Increase in the number of new cases of ANCA-associated vasculitis in the COVID-19 vaccine era.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune vasculitis characterized by the production of antibodies against ANCA, with unclear pathogenesis. With the ongoing COVID-19 pandemic, COVID-19 mRNA vaccination has been available in Japan since February 2021. Although autoimmune symptoms have been reported after COVID-19 vaccinations, there have been no clinical investigations regarding the relationship between COVID-19 mRNA vaccines and the pathogenesis of AAV. Thus, the present study aimed to investigate whether the administration of COVID-19 mRNA vaccines affects the development of AAV. The study identified patients with new-onset AAV who were MPO-ANCA or PR3-ANCA positive and met the entry criteria of the AAV EMA classification algorithm. The study compared the number of new AAV cases per year before and after the start of the COVID-19 mRNA vaccine program in Japan. The study found that the annual number of new cases of AAV in Japan's Nagasaki Prefecture increased by approximately 1.5-fold since the COVID-19 vaccine program was initiated, suggesting a possible link between the COVID-19 mRNA vaccines and the development of AAV. Although the study provides insight into the clinical evaluation and management of autoimmune symptoms following COVID-19 vaccination, further investigation of the possible association between COVID-19 mRNA vaccines and the pathogenesis of AAV is required.

Cartography of SARS-CoV-2 variants based on the susceptibility to therapeutic monoclonal antibodies.

A comprehensive picture of a phenotypic relationship among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has been poorly studied. Here, this study presents cartography showing how the wild-type strain of SARS-CoV-2 and 14 variants are alike or different from the perspective of the susceptibility to 12 therapeutic monoclonal antibodies. The Alpha variant is close to the wild-type strain, whereas the Beta, Gamma, and Delta variants diverge from the wild-type. The map highlights the very unique property of the Omicron variant. Interestingly, sublineages of the Omicron variants, BA.1, BA.2, and BA.4/5, differ substantially in the cartography.

Age-Stratified Seroprevalence of SARS-CoV-2 Antibodies before and during the Vaccination Era, Japan, February 2020-March 2022.

Japan has reported a relatively small number of COVID-19 cases. Because not all infected persons receive diagnostic tests for COVID-19, the reported number must be lower than the actual number of infections. We assessed SARS-CoV-2 seroprevalence by analyzing >60,000 samples collected in Japan (Tokyo Metropolitan Area and Hokkaido Prefecture) during February 2020-March 2022. The results showed that ≈3.8% of the population had become seropositive by January 2021. The seroprevalence increased with the administration of vaccinations; however, among the elderly, seroprevalence was not as high as the vaccination rate. Among children, who were not eligible for vaccination, infection was spread during the epidemic waves caused by the SARS-CoV-2 Delta and Omicron variants. Nevertheless, seroprevalence for unvaccinated children <5 years of age was as low as 10% as of March 2022. Our study underscores the low incidence of SARS-CoV-2 infection in Japan and the effects of vaccination on immunity at the population level.

Analysis of sociodemographic and clinical factors associated with Lassa fever disease and mortality in Nigeria.

Over past decades, there has been increasing geographical spread of Lassa fever (LF) cases across Nigeria and other countries in West Africa. This increase has been associated with significant morbidity and mortality despite increasing focus on the disease by both local and international scientists. Many of these studies on LF have been limited to few specialised centres in the country. This study was done to identify sociodemographic and clinical predictors of LF disease and related deaths across Nigeria. We analysed retrospective surveillance data on suspected LF cases collected during January-June 2018 and 2019. Multivariable logistic regression analyses were used to identify the factors independently associated with laboratory-confirmed LF diagnosis, and with LF-related deaths. There were confirmed 815 of 1991 suspected LF cases with complete records during this period. Of these, 724/815 confirmed cases had known clinical outcomes, of whom 100 died. LF confirmation was associated with presentation of gastrointestinal tract (aOR 3.47, 95% CI: 2.79-4.32), ear, nose and throat (aOR 2.73, 95% CI: 1.80-4.15), general systemic (aOR 2.12, 95% CI: 1.65-2.70) and chest/respiratory (aOR 1.71, 95% CI: 1.28-2.29) symptoms. Other factors were being male (aOR 1.32, 95% CI: 1.06-1.63), doing business/trading (aOR 2.16, 95% CI: 1.47-3.16) and farming (aOR 1.73, 95% CI: 1.12-2.68). Factors associated with LF mortality were a one-year increase in age (aOR 1.03, 95% CI: 1.01-1.04), bleeding (aOR 2.07, 95% CI: 1.07-4.00), and central nervous manifestations (aOR 5.02, 95% CI: 3.12-10.16). Diverse factors were associated with both LF disease and related death. A closer look at patterns of clinical variables would be helpful to support early detection and management of cases. The findings would also be useful for planning preparedness and response interventions against LF in the country and region.

Epidemiological Factors Associated with COVID-19 Clusters in Medical and Social Welfare Facilities.

The characteristics of coronavirus disease 2019 (COVID-19) clusters in medical and social welfare facilities and the factors associated with cluster size are still not yet fully understood. We reviewed COVID-19 cases in Japan identified from January 15 to April 30, 2020 and analyzed the factors associated with cluster size in medical and social welfare facilities. In this study, COVID-19 clusters were identified in 56 medical and 34 social welfare facilities. The number of cases in those facilities peaked after the peak of the general population. The duration of occurrence of new cases in clusters was positively correlated with the number of cases in both types of facilities (rho = 0.44, P < 0.001; and rho = 0.69, P < 0.001, respectively). However, the number of days between the first case in a prefecture and the onset of clusters was negatively correlated with the number of cases only in clusters in social welfare facilities (rho = - 0.4, P = 0.004). Our results suggest that COVID-19 cases in those facilities were prevalent in the latter phase of the disease's community transmission, although the underlying mechanisms for such a trend could differ between medical and social welfare facilities.

Integration of publicly available case-based data for real-time coronavirus disease 2019 risk assessment, Japan.

In response to the outbreak of coronavirus disease 2019 (COVID-19) in Japan, a national COVID-19 cluster taskforce (comprising governmental and nongovernmental experts) was established to support the country's Ministry of Health, Labour and Welfare in conducting daily risk assessment. The assessment was carried out using established infectious disease surveillance systems; however, in the initial stages of the pandemic these were not sufficient for real-time risk assessment owing to limited accessibility, delay in data entry and inadequate case information. Also, local governments were publishing anonymized data on confirmed COVID-19 cases on their official web sites as daily press releases. We developed a unique database for nationwide real-time risk assessment that included these case lists from local government web sites and integrated all case data into a standardized format. The database was updated daily and checked systematically to ensure comprehensiveness and quality. Between 15 January 2020 and 15 June 2021, 776 459 cases were logged in the database, allowing for analysis of real-time risk from the pandemic. This semi-automated database was used in daily risk assessments, and to evaluate and update control measures to prevent community transmission of COVID-19 in Japan. The data were reported almost every week to the Japanese Government Advisory Panel on COVID-19 for public health responses.

Properties of the Omicron Variant of SARS-CoV-2 Affect Public Health Measure Effectiveness in the COVID-19 Epidemic.

Nonpharmaceutical and pharmaceutical public health interventions are important to mitigate the coronavirus disease 2019 (COVID-19) epidemic. However, it is still unclear how the effectiveness of these interventions changes with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel variants. This simulation study utilized data from Japan and investigated how the characteristic properties of the Omicron variant, which emerged in late 2021, influence the effectiveness of public health interventions, including vaccination, the reduction of interpersonal contact, and the early isolation of infectious people. Although the short generation time of the Omicron variant increases the effectiveness of vaccination and the reduction of interpersonal contact, it decreases the effectiveness of early isolation. The latter feature may make the containment of case clusters difficult. The increase of infected children during the Omicron-dominant epidemic diminishes the effects of previously adult-targeted interventions. These findings underscore the importance of monitoring viral evolution and consequent changes in epidemiological characteristics. An assessment and adaptation of public health measures against COVID-19 are required as SARS-CoV-2 novel variants continue to emerge.

Simulation of future COVID-19 epidemic by vaccination coverage scenarios in Japan.

BACKGROUND: COVID-19 continues to impose significant morbidity and mortality in Japan even after implementing the vaccination program. It would remain elusive if restrictions for its mitigation were to be lifted or relaxed in the future. METHODS: A simulation study that explored possible vaccination coverage scenarios and changes in the intensity of nonpharmaceutical intervention restrictions was performed to assess the impact of COVID-19 based on death count. RESULTS: Assuming the basic reproduction number of circulating viruses was 5.0, vaccines could prevent 90% of infections and 95% of deaths, and the vaccination coverage rate was high (75%, 80%, and 90% in people aged 12-39 years, 40-59 years, ≥60 years, respectively), approximately 50 000 deaths would occur over 150 days in Japan if all restrictions were lifted. Most deaths would occur among older adults, even if their vaccination coverage was assumed to be especially high. A low vaccination coverage scenario (45%, 60%, and 80% in people aged 12-39 years, 40-59 years, ≥60 years, respectively) would require periodic implementation of strict measures even if the modified lifestyle observed in 2020 was sustained and vaccines were very effective. Some restrictions could be relaxed under high vaccination coverage. However, in the worst-case scenario where vaccines had decreased efficacy, as we have observed for the Delta variant, and people lived a relaxed lifestyle, our simulation suggests that even high vaccination coverage would occasionally require strict measures. CONCLUSIONS: We should carefully explore a manageable degree of restrictions and their relaxation. We will have to keep bracing for occasional surges of COVID-19 infection, which could lead to strict measures, such as those under a state of emergency. Such strategies are essential even after a wide rollout of vaccination.

Simulation study reveals factors that affect the predominance of SARS-CoV-2 novel variant.

The novel variants of the SARS-CoV-2 are a great global concern for the ongoing COVID-19 pandemic. However, how the novel variants predominate and replace existing strains remains elusive. In this study, I simulated the infection spread to investigate what kinds of viral, immunological, and epidemiological factors affect the predominance of SARS-CoV-2 novel variants. The results showed that the increase of the transmissibility of the novel variant substantially enhanced the predominance probability. In addition, the increasing trend of the infection spread, the large case number of the epidemic, and the ability of immune escape of the novel variant increased the predominance probability. A small number of cases and a decreasing trend of an entire epidemic, including not only the novel variant but also earlier strains, are especially important to reduce the chance of the predominance of the novel variant and delay the process. Good control of the COVID-19 epidemic could make the disease burden small and sequester the spread of the SARS-CoV-2 novel variants.

Secondary transmission of SARS-CoV-2 during the first two waves in Japan: Demographic characteristics and overdispersion.

OBJECTIVES: Super-spreading events caused by overdispersed secondary transmission are crucial in the transmission of COVID-19. However, the exact level of overdispersion, demographics, and other factors associated with secondary transmission remain elusive. In this study, we aimed to elucidate the frequency and patterns of secondary transmission of SARS-CoV-2 in Japan. METHODS: We analyzed 16,471 cases between January 2020 and August 2020. We generated the number of secondary cases distribution and estimated the dispersion parameter (k) by fitting the negative binomial distribution in each phase. The frequencies of the secondary transmission were compared by demographic and clinical characteristics, calculating the odds ratio using logistic regression models. RESULTS: We observed that 76.7% of the primary cases did not generate secondary cases with an estimated dispersion parameter k of 0.23. The demographic patterns of primary-secondary cases differed between phases, with 20-69 years being the predominant age group. There were higher proportions of secondary transmissions among older individuals, symptomatic patients, and patients with 2 days or more between onset and confirmation. CONCLUSIONS: The study showed the estimation of the frequency of secondary transmission of SARS-CoV-2 and the characteristics of people who generated the secondary transmission.

Roles of Children and Adolescents in COVID-19 Transmission in the Community: A Retrospective Analysis of Nationwide Data in Japan.

Background: Roles of children and adolescents in spreading coronavirus disease 2019 (COVID-19) in the community is not fully understood. Methods: We analyzed the data of 7,758 children and adolescents with COVID-19 and characteristics of secondary transmission generated by these cases using case information published by local governments. Ratio of pediatric and adolescent cases generating secondary transmission was calculated for various social settings. Results: The incidence of COVID-19 was 24.8 cases per 105 population aged between 0 and 9 years, and 59.2 among those aged between 10 and 19 years, which was lower than that among individuals of all age groups (79.6 per 105 population) between January 15 and October 31, 2020. The proportion of cases generating secondary cases was 8.3% among infants and young children in nursery schools and kindergartens, 16% among children and adolescents attending primary schools, 34% among those attending junior high schools, 43% among those attending high schools, 31% among those attending professional training colleges, and 24% in those attending universities. Households were the most common setting for secondary transmission. Conclusion: The risk of generating secondary cases might be limited among pediatric and adolescent cases with COVID-19, especially in settings outside households. Effectiveness of traditional mitigation measures (e.g., school closures) to suppress COVID-19 transmissions should be carefully evaluated.

Relationship of Test Positivity Rates with COVID-19 Epidemic Dynamics.

Detection and isolation of infected people are believed to play an important role in the control of the COVID-19 pandemic. Some countries conduct large-scale screenings for testing, whereas others test mainly people with high prior probability of infection such as showing severe symptoms and/or having an epidemiological link with a known or suspected case or cluster of cases. However, what a good testing strategy is and whether the difference in testing strategy shows a meaningful, measurable impact on the COVID-19 epidemic remain unknown. Here, we showed that patterns of association between effective reproduction number (Rt) and test positivity rate can illuminate differences in testing situation among different areas, using global and local data from Japan. This association can also evaluate the adequacy of current testing systems and what information is captured in COVID-19 surveillance. The differences in testing systems alone cannot predict the results of epidemic containment efforts. Furthermore, monitoring test positivity rates and severe case proportions among the nonelderly can predict imminent case count increases. Monitoring test positivity rates in conjunction with the concurrent Rt could be useful to assess and strengthen public health management and testing systems and deepen understanding of COVID-19 epidemic dynamics.

Familial Clusters of Coronavirus Disease in 10 Prefectures, Japan, February-May 2020.

The overall coronavirus disease secondary attack rate (SAR) in family members was 19.0% in 10 prefectures of Japan during February 22-May 31, 2020. The SAR was lower for primary cases diagnosed early, within 2 days after symptom onset. The SAR of asymptomatic primary cases was 11.8%.

Identifying Potentially Beneficial Genetic Mutations Associated with Monophyletic Selective Sweep and a Proof-of-Concept Study with Viral Genetic Data.

Genetic mutations play a central role in evolution. For a significantly beneficial mutation, a one-time mutation event suffices for the species to prosper and predominate through the process called "monophyletic selective sweep." However, existing methods that rely on counting the number of mutation events to detect selection are unable to find such a mutation in selective sweep. We here introduce a method to detect mutations at the single amino acid/nucleotide level that could be responsible for monophyletic selective sweep evolution. The method identifies a genetic signature associated with selective sweep using the population genetic test statistic Tajima's D We applied the algorithm to ebolavirus, influenza A virus, and severe acute respiratory syndrome coronavirus 2 to identify known biologically significant mutations and unrecognized mutations associated with potential selective sweep. The method can detect beneficial mutations, possibly leading to discovery of previously unknown biological functions and mechanisms related to those mutations.IMPORTANCE In biology, research on evolution is important to understand the significance of genetic mutation. When there is a significantly beneficial mutation, a population of species with the mutation prospers and predominates, in a process called "selective sweep." However, there are few methods that can find such a mutation causing selective sweep from genetic data. We here introduce a novel method to detect such mutations. Applying the method to the genomes of ebolavirus, influenza viruses, and the novel coronavirus, we detected known biologically significant mutations and identified mutations the importance of which is previously unrecognized. The method can deepen our understanding of molecular and evolutionary biology.

Genomic sequencing effort for SARS-CoV-2 by country during the pandemic.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), tremendous efforts have been made to sequence the viral genome from samples collected throughout the world. Here, we evaluate how various countries have performed in sequencing from the perspectives of "fraction", "timeliness", and "openness". We found that high proportions of samples were sequenced in the UK, the USA, Australia, and Iceland; sequencing was performed promptly in Iceland, the Netherlands, and the Democratic Republic of the Congo; and data were shared timely from the Netherlands, the USA, Iceland, and the UK. Although many developing countries have high numbers of SARS-CoV-2 infected cases but few published sequences, we observed good performance on sequencing efforts for some low- and middle-income countries. Further strengthening of the sequencing capacity at a global level would help in the fight against not only the current pandemic but also future outbreaks of viral diseases.