How Now Viruses?

What’s behind bio-containment door number 3?

Just a short step back in time it seemed the only viruses most people worried about were the ones that crept into you computer, freezing you data and demanding a ransom in bitcoin be sent to some guys in Russia or Ukraine. Now that bitcoin is devalued, it’s missiles we send to Ukraine; and tiny packets of genetic code, not binary code that command our attention. To quote Kurt Vonnegut, “And so it goes”. One week after the WHO declared Monkeypox to be Public Health Emergency of Global Concern, the US Department of Health and Human Services is debating whether they will follow suit, with almost 5000 cases confirmed here. The vast majority of cases are in New York and California, and San Francisco just declared a Health Emergency yesterday. Against this backdrop we are seeing an interesting phenomenon. People are lining up, in numbers that overwhelmed the available supply, to take a live inactivated vaccine, that’s efficacy in preventing Monkeypox has never been directly established in human beings. The data supporting efficacy is all based on immuno-bridging, and assuming that a certain level of antibodies, which protect simians, will have the same effect in humans. Even though the virus has undergone some changes from the strain used to develop the vaccine, my guess is that it will still be effective, primarily because it is a whole viral vaccine. It was tested on a total of about 7,000 people, and as we recently learned from the COVID vaccine experience, we will need to be on the lookout for unusual vaccine side effects as larger numbers are vaccinated.

There are several items worth reviewing on the COVID vaccination front. The quote below is taken from the Kaiser Family Foundation update of July 22, detailing the rapidly slowing uptake of vaccinations in the 6 mo - 5 yo age group.

• As of July 20, approximately 544,000 children under the age of 5 had received at least one COVID-19 vaccine dose. This represents 2.8% of the approximately 19 million children in this age group. At a similar point in their vaccine roll-out, more than 5.3 million children ages 5-11 (18.5% of 5-11 year-olds) had received their first dose.

• Vaccinations peaked among those under 5 about two-weeks into their eligibility, even before the July 4 holiday. After a quick rise in vaccinations soon after they became eligible, the rate of vaccination (as measured by the 7-day rolling average of new doses administered) peaked at just over 28,000 on July 1. It then began to decrease and was about 13,000 on July 20.

This peak is significantly below where their 5-11 counterparts were at a similar stage. While vaccinations also peaked among 5-11 year-olds about two-weeks into their eligibility, they peaked at 271,000 average daily doses; at that point, almost 2.7 million 5-11 year-olds, or 9.3% of the age group, had received their first dose. This compares to about 283,000 children under age 5, or 1.4%, at their July 1 peak.

For quite a long time I have been discussing the failing vaccine strategy of chasing the latest dominant variant with an updated Spike RNA vaccine. We have been playing catch up, “Whack a Mole”, for more than a year since the first significant, more transmissible COVID variant, Alpha, swept the world. Three days ago, senior public health officials, scientists and pharmaceutical industry representative were invited to the White House for a discussion of future directions in vaccine development. As Professor Eric Topol recently said, “It’s the Virus Stupid”. We know very clearly that new vaccine development needs to focus on a parenteral pan-Corona virus vaccine, as well as a nasal vaccine that will induce reliable immunity in the respiratory tract—something which the current jabs do not accomplish. There are multiple promising candidate vaccines in both categories. While it’s good to see an acknowledgement that the current approach is failing, it’s well past time for a highly organized, focused rapid development program like Warp Speed. To the argument, “There’s just not enough money available”; I would respond, “We just printed 60 billion to send to Ukraine.” Maybe someone can convince me that if we used $3 billion for a new Lightening Speed program, and sent $57 billion to Ukraine, that 6% fewer dead Russian soldiers would make a difference in the outcome of that conflict. I’m fairly certain that Vladimir Putin has decided it will not.

I’m skipping the detailed COVID numbers this week, nothing has materially changed, with hospitalizations continuing on the up slope. Everyone who reads here regularly is well aware of what’s going on. There is some interesting science regarding exactly why BA.5 is so successful in evading our prior immunity, and causing so many reinfections. First, I have to correct a bit of oversimplification in my prior summaries of how our immune system works. I have referenced the common view that Neutralizing Antibodies, and the Innate Immune system, determine whether you get infected in the first place, and that T-cell and B-cell memory immunity mostly determine how sick you eventually get. There is, in fact, a significant amount of overlap. For instance, higher levels of Neutralizing Antibodies seem to play a role in limiting the spread of the virus from it’s initial foothold in the respiratory epithelium, and hence also contribute to limiting the severity of disease. A recent study from Science, referenced below, shows in humans that the vaccines we are using now fail to generate significant levels of NABs and T-cell/B-cell memory cells against Omicron in the secretions and epithelium of the respiratory track, making the development of topically administered vaccines of paramount importance. Of note in these experiments is the finding that prior infection is much more effective in generating this mucosal immunity than the vaccines…duh.

Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination https://www.science.org/doi/10.1126/sciimmunol.add4853

The Innate Immune system is the rapid action division of our protection, and recent evidence in preprint details how BA.5 is more adept at side stepping this than most of the earlier variants. The Innate system relies on the immediate release of a potent antiviral chemical, Interferon, which then triggers the action of a wide variety of downstream genes, whose products activate cellular defenses. These series of experiments now show that BA.5 very effectively inhibits this Interferon system, and consequently replicates much more rapidly in the cells of our respiratory track than the original Wuhan, Omicron Original and the other Sons of Omicron. BA.5 is packing this punch, in addition to its near complete evasion of NABs created to the ancestral Wuhan spike protein. It’s down to our still effective T/B-memory cell immunity, which is preventing BA.5 from completely filling hospitals and ICUs. Anyone who doubts that the continued, uncontrolled replication of this virus around the world could lead to the sudden appearance of a variant with even more immune evasion and general nastiness, can contact me later about acquiring partial ownership of a popular bridge for sale in Brooklyn.

https://www.biorxiv.org/content/10.1101/2022.07.12.499603v1

The last virus for review today is the recently infamous parechovirus. The CDC just alerted us to an apparent increase in the number of cases around the country. This is a disease of children, and mostly very young children. The vast majority of cases lead to a relatively mild illness with some respiratory symptoms, fever and sometimes a rash. Unfortunately in young infants, especially under 1 month and up to 3 months, the disease can be much more severe and cause a sepsis like picture with infection of the spinal fluid and brain. The ability to accurately diagnose this viral infection is a relatively new development at most community hospitals. My initial reaction was to think that perhaps we were simply seeing an increase in the diagnosis of a virus which has always been around, and is known to peak in the summer of alternate years— for completely unknown reasons. An article appearing in this weeks MMWR has changed my thoughts on that.

Notes from the Field: Cluster of Parechovirus Central Nervous System Infections in Young Infants — Tennessee, 2022 | MMWR https://www.cdc.gov/mmwr/volumes/71/wr/mm7130a5.htm

At this Tennessee children’s referral hospital, the ability to accurately and rapidly diagnose parechovirus has been in place since mid 2018. During a 6 week period of April through May of this year, they diagnosed more cases (23) of severe meningoencephalitis than during 5 months of a similar “baseline period”. Other locations around the country are reporting a substantial increase in cases, like the cluster from Tennessee. Perhaps this is another manifestation of removing the social distancing regimens which were in place previously for COVID. We certainly have seen similar increases in other childhood viruses, and disruption of previously well established patterns of seasonality. The vast majority of people have been infected by this virus during childhood and are immune. Parents of older toddlers can be reassured that disease occurring after early infancy is almost always mild and benign.

I was going to introduce all of you to a game I have invented where you score points by using your hard earned knowledge of the last 2 1/2 years to match stupid or inaccurate statements and policies about COVID and the Pandemic with politicians from around the world. You are going to be spared however, since I’m still pitching it to Milton Bradley. They seem interested, but warned me I might want to enter the witness protection program if they decide to market it.

Thanks for spending time with the Viruses, be well and please, indicate the Like Button, forward and subscribe. Comments are welcome.