A new pandemic

A decade ago, some experts were still bitterly divided over the impact of  migratory birds on the spread of avian flu (see 2014's Bird Flu Spread: The Flyway Or The Highway?).  Many conservationists had long insisted  that `sick birds don't fly', and that it was illicit poultry trade that was driving the spread of the virus. 

A 2015 statement by UN CMS/FAO Co-Convened Scientific Task Force on Avian Influenza and Wild Birds maintained that `. . .  typically the spread of HPAI virus is via contaminated poultry, poultry products and inanimate objects although wild birds may also play a role.'

While the poultry industry undoubtedly contributed to the local spread of the virus, after the H5N8 virus crossed the Pacific in late 2014 and sparked a major North American Epizootic (see map below), the role of migratory birds became much harder to ignore.

NPJ Vaccines: Modeling the Impact of Early Vaccination in an Influenza Pandemic in the United States

While once thought of as a `once-in-a-generation' event, in my lifetime I've already experienced 4 legitimate pandemics (1957, 1968, 2009, 2020), 2 pseudo-pandemics (1977, 2003), and one `near-miss ' (1976).

Which brings us the question: is it better to have a less-well-matched vaccine earlier (at 3 months), or wait (6 months or more) for a well-matched vaccine?

It is not an easy question to answer, because there are so many unknown variables.  As the old saying goes, `If you've seen one pandemic . . . . you've seen one pandemic'.  The speed of transmission (R0), its place of origin, its virulence (CFR and Attack Rate), and even its impact on different age groups, all change the outcome. 

We've a study today that attempts to model the impact of early vs. late vaccination in a variety of pandemic scenarios, juggling virulence (moderate or severe), and vaccine effectiveness (high, moderate, or  low), in order to try to quantify the probable benefits. 

In order to keep all of this manageable the authors had to make a number of assumptions that may, or may not, hold true in the next pandemic; an origin in the Southern Hemisphere, a greater impact on older patients, and a single wave, etc.   

Vaccination from 3 months with a high, moderate, or low effectiveness vaccine would prevent ~95%, 84%, or 38% deaths post-vaccination, respectively, compared with 21%, 18%, and 8%, respectively following vaccination at 6 months, irrespective of pandemic severity.

While the pandemic curve would not be flattened from vaccination from 6 months, a moderate/high effectiveness vaccine could flatten the curve if administered from 3 months.

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This study uses a lot of epidemiological assumptions, which may (or may not) be a good fit for the next pandemic.  Much will also depend upon how society reacts to the next pandemic.  

• Will lockdowns be tolerated, or will people refuse masks and social distancing?   

• Assuming a vaccine could be produced in quantity in 3 months, would large segments of the public actually embrace it?  How much extra resistance against an mRNA vaccine? 

• How much tolerance would the public have for (real or imagined) vaccine side effects, particularly in a low VE jab?  

While I'm not particularly hopeful that an emergency vaccine of any VE can be produced and deployed within the first 3 months of a novel pandemic - in the event of a severe disease - this study strongly suggests that the earlier that can happen, the better. 

While there are no records of humans ever having dealt with an H5 influenza pandemic (going back 130+ years), those who were born before before 1967 appeared far less susceptible to the virus - and those born before 1958 - even more so. 

 A lot of theories were proposed, but answers were elusive. Then, in 2013 an equally novel avian H7N9 virus emerged in China - sparking 5 years of seasonal infections - which skewed dramatically toward those over 40

2009 H1N1 Pandemic Hits the Young Especially Hard

This study estimated that 80% of 2009 H1N1 deaths were in people younger than 65 years of age which differs from typical seasonal influenza epidemics during which 80-90% of deaths are estimated to occur in people 65 years of age and older.

Over time, this theory was refined to say that the HA Group type (I or II) you are exposed to first could substantially affect your immune response to influenza A (see Science: Protection Against Novel Flu Subtypes Via Childhood HA Imprinting).

The idea is that if your first influenza exposure was to H1N1 or H2N2 (Group 1), you may carry some limited degree of immunity to H5 viruses (H5N1, H5N6, etc.), while if your first exposure was to H3N2 (Group 2), you may carry some degree of protection against H7 viruses instead

Although the oft-quoted 50% CFR (Case Fatality Rate) of H5N1 is probably greatly exaggerated (see discussions here and here), even a more reasonable 2%-5% CFR would represent a public health crisis unlike anything we've seen in the modern era.