What will this flu season be like? My prediction is that it will not be severe. The flu spreads the same way that Covid-19 spreads and if we do the things that reduce the spread of one, it should reduce the spread of the other. We have seen tremendous interest in the flu vaccine this year. As much interest as we saw in the Swine flu of 2009. In the first three weeks of getting the flu vaccine, we’ve already given over 200 doses.
It’s more than an educated guess. Usually flu activity in the southern hemisphere where it starts before our flu season is a useful predictor of what we can expect. Here is an article from The Guardian. Following that is information on this year’s flu vaccines available from the Medical Letter.
Health systems across the southern hemisphere were bracing a few months ago for their annual surge in influenza cases, which alongside Covid-19 could have overwhelmed hospitals. They never came.
Many countries in the southern half of the globe have instead experienced either record low levels of flu or none at all, public health specialists in Australia, New Zealand and South America have said, sparing potentially tens of thousands of lives and offering a glimmer of hope as winter approaches in the northern hemisphere.
General practitioners in New Zealand have not detected a single influenza case since they started screening patients in June, health data shows; last year about 57% of the samples they collected were positive.
The last flu cases detected by major hospitals in Auckland, the country’s largest city, were in April. “It’s amazing. There’s just nothing there at all. No influenza,” said Michael Baker, professor of public health at the University of Otago in Wellington.
New Zealand’s Covid-19 rates are among the lowest in the world, but even notwithstanding the pandemic, people in the country have experienced their healthiest cold months on record. “Our excess winter mortality peak has largely disappeared,” Baker said.
A tracking system that monitors a cohort of at least 30,000 people for influenza-like symptoms shows as few as 0.3% of New Zealanders reported coughs or fevers some weeks during their winter, a tenfold decrease on some previous years.
The trend holds true across the Tasman Sea in Australia, where Covid-19 restrictions have also deeply dented rates of flu and other respiratory illnesses. The country recorded more than 131,000 influenza cases in the peak months of July and August last year, according to government data. Over the same period this year, there were 315.
“Cases have fallen off a cliff since March,” said Prof Ian Barr, deputy director of the World Health Organization’s collaborating centre for reference and research on influenza, in Melbourne.
Fewer than 40 Australians have died from influenza this year, compared to more than 950 last year, “and there haven’t been any deaths for the past three to four months”, Barr added.
Even across South America and in South Africa, where lockdowns have been patchy or harder to enforce, and Covid-19 has spread widely and killed tens of thousands of people, flu rates have been well below historical rates or nonexistent – despite increased testing for it in the Americas, according to the Pan American Health Organisation.
This apparent contradiction – Sars-CoV-2 growing exponentially while influenza virtually disappears – illustrates a key difference between the two viruses. The seasonal flu is not just less deadly, but significantly less virulent, Baker said.
Populations have higher immunity to seasonal influenza, whether acquired naturally or through vaccines, while travel bans instituted from March interrupted the normal migration of the virus from the northern hemisphere to the south.
As an unprecedented live experiment on a massive population, it could offer some good news for northern hemisphere countries heading into their own flu season, just as drier air and more time indoors are expected to drive up Covid-19 rates. Even relatively less stringent quarantines appear to be surprisingly potent at suppressing influenza and other common respiratory illnesses.
“You would still see a flu season, but I expect it would be much less intense,” Baker said. “Northern hemisphere countries that are actively suppressing Covid-19 to some degree should get a lot of protection [from influenza] by doing that.”
It could mean that more people are susceptible to flu strains in the years ahead, having not acquired any kind of immunity this year, Barr said, though he added the threat would significantly decrease if people kept washing their hands thoroughly and wore masks in crowded areas even after the pandemic subsides.
In a year that will be studied by public health specialists for decades, it also points to new ways of fighting the future influenza pandemics that some scientists regard as inevitable.
“[Before,] it was thought that when a new influenza pandemic virus arrives, all you can do is dampen it down, you can’t stop it,” he said. “We now know that if you had a pandemic flu virus of sufficient severity, you could take the elimination approach, or even the exclusion approach, as Taiwan has done with Covid-19.”
Annual vaccination against influenza A and B viruses is recommended for everyone ≥6 months old without a contraindication.1 Vaccination of all eligible persons can reduce the prevalence of influenza illness and symptoms that might be confused with those of COVID-19. Available vaccines and recommendations for specific patient populations for the 2020-2021 season are listed in Tables 2 and 3. Lower rates of influenza illness have been observed this season in the Southern Hemisphere, probably because of masking, social distancing, school closures, and travel restrictions.2
TIMING — In the US, vaccination against influenza should be offered by the end of October and should continue to be offered as long as influenza is circulating in the community. In most adults, serum antibody levels peak about two weeks after vaccination. Early vaccination (i.e., in July or August) may result in suboptimal immunity before the end of the influenza season, especially in older adults. Children who require 2 doses (see Table 3, footnote 2) should receive the first dose as early as possible so that the second dose can be given by the end of October. Vaccination should be postponed for persons with suspected or laboratory-confirmed COVID-19 infection, regardless of symptoms, until they are no longer acutely ill and no longer require isolation.
COMPOSITION — Influenza A viruses are the main cause of influenza-related morbidity and mortality, particularly in infants and older adults. Children are more likely than adults to become infected with influenza B.3
All seasonal influenza vaccines available in the US contain two influenza A virus antigens (see Table 1). Trivalent vaccines contain only one influenza B virus antigen; Fluad, an adjuvanted inactivated vaccine, is the only trivalent influenza vaccine available in the US this season. Quadrivalent vaccines contain influenza B virus antigens from both genetic lineages that have been circulating globally since the 1980s, increasing the likelihood that the vaccine will provide protection against currently circulating strains.4,5 The selected antigens may be altered during production of egg-based vaccines, possibly resulting in a less desirable match between the vaccine and circulating strains.
EFFECTIVENESS — Influenza vaccination reduces the incidence of laboratory-confirmed influenza and can reduce the risk of serious complications and death associated with influenza illness in children and adults.6-9
The effectiveness of the seasonal influenza vaccine in preventing laboratory-confirmed influenza illness depends on several factors, including the match between the vaccine and circulating strains and the immunologic response of the recipient. Vaccine effectiveness is greatest when the match is close, but even when it is suboptimal, vaccination can still substantially reduce the risk of influenza-related hospitalization and death.10-12
The interim adjusted overall effectiveness of the influenza vaccine in preventing laboratory-confirmed influenza infection during the 2019-2020 season was 45% (55% in children 6 months-17 years old). Effectiveness was 50% against influenza B viruses and 37% against influenza A(H1N1).13
In one observational cohort study, an increase in vaccination rates among preschool and elementary school children was associated with lower rates of hospitalization for influenza in older children and adults ≥65 years old.14
LIVE-ATTENUATED VACCINE — FluMist Quadrivalent, the intranasal live-attenuated influenza vaccine, is FDA-approved for use in healthy nonpregnant persons 2-49 years old (see Table 2, footnote 18 for contraindications). The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend the live-attenuated vaccine as an option this season.1,15 It was not a recommended option during the 2016-2017 and 2017-2018 seasons because of concerns about its efficacy against influenza A(H1N1)pdm09-like viruses.16-18 It was a recommended option for the 2018-2019 and 2019-2020 seasons based on changes in the A(H1N1)pdm09-like strain.
OLDER ADULTS — Older adults may have weaker immunogenic responses to influenza vaccination than younger adults, and their antibody levels may decline more rapidly, decreasing vaccine effectiveness.19,20 Recombinant, high-dose, and adjuvanted vaccines can improve antibody responses in older patients, but whether they reduce the risk of hospitalization and death remains to be established in randomized, controlled trials (see Table 4).21
Recombinant Vaccine – Flublok Quadrivalent, a recombinant vaccine produced without the use of influenza virus or chicken eggs, contains 3 times the amount of antigen included in standard-dose influenza vaccines It is FDA-approved for use in persons ≥18 years old. In adults 50-64 years old, a recombinant trivalent vaccine used before approval of Flublok Quadrivalent produced greater antibody responses to influenza A antigens than a nonadjuvanted standard-dose inactivated trivalent vaccine.22
In a randomized, double-blind trial during the A/H3N2-predominant 2014-2015 season, the recombinant quadrivalent vaccine was 30% more effective than a nonadjuvanted standard-dose inactivated quadrivalent vaccine in preventing laboratory-confirmed influenza illness in 8604 adults ≥50 years old (42% more effective in persons 50-64 years old and 17% more effective in those ≥65 years old).23
High-Dose Vaccine – Fluzone High-Dose, an inactivated quadrivalent vaccine (last season’s high-dose vaccine was trivalent) that contains 4 times the amount of antigen included in standard-dose influenza vaccines, is FDA-approved for use in persons ≥65 years old. No published efficacy trials of the high-dose quadrivalent vaccine are available, but it offers broader protection than last year’s high-dose trivalent vaccine because of the added B strain.24,25 In a randomized, double-blind trial in 31,989 adults ≥65 years old during two influenza seasons, the high-dose trivalent vaccine induced significantly greater antibody responses than a standard-dose inactivated trivalent vaccine, and was 24.2% more effective in preventing laboratory-confirmed influenza illness.26 In observational studies and one meta-analysis in adults ≥65 years old, the high-dose trivalent vaccine was associated with a reduced risk of respiratory-related and all-cause hospitalization and death compared to standard-dose trivalent vaccines.27-30 In a retrospective cohort study, use of the high-dose trivalent vaccine during the 2016-2017 and 2017-2018 influenza seasons was associated with fewer respiratory hospitalizations than use of the adjuvanted trivalent vaccine.31
Adjuvanted Vaccine – The adjuvanted inactivated influenza vaccines Fluad and Fluad Quadrivalent are FDA-approved for use in persons ≥65 years old.32 They contain MF59, an oil-in-water emulsion of squalene oil that increases the immune response by recruiting antigen-presenting cells to the injection site and promoting uptake of influenza virus antigens.
In a randomized trial in 7082 adults ≥65 years old, the adjuvanted trivalent vaccine elicited significantly greater antibody responses against all three influenza strains than a nonadjuvanted trivalent vaccine, but the prespecified criteria for superiority were not met.33 In observational studies, older adults who received the adjuvanted trivalent vaccine were less likely than those who received a nonadjuvanted standard-dose trivalent vaccine to develop symptomatic influenza illness or to be hospitalized for influenza or pneumonia.34,35 Randomized controlled trials demonstrating the efficacy of the adjuvanted vaccines in preventing laboratory-confirmed influenza in older adults are lacking.
PREGNANCY — The ACIP and the American College of Obstetricians and Gynecologists recommend that pregnant women be vaccinated against influenza without regard to the trimester of pregnancy,36,37 but they should not receive the live-attenuated vaccine. Vaccination protects pregnant women against influenza-associated illness, which can be especially severe during pregnancy, and protects their infants for up to the first 6 months after birth.38-40
Most studies have not found an association between influenza vaccination and adverse pregnancy outcomes, but data demonstrating the safety of vaccination during the first trimester are limited.
ALLERGY — A history of a severe allergic reaction to any component of the influenza vaccine is listed as a contraindication in the labeling of all influenza vaccines. In 28 studies that included 4315 patients with egg allergy (656 with a history of a severe allergic reaction), there were no reports of anaphylaxis after administration of egg-based inactivated influenza vaccines; some mild reactions did occur.41 The ACIP, the American Academy of Allergy, Asthma and Immunology, and the American College of Allergy, Asthma and Immunology state that any age-appropriate influenza vaccine can be administered to persons who report a history of hives related to egg exposure. Persons with more severe egg allergy can also receive any age-appropriate influenza vaccine, but those who receive egg-based vaccines should be vaccinated in a healthcare setting with supervision by a healthcare provider experienced in recognizing and managing severe allergic reactions. The recombinant vaccine (Flublok Quadrivalent) and the cell culture-based inactivated vaccine (Flucelvax Quadrivalent) are not prepared by propagation of virus in embryonated eggs.
IMMUNOCOMPROMISED PERSONS — The live-attenuated influenza vaccine should not be used in immunocompromised persons. Inactivated and recombinant vaccines are generally considered safe for use in such persons, but the immune response may be reduced. Separation in time of influenza vaccination from an immunocompromising intervention might be considered.
In solid-organ transplant recipients ≥18 years old, the high-dose vaccine induced significantly greater antibody and cellular responses than standard-dose vaccines.42,43 In a randomized trial in 279 patients with rheumatoid arthritis treated with various immunosuppressive drugs, immune responses to the influenza vaccine were higher in patients given a high-dose vaccine than in those given a standard-dose vaccine.44
ADVERSE EFFECTS — Influenza vaccination has been associated with Guillain-Barré syndrome, but the absolute risk is very low (about 1-2 additional cases per million persons vaccinated). Influenza infection itself has been associated with the syndrome (about 17 cases per million influenza infection encounters).45,46
Except for soreness at the injection site, adverse reactions to inactivated influenza vaccines are uncommon. In clinical trials, Fluzone High-Dose (trivalent formulation) caused more injection-site reactions than standard-dose influenza vaccines. Pain and tenderness at the injection site occurred more frequently with Fluad (trivalent) than with a nonadjuvanted vaccine. Delivery of Afluria by needle-free jet injector has resulted in more mild to moderate local reactions than delivery by standard needle and syringe.
The most common adverse reactions associated with the live-attenuated vaccine are runny nose, nasal congestion, fever, and sore throat. The vaccine can increase the risk of wheezing, especially in children <5 years old with recurrent wheezing and in persons of any age with asthma. Persons who receive the live-attenuated vaccine may shed the vaccine-strain virus for a few days after vaccination, but person-to-person transmission has been rare, and serious illness resulting from transmission has not been reported. Nevertheless, persons who care for severely immunocompromised patients in protected environments should not receive the live-attenuated vaccine or should avoid contact with such patients for 7 days after receiving it.
USE WITH OTHER VACCINES — Inactivated and recombinant influenza vaccines can be administered concomitantly or sequentially with live or other inactivated vaccines. The live-attenuated influenza vaccine can be given simultaneously with inactivated or other live vaccines. Other live vaccines not administered simultaneously should be given at least 4 weeks later. Use of a nonadjuvanted influenza vaccine could be considered in persons receiving an adjuvanted vaccine (e.g., Shingrix, Heplisav-B); coadministration of Shingrix and a nonadjuvanted inactivated quadrivalent vaccine has not been associated with decreased immunogenicity to either vaccine.47
USE WITH INFLUENZA ANTIVIRALS — Use of oseltamivir or zanamivir within 48 hours before, peramivir within 5 days before, or baloxavir marboxil within 17 days before or <2 weeks after administration of the intranasal live-attenuated influenza vaccine could inhibit replication of the vaccine virus, reducing the vaccine’s efficacy.
CONCLUSION — Vaccination against seasonal influenza is recommended for all persons ≥6 months old, including pregnant women. Quadrivalent vaccines offer broader coverage against influenza B viruses. The intranasal live-attenuated vaccine is a recommended option for the 2020-2021 season. Recombinant, high-dose, and adjuvanted vaccines elicit greater antibody responses than nonadjuvanted standard-dose vaccines in persons ≥65 years old, and randomized controlled trials have shown that the high-dose and recombinant vaccines are more effective for prevention of laboratory-confirmed influenza in older persons.
- LA Grohskopf et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices – United States, 2020-21 influenza season. MMWR Recomm Rep 2020; 69:1.
- World Health Organization. Influenza update – 375. Available at: https://bit.ly/3i8IAOB. Accessed September 10, 2020.
- W Schaffner et al. Seasonal influenza immunisation: strategies for older adults. Int J Clin Pract 2018; 72:e13249.
- R Ray et al. A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control. Hum Vaccin Immunother 2017; 13:1640.
- WEP Beyer et al. Rationale for two influenza B lineages in seasonal vaccines: a meta-regression study on immunogenicity and controlled field trials. Vaccine 2017; 35:4167.
- C Arriola et al. Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza. Clin Infect Dis 2017; 65:1289.
- B Flannery et al. Influenza vaccine effectiveness against pediatric deaths: 2010-2014. Pediatrics 2017; 139:e20164244.
- AP Campbell et al. Influenza vaccine effectiveness against laboratory-confirmed influenza in children hospitalized with respiratory illness in the United States, 2016-17 and 2017-18 seasons. Presented at ID Week, Washington, DC, October 2-6, 2019. Abstract 899. Available at: https://bit.ly/35bFoOL. Accessed September 10, 2020.
- S Garg et al. Influenza vaccine reduces risk of severe outcomes among adults hospitalized with influenza A(H1N1)pdm09, FluServ-NET, 2013-2018. Presented at ID Week, Washington, DC, October 2-6, 2019. Abstract 898. Available at: https://bit.ly/3lIEr6e. Accessed September 10, 2020.
- EA Belongia et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis 2016; 16:942.
- M Darvishian et al. Effectiveness of seasonal influenza vaccine in community-dwelling elderly people: a meta-analysis of test-negative design case-control studies. Lancet Infect Dis 2014; 14:1228.
- MA Rolfes et al. Effects of influenza vaccination in the United States during the 2017-2018 influenza season. Clin Infect Dis 2019; 69:1845.
- FS Dawood et al. Interim estimates of 2019-20 seasonal influenza vaccine effectiveness – United States, February 2020. MMWR Morb Mortal Wkly Rep 2020; 69:177.
- J Benjamin-Chung et al. Evaluation of a city-wide school-located influenza vaccination program in Oakland, California, with respect to vaccination coverage, school absences, and laboratory-confirmed influenza: a matched cohort study. Plos Medicine 2020; 17:e1003238.
- Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2020-2021. Pediatrics 2020 September 8 (epub).
- JR Chung et al. Live attenuated and inactivated influenza vaccine effectiveness. Pediatrics 2019; 143:e20182094.
- ML Jackson et al. Influenza vaccine effectiveness in the United States during the 2015-2016 season. N Engl J Med 2017; 377:534.
- SA Buchan et al. Effectiveness of live attenuated vs inactivated influenza vaccines in children during the 2012-2013 through 2015-2016 influenza seasons in Alberta, Canada: a Canadian Immunization Research Network (CIRN) study. JAMA Pediatr 2018; 172:e181514.
- B Young et al. Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis. Vaccine 2017; 35:212.
- JY Song et al. Long-term immunogenicity of influenza vaccine among the elderly: risk factors for poor immune response and persistence. Vaccine 2010; 28:3929.
- ML Anderson et al. The effect of influenza vaccination for the elderly on hospitalization and mortality: an observational study with a regression discontinuity design. Ann Intern Med 2020; 172:445.
- R Baxter et al. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine 2011; 29:2272.
- LM Dunkle et al. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med 2017; 376:2427.
- EB Chahine. High-dose inactivated influenza vaccine quadrivalent for older adults. Ann Pharmacother 2020 Jun 24 (epub).
- LJ Chang et al. Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: a phase 3 randomized clinical trial. Vaccine 2019; 37:5825.
- CA DiazGranados et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014; 371:635.
- S Gravenstein et al. Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: a cluster-randomised trial. Lancet Respir Med 2017; 5:738.
- DK Shay et al. Comparative effectiveness of high-dose versus standard-dose influenza vaccines among US Medicare beneficiaries in preventing postinfluenza deaths during 2012-2013 and 2013-2014. J Infect Dis 2017; 215:510.
- JKH Lee et al. Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis. Expert Rev Vaccines 2018; 17:435.
- Y Young-Xu et al. High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/2015. Vaccine 2020; 25:1900401.
- R van Aalst et al. Comparative effectiveness of high dose versus adjuvanted influenza vaccine: a retrospective cohort study. Vaccine 2020; 38:372.
- Fluad – an adjuvanted seasonal influenza vaccine for older adults. Med Lett Drugs Ther 2016; 58:8.
- SE Frey et al. Comparison of the safety and immunogenicity of an MF59-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine 2014; 32:5027.
- PG Van Buynder et al. The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine 2013; 31:6122.
- S Mannino et al. Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am J Epidemiol 2012; 176:527.
- CDC. Addressing concerns pregnant women might have about influenza vaccine safety. Available at: https://bit.ly/3jDkTyg. Accessed September 10, 2020.
- ACOG Committee Opinion No. 732: influenza vaccination during pregnancy. Obstet Gynecol 2018; 131:e109.
- MG Thompson et al. Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010-2011 and 2011-2012 influenza seasons. Clin Infect Dis 2014; 58:449.
- MG Thompson et al. Influenza vaccine effectiveness in preventing influenza-associated hospitalizations during pregnancy: a multi-country retrospective test negative design study, 2010-2016. Clin Infect Dis 2019; 68:1444.
- SG Sullivan et al. Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations. Ther Adv Vaccines Immunother 2019; 7:1.
- M Greenhawt et al. Administration of influenza vaccines to egg allergic recipients: a practice parameter update 2017. Ann Allergy Asthma Immunol 2018; 120:49.
- Y Natori et al. A double-blind, randomized trial of high-dose vs standard-dose influenza vaccine in adult solid-organ transplant recipients. Clin Infect Dis 2018; 66:1698.
- AG L’Huillier et al. Cell-mediated immune responses after influenza vaccination of solid organ transplant recipients: secondary outcomes analyses of a randomized controlled trial. J Infect Dis 2020; 221:53.
- I Colmegna et al. Efficacy of high-dose versus standard-dose influenza vaccine in seropositive rheumatoid arthritis patients. Arthritis Rheumatol 2018; 70 (suppl 10). Abstract 837.
- JC Kwong et al. Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study. Lancet Infect Dis 2013; 13:769.
- LL Polakowski et al. Chart-confirmed Guillain-Barré syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010. Am J Epidemiol 2013; 178:962.
- TF Schwarz et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine coadministered with seasonal influenza vaccine in adults aged 50 years or older. J Infect Dis 2017; 216:1352.