Even in the shadow of COVID-19, influenza poses pandemic threat

The ability of any infectious agent to maintain constant transmission allows it to be a permanent threat to public health. Few pathogens have been more successful in terms of the potential for continuous transmission than the influenza virus.

The influenza virus causes an acute infection of the respiratory tract. The duration of virus replication in a human host is generally limited to 7 to 21 days after symptom onset, with peak viral shedding occurring within the first 10 days.1 The typical seasonal influenza virus has a basic reproductive index (R0) typically ranging from 1.0 to 1.5. Pandemic influenza such as the 1918 and 2009 strains may have had a slightly higher reproduction rate of 1.3 to 2.7.2-4.

The world has been given a crash course on respiratory infectious diseases in the past 20 months. The emergence of SARS-CoV-25 coincided with the annual influenza season in the northern hemisphere (Figure 1). The 2 viruses share similarities in that they are transmitted primarily by inhalation, are capable of infecting a wide range of hosts, and may have similar clinical manifestations, including fever, myalgia, and respiratory distress.6

Globally, influenza is responsible for tens of millions of infections and hundreds of thousands of deaths each year, particularly in young, elderly and immunocompromised / immunocompromised populations. The influenza virus is a common cause of pneumonia in people with AIDS and one of the leading causes of AIDS-related deaths each year.7 Multiple pandemic events involving influenza have occurred since the turn of the 20th century, most notably the H1N1 pandemics of 1918 and 2009. The infamous 1918 influenza pandemic is estimated to have infected over 33% of people worldwide and caused more deaths than the two world wars combined. The origins of the 1918 influenza strain remain obscure to this day.8

Two characteristics of influenza viruses make them a particularly formidable and constant threat to public health: their wide host range and their ability to reassort their genomes. Influenza viruses are encoded by segmented RNA genomes that are packaged in the viral particle and transmitted. In the case of an influenza superinfection (an infection in addition to an existing influenza infection), the virus may group together segments of several infectious influenza viruses. Most of the time, this results in a non-functioning descendant virus. However, this sometimes results in a new influenza virus by reassortment. (Figure 2). The 2009 H1N1 virus was a prime example of the emergence of a new influenza virus via this mechanism, being a mixture of avian, human and swine influenza viruses that were further reassorted in pigs.9 The resulting H1N1, then called “swine flu”, infected around 20% of the world’s population. Although the clinical results were much better than those of the 1918 influenza strain, the 2009 pandemic demonstrated the ability of influenza viruses to have pandemic potential largely due to their wide host range and their ability to replenish host species.

Outlook for influenza 2021-2022

Almost certainly, we can expect the next flu season to coincide with the ongoing COVID-19 pandemic. Routine annual influenza vaccination is recommended for all people 6 months of age or older who have no contraindications, and vaccination will be essential this season to help reduce similar symptoms between influenza and COVID- 19. Likewise, influenza and SARS-CoV-2 vaccinations will have a synergistic reduction in healthcare-related stress and help alleviate bed shortages and staffing issues during the pandemic. This is all the more important as other respiratory viruses, such as respiratory syncytial virus, similarly increase and put additional strain on the healthcare system.

The Advisory Committee on Immunization Practices (ACIP) provided updates on the use of seasonal influenza vaccines in the United States during the 2021-2022 influenza season.ten The committee made 6 main updates to its report:

  • All seasonal influenza vaccines available in the United States for the 2021-2022 season are expected to be quadrivalent;
  • The 2021-2022 US influenza vaccine lineup includes updates to the components of influenza A (H1N1) pdm09 and influenza A (H3N2). Influenza vaccines licensed in the United States will contain hemagglutinin derived from virus type A / Victoria / 2570/2019 (H1N1) pdm09 or virus type A / Wisconsin / 588/2019 (H1N1) pdm09; influenza A / Cambodia / e0826360 / 2020 (H3N2) virus; an influenza B / Washington / 02/2019 virus (Victoria line); and a virus similar to influenza B / Phuket / 3073/2013 (Yamagata lineage);
  • The approved age indication for the cell culture-based inactivated influenza vaccine has been extended from 4 years and over to 2 years and over;
  • The discussion of administering influenza vaccines with other vaccines includes considerations for co-administering influenza vaccines and COVID-19 vaccines;
  • Guidelines for timing of influenza vaccination now indicate that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester; and
  • Contraindications and precautions for the use of cell culture-based inactivated influenza vaccines (ccIIV4) and recombinant influenza vaccine (RIV4) have been changed, especially for people with a history of severe allergic reactions (e.g. ., anaphylaxis) to an influenza vaccine. A history of severe allergic reaction to a previous dose of any influenza IIV, ccIIV, or live attenuated egg vaccine, regardless of its valence, is a precaution for the use of RIV4. The use of ccIIV4 and RIV4 in such cases should be done in an inpatient or outpatient setting under the supervision of a provider capable of recognizing and managing a severe allergic reaction; providers may also consider seeing an allergist to help them identify which component of the vaccine is causing the reaction.

Beyond the 2021-2022 influenza season

Recent human overflows of highly pathogenic strains of avian influenza virus (HPAI) have raised international concern due to high case fatality rates and the source of a constant animal reservoir. Although these events resulted in little or no subsequent human-to-human transfer, the continued transmission of HPAI in non-human hosts allows the virus to accumulate a number of intrinsic recombinant mutations and replication errors. This “dead-end transmission” after the spillover is reminiscent of individuals who showed antibodies against the SARS-related coronaviruses harbored by bats in 2015 before the emergence of SARS-CoV-2. Although human-to-human transmission of SARS-related coronaviruses after the overflow has not been observed, continued transmission of the virus in their bat host reservoir allows SARS-related coronaviruses to persist in the wild.11 HPAI and other flu variants work in a similar way. Previous research concluded that very little change was needed for mammalian adaptation of HPAI to airborne transmission.12.13 Therefore, the continued harboring of influenza viruses in non-human reservoirs poses a major risk for the emergence of not only seasonal influenza, but also highly pathogenic strains with pandemic potential.

In short, influenza viruses, presenting a wide host range, constitute a constant threat to public health. They spread continuously in several hosts and their replication cycle allows the reassortment of gene segments during superinfection. Combined with the inherent replication error rates, the generation of new variants and strains of the influenza virus can occur at a high frequency. Influenza pandemics are not uncommon and the close interaction between humans and wild hosts allows spillover events to occur. Most of these events do not result in direct transmission, but it is only a matter of time before the next influenza pandemic. Until then, seasonal flu, which kills tens of thousands of people every year, will continue to be an annual threat to public health.

Ryan P. McNamara, PhD, is a virologist and associate researcher at the University of North Carolina at Chapel Hill School of Medicine.

Rodney E. Rohde, PhD, SV / SM / MB (ASCP) CM, FACSc is Professor and Chair of the Clinical Laboratory Sciences (CLS) Program at the College of Health Professions (CHP) at Texas State University. . He was Associate Dean of Research for nine years at CHP and is now Associate Director of the Center for Translational Health Research. He is also an Associate Associate Professor of Biology at Austin Community College. Rohde is Global Fellow and Honorary Professor of International Studies. He is an ASCP certified specialist in virology, microbiology and molecular biology.

This article originally appeared in Contagion®.

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