Pandemic H1N1 Influenza Research Articles

How Do MNEs and Domestic Firms Respond Locally to a Global Demand Shock? Evidence from a Pandemic

Global shocks bring unanticipated changes in the business environment of foreign multinational enterprises (MNEs) and rival domestic firms. We examine whether there is a difference between how MNEs and domestic firms react in heterogeneous local or subnational markets to a global demand shock. Leveraging the 2009–2010 H1N1 influenza pandemic as a source of exogenous variation in global demand for influenza vaccines, we investigate the role of subnational heterogeneity in economic resources, industry infrastructure, and political alignment within an emerging economy on the behavior of incumbent MNEs and rival domestic firms. We find that following the pandemic, MNE market share in the influenza vaccine market relative to the noninfluenza vaccine markets declines more in regions with lower government health spending per capita and also, in regions unaligned with the federal government. Additional analyses suggest that these changes in market share are not caused by a reduction in MNE revenues. Rather, they are caused by domestic firms that were already present in noninfluenza vaccine markets diversifying by entering the highly related influenza vaccine market. Finally, a granular examination of the differential responses reveals that such responses are not related to preshock differences in regional coverage of MNEs and domestic firms. This study contributes to the extant literature by suggesting that the direct costs or opportunity costs of new market and region entry are relatively greater for MNEs than for domestic firms, particularly in regions that have inadequate health infrastructure and are politically not aligned. This paper was accepted by Joshua Gans, business strategy. Funding: The authors acknowledge funding support from the National University of Singapore [Start-up Research Grant R-313-000-143-133]; the University of Minnesota [Summer Research Grant]; the Industrial Credit and Investment Corporation of India Bank Chair at Indian Institute of Management Ahmedabad; and the Campbell and Teller National Fellow Program at Hoover Institution, Stanford University. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4313 .

Prevalence, Genetics and Evolutionary Properties of Eurasian Avian-like H1N1 Swine Influenza Viruses in Liaoning.

Swine influenza virus (SIV) is an important zoonosis pathogen. The 2009 pandemic of H1N1 influenza A virus (2009/H1N1) highlighted the importance of the role of pigs as intermediate hosts. Liaoning province, located in northeastern China, has become one of the largest pig-farming areas since 2016. However, the epidemiology and evolutionary properties of SIVs in Liaoning are largely unknown. We performed systematic epidemiological and genetic dynamics surveillance of SIVs in Liaoning province during 2020. In total, 33,195 pig nasal swabs were collected, with an SIV detection rate of 2%. Our analysis revealed that multiple subtypes of SIVs are co-circulating in the pig population in Liaoning, including H1N1, H1N2 and H3N2 SIVs. Furthermore, 24 H1N1 SIVs were confirmed to belong to the EA H1N1 lineage and divided into two genotypes. The two genotypes were both triple reassortant, and the predominant one with polymerase, nucleoprotein (NP), and matrix protein (M) genes originating from 2009/H1N1; hemagglutinin (HA) and neuraminidase (NA) genes originating from EA H1N1; and the nonstructural protein (NS) gene originating from triple reassortant H1N2 (TR H1N2) was detected in Liaoning for the first time. According to our evolutionary analysis, the EA H1N1 virus in Liaoning will undergo further genome variation.

Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity.

Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.

Factors Associated with Health Inequalities in Infectious Disease Pandemics Predating COVID-19 in the United States: A Systematic Review

ObjectivePrevious pandemics may offer evidence on mediating factors that contributed to disparities in infection and poor outcomes, which could inform the effort to mitigate potential unequal outcomes during the current COVID-19 pandemic. This systematic review sought to examine those factors.MethodsWe searched MEDLINE, PsycINFO, and Cochrane to May 2020. We included studies examining health disparities in adult U.S. populations during infectious disease epidemics or pandemics. Two investigators screened abstracts and full text. We assessed study quality using the Newcastle/Ottawa Scale or the Critical Appraisal Skills Programme Checklist for Qualitative Studies.ResultsSixteen articles were included, of which 14 focused on health disparities during the 2009 H1N1 influenza pandemic. Studies showed that disparities during the H1N1 pandemic were more related to differential exposure to the virus than to susceptibility or access to care. Overall, pandemic-related disparities emanate primarily from inequalities in social conditions that place racial and ethnic minorities and low socioeconomic status populations at greater risk of exposure and infection, rather than individual-level factors such as health behaviors and comorbidities.ConclusionsPolicy- and systems-level interventions should acknowledge and address these social determinants of heightened risk, and future research should evaluate the effects of such interventions to avoid further exacerbation of health inequities during the current and future pandemics.

Transcriptome Differences in Normal Human Bronchial Epithelial Cells in Response to Influenza A pdmH1N1 or H7N9 Virus Infection.

Avian influenza A (H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. The emergence of H7N9 virus infections is a serious public health threat. To identify virus–host interaction differences between the highly virulent H7N9 and pandemic influenza H1N1 (pdmH1N1), RNA sequencing was performed of normal human bronchial epithelial (NHBE) cells infected with either virus. The transcriptomic analysis of host cellular responses to viral infection enables the identification of potential cellular factors related to infection. Significantly different gene expression patterns were found between pdmH1N1- and H7N9-infected NHBE cells. In addition, the H7N9 virus infection induced strong immune responses, while cellular repair mechanisms were inhibited. The differential expression of specific factors observed between avian H7N9 and pdmH1N1 influenza virus strains can account for variations in disease pathogenicity. These findings provide a framework for future studies examining the molecular mechanisms underlying the pathogenicity of avian H7N9 virus.

Exercise after influenza or COVID-19 vaccination increases serum antibody without an increase in side effects

Vaccination is an effective public health measure, yet vaccine efficacy varies across different populations. Adjuvants improve vaccine efficacy but often increase reactogenicity. An unconventional behavioral “adjuvant” is physical exercise at the time of vaccination. Here, in separate experiments, we examined the effect of 90-minute light- to moderate-intensity cycle ergometer or outdoor walk/jog aerobic exercise performed once after immunization on serum antibody response to three different vaccines (2009 pandemic influenza H1N1, seasonal influenza, and COVID-19). Exercise took place after influenza vaccination or after the first dose of Pfizer-BioNTech COVID-19 vaccine. A mouse model of influenza A immunization was used to examine the effect of exercise on antibody response and the role of IFNα as a potential mechanism by treating mice with anti-IFNα antibody. The results show that 90 min of exercise consistently increased serum antibody to each vaccine four weeks post-immunization, and IFNα may partially contribute to the exercise-related benefit. Exercise did not increase side effects after the COVID-19 vaccination. These findings suggest that adults who exercise regularly may increase antibody response to influenza or COVID-19 vaccine by performing a single session of light- to moderate-intensity exercise post-immunization.

The long road of pandemic vaccine development to rollout: A systematic review on the lessons learnt from the 2009 H1N1 influenza pandemic

BackgroundThe 2009 Influenza A(H1N1) pandemic prompted one of the largest public health responses in history. The continuous emergence of new and deadly pathogens has highlighted the need to reflect upon past experiences to improve pandemic preparedness. The aim of this study was to examine the development and rollout of 2009 influenza A(H1N1) pandemic vaccine and knowledge challenges for the effective implementation of vaccination programs for COVID-19 and future influenza pandemics.MethodsA systematic review was conducted searching EMBASE (inception to current date) and PUBMED (from January 2009 to current date) databases for relevant published studies about influenza A(H1N1) pandemic vaccines. A Google search was conducted to identify relevant documents from gray literature. Selected Studies were reviewed and summarized.ResultsA total of 22, comprising of 12 original studies and 10 relevant documents met the inclusion criteria. Fourteen papers reported an initial high demand that outweighed production capacity and caused vaccine shortages. Vaccine procurement and supply were skewed toward high-income countries. Low vaccination rates of about 5%-50% were reported in all studies mainly due to a low-risk perception of getting infected, safety concerns, and the fear of adverse effects.ConclusionsSafety concerns about the approved H1N1 vaccines resulted in many unsuccessful vaccination campaigns worldwide. Understanding the factors that influence people's decision to accept or refuse vaccination, effective risk communication strategies, adequate resources for vaccine deployment initiatives and building local capacities through shared knowledge and technology transfer may help to improve COVID-19 vaccine uptake and accelerate pandemic control.

Intersecting Pandemics of HIV and SARS-CoV-2: Commentary on the Special Issue.

Purpose of ReviewThis editorial introduces this special Global Health Section on the interface of the HIV/AIDS and COVID-19 pandemics.Recent FindingsAuthors of articles in this special issue take on a variety of topics that capture how the acute COVID-19 pandemic affected global efforts towards HIV control, and how co-infection, stigma, and social determinants of disease have affected populations on multiple continents.SummaryTwo historic pandemics -- HIV/AIDS and COVID-19 -- have affected the world in our lifetimes at a level reminiscent of the 1918-1919 H1N1 influenza pandemic. We have much to learn from both experiences to optimize pandemic disease control, prevention, and management.

Competitive Endogenous RNA Network Activates Host Immune Response in SARS-CoV-2-, panH1N1 (A/California/07/2009)-, and H7N9 (A/Shanghai/1/2013)-Infected Cells.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.

Purifying Selection Determines the Short-Term Time Dependency of Evolutionary Rates in SARS-CoV-2 and pH1N1 Influenza.

High-throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Crucially, there are an increasing number of molecular clock analyses using external evolutionary rate priors to infer evolutionary parameters. However, it is not clear which rate prior is appropriate for a given time window of observation due to the time-dependent nature of evolutionary rate estimates. Here, we characterize the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and data set sizes affect the accuracy of parameter estimation. We further use a generalized McDonald–Kreitman test to estimate the number of segregating nonneutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by ∼50% and ∼100%, respectively, over the course of 1 year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2–4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating nonneutral sites, demonstrating the role of purifying selection in generating the time dependency of evolutionary parameters during pandemics.

Using social contact data to improve the overall effect estimate of a cluster-randomized influenza vaccination program in Senegal.

This study estimates the overall effect of two influenza vaccination programs consecutively administered in a cluster-randomized trial in western Senegal over the course of two influenza seasons from 2009-2011. We apply cutting-edge methodology combining social contact data with infection data to reduce bias in estimation arising from contamination between clusters. Our time-varying estimates reveal a reduction in seasonal influenza from the intervention and a nonsignificant increase in H1N1 pandemic influenza. We estimate an additive change in overall cumulative incidence (which was 6.13% in the control arm) of -0.68 percentage points during Year 1 of the study (95% CI: -2.53, 1.18). When H1N1 pandemic infections were excluded from analysis, the estimated change was -1.45 percentage points and was significant (95% CI, -2.81, -0.08). Because cross-cluster contamination was low (0-3% of contacts for most villages), an estimator assuming no contamination was only slightly attenuated (-0.65 percentage points). These findings are encouraging for studies carefully designed to minimize spillover. Further work is needed to estimate contamination - and its effect on estimation - in a variety of settings.

Efficacy of disinfectants to inactivate H1N1 influenza A virus isolated from pigs

ABSTRACT: The aim of this study was to access the efficacy of four disinfectants to inactivate influenza A [H1N1] 0 hour and 72 hours after disinfectant dilution. A pandemic H1N1 influenza virus isolated from a pig with respiratory disease was used to obtain inoculums containing 6.4log10 EID50/mL; 5.4log10 EID50/mL; 4.4log10 EID50/mL and 3.4log10 EID50/mL. Suspension test was composed of 400μL of viral inoculum, 100μL of organic load and 500μL of each individually diluted disinfectant and incubated for ten minutes of contact time. After a neutralizing step, each mixture was filtered on a 0.22μm membrane and 0.2mL was inoculated in six 9-day-old embryo chicken egg through allantoic route. The allantoic fluid from eggs was harvest for RT-PCR and hemagglutination test. The experiment was repeated 72 hours after disinfectant dilution. On the first assessment with fresh disinfectant, influenza virus was inactivated by oxidizing compost disinfectant and phenolic disinfectant in all virus concentrations, the quaternary ammonium compound (QAC) and glutaraldehyde association inactivated the virus up to a concentration of 5.4log10 EID50/mL. QAC disinfectant did not eliminate virus viability. Seventy-two hours after disinfectants were diluted, oxidizing compost disinfectant and QAC and glutaraldehyde association disinfectant demonstrated the same result as the evaluation with fresh disinfectant solution. Phenolic disinfectant inactivated viral inoculum up to a concentration of 5.4log10 EID50/mL. QAC had no effect on inactivating 3.4log10 EID50/mL of influenza virus. In conclusion, three of the four disinfectants tested were effective to inactivate pandemic H1N1 influenza virus in the presence of organic load. Test result performed 72hours after disinfectant dilution suggest a decrease in the effectiveness of one disinfectant.

A Combination of Deworming and Prime-Boost Vaccination Regimen Restores Efficacy of Vaccination Against Influenza in Helminth-Infected Mice.

Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying Litomosoides sigmodontis infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, L. sigmodontis-infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable L. sigmodontis parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in L. sigmodontis-infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that L. sigmodontis-infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly L. sigmodontis-infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated L. sigmodontis-infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection.

Viral Evasion of Innate Immune Defense: The Case of Resistance of Pandemic H1N1 Influenza A Virus to Human Mannose-Binding Proteins.

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IAV in vitro and in vivo, and to inhibit pandemic H1N1 in vitro, failed to protect mice from pandemic H1N1 in vivo in the current study. We attempted a variety of maneuvers to improve the activity of the mutant NCRDs vs. the 2009 pandemic H1N1, including the formation of full-length SP-D molecules containing the mutant NCRD, cross-linking of NCRDs through the use of antibodies, combining SP-D or NCRDs with alpha-2-macroglobulin, and introducing an additional mutation to the double mutant NCRD. None of these substantially increased the antiviral activity for the pandemic H1N1. We also tested the activity of bacterial and algal mannose-binding lectins, cyanovirin, and griffithsin, against IAV. These had strong activity against seasonal IAV, which was largely retained against pandemic H1N1. We propose mechanisms to account for differences in activity of SP-D constructs against pandemic H3N2 and H1N1, and for differences in activity of cyanovirin vs. SP-D constructs.

Tennessee Academy of Science Executive Committee Meeting Minutes, May 2020

Tennessee Academy of Science Executive Committee Meeting Minutes, May 2020

Eurasian Avian-like M1 Plays More Important Role than M2 in Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.

Reassortant variant viruses generated between 2009 H1N1 pandemic influenza virus [A(H1N1)pdm09] and endemic swine influenza viruses posed a potential risk to humans. Surprisingly, genetic analysis showed that almost all of these variant viruses contained the M segment from A(H1N1)pdm09, which originated from Eurasian avian-like swine influenza viruses. Studies have shown that the A(H1N1)pdm09 M gene is critical for the transmissibility and pathogenicity of the variant viruses. However, the M gene encodes two proteins, M1 and M2, and which of those plays a more important role in virus pathogenicity remains unknown. In this study, the M1 and M2 genes of A(H1N1)pdm09 were replaced with those of endemic H3N2 swine influenza virus, respectively. The chimeric viruses were rescued and evaluated in vitro and in mice. Both M1 and M2 of H3N2 affected the virus replication in vitro. In mice, the introduction of H3N2 M1 attenuated the chimeric virus, where all the mice survived from the infection, compared with the wild type virus that caused 100 % mortality. However, the chimeric virus containing H3N2 M2 was still virulent to mice, and caused 16.6% mortality, as well as similar body weight loss to the wild type virus infected group. Compared with the wild type virus, the chimeric virus containing H3N2 M1 induced lower levels of inflammatory cytokines and higher levels of anti-inflammatory cytokines, whereas the chimeric virus containing H3N2 M2 induced substantial pro-inflammatory responses, but higher levels of anti-inflammatory cytokines. The study demonstrated that Eurasian avian-like M1 played a more important role than M2 in the pathogenicity of A(H1N1)pdm09 in mice.

Influence of the H1N1 influenza pandemic on the humoral immune response to seasonal flu vaccines.

In this study, we hypothesized that the humoral response to trivalent seasonal influenza virus vaccines was influenced by rapid antigenic switching of H1 HA. We tested archived sera and peripheral blood mononuclear cells (PBMC) collected at prior to vaccination at day 0, as well as days 30 and 90 after vaccination during the 2009/2010 and 2010/2011 influenza virus seasons. During the 2009/2010 season, vaccination successfully induced antibodies with hemagglutinin inhibition (HAI) activity against both H1N1 and H3N2 vaccine components. For the 2010/2011 season, the A/California/04/2009 (CA/09) H1N1 elicited seroconversion (HAI titer = 1:40) and novel memory B cell (Bmem) responses from most individuals. However, the H3N2 influenza virus component of the vaccine, A/Perth/16/2009 (Perth/09), back-boosted and elicited antibodies with HAI activity and Bmem response to historical H3N2 influenza virus strains. Following stratification of the pre-existing antibody with HAI against the CA/09 H1N1, there was a negative correlation with HAI seroconversion to other vaccine strains. Overall, strong immune responses against CA/09 H1N1 influenza virus negatively influenced the induction of novel humoral responses.

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures.

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies.MethodsHere, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients.ResultsHost transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient–patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza.ConclusionCollectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.

Genotypic Variants of Pandemic H1N1 Influenza A Viruses Isolated from Severe Acute Respiratory Infections in Ukraine during the 2015/16 Influenza Season.

Human type A influenza viruses A(H1N1)pdm09 have caused seasonal epidemics of influenza since the 2009–2010 pandemic. A(H1N1)pdm09 viruses had a leading role in the severe epidemic season of 2015/16 in the Northern Hemisphere and caused a high incidence of acute respiratory infection (ARI) in Ukraine. Serious complications of influenza-associated severe ARI (SARI) were observed in the very young and individuals at increased risk, and 391 fatal cases occurred in the 2015/16 epidemic season. We analyzed the genetic changes in the genomes of A(H1N1)pdm09 influenza viruses isolated from SARI cases in Ukraine during the 2015/16 season. The viral hemagglutinin (HA) fell in H1 group 6B.1 for all but four isolates, with known mutations affecting glycosylation, the Sa antigenic site (S162N in all 6B.1 isolates), or virulence (D222G/N in two isolates). Other mutations occurred in antigenic site Ca (A141P and S236P), and a subgroup of four strains were in group 6B.2, with potential alterations to antigenicity in A(H1N1)pdm09 viruses circulating in 2015/16 in Ukraine. A cluster of Ukrainian isolates exhibited novel D2E and N48S mutations in the RNA binding domain, and E125D in the effector domain, of immune evasion nonstructural protein 1 (NS1). The diverse spectrum of amino-acid substitutions in HA, NS1, and other viral proteins including nucleoprotein (NP) and the polymerase complex suggested the concurrent circulation of multiple lineages of A(H1N1)pdm09 influenza viruses in the human population in Ukraine, a country with low vaccination coverage, complicating public health measures against influenza.

PREDICTORS AND OUTCOMES OF BACTERIAL AND FUNGAL SUPERINFECTIONS IN CRITICALLY ILL PATIENTS WITH COVID-19

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Secondary infections are well-described complications in patients with viral pneumonia and are associated with increased mortality and morbidity (1). A recent meta-analysis reported that secondary infections in critically ill Coronavirus Disease 19 (COVID-19) patients in intensive care unit (ICU) are around 14% (2). Most of the studies are limited by false-positive cultures in non-sterile body fluids (2). Our study aims to assess the burden of secondary infections by focusing on the positive rate of sterile body fluid cultures in ICU patients, to examine associated risk factors and to assess their impact on outcome. METHODS: Retrospective analysis of all adult patients with COVID-related acute respiratory distress syndrome (ARDS) admitted to the ICUs of a quaternary care hospital between 03/01/2020 and 05/31/2020. Patients who had positive sterile body fluid (blood, peritoneal, pleural or cerebrospinal fluid) cultures for bacteria or fungi, were compared with those without positive cultures. RESULTS: Of the 210 patients admitted to our ICU with COVID-19 related ARDS, 55 patients (26%) had positive sterile body fluid cultures, of which 37 grew bacteria, 7 fungi and 11 both. Patients with positive cultures were similar in terms of baseline demographics, comorbidities and severity of illness at ICU admission to those patients without positive cultures. Peak inflammatory markers were significantly higher in the positive culture group. In the positive culture group, the rates of receipt of steroids (78% vs. 61%, p=0.02) and convalescent plasma (64% vs. 45%, p=0.03) were significantly higher. The prevalence of acute kidney injury (AKI) requiring dialysis was significantly greater in the positive culture group (55% vs. 28%, p<0.001). There was no difference in terms of mortality between the two groups. However, mechanical ventilation (MV) free days at day 28 were significantly lower in the positive culture group (Mean ± S.D: 2.7 ± 5.7 vs. 6 ± 9.9, p=0.004). CONCLUSIONS: Our study shows that the incidence of superinfections in COVID-19 patients admitted to ICUs is higher than previously reported. The higher incidence is comparable to the rate of superinfections in the H1N1 influenza pandemic of 2009 (2). However, the high rates of steroid and plasma administration in our positive culture group may also have contributed to the high incidence of secondary infections. Our results have also shown that these infections may prolong ventilatory support as well as increase the likelihood of developing AKI requiring dialysis. Therefore, intensivists need to be vigilant about not missing superinfections in patients with COVID-19 which can negatively impact patient outcomes. CLINICAL IMPLICATIONS: This study will help to identify the risk factors associated with higher incidence of secondary infections in patients with COVID-19, and will assist physicians to identify and treat them early in the course of disease. 1. I. Martin-Loeches, A. Sanchez-Corral, E. Diaz, R.M. Granada, et al., H1N1 SEMICYUC Working Group Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus. Chest, 139 (2011), pp. 555-562. 2. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):266-275. DISCLOSURES: No relevant relationships by ALEENA ARSHAD, source=Web Response No relevant relationships by Dipak Chandy, source=Web Response No relevant relationships by Oleg Epelbaum, source=Web Response No relevant relationships by Daniel Greenberg, source=Web Response No relevant relationships by Muhammad Rizwan, source=Web Response No relevant relationships by Hamid Yaqoob, source=Web Response