Avian Flu Diary: Looking Forward By Looking Back

#16,860

Eleven months ago - when many world leaders were touting the `imminent end of the pandemic' - the UK's SAGE (Scientific Advisory Group for Emergencies) on COVID released a series of detailed reports on the SARS-CoV-2 pandemic, and where they thought things might go from there.

Much of it was based on informed speculation - since no one can truly predict what will happen with a rapidly evolving virus - but these reports laid out various plausible scenarios, some of which have already come to pass.

The most prescient of these reports was filed under Long term evolution of SARS-CoV-2, 26 July 2021, but this 15-page PDF was titled:

Can we predict the limits of SARS-CoV-2 variants and their phenotypic consequences?

As eradication of SARS-CoV-2 will be unlikely, we have high confidence in stating that there will always be variants. The number of variants will depend on control measures.

We describe hypothetical scenarios by which SARS-CoV-2 could further evolve and acquire, through mutation, phenotypes of concern, which we assess according to possibility. For this purpose, we consider mutations in the ‘body’ of the virus (the viral genes that are expressed in infected cells and control replication and cell response), that might affect virus fitness and disease severity, separately from mutations in the spike glycoprotein that might affect virus transmission and antibody escape.

We assess which scenarios are the most likely and what impact they might have and consider how these scenarios might be mitigated. We provide supporting information based on the evolution of SARS-CoV-2, human and animal coronaviruses as well as drawing parallels with other viruses.

The body of this report then went on to explore 4 specific scenarios, which ranged from very bad (a much more lethal virus), to pretty bad (vaccine escape or drug resistance), to good (decreased virulence over time), providing both the rationale and the plausibility for each.

The worst scenario (below), has thankfully not happened (yet):

Scenario One: A variant that causes severe disease in a greater proportion of the population than has occurred to date. For example, with similar morbidity/mortality to other zoonotic coronaviruses such as SARS-CoV (~10% case fatality) or MERS-CoV (~35% case fatality).

Despite claiming over 6 million lives (likely a low estimate), we've been lucky in that this COVID pandemic has (so far) been a relatively low-mortality/high morbidity event - at least when compared to the Case Fatality Rate (but not total deaths) from other coronaviruses like SARS-CoV and MERS-CoV.

Thankfully, COVID has lost some of its bite since Delta - aided and abetted by relatively high vaccine uptake - which was addressed in this report's Scenario Four: SARS-CoV-2 follows an evolutionary trajectory with decreased virulence.

But Omicron makes up for its decreased virulence with increased transmissibility, and there are no guarantees that a future variant won't emerge that produces greater severity than Delta. This is one of the reasons we watch COVID spillovers into non-human hosts (i.e. deer, mink, rodents, etc.) with such interest.

While unlikely, there are also theoretical concerns that SARS-CoV-2 could recombine with other coronaviruses in the wild (see here, here, and here), with unpredictable results.

The SAGE group's second scenario - A variant that evades current vaccines - is pretty much already here. While vaccines still provide significant protection against severe illness, hospitalization, and death - their ability to prevent `breakthrough infections' has waned considerably since the arrival of Omicron last November.

This impact has been great enough that last week the FDA Recommended Adding BA.4/5 Spike Protein To Create A Bivalent COVID Booster Shot,

While BA.4/5 are currently on the ascendant - given the speed at which COVID reinvents itself - they may both have been supplanted by something new by the time the booster becomes available.

It's a gamble, but then, sticking with the current formula has very little upside.

SAGE's 3rd scenario - Emergence of a drug resistant variant after anti-viral strategies - has also largely come to pass; in late January we saw the FDA Remove Authorization For Two Monoclonal Antibody Therapies Due To Omicron, which was followed two months later by FDA Limits Use Of Sotrovimab Monoclonal Antibody As Rising BA.2 Erodes Effectiveness.

While the pharmaceutical cupboard isn't completely bare, treatment options have decreased markedly over the past 6 months, and newer variants could further erode our medical armamentarium against COVID.

In less than a year, 3 of the 4 scenarios offered in this SAGE report have - to varying degrees - already occurred. And the SARS-CoV-2 virus continues to evolve. BA.4/5 are unlikely to be the last variants to sweep the globe, as this pandemic appears far from over.

As we go into tomorrow's 4th of July Celebrations, the United States is reporting a five-fold higher number of COVID cases (weekly avg 113,000 vs 20,000) than it did at this time last year, when testing and reporting were far more robust.

Last year's summer holiday was followed by a 7-fold jump in Delta cases by early fall, before the big Omicron wave hit in December. This year, we've got a far more transmissible BA.4/5 to deal with, and so another post-Independence day surge seems inevitable.

Increased vaccine (and booster) uptake, and a return to wearing face masks in public, might mitigate some of this coming wave, but few appear inclined to adopt these basic precautions anymore. I rarely see anyone wearing masks where I shop, although I continue to do so.

On top of BA.4/5, we've got what appears to be an aggressive wave of H3N2 seasonal influenza in the Southern Hemisphere, and much of Southern China, which raises concerns over a potential `twindemic' of COVID and Flu this fall.

COVID confections (with Influenza, RSV, Adenovirus, etc.) have been shown to produce significantly higher mortality (see The Lancet: SARS-CoV-2 Co-infection With Influenza Viruses, RSV, or Adenoviruses).

Add in what we know about the devastating effects of `long COVID', recent reports of risks to unborn children in the womb, and Outcomes of SARS-CoV-2 Reinfection suggesting that successive reinfections with COVID can lead to higher all-cause mortality, and we could be faced with another challenging fall wave.

And already scientists have their eye on a potential contender for becoming the next big COVID variant - BA.2.75 - which has been detected primarily in India, and in a handful of other countries (see JPost Scientists keeping an eye on new COVID variant BA.2.75).

While these are early days - and the future of BA.2.75 is far from certain - SARS-CoV-2 continues to reinvent itself with remarkable regularity. Something will follow BA.4/5. You can pretty much count on it.