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@#Utilizing data presented in the article by Miyashita et al., we illustrate the importance of testing data when assessing surveillance data. Accounting for the number of tests (denominator) and positivity (proportion of tests positive for a specific pathogen(s)) improves data interpretation in ways not possible from numerator case data alone.
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AbstractImmunity to SARS-CoV-2 in COVID-19 cases has diversified due to complex combinations of exposure to vaccination and infection. Elucidating the drivers for upgrading neutralizing activity to SARS-CoV-2 in COVID-19 cases with pre-existing immunity will aid in understanding immunity to SARS-CoV-2 and improving COVID-19 booster vaccines with enhanced cross-protection against antigenically distinct variants. This study revealed that the magnitude and breadth of neutralization responses to SARS-CoV-2 infection in breakthrough infections are determined by upper respiratory viral load and vaccination-infection time interval, but not by the lineage of infecting viruses. Notably, the time interval, but not the viral load, may play a critical role in expanding the breadth of neutralization to SARS-CoV-2. This illustrates the importance of dosing interval optimization in addition to antigen design in the development of variant-proof booster vaccines. One-Sentence SummaryViral load and infection timing define the magnitude and breadth of SARS-CoV-2 neutralization after breakthrough infection.
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BackgroundThe immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories. MethodsThe neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination. FindingsThe Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. ConclusionsImmune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants. FundingThis study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
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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.
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Objective: To establish seasonal and alert thresholds and transmission intensity categories for influenza to provide timely triggers for preventive measures or upscaling control measures in Cambodia. Methods: Using Cambodia’s influenza-like illness (ILI) and laboratory-confirmed influenza surveillance data from 2009 to 2015, three parameters were assessed to monitor influenza activity: the proportion of ILI patients among all outpatients, proportion of ILI samples positive for influenza and the product of the two. With these parameters, four threshold levels (seasonal, moderate, high and alert) were established and transmission intensity was categorized based on a World Health Organization alignment method. Parameters were compared against their respective thresholds. Results: Distinct seasonality was observed using the two parameters that incorporated laboratory data. Thresholds established using the composite parameter, combining syndromic and laboratory data, had the least number of false alarms in declaring season onset and were most useful in monitoring intensity. Unlike in temperate regions, the syndromic parameter was less useful in monitoring influenza activity or for setting thresholds. Conclusion: Influenza thresholds based on appropriate parameters have the potential to provide timely triggers for public health measures in a tropical country where monitoring and assessing influenza activity has been challenging. Based on these findings, the Ministry of Health plans to raise general awareness regarding influenza among the medical community and the general public. Our findings have important implications for countries in the tropics/subtropics and in resource-limited settings, and categorized transmission intensity can be used to assess severity of potential pandemic influenza as well as seasonal influenza.