What Inning is it in the COVID Ballgame?

How Many are on the Injured Reserve List?

Those are questions at the top of many people’s minds right now, unfortunately we don’t even have a program to tell us who the COVID on deck-batter is. Worse than that, a very large number of our team are out with the virus, and the number keeps growing. Right on schedule, as predicted during its first month of appearance, BA.2.12.1 has now taken over from BA.2 as the most prevalent viral sub-lineage in the country. It is also driving the current, officially underestimated, wave of disease activity. In the usual pattern, it has spread from the northeast across the country, and most regions are now on the upswing. How badly is the CDC under estimating cases? Anecdotally it sure seems like a massive wave. F. Perry Wilson, the Yale epidemiologist, takes a good stab at estimating the true number of cases in his May 18 Medscape commentary: One Million COVID cases a Day? Utilizing the ratio of hospitalized cases to total case number, he shows very nicely that the ratio is now much higher than it was during the Omicron wave. Assuming that BA.2.12.1 is not substantially more severe than Omicron, and there is no reason to think it is, then the increased ratio must be due to the undercounting of non-hospitalized cases. Following this reasoning he estimates about 360,000 new cases a day. He then looks at national waste water COVID levels, and using retrospective norms relating identified cases to levels of viral RNA in the waste water, he comes up with a figure of 380,000 cases a day. Given that the CDC has estimated in the past that testing identified one half to one quarter of actual cases, Wilson makes the case that we may actually have over a million new infections a day. I don’t think we can necessarily assume that the proportion of infected people testing today is the same as it was in the era when you had to go to the mass testing site for a PCR, but even at the very reasonable 380,000-400,000 case per day level, we are higher than at any point in the Pandemic other than the peak of Omicron. Ashish Jha, the Administration COVID Coordinator, recently stressed that hospitalizations are at low levels despite the surge in cases; and while that’s true, we can expect them to rise substantially after the typical lag period.

What is unique about the variant du jour’s, ability to partially evade prior immunity might come down to one mutation at a site numbered 452 on the spike protein. The Delta variant, which caused so much trouble last summer, contained a mutation at that site which substituted the amino acid arginine for the Wuhan classic leucine. Specialists in protein structure identified this change early on as likely to interfere with immunity from the vaccine or prior infection, and they were correct. Omicron and the BA.2 variant did not have that mutation, and spread rapidly thanks to other wily changes in their structure. The current bad boy BA.2.12.1 has perhaps upped its game by combining many of the features of Omicron, plus a unique change, substituting glutamine at this immunologically critical 452 site. The combination of such subtle changes, together with the markedly reduced social mitigation efforts across the country are facilitating the rapid spread of the new variant. Some good news is that BA.4/.5 appears to be petering out in South Africa after threatening a large fifth wave. These variants contain the same argininine substitution as Delta at site 452, and it’s just possible that there was sufficient prior Delta immunity around to stem the expansion.

Anyone who has been reading these posts for a while will know that I don’t shy away from presenting new data that might conflict with my ideas and evidence based convictions. In short, I am not CNN, MSNBC or Fox news. I have been vocal about my opinion that properly worn, good quality masks help to reduce transmission, and this was supported last year by several studies reported by the CDC in MMWR. A new study in preprint form in The Lancet, from the University of Toronto, finds that masks in schools could not be correlated with reduced community incidence of pediatric COVID cases.

Chandra, Ambarish and Høeg, Tracy Beth, Revisiting Pediatric COVID-19 Cases in Counties With and Without School Mask Requirements—United States, July 1—October 20 2021. Available at SSRN: https://ssrn.com/abstract=4118566 or http://dx.doi.org/10.2139/ssrn.4118566

This is obviously of great importance, and the issue has engendered some of the most intense and vitriolic debate of the Pandemic. To very briefly summarize, the CDC paper last summer evaluated all the school districts in two Arizona counties which fit study criteria, and found that mask requirements in school correlated with a lower rate of community pediatric COVID cases. In order to assure their methodology was similar to the CDC’s, the current study authors first looked at the same time period and counties, and found the same negative correlation between masks and COVID cases. They then expanded their study to include many more counties around the country and extended the time frame by about 2 months. Looking at the larger data set they could not find a correlation. The results are disappointing to me, but are hardly the last word. For one thing both studies are looking at community wide COVID cases. Children spend a fraction of their day in school, and then take off their masks to play and interact with their friends, play on sports teams and go home to their parents and siblings, where they are exposed to the general community level of disease. Realistically, masks in school could never have been expected to lower the overall rate of pediatric COVID infection. A more practical goal was to prevent clustered infection events that would close classrooms, grades or whole schools. A child might contract COVID in the community and while pre-symptomatic or asymptomatic, masks could be expected to decrease their transmission to close school contacts. These studies are not equipped to investigate this potential benefit, but undoubtedly will be of great comfort and ammunition to those convinced of the futility of masks in schools.

There is no substantive new information on the Monkey Business or the syndrome of fulminant hepatitis in children, except that cases continue to increase around the world. Given a pox virus disease with an incubation period of 21 days, there is nothing surprising about the continued increasing Monkey Pox cases, which world wide number in the low hundreds. My intricate, proprietary epidemiological model continues to forecast that your risk of dying from Monkey Pox is similar to your risk of dying while base jumping in Kansas during a July snowstorm. Three competing theories have emerged regarding these micro pandemics which I think are worth examining. The first is that these diseases have been percolating along for quite sometime and we just never noticed them. I reject that for the childhood cases of hepatitis which have risen to levels in first world countries where it seems impossible they would have been missed. Given the historical record of HIV/AIDS in Africa that argument has some greater weight for Monkey Pox, but I still believe the novel means of transmission, and the modified clinical course observed currently would have been reported earlier. The second theory is that social isolation during the Pandemic has allowed immunity to a virus (possibly adenovirus 41) to wane to a point where many more children are getting infected, and consequently we are identifying cases of hepatitis due to this virus that were missed previously. In the case of Monkey Pox, the reasoning goes that immunity to pox viruses has been waning since we stopped vaccinating people for Smallpox in the 1970’s. The third possibility, which I favor, is that there has been a mutational change in the respective viruses, which in the case of the undetermined hepatitis virus has enhanced its pathogenicity or organ tropism. I’m also betting on small change in the Monkey Pox virus, but I’ll stay away from the high stakes table there.

Two items remain in the, “Don’t try this at home kids”, motif. The last Monkey Pox outbreak in the US was traced to the importation of Giant Gambian Pouched Rats, African Rope Squirrels and a few other rodents, which infected Prairie Dogs, all sold as exotic pets. A safer bet is to stick with pets your grandparents would have kept or at least heard of. North Korea watch reports that they have over 3.5 million cases of COVID in two weeks and the government has bragged they have only 65 deaths, or a .000018 mortality rate. That is markedly superior to any other nation in the world, and no doubt has to do with ordering pharmacies, which have no COVID pharmaceuticals to remain open 24 hours, and mobilizing the army to efficiently distribute acetaminophen and ibuprofen, along with a cocktail made from onions and earth worms. Before your criticize North Korea, realize that everyone there who is eligible for a vaccine dose is lining up and cheering. It’s all about the messaging, and we could learn a thing or two. Instead of calling it a vaccine, the North Koreans have mobile load speaker trucks announcing that it is a, “Supreme love potion gift from the Highest Dignity (that’s Kim). Who knows how it might have gone here if we had only substituted the names, Donald or Joe?