk of infection. MethodsA discrete-time SEIR model was used as the infectious disease model, and equations for calculating the conditional probability of non-infection status given negative test results on two different days were derived. ResultsThe respective non-infection probabilities with two negative PCR test results, and with one negative PCR test result and one antigen test result, were quantified. By substituting initial parameters of the SEIR model into these probabilities, the present study revealed the following: (1) isolating close contact individuals can reduce by 80% the risk of infection during the first five days, but five more days are needed to reduce the risk 10% more, and seven more days to reduce the risk 20% more; and (2) if an individual with a negative PCR test result has a negative antigen test result the next day, then his or her infection probability is between 0.6% and 0.7%. ConclusionsFive-day isolation has a proportionally greater effect on risk reduction, compared to longer isolation; and thus, if an isolation period of longer than five days is contemplated, both the risk reduction and the negative effects from such increased isolation should be considered. Regarding negative test certification, our results provide those in managerial positions, who must decide whether to accept the risk and hold mass-gathering events, with quantitative information that may be useful in their decision-making.

Quantitative risk assessment of COVID-19 and serious illness among spectators at mass gathering events with vaccine-testing package implementation

While mass gathering events have resumed in conjunction with vaccine-testing (VT) packages, their effects on reducing COVID-19 risk remain unclear. Here, we used an environmental exposure model to analyze the effects of vaccinations and proof of negative test results on reducing infection risk and serious illness among spectators at mass gathering events. We then analyzed the difference in risk with and without VT and regular seat zoning. Risk of infection and serious illness were quantified using a model incorporating parameters such as vaccination coverage, vaccine prevention effectiveness, and sensitivity of polymerase chain reaction (PCR) or qualitative antigen tests. When vaccine prevention effectiveness was 50% (corresponding to 4 months for the delta variant and 1-2 months for the omicron variant after the second vaccine dose), the risk of infection and serious illness among vaccinated spectators were 0.32-0.40 and 0.13-0.16 times of those who tested negative, respectively. In contrast, the risks of infection and serious illness among vaccinated spectators without measures such as mask wearing were 4.0 and 1.6 times higher than those among unvaccinated spectators with such measures, respectively. The risk of infection with an 80% vaccination coverage and a vaccine prevention effectiveness of 20% (corresponding to 5-6 months for the delta variant or 3-4 months for the omicron variant after the second vaccine dose) was comparable to that of a 20% vaccine coverage and a vaccine prevention effectiveness of 80% (corresponding to 1-3 months for delta variant after the second vaccine dose). Regarding zoning, there was little difference in risk with a vaccination coverage of [≥]80%. Adherence to individual measures after vaccination and maintenance of high vaccine effectiveness among spectators at stadiums are important for reducing risk of infection and serious illness. Furthermore, seat zoning did not affect overall infection risk reduction.

COVID-19 testing systems and their effectiveness in small, semi-isolated groups for sports events

In this study, we quantitatively assessed the effectiveness of systems for COVID-19 testing in small groups of sport teams that are semi-isolated from the general population by countermeasures against infection. Two types of group were assumed, and the dynamics of infection within each group was modeled by using a compartment model of infectious disease. One group (Group A) comprised domestic professional sports teams that play many games over a season while remaining within a relatively small region. Polymerase chain reaction (PCR) tests were routinely conducted once every 2 weeks, and the number of infected individuals that could not be removed after identification by testing or checking for symptoms was defined as the risk. The other group (Group B) comprised teams that travel across borders for mass-gathering events like the Olympic and Paralympic Games. The teams were isolated for 2 weeks at their destination; frequent testing and checking for symptoms was conducted, and any infected individuals were removed. The number of infected individuals participating in games after the isolation period was defined as the risk. In Group A, the number of infected individuals detected by routinely conducted PCR testing was lower than the number of infected individuals detected by checking for symptoms, indicating that routine testing every 2 weeks was not very effective. In Group B, daily PCR testing was the most effective, followed by daily antigen testing. Dual testing, in which individuals with a positive antigen test were given an additional PCR test, was the least effective with an effect equal to PCR testing every other day. These results indicate that repeated testing does not necessarily increase the detection of infected individuals.

Cross-border transmissions of delta substrain AY.29 during Olympic and Paralympic Games

Tokyo Olympic and Paralympic Games, postponed for COVID-19 pandemic, were finally held in summer of 2021. Just before the games, alpha variant was being replaced with more contagious delta variant (B.1.617.2). AY.4 substrain AY.29, which harbors two additional characteristic mutations of 5239C>T (NSP3 Y840Y) and 5514T>C (NSP3 V932A), emerged in Japan and became the dominant strain in Tokyo by the time of the Olympic Games. As of October 18, 98 AY.29 samples are identified in 16 countries outside of Japan. Phylogenetic analysis and ancestral searches identified 46 distinct introductions of AY.29 strains into those 16 countries. United States has 44 samples with 10 distinct introductions, and United Kingdom has 13 distinct AY.29 strains introduced in 16 samples. Other countries or regions with multiple introductions of AY.29 are Canada, Germany, South Korea, and Hong Kong while Italy, France, Spain, Sweden, Belgium, Peru, Australia, New Zealand, and Indonesia have only one distinct strain introduced. There exists no unambiguous evidence that Olympic and Paralympic Games induced cross-border transmission of the delta substrain AY.29. Since most of unvaccinated countries are also under sampled for genome analysis with longer lead time for data sharing, it will take longer to capture the whole picture of cross-border transmissions of AY.29.

Assessment of COVID-19 risk and prevention effectiveness among spectators of mass gathering events

There is a need to evaluate and minimise the risk of novel coronavirus infections at mass gathering events, such as sports. In particular, to consider how to hold mass gathering events, it is important to clarify how the local infection prevalence, the number of spectators, the capacity proportion, and the implementation of preventions affect the infection risk. In this study, we used an environmental exposure model to analyse the relationship between infection risk and infection prevalence, the number of spectators, and the capacity proportion at mass gathering events in football and baseball games. In addition to assessing risk reduction through the implementation of various preventive measures, we assessed how face-mask-wearing proportion affects infection risk. Furthermore, the model was applied to estimate the number of infectors who entered the stadium and the number of newly infected individuals, and to compare them with actual reported cases. The model analysis revealed an 86%-95% reduction in the infection risk due to the implementation of face-mask wearing and hand washing. Among the individual measures, face-mask wearing was particularly effective, and the infection risk increased as the face-mask-wearing proportion decreased. A linear relationship was observed between infection risk at mass gathering events and the infection prevalence. Furthermore, the number of newly infected individuals was also dependent on the number of spectators and the capacity proportion independent of the infection prevalence, confirming the importance of considering spectator capacity in infection risk management. These results highlight that it is beneficial for organisers to ensure prevention compliance and to mitigate or limit the number of spectators according to the prevalence of local infection. Both the estimated and reported numbers of newly infected individuals after the events were small, below 10 per 3-4 million spectators, despite a small gap between these numbers.

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.

Prediction Model for Deficiency-Excess Patterns, Including Medium Pattern / 日本東洋医学雑誌

We have previously reported on a predictive model for deficiency-excess pattern diagnosis that was unable to predict the medium pattern. In this study, we aimed to develop predictive models for deficiency, medium,and excess pattern diagnosis, and to confirm whether cutoff values for diagnosis differed between the clinics. We collected data from patients' first visit to one of six Kampo clinics in Japan from January 2012 to February 2015. Exclusion criteria included unwillingness to participate in the study, missing data, duplicate data, under 20 years old, 20 or less subjective symptoms, and irrelevant patterns. In total, 1,068 participants were included. Participants were surveyed using a 153-item questionnaire. We constructed a predictive model for deficiency, medium, and excess pattern diagnosis using a random forest algorithm from training data, and extracted the most important items. We calculated predictive values for each participant by applying their data to the predictive model, and created receiver operating characteristic (ROC) curves with excess-medium and medium-deficiency patterns. Furthermore, we calculated the cutoff value for these patterns in each clinic using ROC curves, and compared them. Body mass index and blood pressure were the most important items. In all clinics, the cutoff values for diagnosis of excess-medium and medium-deficiency patterns was > 0.5 and < 0.5, respectively. We created a predictive model for deficiency, medium, and excess pattern diagnosis from the data of six Kampo clinics in Japan. The cutoff values for these patterns fell within a narrow range in the six clinics.