Background Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019–20 influenza vaccination and COVID-19. Methods We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March–August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019–20 influenza vaccination and clinical information documented. Using logistic regression we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with <15% of missing influenza vaccination. In secondary analyses, we included five countries, using multiple imputation with chained equations to account for missing data. Results We included 257 COVID-19 cases and 1631 controls in the main analysis (three countries). The overall aOR between influenza vaccination and COVID-19 was 0.93 (95% CI: 0.66–1.32). The aOR was 0.92 (95% CI: 0.58–1.46) and 0.92 (95%CI: 0.51–1.67) among those aged 20–59 and ≥60 years, respectively. In secondary analyses, we included 6457 cases and 69272 controls. The imputed aOR was 0.87 (95% CI: 0.79–0.95) among all ages and any delay between swab and symptom onset. Conclusions There was no evidence that COVID-19 cases were more likely to be vaccinated against influenza than controls. Influenza vaccination should be encouraged among target groups for vaccination. I-MOVE-COVID-19 will continue documenting influenza vaccination status in 2020-21, in order to learn about effects of recent influenza vaccination.
Background: Tens of thousands of Australians become ill with influenza annually, causing thousands of severe infections that require hospitalisation. However, only 40% of adults receive the annual influenza vaccine. We surveyed Australian adults to provide up-to-date data on the predictors and barriers of seasonal influenza vaccination. Methods: We administered an online survey to a nationally representative sample of Australian adults. We designed survey questions using the constructs of the health belief model. Using simple and multivariable Poisson regression, we identified attitudes and beliefs associated with influenza vaccination in 2019. Results: Among 1,444 respondents, 51.7% self-reported influenza vaccination in 2019. We estimated vaccine coverage to be 44% for adults under 45, 46% for adults aged 45 to 64, and 77% for adults aged 65 and over. The strongest individual predictors of self-reported vaccination were believing the vaccine is effective at preventing influenza (APR = 3.71; 95% CI = 2.87-4.80), followed by recalling their doctor recommending the vaccine (APR = 2.70; 95%CI = 2.31-3.16). Common perceived barriers that predicted self-reported vaccination included believing the vaccine could give you influenza (APR = 0.59; 95% CI = 0.52-0.67), believing the vaccine can make you ill afterwards (APR = 0.68; 95% CI = 0.62-0.74), and preferring to develop immunity “naturally” (APR = 0.38; 95% CI = 0.32-0.45). Conclusion: Although vaccine uptake in 2019 appears to be higher than previous years, there are perceived barriers which may limit uptake among Australians. Tailored interventions are needed to combat widespread influenza vaccine hesitancy, particularly among high risk grou
Background: Although the burden of influenza is well characterized, the burden of community-onset non-influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non-influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines. Methods: From October 2017 to September 2019, a retrospective study was performed in a pre-defined catchment area to estimate the population-based incidence of community-onset respiratory viruses associated with hospitalization. Included patients were >18 years old, resided in New York City, were hospitalized for >24 hours, and had a respiratory virus detected within 3 calendar-days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in-hospital mortality and compared among those with laboratory-confirmed influenza versus those with laboratory-confirmed non-influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus). Results: During the study period, 4,232 eligible patients were identified of whom 50.9% were >65 years of age. For each virus, the population-based incidence was highest for those >80 years of age. When compared to those with influenza viruses detected, those with non-influenza respiratory viruses detected (combined) had higher population-based incidence, significantly more ICU admissions, and higher in-house mortality. Conclusions: The burden of non-influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non-influenza respiratory viruses, particularly for older adults.
With the rapid increase of reported COVID-19 cases, German policymakers announced a 4-week “shutdown light” starting on Nov 2, 2020. Applying mathematical models, possible scenarios for the evolution of the outbreak in Germany are simulated. The results indicate that independent of the effectiveness of the current restrictive measures they might not be sufficient to mitigate the outbreak. Repeated shutdown periods or permanently applied measures over the winter could be successful alternatives.
Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections.
Background Reliable diagnostics are key to identifying influenza infections. Our objectives were to describe detection of influenza among severe acute respiratory infection (SARI) cases, to compare test results from the FTD-33 kit for influenza detection to the Centers for Disease Control (CDC) human influenza virus detection and characterization panel, and to assess seasonality of influenza in Burkina Faso. Methods: Nasopharyngeal and oropharyngeal specimens from SARI cases (hospitalized patients with fever, cough, and onset in the previous 10 days) were tested using the FTD-33 kit and the CDC rRT-PCR influenza assays. We assessed sensitivity and specificity of the FTD-33 kit for detecting Influenza A, Influenza B, and the influenza A(H1N1)pdm09 strain using the CDC human influenza rRT-PCR panel as the gold standard. Results: From December 2016 to February 2019, 1706 SARI cases were identified, 1,511 specimens were tested, and 211 were positive for influenza A (14.0%) and 100 for influenza B (6.6%) by either assay. Higher influenza circulation occurred between November and April with varying peaks of influenza A and B. Sensitivity of the FTD-33 assay was 91.9% for influenza A, 95.7% for influenza B, and 93.8% for A(H1N1)pdm09 subtype. Specificity was over 99% for all three tests. Conclusions: Our study indicates that Burkina Faso has one peak of influenza each year which is similar to the Northern Hemisphere and differs from other countries in West Africa. We found high concordance of influenza results between the two assays indicating FTD-33 can be used to reliably detect influenza among SARI cases.
Abstract. The Controlled Human Infection Model and specifically the Human Viral Challenge Model are not dissimilar to standard clinical trials while adding another layer of complexity and safety considerations. The models deliberately infect volunteers, with an infectious challenge agent (CA) to determine the effect of the infection and the potential benefits of the experimental interventions. The Human Viral Challenge Model studies can shorten the time to assess the efficacy of a new vaccine or treatment by combining this with the assessment of safety. The newly emerging SARS-COV-2 virus is highly contagious and the cause pandemic disease COVID-19. An urgent race in is on to develop a new vaccine against this virus in a timeframe never attempted before. The use of the Human Viral Challenge Model has been proposed to accelerate the development of the vaccine. In the early 2000’s the authors successfully developed a pathogenic Human Viral Challenge Model for another virus for which there was no effective treatment and established it to evaluate potential therapies and vaccines against Respiratory Syncytial Virus. The authors feel that the experience gained in the development of that model can help with the development of a COVID-19 HVCM and describe it here. Word count: 197
Background: Baloxavir marboxil (BXM) is an approved drug that selectively targets cap-dependent endonuclease on PA subunit in the RNA polymerase complex of influenza A and B viruses. Amino acid substitutions at position 38 in the PA subunit were identified as a major pathway for reduced susceptibility to baloxavir acid (BXA), the active form of BXM. Additionally, substitutions found at positions E23, A37, and E199 in the PA subunit impact BXA susceptibility by less than 10-fold. Methods: We comprehensively evaluated the impact of novel amino acid substitutions identified in PA, PB1 and PB2 subunits in BXM clinical trials and influenza sequence databases by means of drug susceptibility and replicative capacity. Results: PA/I38N in A(H1N1) and PA/I38R in A(H3N2) were newly identified as treatment-emergent substitutions in the CAPSTONE-2 study. The I38N substitution conferred reduced susceptibility by 24-fold, whereas replicative capacity of the I38N-substituted virus was impaired compared to the wild-type. The I38R-substituted virus was not viable in cell culture. All other mutations assessed in this extensive study did not significantly affect BXA susceptibility (< 2.4-fold change). Conclusion: These results provide additional information on the impact of amino acid substitutions in the trimeric viral polymerase complex to BXA susceptibility and will further support influenza surveillance.
Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short communication assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts and further evaluation is needed. Reliable SARS CoV2-specific POCTs – when they become available – are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.
Background: It has long been known that nasal inoculation with influenza A virus produces asymptomatic to febrile infections. Uncertainty persists about whether these infections are sufficiently similar to natural infections for studying human-to-human transmission. Methods: We compared influenza A viral aerosol shedding from volunteers nasally inoculated with A/Wisconsin/2005 (H3N2) and college community adults naturally infected with influenza A/H3N2 (2012-2013), selected for influenza-like illness with objectively measured fever or a positive Quidel QuickVue A&B test. Propensity scores were used to control for differences in symptom presentation observed between experimentally and naturally infected groups. Results: Eleven (28%) experimental and 71 (86%) natural cases shed into fine particle aerosols (p<0.001). The geometric mean (geometric standard deviation) for viral positive fine aerosol samples from experimental and natural cases was 5.1E+3 (4.72) and 3.9E+4 (15.12) RNA copies/half hour, respectively. The 95th percentile shedding rate was 2.4 log10 greater for naturally infected cases (1.4E+07 versus 7.4E+04). Certain influenza-like illness related symptoms were associated with viral aerosol shedding. The almost complete lack of symptom severity distributional overlap between groups did not support propensity score adjusted shedding comparisons. Conclusions: Due to selection bias, the natural and experimental infections had limited symptom severity distributional overlap precluding valid, propensity score adjusted comparison. Relative to the symptomatic naturally infected cases, where high aerosol shedders were found, experimental cases did not produce high aerosol shedders. Studying the frequency of aerosol shedding at the highest observed levels in natural infections without selection on symptoms or fever would support helpful comparisons.