COVID Reference

The COVID Textbook

Top 10: September 21

Home | Daily Science: TOP 10 | TOP 10 BOOK (PDF)

By Christian Hoffmann &
Bernd S. Kamps

 

This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing the text to give it early visibility.

21 September

Vaccinate for seasonal influenza and (hopefully soon) for COVID-19

Several authors (Richmond 2020, Jaklevic 2020, Singer 2020, Rubin 2020, Maltezoua 2020) and public health agencies are recommending expanding seasonal flu vaccination in the context of the COVID-19 pandemic. This follows concerns about the potential “double epidemic” of COVID-19 and seasonal flu during the winter months (Balakrishnan 2020, Gostin 2020). There are indeed many similarities (but also a few important differences) between the two diseases (Solomon 2020, Zayet 2020, Faury 2020) which may complicate the differential diagnosis for symptomatic patients, e.g. similar transmission routes, similar symptoms for mild cases (except for signs of neurological involvement like anosmia), similar high-risk groups for severe complications and mortality. A “double epidemic” could overburden both primary care services and hospitals, require a major increase in diagnostic capacities, lead to unnecessary isolation and quarantine of influenza cases and even increase stigma and discrimination of anyone presenting with symptoms of a respiratory infection (Rubin 2020). The possibility of COVID-19 and flu co-infection should also not be ruled out (Kim 2020). Combined SARS-CoV-2 and flu diagnostic tests, as recently approved by the FDA and being evaluated in some countries in Europe, could be useful in quickly identifying the pathogen(s) involved from a single sample.

Increasing coverage of seasonal influenza vaccination among high-risk groups is a good public health measure on its own, as influenza is estimated to cause close to 10 million hospitalizations and between 294,000 and 518,000 deaths every year (Paget 2019, CDC-US). It is also an essential measure with COVID-19 to avoid a potential breakdown of health care systems and the related increase in mortality and morbidity. Unfortunately, the normal uptake of flu vaccination in high-risk groups (> 65 years of age) has been largely insufficient, averaging around 50% in OECD countries. Along with efforts to increase coverage in the recommended risk groups, additional measures being suggested include reducing the recommended age for vaccination from 65 to 60 years, universal vaccination of children aged 6 months to 17 years, mandatory vaccination for all health-care workers, including all workers and visitors of long-term care facilities (Balakrishnan 2020, Gostin 2020, CDC).

However, widespread implementation of these additional measures will not be simple. The usual misguided concerns about the safety of vaccines and more recent social media fake news reports about the possibility of flu vaccine causing COVID-19 will need to be addressed. Possible reduced healthcare seeking behaviors due to fear of SARS-CoV-2 infection could also be a challenge. In addition, despite efforts by vaccine manufacturers and a major increase in flu vaccine production capacities in the last decade due in part to preparation for a possible flu pandemic (Rockman 2020), vaccine availability is unlikely to be sufficient to meet such an increase in demand, at least for the coming northern hemisphere flu season in 2020-21.

The definition of the composition of the seasonal flu vaccine is agreed by a WHO advisory group of flu experts based on an analysis of the data generated by the WHO Global Influenza Surveillance and Response System (GISRS). The group reviews the results of flu surveillance, laboratory and clinical studies and makes recommendations on the composition of the influenza vaccine based on the best match with available vaccine viruses. The advisory group meetings are held in February (for the northern hemisphere’s seasonal influenza vaccine) and in September (for the southern hemisphere’s vaccine) to allow sufficient time (7-9 months) for the production of the required doses of vaccine.  (Dunning 2020).

Influenza vaccine effectiveness can vary from season to season depending on the similarity or “match” between the flu vaccine and the flu viruses actually spreading in the community. During those years when the flu vaccine is not well matched to circulating influenza viruses, effectiveness can be as low as 20%, rising to 60% for the years when there is a good match between the flu vaccine and circulating viruses.  However, even less effective influenza vaccines have been shown to reduce considerably the burden of severe cases of influenza, admission to ICUs, and flu-related deaths (Thompson 2018, Ferdinands 2019).

Several recent studies have reported that indicators of influenza activity have been declining substantially in 2020 in both the northern (e.g. in Asia and the US) and the southern hemispheres, including in countries that implemented limited lockdown measures (Soo 2020, Olsen 2020, Itaya 2020). The decreased influenza activity was closely associated with the introduction of interventions to reduce SARS-CoV-2 transmission. (Choe 2020). This is really good news, as the evidence on the effectiveness of public health interventions in slowing the spread of a pandemic virus has been otherwise limited (Fong 2020, Xiao 2020, Ryu 2020). If these findings are confirmed during the coming winter season in the northern hemisphere, not only this would avoid the danger of a “dual epidemic” but it will also underscore that non-pharmaceutical interventions are essential in the response to future pandemics and could become standard interventions, in addition to vaccination, for reducing the health burden of seasonal influenza and other respiratory infections in high risk groups.

On the down side, the limited detection and isolation of flu viruses by the WHO surveillance system will reduce the availability of updated and robust data for the decision on the composition of the flu vaccine for 2021, raising the danger of a poor match between future influenza vaccines and circulating flu viruses.

 

Figure 1. The southern hemisphere skipped flu season in 2020 | Efforts to stop covid-19 have had at least one welcome side-effect. The Economist 2020, published 12 September. Full-text: https://www.economist.com/graphic-detail/2020/09/12/the-southern-hemisphere-skipped-flu-season-in-2020. Reproduced with permission.

 

Additional potential good news could come from research on the effects of influenza vaccination on the severity of SARS-CoV-2 infection. Among the few studies available, a recently pre-published paper (Fink 2020) reports on the analysis of data from 92,664 confirmed COVID-19 cases in Brazil showing that patients who received a trivalent influenza vaccine during the last campaign (March 2020) (how recent is recent?) experienced on average 8% lower odds of needing intensive care treatment (95% CIs [0.86, 0.99]), 18% lower odds of requiring invasive respiratory support (0.74, 0.88) and 17% lower odds of death (0.75, 0.89). Similar conclusions were reached in another pre-print paper modelling COVID-19 mortality data and recent influenza vaccination coverage in the US (Zanettini 2020).

More studies are clearly required before reaching conclusions, but the available evidence does suggest that increasing coverage of influenza vaccination would result in both direct and indirect benefits in terms of reduced morbidity and mortality from both COVID-19 and influenza.  These efforts could also have long-term benefits in expanding influenza vaccine production and uptake, both for seasonal influenza and in preparation for future flu pandemics.

Experience and lessons learned from these efforts will be of great value once a COVID-19 vaccine becomes available, since production, distribution and promotion of uptake for the new vaccine will face similar challenges and will need to prioritize the same vulnerable populations (Jaklevic 2020, Mendelson 2020).

26 References

  1. Solomon DA, Sherman AC, Kanjilal S. Influenza in the COVID-19 Era. 2020 Aug 14. PubMed: https://pubmed.gov/32797145. Full-text: https://doi.org/10.1001/jama.2020.14661
  2. Richmond H, Rees N, McHale S, Rak A, Anderson J. Seasonal influenza vaccination during a pandemic. Hum Vaccin Immunother. 2020 Jul 31:1-3. PubMed: https://pubmed.gov/32735161. Full-text: https://doi.org/10.1080/21645515.2020.1793713
  3. Jaklevic MC. Flu Vaccination Urged During COVID-19 Pandemic. JAMA. 2020 Sep 8;324(10):926-927. PubMed: https://pubmed.gov/32818238. Full-text: https://doi.org/10.1001/jama.2020.15444
  4. Singer COVID-19 and the next influenza season. Sci Adv. 2020 Jul 29;6(31):eabd0086. PubMed: https://pubmed.gov/32789184. Full-text: https://doi.org/10.1126/sciadv.abd0086
  5. Rubin R. What Happens When COVID-19 Collides With Flu Season? 2020 Sep 8;324(10):923-925. PubMed: https://pubmed.gov/32818229. Full-text: https://doi.org/10.1001/jama.2020.15260
  6. Maltezou HC, Theodoridou K, Poland G. Influenza immunization and COVID-19. 2020 Sep 3;38(39):6078-6079. PubMed: https://pubmed.gov/32773245. Full-text: https://doi.org/10.1016/j.vaccine.2020.07.058
  7. Balakrishnan In preparation for a COVID-19-influenza double epidemic Lancet Microbe 2020, Volume 1, ISSUE 5, e199, published: September 2020. Fulltext: https://doi.org/10.1016/S2666-5247(20)30130-0
  8. Gostin LO, Salmon DA. The Dual Epidemics of COVID-19 and Influenza: Vaccine Acceptance, Coverage, and Mandates. JAMA. 2020 Jul 28;324(4):335-336. PubMed: https://pubmed.gov/32525519. Full-text: https://doi.org/10.1001/jama.2020.10802
  9. Zayet S, Kadiane-Oussou NJ, Lepiller Q, et al. Clinical features of COVID-19 and influenza: a comparative study on Nord Franche-Comte cluster. Microbes Infect. 2020 Jun 16:S1286-4579(20)30094-0. PubMed: https://pubmed.gov/32561409. Full-text: https://doi.org/10.1016/j.micinf.2020.05.016
  10. Faury H, Courboulès C, Payen M, et al. Medical features of COVID-19 and influenza infection: A comparative study in Paris, France. J Infect. 2020 Aug 14:S0163-4453(20)30551-X. PubMed: https://pubmed.gov/32798533. Full-text: https://doi.org/10.1016/j.jinf.2020.08.017
  11. Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens. 2020 May 26;323(20):2085-2086. PubMed: https://pubmed.gov/32293646. Full-text: https://doi.org/10.1001/jama.2020.6266
  12. Paget J, Spreeuwenberg P, Charu V, et al. Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project. J Glob Health. 2019 Dec;9(2):020421. PubMed: https://pubmed.gov/31673337. Full-text: https://doi.org/10.7189/jogh.09.020421
  13. Rockman S, Laurie K, Barr I. Pandemic Influenza Vaccines: What did We Learn from the 2009 Pandemic and are We Better Prepared Now? Vaccines (Basel). 2020 May 7;8(2):211. PubMed: https://pubmed.gov/32392812. Full-text: https://doi.org/10.3390/vaccines8020211
  14. Thompson MG, Pierse N, Sue Huang Q et al. Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012-2015. Vaccine. 2018; 36(39):5916-5925. https://doi.org/10.1016/j.vaccine.2018.07.028
  15. Ferdinands JM, Gaglani M, Martin ET, et al. Prevention of Influenza Hospitalization Among Adults in the United States, 2015-2016: Results From the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). J Infect Dis. 2019 Sep 13;220(8):1265-1275. PubMed: https://pubmed.gov/30561689. Full-text: https://doi.org/10.1093/infdis/jiy723
  16. Dunning J, Thwaites RS, Openshaw PJM. Seasonal and pandemic influenza: 100 years of progress, still much to learn. Mucosal Immunol. 2020 Jul;13(4):566-573. PubMed: https://pubmed.gov/32317736. Full-text: https://doi.org/10.1038/s41385-020-0287-5
  17. Soo, R., Chiew, C. J., Ma, S., Pung, R., & Lee, V. (2020). Decreased Influenza Incidence under COVID-19 Control Measures, Singapore. Emerging Infectious Diseases, 26(8), 1933-1935. https://dx.doi.org/10.3201/eid2608.201229.
  18. Olsen SJ, Azziz-Baumgartner E, Budd AP, et al. Decreased Influenza Activity During the COVID-19 Pandemic – United States, Australia, Chile, and South Africa, 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 18;69(37):1305-1309. PubMed: https://pubmed.gov/32941415. Full-text: https://doi.org/10.15585/mmwr.mm6937a6
  19. Itaya T, Furuse Y, Jindai K. Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020. Int J Infect Dis. 2020 Aug;97:78-80. PubMed: https://pubmed.gov/32492532. Full-text: https://doi.org/10.1016/j.ijid.2020.05.088
  20. Choe YJ, Lee JK. The Impact of Social Distancing on the Transmission of Influenza Virus, South Korea, 2020. Osong Public Health Res Perspect. 2020 Jun;11(3):91-92. PubMed: https://pubmed.gov/32494566. Full-text: https://doi.org/10.24171/j.phrp.2020.11.3.07
  21. Fong MW, Gao H, Wong JY, et al. Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Social Distancing Measures. Emerg Infect Dis. 2020 May;26(5):976-984. PubMed: https://pubmed.gov/32027585. Full-text: https://doi.org/10.3201/eid2605.190995
  22. Xiao J, Shiu EYC, Gao H, et al. Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Personal Protective and Environmental Measures. Emerg Infect Dis. 2020 May;26(5):967-975. PubMed: https://pubmed.gov/32027586. Full-text: https://doi.org/10.3201/eid2605.190994
  23. Ryu S, Gao H, Wong JY, et al. Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-International Travel-Related Measures. Emerg Infect Dis. 2020 May;26(5):961-966. PubMed: https://pubmed.gov/32027587. Full-text: https://doi.org/10.3201/eid2605.190993
  24. Guenther Fink, Nina Orlova-Fink, Tobias Schindler, Sandra Grisi, Ana Paula Ferrer, Claudia Daubenberger, Alexandr Brentani Inactivated trivalent influenza vaccine is associated with lower mortality among Covid-19 patients in Brazil medRxiv 2020.06.29.20142505- Full-text: https://doi.org/10.1101/2020.06.29.20142505
  25. Zanettini C, Omar M, Dinalankara W, et al. Influenza Vaccination and COVID19 Mortality in the USA. 2020 Jun 26:2020.06.24.20129817. PubMed: https://pubmed.gov/32607525. Full-text: https://doi.org/10.1101/2020.06.24.20129817
  26. Mendelson M. Could enhanced influenza and pneumococcal vaccination programs help limit the potential damage from SARS-CoV-2 to fragile health systems of southern hemisphere countries this winter? Int J Infect Dis. 2020 May;94:32-33. PubMed: https://pubmed.gov/32194236. Full-text: https://doi.org/10.1016/j.ijid.2020.03.030