HIV and ID Observations

We’ve been burned so many times making predictions about COVID-19 that I should post this conspicuously by my computer:

The famous pundit meant, of course, that “you don’t know anything” — we know his true intentions since he also said “Nobody goes there anymore. It’s too crowded.”

The “know nothing” quotation is a reminder that COVID-19 is a new disease. While we do in fact know more than nothing, we still have so much to learn. This applies to pretty much the whole COVID-19 universe, including its origins, virology, immunology, epidemiology, prevention, clinical manifestations, diagnosis, treatment, and complications. Constantly learning, constantly updating assumptions, guidelines, and messages.

With that humble start, I’m about to write a sentence that fills me both with excitement and, I confess, some trepidation.

It looks like Omicron causes less severe disease than prior variants.

Why trepidation? Well obviously I don’t want to jinx it, we’re still in the midst of a very major surge.

As anyone with a pulse knows, a lot of people have been diagnosed with COVID-19 in the past few weeks, more than we’ve seen at any point in the pandemic.

In fact, our world right now is a mess. (I’ve gone back and emphasized this sentence with bolding and italics, as some readers have told me they missed my acknowledging this stark truth.) Some have a mild or asymptomatic case, but some are miserably ill, recuperating at home. A smaller number are hospitalized with severe COVID-19, especially the unvaccinated or those with impaired immune systems. Some proportion of all these cases could end up with long COVID, a dreaded complication with still no clear treatment.

Plus, each new diagnosis — regardless of severity — enormously disrupts family, school, work, and social life. What I’m about to write does not in any way to diminish how awful the pandemic is right now for just about everyone.

But looking at the evidence and clinical experience on severity, I’m going to poke the beast and conclude that Omicron does appear milder.

First, the big picture — we have a record number of cases pretty much everywhere in North America and Europe.

(1) The massive number of infections in European countries is "real".
Yes, more people got tested for Christmas, and there have been some backlog issues in many countries.
But the 7-day positive rates have been rising rapidly, and nothing indicates that cases are "over-counted". pic.twitter.com/YFClWuXDYa

— Edouard Mathieu (@redouad) December 29, 2021

However, despite this extraordinary spike in cases, deaths from COVID-19 are numerically lower than they have been at any point since way back in October 2020, more than a year ago. Record high case numbers and fewer deaths means that the global case fatality rate has dropped — it’s now below 1% for the very first time during the pandemic. 

It’s even more encouraging when you consider that we are undoubtedly undercounting cases, both because people with mild symptoms are less likely to be tested, and because positive home tests are rarely reported. That denominator keeps getting bigger.

What these remarkable data tell us is that Omicron’s mutations may fool our antibodies, but our protection is far from useless — infection with Omicron occurs, but our primed cellular immunity (from prior infection or vaccines or both) quickly kicks in and takes it out. Go T-cells!

Second, let’s look at Omicron — the virus itself — in the lab, and compare it with other variants in its ability to inflict damage on various cells. Soon after Omicron appeared, a lab in Hong Kong reported that it grew less well in lung tissue than other variants.

Just one lab? Interesting, but let’s see what others find … and now we have no fewer than four others all reporting similar data, a veritable world tour that started in Hong Kong, but now includes Liverpool, Belgium, Japan, and Cambridge:

5 Studies, 5 Figures. All consistent, independent replications in vivo, in vitro. Omicron can't infect lungs or lung cells as well as prior variants.@KU_Leuven @SystemsVirology @GuptaR_lab @hkumed @LivUni pic.twitter.com/X9jbugx0vs

— Eric Topol (@EricTopol) December 29, 2021

Less virus activity in the lung could mean less lung damage, the primary organ targeted in severe — and fatal — COVID-19. Hope.

Third, let’s talk with the front-line clinicians — people like you and me. The doctors and nurses seeing cases in South Africa told us repeatedly in late November that this Omicron-related COVID-19 was different, that patients were less sick.

They generated data to confirm their impressions, yet somehow some northern hemisphere docs still didn’t buy it.

South Africa just had a devastating Delta surge, the thinking went, so there was natural immunity protecting them — the lower severity may not apply here. And remember, it’s summer down there. Plus, can the data be trusted if not collected here?

But now, our data and our anecdotal impressions match theirs — in plain speak, they were right. Anyone doing clinical care currently in the United States would agree that most cases we see right now are truly mild.

Not just mild in the over-inclusive category of “not requiring hospital care.” But mild like any generic endemic respiratory bug — remember those? Many of the clinical encounters with patients with COVID-19 occur over the telephone, and even their voice sounds different from prior variants — stronger, more confident they’ll recover, less afraid. That’s highly anecdotal, I know, but it’s just what I’m hearing.

So what does this giant Omicron surge, with a seemingly less-dangerous variant, mean for the future of COVID-19?

What does it mean for the “average” patient who gets it? How about for the immunocompromised, the elderly? For young children?

What does it mean for the logistics of patient care, work, schooling, getting together with friends and family, or just trying to live our lives in some tolerable way until the surge abates?

What should it mean from a policy or public health perspective?

What do these early data on cross-immunity with Delta mean? Sounds promising, but what does it mean for protection against future surges, or the inevitable next variant?

I could speculate, both on the optimistic and pessimistic side.

But I don’t know nothing.

Happy New Year, folks.