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ABSTRACTIntroduction Influenza causes significant morbidity and mortality, but influenza vaccine uptake remains below most countries’ targets. Vaccine policy recommendations vary, as do procedures for reviewing and appraising the evidence.Areas Covered During a series of roundtable discussions, we reviewed procedures and methodologies used by health ministries in four European countries to inform vaccine recommendations. We review the type of evidence currently recommended by each health ministry and the range of approaches toward considering randomized controlled trials (RCTs) and real-world evidence (RWE) studies when setting influenza vaccine recommendations.Expert Opinion Influenza vaccine recommendations should be based on data from both RCTs and RWE studies of efficacy, effectiveness, and safety. Such data should be considered alongside health-economic, cost-effectiveness, and budgetary factors. Although RCT data are more robust and less prone to bias, well-designed RWE studies permit timely evaluation of vaccine benefits, effectiveness comparisons over multiple seasons in large populations, and detection of rare adverse events, under real-world conditions. Given the variability of vaccine effectiveness due to influenza virus mutations and increasing diversification of influenza vaccines, we argue that consideration of both RWE and RCT evidence is the best approach to more nuanced and timely updates of influenza vaccine recommendations.

Abstract Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity may indicate subsequent infection. In this observational study, individuals with prior infection (n = 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n = 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections.

Multiple formulations and technologies for vaccinating against SARS-CoV-2 exist but how the use of these in homologous or heterologous format impacts immunogenicity is far from clear. Here the authors compare a range of heterologous and homologous SARS-CoV-2 vaccination strategies and assess the induced humoral and cellular immune response.

Abstract Background Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019. Methods We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES). Results After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for almost the half of all infections and that they exhibited the highest degree of seasonality. Coinfections of viruses are frequent; the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection. Conclusions The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.

Introduction: Increased risk of thromboembolic events has been associated with SARS-CoV-2 infections and more recently, with COVID-19 vaccination. To date, however, there are no reports of an association between the COVID-19 vaccination and retinal artery occlusions. We report a case of a patient who developed central retinal artery occlusion (CRAO) 2 days following the administration of the AstraZeneca COVID-19 vaccine. Case description: A 76-year-old woman presented to our Department of Ophthalmology complaining of painless vision loss in her left eye 48 hours after she had received her first dose of the AstraZeneca COVID-19 vaccine. Her best-corrected visual acuity was only hand movement in the left eye. Left eye ophthalmologic examination showed the presence of arterial narrowing and a cherry red spot. Optical coherence tomography showed severe macular swelling of the inner retinal layers in the left eye Fluorescein angiography performed the following day confirmed the diagnosis. The cardiovascular examination including Holter ECG was unremarkable. Complete blood count was within normal limits, without thrombocytopenia. A subsequent cerebral CT and CT-angiography scans did not show any other acute vascular event. Doppler angiography of the carotid artery was performed and showed normal flow without clinically significant plaques, stenoses, occlusions or dissections. Conclusions: To our knowledge, this is the first case of an isolated CRAO following the administration of the AstraZeneca COVID-19 vaccine. Further studies are needed to evaluate this potential association and identify pathophysiologic relationships between COVID-19 vaccinations and CRAO.

Background: Liberal PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to contain the coronavirus disease 2019 (COVID-19) pandemic. Combined multi-sample testing in pools instead of single tests might enhance laboratory capacity and reduce costs, especially in low- and middle-income countries. Objective: The purpose of our study was to assess the value of a simple questionnaire to guide and further improve pooling strategies for SARS-CoV-2 laboratory testing. Methods: Pharyngeal swabs for SARS-CoV-2 testing were obtained from healthcare and police staff, hospital inpatients, and nursing home residents in the southwestern part of Germany. We designed a simple questionnaire, which included questions pertaining to a suggestive clinical symptomatology, recent travel history, and contact with confirmed cases to stratify an individual’s pre-test probability of having contracted COVID-19. The questionnaire was adapted repeatedly in face of the unfolding pandemic in response to the evolving epidemiology and observed clinical symptomatology. Based on the response patterns, samples were either tested individually or in multi-sample pools. We compared the pool positivity rate and the number of total PCR tests required to obtain individual results between this questionnaire-based pooling strategy and randomly assembled pools. Findings: Between March 11 and July 5, 2020, we processed 25,978 samples using random pooling (n = 6,012; 23.1%) or questionnaire-based pooling (n = 19,966; 76.9%). The overall prevalence of SARS-CoV-2 was 0.9% (n = 238). Pool positivity (14.6% vs. 1.2%) and individual SARS-CoV-2 prevalence (3.4% vs. 0.1%) were higher in the random pooling group than in the questionnaire group. The average number of PCR tests needed to obtain the individual result for one participant was 0.27 tests in the random pooling group, as compared to 0.09 in the questionnaire-based pooling group, leading to a laboratory capacity increase of 73% and 91%, respectively, as compared to single PCR testing. Conclusions: Strategies that combine pool testing with a questionnaire-based risk stratification can increase laboratory testing capacities for COVID-19 and might be important tools, particularly in resource-constrained settings.

Background: Influenza vaccines are the main tool to prevent morbidity and mortality of the disease; however, egg adaptations associated with the choice of the manufacturing process may reduce their effectiveness. This study aimed to estimate the impact of egg adaptations and antigenic drift on the effectiveness of trivalent (TIV) and quadrivalent (QIV) influenza vaccines. Methods: Nine experts in influenza virology were recruited into a Delphi-style exercise. In the first round, the experts were asked to answer questions on the impact of antigenic drift and egg adaptations on vaccine match (VM) and influenza vaccine effectiveness (IVE). In the second round, the experts were presented with the data from a systematic literature review on the same subject and aggregated experts’ responses to round one questions. The experts were asked to review and confirm or amend their responses before the final summary statistics were calculated. Results: The experts estimated that, across Europe, the egg adaptations reduce, on average, VM to circulating viruses by 7–21% and reduce IVE by 4–16%. According to the experts, antigenic drift results in a similar impact on VM (8–24%) and IVE (5–20%). The highest reduction in IVE was estimated for the influenza virus A(H3N2) subtype for the under 65 age group. When asked about the frequency of the phenomena, the experts indicated that, on average, between the 2014 and 19 seasons, egg adaptation and antigenic drift were significant enough to impact IVE that occurred in two and three out of five seasons, respectively. They also agreed that this pattern is likely to reoccur in future seasons. Conclusions: Expert estimates suggest there is a potential for 9% on average (weighted average of “All strains” over three age groups adjusted by population size) and up to a 16% increase in IVE (against A(H3N2), the