Monday, December 04, 2023

J.I.D.: Influenza Vaccine Effectiveness (VE) Against Flu-Related Emergency Department, Urgent Care, and Hospitalization Encounters Among U.S. adults, 2022-2023


CDC's New Wild to Mild Flu Campaign


Quantifying how well the flu vaccine works every year is no easy task, since millions of people get mild-to-moderate`influenza-like illnesses' (ILIs) but never seek medical attention, and are therefore never tested or counted. 

Their illnesses could be due to flu, or to a long list of `other' respiratory pathogens (see ILI’s Aren’t Always The Flu). Even in October 2009, at the height of the H1N1 pandemic (see chart below) non-influenza illnesses (e.g RSV, Adenoviruses, Rhinoviruses, etc) outnumbered influenza by more than 3 to 1. 


Many who get the flu shot, only to get sick with the `flu', are infected with a non-influenza virus against which the vaccine has no effect. But to them, it is a sign that the vaccine didn't work.  

Up until about a dozen years ago, the CDC and other public health agencies tended to overestimate the effectiveness of the flu vaccine, often stating: ". . . for healthy adults under the age of 65, in years when the vaccine is a good match to circulating strains, effectiveness ranges from 70%-90%."

In 2011 the CDC lowered those estimates somewhat, to 50-70%. But over the past decade we've seen flu shots struggle to even reach that 50% vaccine effectiveness (VE) mark, particularly when H3N2 influenza was the dominant subtype.  The CDC now states:

How effective are flu vaccines?

CDC conducts studies each year to determine how well influenza (flu) vaccines protect against flu. While vaccine effectiveness (VE) can vary, recent studies show that flu vaccination reduces the risk of flu illness by between 40% and 60% among the overall population during seasons when most circulating flu viruses are well-matched to those used to make flu vaccines. In general, current flu vaccines tend to work better against influenza B and influenza A(H1N1) viruses and offer less protection against influenza A(H3N2) viruses.

Given how difficult it is to parse out influenza infections from other respiratory illnesses in the general population, a more reasonable metric is how well flu vaccines prevent ER & Urgent Care visits, and Hospitalizations, from lab-confirmed influenza infections. 

We've seen a shift towards this sort of targeted VE analysis (see last months C.I.D. VE Report on Pediatric Medical encounters for Influenza), and last September the CDC unveiled a new strategy, hoping to `reset' public expectations this fall as to what benefits they can realistically expect from the flu vaccine, emphasizing a reduction in severity over simply preventing infection. 

This week, researchers at the Influenza Division, Centers for Disease Control and Prevention, have published an analysis of the effectiveness of last year's flu shot in Adults in the Journal of Infectious Diseases, which finds a moderate VE (44%) against flu-related medical encounters.

I've only posted the Abstract, so follow the link to read it in its entirety.  I'll have a postscript after the break. 
Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023
Mark W Tenforde, MD, PhD, Zachary A Weber, PhD, MS, Duck-Hye Yang, PhD, Malini B DeSilva, MD, MPH, Kristin Dascomb, MD, PhD, Stephanie A Irving, MHS, Allison L Naleway, PhD, Manjusha Gaglani, MBBS, Bruce Fireman, Ned Lewis, MPH
The Journal of Infectious Diseases, jiad542,
Published: 02 December 2023 Article history




The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed.

Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza-A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022-March 2023 among adults (age ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test-positive by molecular assay) and controls (influenza test-negative), applying inverse-propensity-to-be-vaccinated weights.

The analysis included 85,389 ED/UC ARI encounters (17.0% influenza-A-positive; 37.8% vaccinated overall) and 19,751 hospitalizations (9.5% influenza-A-positive; 52.8% vaccinated overall). VE against influenza-A-associated ED/UC encounters was 44% (95% confidence interval [95%CI]: 40-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively.
VE against influenza-A-associated hospitalizations was 35% (95%CI: 27-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively.

VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

Even in seasons with moderate VE like the 2022-2023 season, however, vaccination is likely to have a substantial public health impact by preventing millions of medical visits, tens of thousands of hospitalizations, and thousands of deaths [20-22]. This reduction in medically attended illness and associated morbidity and mortality is especially critical to reduce burden on health care resources should influenza, SARS-CoV-2, RSV, and other respiratory viruses continue to co-circulate in high numbers.

          (Continue . . . )

Although flu vaccines have improved greatly over the past 15 years (e.g. cell culture-propagated vaccines , adjuvanted and high dose vaccines, quadrivalent formulas, etc.), most years they still only provide moderate protection against influenza infection, and are pretty much `strain-specific'.

Work continues on developing a `Universal Flu Vaccine' (see NIH: Clinical Trial of Universal Hexavalent Flu Vaccine Candidate Begins), but even then, the immediate goals are fairly modest.

The good news is that - even if the current flu vaccine doesn't always prevent infection, it can often reduce the severity of one's illness - and that can have both immediate and long term benefits

Something we've looked at repeatedly over the years (see here, here, and here) has been the flu vaccine's apparent impact on reducing heart attacks, strokes, and possibly even dementia later in life.

  • `. . . compelling evidence that influenza vaccination is associated with a decreased risk of major cardiovascular events'.
  • Specifically, the authors found that ". . . patients who received the influenza vaccine experienced a remarkable risk reduction of over 20% in cardiovascular death". This particular analysis focused on patients with an existing diagnosis of CVDs (Cardiovascular diseases).

While a VE of less than 50% is disappointing, a fifty percent reduction in severe flu is still significant -  and when you add in the reduced risk of cardiovascular events - the flu shot undoubtedly saves a lot of lives every year. 

Which is why I get the flu shot every year, and urge others to do the same.