Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F.
Perry Wilson of the Yale School of Medicine. It’s a new year, and like many of you I have
been spending time reflecting on the past 21 months of the Coronavirus pandemic – the
most exceptional 21 months in my life. With Omicron cases cresting, there is a
palpable sense of hope that, though we may not be out of the tunnel yet, there is light at the end.
The pandemic has been a tragedy by any standard. Nearly a million deaths in the US and more than
five and a half million worldwide means that more people have died of COVID during this pandemic
than in the past 30 years of influenza. And, even as I think about that,
it’s hard for me not to let my mind imagine the myriad ways this could have been worse.
I don’t mean to be insensitive to those of us who have lost loved ones during the pandemic, or
who are still suffering from the effects of infection, but the fact is we caught quite a
few breaks over the past two years. And I want to discuss those things not to try to make us feel
better about this collective tragedy, but to remind us that there are lessons to be learned
here. In the next pandemic – and there will be another, eventually – we may not be so lucky.
Here are three of my COVID what ifs… 1. What if COVID were most severe in Children,
and least severe in adults? A key feature of COVID-19,
identified from the earliest days of the pandemic, was its predilection to cause
the most severe disease in older people. At this point, we know that those above age 75 are around
20 times more likely to be hospitalized due to COVID and around 200 times more
likely to die from it than 18 to 29 year olds. It’s not unusual for infectious disease to be
most severe in the elderly and the frail. But many infectious diseases show the opposite pattern. 57%
of malaria deaths in the world are in children less than 5 years old.
In 2020, diarrheal illnesses killed 500,000 children under age 5 – around a third
of total deaths. And of course, the H1N1 Influenza pandemic of 1918 famously struck down the very
young and those in the prime of their lives. If a similar mortality curve had come out
in the beginning of the COVID pandemic, the effects on society would have been catastrophic.
I was attending on one of our COVID units during the first peak in April of 2020.
With three small children at home, could I have brought myself to go
into the hospital every day? What about the thousands of trainees – interns, residents,
fellows just starting families. Our hospital workers, particularly at big, urban centers,
are young. Many might have packed up their kids and headed for the hills.
We have been lucky that COVID-19 is so mild in children. Our risk tolerance for ourselves
is much higher than it is for our offspring. 2. What if the vaccines hadn’t been so effective?
By any metric, we got astonishingly lucky with our COVID vaccines. Sure, we haven’t
been using them as best we can, or sharing them equitably, but from a purely scientific standpoint
they blew expectations out of the water. The RNA vaccines were developed astonishingly
quickly. This, of course, has led to some vaccine hesitancy,
but it is worth pointing out that one of the reasons they were able to be developed so quickly
is because work on RNA vaccines started during the prior SARS epidemic of 2003. That one burned
out before vaccines became available, but the research continued, allowing for the remarkable
achievement of having a vaccine ready for clinical use within a year of the virus being identified.
And of course, the efficacy of the vaccines is more than we could have expected. Against the
original Wuhan strain, the mRNA vaccines showed a staggering 95% protection against infection – far
beyond the 50% that was pre-specified as the threshold for FDA authorization.
Of course, that efficacy has waned, but new data from the CDC shows that – when you include
boosters – the mRNA vaccines still show 95% effectiveness against death from COVID-19.
It is not at all inconceivable that these vaccines would have failed in clinical trials.
Many vaccines do. If you had told me, in April of 2020, that we would not have a vaccine by
January of 2022, I would be disappointed, but not surprised. According to the Commonwealth Fund,
the vaccination program has saved more than 1 million lives in the US as of November 2021.
Put another way, you are as likely to know someone whose life was saved by a COVID vaccine
as you are to know someone who died from COVID itself. It could have been worse.
3. What if Omicron were more like Delta? The Omicron variant is amazingly,
fantastically infectious. Where the original Wuhan strain had a basic reproduction number – that’s
the number of people the average infected person infects without mitigation – of 2.5, Omicron may
be as high as 10. This makes it more infectious than smallpox, more infectious than chicken pox.
That leads to exponential infectious growth, which is of course just what we’ve seen. But we have
been fortunate that Omicron is less virulent than other strains of SARS-CoV-2, even among
those who are unvaccinated. Despite that, our hospitals are bursting under the strain of the
Omicron wave – with more hospitalized patients than at any other time during the pandemic.
If Omicron were as virulent as Delta, imagine where we would be.
We might be seeing twice as many hospitalizations, twice as many deaths.
Now you might think this isn’t a lucky break – this is evolution. There’s a trope going around
that infectious diseases become more infectious and less virulent over time – the better to spread
their genetic material around the globe. This is over-simplified. Yes, evolution selects variants
that can better transmit to other individuals – but there are multiple evolutionary paths to that
end. Omicron’s path led to a virus that attaches more efficiently to upper respiratory epithelia,
sparing deeper lung involvement. An equally, or even more successful evolutionary path
might see a virus that replicates more aggressively in the lungs – leading to
more coughing and thus more disease spread. Remember, SARS-CoV-2 is not Ebola. It has a
case-fatality rate of about 1.5%. A doubling to 3% in service of creating a sicker host who can
more effectively spray viral particles around may well be worth it in the evolutionary sense,
since most hosts will survive in either case. In other words, yes, we were lucky with Omicron.
It’s incredible infectiousness, coupled with its lower pathogenicity,
means that SARS-CoV-2 is now spreading to the nooks and crannies of the susceptible population,
dramatically increasing population immunity. It is a process that comes with substantial cost
– 2000 deaths a day currently – but it could have been much, much worse.
What about the next time? In the next pandemic, we may
not be so lucky. We may be up against a pathogen that strikes harder at children, that is better
at evading vaccine-induced immunity, that is both highly infectious and more lethal. This pathogen
could emerge at any time, and, given the rate at which humans are expanding into novel territory,
it may emerge sooner rather than later. So what do we do?
First, we need to dramatically improve the public health infrastructure of the US and the world.
We may not have time to “scale up” for the next pandemic. We need to invest in novel treatments,
vaccine development, pathogen sequencing, and outbreak surveillance. We need to ensure
the national stockpile of PPE is maintained, updated, and ready to be deployed when necessary.
We need to reinforce our healthcare workforce – investing in the next generation of doctors,
nurses, pharmacists, and medical assistants. We have to acknowledge that the best
communicators of medical information are not people like me, but primary care physicians in
one-on-one conversations with patients. Every American should have, and be able to identify
their PCP. They should have a relationship with them, even if they don’t need it immediately.
Currently, we’re moving backward on this. We need to support research in emerging infectious
diseases and invest in technologies to mitigate the impact of airborne pathogens in public places.
Personally, I believe the end of the COVID-19 pandemic is in sight. Six months from now,
we may look back at the Omicron wave as the last gasp of one of our greatest natural adversaries.
What we need to start grappling with now is the harsh reality that, despite the losses,
the pain, the disruption, the isolation of the past two years, if we don’t prepare properly,
the next time could be worse. For Medscape, I'm Perry Wilson