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Since 2022, many countries have reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in Streptococcus pyogenes carriage rates or emergence of strains with potentially altered virulence, such as emm 1 variants M1 UK and M1 DK , contributed to the 2022/2023 surge in the Netherlands. We determined emm (sub)type distribution for 2,698 invasive and 351 S . pyogenes carriage isolates collected between January 2009 and March 2023. Genetic evolution of emm 1 was analyzed by whole-genome sequencing of 497 emm 1 isolates. The nationwide iGAS upsurge coincided with a sharp increase of emm 1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fisher's exact test, P < 0.0001). M1 UK became dominant among invasive emm 1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1 UK clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of emm 1 isolates. S. pyogenes carriage rates and emm 1 proportions in carriage isolates remained stable during this surge, and the expansion of M1 UK in iGAS was not reflected in carriage isolates. During the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1 UK clades was observed among invasive isolates, but not carriage isolates, suggesting increased virulence and fitness of M1 UK compared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.IMPORTANCEThis study describes the molecular epidemiology of invasive group A streptococcal (iGAS) infections in the Netherlands based on >3,000 Streptococcus pyogenes isolates from both asymptomatic carriers and iGAS patients collected before, during, and after the COVID-19 pandemic period (2009-2023) and is the first to assess whether changes in carriage rates or carried emm types contributed to the alarming post-COVID-19 upsurge in iGAS infections. We show that the 2022/2023 iGAS surge coincided with a sharp increase of emm 1, particularly the toxicogenic M1 UK variant, in invasive isolates, but not in carriage isolates. These findings suggest that increased virulence and fitness of M1 UK likely contributes to an increased dissemination between hosts. The emergence of a more virulent and fit lineage has important implications for iGAS control interventions such as antibiotic prophylaxis for close contacts of iGAS patients and calls for a reappraisal of iGAS control interventions and guidelines., Competing Interests: N.M.V.S. reports fee for service and presentations from MSD and GSK, grants from the Dutch Health Council (ZonMW; all directly paid to the institution), contract research with Argenx (unrelated to this work), a patent on vaccine development against S. pyogenes (licensee: University of California San Diego, inventors Nina van Sorge and Victor Nizet; licensed by Vaxcyte; personal revenue), and participation in the science advisory board of the ItsME foundation (no honorarium; https://itsme-foundation.com/en/) and Rapua te me ngaro ka tau, a project facilitating Strep A vaccine development for Aotearoa New Zealand (honorarium paid directly to the institution). M.A.V.H. reports grants or contracts with Pfizer (RSV prevention uptake study) and consulting fee from Pfizer on RSV vaccination (both unrelated to this work). Other authors have nothing to disclose.

BackgroundAfter most COVID-19 pandemic control measures were lifted in 2022, many infectious diseases re-emerged. An increase in invasive group A streptococcal (iGAS) infections among adults and young children was reported by several countries. Viral infections including influenza and varicella, known risk factors for iGAS infection, also increased.AimTo estimate the proportion of GAS skin and soft tissue infections (SSTI) and pneumonia/sepsis in children (≤ 5 years) attributable to varicella, and the proportion of GAS pneumonia/sepsis in children and adults attributable to potentially predisposing respiratory viruses influenza A and B, RSV, hMPV and SARS-CoV-2 in the Netherlands.MethodsWe performed time series regression using weekly data on respiratory viruses, varicella and non-invasive GAS infections and GAS isolates cultured from blood, lower airways, skin, pus and wounds, from January 2010 to March 2023.ResultsIn 2010-19, 50% (95% CI: 36-64) of GAS SSTI in children were attributable to varicella. Between January 2022 and March 2023, 34% (95% CI: 24-43) of GAS SSTI cases were attributable to varicella. Of iGAS pneumonia/sepsis between January 2022 and March 2023, 34% (95% CI: 20-49) and 25% (95% CI: 18-32) was attributable to respiratory virus infections in children and adults, respectively, with the largest contributor (17%) being influenza A.ConclusionsPredisposing viral infections likely contributed to, but cannot fully explain, the observed iGAS increase among children and adults in 2022-23 in the Netherlands. Public health measures to control viral infections, such as vaccination against varicella or influenza, might reduce the iGAS disease burden.

Objectives: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of nonconsenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in vaccine effectiveness (VE) estimates., Study Design and Setting: National data were used for the period dominated by the SARS-CoV-2 Delta variant (July 11 to November 15, 2021). VE ((1-relative risk)∗100%) against COVID-19 hospitalization and intensive care unit (ICU) admission was estimated for individuals 12 to 49, 50 to 69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iteratively imputing corrected vaccination status. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected/corrected relative risk., Results: A total of 8804 COVID-19 hospitalizations and 1692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the nonconsent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79)., Conclusion: VE estimates can be substantially biased with modest nonconsent percentages for vaccination data registration. Data on covariate-specific nonconsent percentages should be available to correct this bias., Competing Interests: Declaration of competing interest C.H. van Werkhoven declares financial and nonfinancial research support from DaVolterra and bioMérieux; financial research support from LimmaTech; consultancy fees from MSD and Sanofi-Pasteur (all payments to the University Medical Center Utrecht, not related to the current manuscript). There are no competing interests for any other author., (Copyright © 2024. Published by Elsevier Inc.)

Using a common protocol across seven countries in the European Union/European Economic Area, we estimated XBB.1.5 monovalent vaccine effectiveness (VE) against COVID-19 hospitalisation and death in booster-eligible ≥ 65-year-olds, during October-November 2023. We linked electronic records to construct retrospective cohorts and used Cox models to estimate adjusted hazard ratios and derive VE. VE for COVID-19 hospitalisation and death was, respectively, 67% (95%CI: 58-74) and 67% (95%CI: 42-81) in 65- to 79-year-olds and 66% (95%CI: 57-73) and 72% (95%CI: 51-85) in ≥ 80-year-olds. Results indicate that periodic vaccination of individuals ≥ 65 years has an ongoing benefit and support current vaccination strategies in the EU/EEA., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

We estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. VE was 41% (95% CI: 23-55) in 18-59-year-olds and 50% (95% CI: 44-56) in 60-85-year-olds. Sequencing data suggest lower protection against the BA.2.86 (including JN.1) variant from recent prior infection (OR = 2.8; 95% CI:1.2-6.5) and, not statistically significant, from XBB.1.5 vaccination (OR = 1.5; 95% CI:0.8-2.6).

To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021-July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65-79-year-olds.

We present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 XBB.1.5 vaccine against COVID-19 hospitalisation and admission to an intensive care unit (ICU) in previously vaccinated adults ≥ 60 years in the Netherlands. We compared vaccination status of 2,050 hospitalisations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalisation was 70.7% (95% CI: 66.6-74.3), VE against ICU admission was 73.3% (95% CI: 42.2-87.6).