COVID Update

Or How We Learned to Love Virus

I’ve had several inquiries about a non-COVID infectious disease issue that has been in the news, and I thought I would change the format a bit this week to address that, in addition to the usual COVID summary. Daily cases in the US have continued on a gentle straight line increase since hitting a nadir in the last week of March. During this six week period, daily new cases have gone from 30,000 to almost 80,000. Deaths are now showing a predictable increase as well, but still very modest at 500/day. It seems the body politic, the governing powers and the media are in sync with acting like the pandemic is essentially over. This parallels human behavior during the great Influenza Pandemic of 1918. By the time the later waves of disease arrived more than two years into the carnage, many locales, which had been very strict about social mitigation efforts, threw in the towel. Most people just resumed normal lifestyles and tried to ignore what were severe local epidemics, sometimes rivaling what had come earlier. As we saw last week, a free steak dinner in Washington now trumps the risk of voluntarily attending a predictable super spreader event.

In the prior post I hazarded a guess that the sons of Omicron would not have sufficient mojo to cause truly serious new waves of disease here in the US. I was correct about BA.2, but last week a preprint paper appeared from China that may indicate I was wrong about the other siblings.

https://www.researchsquare.com/article/rs-1611421/v1.pdf

A little background review is in order here. Earlier in the Pandemic, the success of a new variant spreading quickly and overtaking the dominant virus, was based almost solely on the variant acquiring mutations which increased its transmissibility. That could mean any of the following: the variant’s spike grabbed hold of the human receptor more avidly, the variant was able to fuse and enter the human cells after attachment more readily, the variant replicated faster and to higher levels in the upper airway of the people it infected (allowing them to spread more virus into the environment), or perhaps that the variant continued to have high levels of virus in the airway for longer periods of time. As the Pandemic evolved, and more and more people developed partial immunity from infection or vaccination, the advantage shifted to variants which could evade that immunity and still cause infection. Omicron was the prime example of this trend. Evolutionary pressure is now most definitely driving the selection of mutations which are Omicron immunity evasive. BA.2 was more transmissible, but lacked any significant degree of Omicron escape. It failed to cause a serious wave here in the US; which had just been Omicron man-handled like a hen house with a fox door. South Africa, with its extensive baseline immunity, is now in the midst of what certainly appears to be a full-fledged fifth wave. Cases over the last two weeks are continuing an exponential increase - and this is being driven by the Omicron sub-lineage BA.4, which we discussed last week. The paper out of China is the first to look at the relative ability of all the various Omicron derived variants to evade prior immunity. We are talking about boosted immunity from three doses of the Chinese vaccine (admittedly somewhat inferior to our mRNA vaccine) and also immunity from three doses of vaccine PLUS an Omicron infection. The paper is extensive, dense and comprehensive, but those results which are not above my pay grade show that BA.4 requires 8 times the neutralizing serum activity compared to Omicron. BA2.12.1, the variant which is rapidly replacing BA.2 around the US, is 3.7 times less susceptible to vaccine and Omicron immune serum. That is impressive, and given what is transpiring in South Africa reason for concern. The phrase, “I was wrong about that”, has been become a new favorite touchstone of mine during the pandemic, and a source of some encouragement, as it indicates I learned something new. Too bad it has not been equally popular among the illuminati guiding us from on high.

You have no doubt seen the reports of a new serious hepatitis of uncertain etiology causing severe disease in young children. The earliest cases appear to date from October and initially were reported from the UK, but it has now been seen in 28 countries. In the US there have now been over 100 cases and 9 deaths. This is occurring in very young children who present with fulminant hepatitis, and is clearly a new syndrome. The most likely candidate so far is an Adenovirus 41. This is a bug which has been recognized for some time and is not new to the scene. Most adenoviruses cause respiratory tract infection, or conjunctivitis. This particular type has been previously associated with gastrointestinal disease. Why is this happening now when the virus has been around and recognized for quite a while? My typical answer of, “Wrong bug in the wrong person at the wrong time”, doesn’t fit here. We would have recognized a steady background occurrence of this syndrome over time, and we are now seeing a large event occurrence spread across the world. My guess is the virus acquired some mutation that allowed it to infect liver cells and to direct the wrath of our immune system towards those cells. The first bit is taken from the history of Zika. That virus was recognized for decades in South America as the cause of a mild febrile illness of little to no consequence. All of a sudden it caused a wave of devastating neurological injury to developing human fetuses. This was found to be the result of the virus acquiring a single mutation that gave it the ability to infect human neural tissue. The second guess, is further out on the limb, but reflects what happens in fulminant Hepatitis B. That virus in itself is not cytotoxic to liver cells. Chronically infected, so called “immune tolerant” people can be infected for years with massive amounts of viral replication, yet minimal to no evidence of liver cell damage. When people rarely develop fulminant and possibly fatal Hepatitis B, it is because their immune system it triggered by the appearance of viral proteins on the surface of liver cells and sends in an army of cytotoxic T lymphocytes to destroy the infected cells. The immune system wins, and the patient dies.

On the vaccine front, the FDA has effectively withdrawn the J&J vaccine from the market, without formally removing it. The agency acted this past week, citing 9 deaths in the US from the devastating vaccine complication TTP, which leads to uncontrolled blood clotting around the body. The vaccine was effective and certainly among the 18 million people who received it, many more lives were saved. The unfortunate reality is that most of these cases occurred in previously healthy young women, and many of the survivors are left with terrible, life altering complications. The final point of discussion is Pfizer requesting the FDA to green light booster doses of vaccine for the 5-11 yo age group. To date only 28% of that age group has received primary vaccination. Two weeks ago, the CDC revised their estimates of COVID infection in the population based on serum antibody surveys and not mathematical models. As reported in MMWR they found over 60 % of the total population has been infected and 75% of kids. That does not of course count multiple episodes of infection. Incredibly, it looks like Omicron infected 25% of the population between December and the beginning of March. There definitely seems to be a “group consciousness” at work, wherein many people assess risk by what they see and hear, on the street and in the local news, and make decisions based on that, rather than on promulgations from government public health authorities. There is no limb involved in making a wager that if the FDA approves this booster dose, that Pfizer, the CDC and the Administration’s marketing and messaging departments will have a hard sell.

Hope to connect with you again soon with good news. Plan for a lovely summer, but expect more COVID trouble in the fall. As always please share with anyone you think would find the information useful.