scholarly journals Mortality of the COVID-19 Outbreak in Sweden in Relation to Previous Severe Disease Outbreaks

2021 ◽  
Vol 9 ◽  
Author(s):  
Anders Ledberg
Keyword(s):  
Influenza Virus ◽  
Severe Disease ◽  
Disease Outbreaks ◽  
Total Mortality ◽  
Case Fatality ◽  
Rapid Onset ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Time Period ◽  
Different Strains

Influenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality. In this work, disease outbreaks in Sweden, in the time period of 1860–2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when death counts start to increase consistently for a period of at least 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods. In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, it is the worst outbreak in Sweden since the “Spanish flu” of 1918–1919.

scholarly journals Mortality of the COVID-19 outbreak in Sweden in relation to previous severe disease outbreaks

2020 ◽  
Author(s):  
Anders Ledberg
Keyword(s):  
Influenza Virus ◽  
Severe Disease ◽  
Disease Outbreaks ◽  
Total Mortality ◽  
Case Fatality ◽  
Rapid Onset ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Time Period ◽  
Different Strains

AbstractInfluenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality.In this work, disease outbreaks in Sweden, in the time period of 1860-2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when deaths counts starts to increase consistently for a period of 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods.In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, it is the worst outbreak in Sweden since the ’Spanish flu’ of 1918-1919.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

scholarly journals Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

2012 ◽  
Vol 87 (3) ◽  
pp. 1400-1410 ◽  
Author(s):  
Donald M. Carter ◽  
Chalise E. Bloom ◽  
Eduardo J. M. Nascimento ◽  
Ernesto T. A. Marques ◽  
Jodi K. Craigo ◽  
...  
Keyword(s):  
Influenza Virus ◽  
H1n1 Influenza ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
The Novel ◽  
Virus Infections ◽  
H1n1 Influenza Virus ◽  
Virus Shedding ◽  
2009 H1n1 ◽  
Novel H1n1 Influenza

ABSTRACTIndividuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses.

scholarly journals Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 133 ◽  
Author(s):  
Magen E. Francis ◽  
Mara McNeil ◽  
Nicholas J. Dawe ◽  
Mary K. Foley ◽  
Morgan L. King ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Time Course ◽  
Recovery Period ◽  
Haemagglutination Inhibition ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Immune Memory ◽  
Sublethal Dose ◽  
Virus Infections

Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines.

Association of Severe Influenza Virus Infections With CD226 (DNAM-1) Variants

2019 ◽  
Vol 220 (7) ◽  
pp. 1162-1165 ◽  
Author(s):  
Monika Redlberger-Fritz ◽  
Hannes Vietzen ◽  
Elisabeth Puchhammer-Stöckl
Keyword(s):  
Influenza Virus ◽  
Intensive Care ◽  
Cell Response ◽  
Nk Cell ◽  
Virus Disease ◽  
Cell Receptor ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Severe Influenza ◽  
Nk Cell Receptor

Abstract Natural killer (NK)-cell response against influenza viruses partly depends on expression of CD112, a ligand for NK-cell receptor CD226 (DNAM-1). We analyzed whether particular CD226 variants were associated with influenza disease severity. Comparison between 145 patients hospitalized with severe influenza at intensive care units (ICU) with 139 matched influenza-positive outpatients showed that presence of the rs763362 G allele (GG, AG) was associated with occurrence of severe influenza infections (P = .0076). Also, a higher frequency of rs727088 G and rs763361 T alleles was observed in the ICU group. Thus, CD226 variants may contribute to the severity of influenza virus disease.

scholarly journals Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 434 ◽  
Author(s):  
Christopher E. Lopez ◽  
Kevin L. Legge
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Virus Infections ◽  
Universal Vaccine

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection.

scholarly journals Pandemic Influenza Vaccines: What did We Learn from the 2009 Pandemic and are We Better Prepared Now?

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 211 ◽  
Author(s):  
Steven Rockman ◽  
Karen Laurie ◽  
Ian Barr
Keyword(s):  
Influenza Virus ◽  
Influenza Pandemic ◽  
Supply And Demand ◽  
Disease Outbreaks ◽  
H1n1 Influenza ◽  
Virus Infections ◽  
Extensive Disease ◽  
Mortality And Morbidity ◽  
International Agencies ◽  
Infectious Disease Outbreaks

In 2009, a novel A(H1N1) influenza virus emerged with rapid human-to-human spread and caused the first pandemic of the 21st century. Although this pandemic was considered mild compared to the previous pandemics of the 20th century, there was still extensive disease and death. This virus replaced the previous A(H1N1) and continues to circulate today as a seasonal virus. It is well established that vaccines are the most effective method to alleviate the mortality and morbidity associated with influenza virus infections, but the 2009 A(H1N1) influenza pandemic, like all significant infectious disease outbreaks, presented its own unique set of problems with vaccine supply and demand. This manuscript describes the issues that confronted governments, international agencies and industries in developing a well-matched vaccine in 2009, and identifies the key improvements and remaining challenges facing the world as the next influenza pandemic inevitably approaches.

scholarly journals Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8+ T-Cell Responses

2009 ◽  
Vol 84 (4) ◽  
pp. 1847-1855 ◽  
Author(s):  
Scott N. Mueller ◽  
William A. Langley ◽  
Elena Carnero ◽  
Adolfo García-Sastre ◽  
Rafi Ahmed
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
B Cell ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Influenza Viruses ◽  
Wild Type Virus ◽  
Virus Infections ◽  
Cell Responses ◽  
B Cell Responses

ABSTRACT The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8+ T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8+ T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.

Phylogeny of Spanish swine influenza viruses isolated from respiratory disease outbreaks and evolution of swine influenza virus within an endemically infected farm

2014 ◽  
Vol 170 (3-4) ◽  
pp. 266-277 ◽  
Author(s):  
Gerard E. Martín-Valls ◽  
Meritxell Simon-Grifé ◽  
Sander van Boheemen ◽  
Miranda de Graaf ◽  
Theo M. Bestebroer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Disease ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Disease Outbreaks ◽  
Influenza Viruses ◽  
Infected Farm

scholarly journals Activity of enisamium, an isonicotinic acid derivative, against influenza viruses in differentiated normal human bronchial epithelial cells

2018 ◽  
Vol 26 ◽  
pp. 204020661881141 ◽  
Author(s):  
David Boltz ◽  
Xinjian Peng ◽  
Miguel Muzzio ◽  
Pradyot Dash ◽  
Paul G Thomas ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Antiviral Activity ◽  
Bronchial Epithelial Cells ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Normal Human Bronchial Epithelial ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Normal Human

Aims New therapeutics for the control of influenza virus infections are needed to alleviate the burden caused by seasonal epidemics and occasional pandemics, and to overcome the potential risk of drug-resistance emergence. Enisamium iodide (Amizon®, Farmak) is currently approved for clinical use for the treatment of influenza in 11 countries which includes Ukraine, Russia, Belarus, Kazakhstan, and Uzbekistan. However, experimental evidence of the antiviral activity of enisamium has not been reported. Methods Antiviral activity of enisamium was assessed by virus yield reduction assays using differentiated normal human bronchial epithelial cells. Permeability of enisamium into differentiated normal human bronchial epithelial cells and its cytotoxicity were also assessed, and comparisons with other cell lines were made. Results Enisamium inhibited replication of multiple subtypes of influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1, seasonal H3N2, the zoonotic H5N1 and H7N9, neuraminidase inhibitor-resistant variant carrying the H275Y NA substitution (N1 numbering), and influenza B virus at doses 23- to 64-fold lower than cytotoxic concentrations. The permeability of enisamium in Madin–Darby canine kidney cells (where no antiviral activity was found) was less than 0.08%, while higher permeability was observed in differentiated normal human bronchial epithelial cells (1.9%). The kinetics of enisamium intracellular uptake in differentiated normal human bronchial epithelial cells was concentration dependent. In time-of-addition experiments in differentiated normal human bronchial epithelial cells, enisamium treatment within 4 h after A(H1N1) virus inoculation resulted in 100-fold or greater reductions in virus titers, suggesting that it affects an early stage of the virus life cycle. Conclusions Enisamium exhibits antiviral activity against influenza viruses in vitro, supporting the reported clinical efficacy against influenza virus infections.

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