July-August 2019

Even though we have just gotten over a heat wave and still expect more warm weather to come, it’s that time of the year where flu shots become available, and getting one “sooner than later” is often recommended (especially for our older population). I’d like to summarize some recent scientific/medical papers that have presented new data about Influenza A & B, as well as flu shot efficacy and timing.

The first series of articles deals with shedding of Influenza viruses by infected people:

• There was an article in the  Journal of infectious Disease, published online this August (doi: 10.1093/infdis/jiy370), titled “Obesity Increases the Duration of Influenza A Virus Shedding in Adults”. It is already known that obesity increases the risk of complications from the flu. It also appears that symptomatic obese adults shed Influenza A virus 42% longer than non-obese people do. Even in obese people with minimal symptoms, the duration of viral shedding is increased by 104%. As an aside, children younger than 4 years old shed both Influenza A & B viruses 40% longer than do adults.
• In a Proceedings of the National Academy Sciences USA article (https://doi.org/10.1073/pnas.1716561115) it was reported that obese college-aged students shed much more virus in their exhaled breath; being positively associated with increasing body mass index, and that sneezing or coughing were not necessary for infectious aerosol generation.
• In a paper presented at the European Congress of Clinical Microbiology and infectious Disease this past spring in the Netherlands, Dr. Stefan Kuster found that upwards of 12.5% of healthcare workers and 10.5% of patients testing positive for influenza were symptom-free - i.e., they  shed infectious virus and showed no symptoms.
• In another article in the Journal of Infectious Disease, published this May (doi.org/10.1093/infdis/jiz221), the authors reported that some patients can be infected with two and sometimes three different Influenza A viruses, or with both type A and Type B Influenza viruses - at the same time. This situation, it appears, can significantly increase the risk of heart complications and death.

This year’s flu season, according to the CDC, was marked by an overall limited protection from the flu shot. This was due to the fact that the H3N2 strain (a Type A Influenza virus) was the dominant one. It accounted for 58% of all Influenza virus subtypes, and there was not a match with the flu shot given. This resulted in an overall efficacy against the A subtypes of only 30%. Although the match for type B influenza viruses was good, they only accounted for 31% of the circulating virus subtypes. Consequently, the overall efficacy for the vaccine this past season was only 38% (adjusted for all ages). Nonetheless, the CDC stated the vaccine likely prevented upwards of 90,000 hospitalizations due to the flu (CIDRAP News, July 02,2019, http://www.cidrap.umn.edu/news-perspective/2019/07/poor-late-season-protection-limited-flu-vaccine-impact-2018-19).
Looking at other CDC data for the period October 1, 2018-March 30,2019 (https://www.cdc.gov/flu/about/burden/preliminary-in-season-estimates.htm), there were approximately 38 million cases of influenza, nearly 18 million flu-related medical visits, upwards of 549,000 hospitalizations due to the flu, and upwards of ~51,000 flu-related deaths.
​
A series of articles looked at how effective the flu shot is:

• A recent article in Intensive Care Medicine (2019) 45: 957 (https://doi.org/10.1007/s00134-019-05648-4)  examined whether influenza vaccination affects the subsequent 1-year risk of myocardial infarction, stroke, heart failure, pneumonia, and death among intensive care unit (ICU) survivors aged ≥ 65 years. They found that in the subsequent year, mortality was decreased among the vaccinated versus the unvaccinated patients, and there was also a decreased risk of stroke.
• An interesting study published in Vaccine (Vol 36, Issue 16, 12 April 2018, pg 2166) demonstrated that regardless of the efficacy of the flu vaccine, it significantly reduced influenza-related ICU admissions and influenza-related deaths.
• This also goes along with a study published in Open Forum Infectious Diseases this past April (https://doi.org/10.1093/ofid/ofz159), where it was shown that all-cause mortality is reduced by 31% in patients with heart failure who get a flu shot, compared to those with the same disease who do not get the flu shot.

There have been a number of papers regarding older adults and influenza vaccine, specifically about which type of vaccine may be the best, how effective the vaccine is in general, and when is the best time to vaccinate:

• One study over 2 years old (The Journal of Infectious Diseases, https://doi.org/10.1093/infdis/jiw641) demonstrated that the high dose vaccine was much more effective in reducing mortality in the elderly population than was the standard-dose vaccine.
• A more recent study this past spring in Vaccine,(https://doi.org/10.1016/j.vaccine.2019.01.063), looking at over 1.7 million VA patients over age 65, clearly demonstrated that the high dose vaccine for the elderly was much more effective than the standard-dose in preventing influenza and pneumonia-associated hospitalizations, heart & lung-related hospitalizations, and all-cause mortality during the flu season.
•  Another paper (Canadian Medical Association Journal| January 8,2018|Vol. 190| Issue 1;  E3-E12) further demonstrated that “repeated influenza vaccination was twice as effective in preventing severe cases of influenza that required admission to a hospital in older patients compared with non-severe cases”, with consistent results irrespective of the influenza season, virus subtypes, and age. It also showed that among older adults, repeated vaccinations over previous seasons was twice as effective in preventing severe influenza compared with non-severe influenza.

Finally, regarding flu shots, the question of when arises:

• In an article in Clinical Infectious Diseases this past May (https://doi.org/10.1093/cid/ciy770), data from seven flu seasons was evaluated, and it was reported that the benefit from the flu shot decreased by ~16% for each additional 28 days after the flu shot was given.
• This past April in the American Journal of Preventive Medicine, an article (https://doi.org/10.1016/j.amepre.2018.11.015) pointed-out that Influenza typically peaks between December and March, yet it is now known that vaccine efficacy decreases from 16% (in some earlier studies 6%-11%) per month after the shot. Their analysis showed that if the flu shot were delayed until October, more than 11,400 influenza cases in older adults could be prevented- providing that delaying the timing did not result in fewer older people getting the shot. However, if this resulted in ~5% or more people not getting a flu shot because of the delay, then no changes in the present recommendation would be favored.
• This analysis resulted in a number of responses; many that expressed concern about patients returning in the late fall for a flu shot, or concerns about an early-peak flu season. In an analysis and prediction model presented in Clinical Infectious Disease (https://doi.org/10.1093/cid/ciz452), the authors concluded that delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. They did state, however, that the consequences of delayed vaccination depended heavily on influenza season timing, rate of waning protection from a vaccination, and overall vaccine efficacy.

 
So, what do we conclude from all of these articles? Flu shots significantly reduce the risk for influenza-related hospitalizations and complications, getting yearly flu shots also reduces risk for a severe infection (independent of efficacy of the vaccine), high dose is more effective that standard-dose shots in the elderly, protection from the flu (efficacy) wanes as the season progresses, and delaying the flu shot until the late fall may make sense (but there are risks that “flu season” could begin earlier than expected). The final message is- get your flu shot, there is no reason not to!!!