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Orthopoxvirus update; might not want to skip this one 

This deserves a preface because I'm going to suggest some scary possibilities. Sit down, find your safe person, smoke a joint, maybe bookmark this for later.

Let me first say this: fear and panic are normal, rational responses to a crisis. I feel those emotions frequently and I work very hard to regulate them. One of the ways I do that is by sharing information here when I feel I've researched and processed enough.

Let's get started.

Orthopoxvirus update; might not want to skip this one 

Last week, Nature Medicine published a peer-reviewed paper on a genome sequenced in Portugal. I couldn't access the paper itself because it was behind a paywall, but I looked at summaries in Forbes and MedPage Today.

DNA viruses are quite different from RNA viruses.

RNA viruses like to replicate quickly, and they're bad spell-checkers. They thus mutate more frequently.

DNA viruses are slower and more thorough, and thus mutate more slowly.

Orthopoxvirus update; might not want to skip this one 

SARS-CoV-2 is an RNA virus, and MPXV is a DNA virus. I checked the length of MPX's genome – it's about 6 times as long as SARS2.

Technically, there is much more room for MPX to make errors and mutate, but I kept in mind that DNA viruses tend to not be very good at that.

I was wrong 🙃

Orthopoxvirus update; might not want to skip this one 

The scientists in Portugal found that their sampled strain, in addition to being more closely related to the one in Nigeria, has 50 mutations.

This is at least six times the number of mutations we'd expect to see in a strain that started infecting Nigerians two years ago.

Orthopoxvirus 

There are a few possible scenarios here, in my unqualified mind.

The first is that the Portuguese sample did not come from human-to-human transmission, but direct zoonosis. E.g., MPXV circulated in a specific rat population until it acquired its current form.

The second is that the West African strain lingered in an immunodeficient human until it had replicated enough times to develop fifty mutations.

The third: it developed a mutation that allows it to replicate more quickly.

Orthopoxvirus 

The fourth is that this Portuguese strain came from a laboratory that was performing gain-of-function engineering.

We can quickly rule out long COVID as a confounding variable, partly because endemic regions have kept their transmission down, and partly because the symptoms of pox are obvious and might even be more severe in a long COVID patient.

The possibility that MPXV has been circulating undetected in Europe and the Americas is also implausible because, again, symptoms.

Orthopoxvirus 

There is a lot of information that we need, and a lot of forces making research as difficult as possible.

1. We need to sample rodents in regions where index cases originated.

2. We need to determine if there is any way that MPXV could naturally evolve, by mutation or recombination, to replicate more quickly.

3. We need to check this genome against all strains that are being studied.

Orthopoxvirus 

The greater concern here is that MPX and smallpox are clinically identical. The only ways to tell the difference are by PCR testing, and by presentation of swollen lymph nodes (MPX).

And we don't have any PCR tests.

So unless you can observe the lymph nodes, it's basically a tossup between a case fatality ratio of 1-10% (MPX) and a case fatality ratio of 40%.

Not great.

Orthopoxvirus 

A few experts have pointed out this week that given the similarity between the diseases, and public health's atrocious lack of interest, smallpox could start circulating and we wouldn't know it until enough people started dying.

Contact tracing and testing have fallen prey to ascertainment bias, because public health has (oddly) latched onto queer people as the main demographic. Forgetting that we do things outside of have sex with each other. 🥴

Orthopoxvirus 

Like, we have lives and children and stuff. We're healthcare workers and massage therapists and athletes – great careers for transmitting infectious diseases.

Anyway. When you take into account the fact that several regions across the world have been studying smallpox in labs for decades (sometimes accidentally releasing it), and scientists have been warning about the potential for the virus to be reweaponized, the possibility of a national security threat enters the picture.

Orthopoxvirus 

I want to emphasize POSSIBILITY. At this point, without additional evidence, the possibility is real, but the probability is low.

FWIW: I don't think anyone will find a wildtype MPXV similar to this strain, because I don't think it exists. Everything I've seen with COVID has me leaning in the direction of lab leak, especially given that accidental lab leaks have been happening almost constantly throughout history.

So I hope I'm wrong. Because the implications would be devastating.

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