Warm Beer or Cold?

Quick, roll up your sleeves and take one (or two?) for the team.

On September 23 the CDC updated their guidance to inform us that hospitals and other healthcare facilities, which are not located in counties with high COVID transmission, no longer need to require the wearing of masks by patients, HCW and visitors. That would encompass a substantial portion of the country at this moment. It’s not hard to see the glaring problems with this decision, but it is difficult to understand the motivation for the CDC’s apparent race to the bottom for respect in the scientific realm and trust in the public domain. After all there are only 30,000 people still hospitalized with COVID and 400 per day dying. We know that official counts of new daily cases are a fiction; the CDC tells us this, and common sense confirms it. States and counties are winding down their public testing, and very few individuals are reporting their positive home antigen tests. So the metric which the CDC suggests should be the defining criteria of whether masks need to be worn in a healthcare facility is completely fallacious. Further recourse to common sense leads to consideration of who comprises the majority of hospitalized patients; and that would be the elderly, the immunocompromised (both groups less likely to have responded to their vaccine doses) and those severely ill with co-morbid conditions. Doesn’t really seem like the ideal environment in which to stop using a low tech, low cost mitigation technique of proven effectiveness, when we are dealing with perhaps the most contagious virus ever seen. I thought the prevention of infectious disease acquisition IN THE HOSPITAL was a primary goal. It does seem true that Omicron variants so far have been less severe than earlier variants, but it might not take a genuine slugger to knock off the elderly guy Joseph, down the hall from the nursing station, with diabetes and congestive heart failure. Perhaps there is a 10% or even 2% chance that having his roommate’s visitors wear masks will keep Joe clear of the ICU or the morgue. I suppose the mavens at the CDC weighed that protection against the inconvenience and irritation of the completely well people in this setting, and Joe came up short. Before you accuse me of being a conspiracy theorist, I want to go on record that I definitely do not believe that this is part of any co-ordinated government plan to diminish Medicare program costs going forward.

In the nearly four weeks that the new COVID bivalent boosters have been available approximately 5 million or 2% of eligible people have received them. The CDC recommends that people at least 2 months out from their most recent booster or 3 months out from most recent infection take a booster now. Is there any solid science backing up that timing recommendation? As far as I can tell the best the CDC can offer is reasoning along the lines of: BA.5 is very prevalent now, so you should get your shot of the new vaccine, ASAP. In previous posts I discussed the relatively meager, nonhuman evidence for an advantage of the new vaccines in terms of neutralizing antibody production, and the lack of any clinical evidence that they will offer a substantial increase in protection, particularly for people with three or more doses of original Wuhan vaccine and those with hybrid immunity.

As far as the CDC timing recommendation goes, it turns out there is quite a bit of scientific evidence suggesting that a much longer interval between booster doses would make more sense. During primary vaccination it has been recognized that significantly higher peak NAB (neutralizing antibodies) are reached, and maintained for longer, when there is more time between the initial two doses. NAB levels after vaccination decline and then plateau around 6 months, and other data shows that the degree of increase in those levels following a booster dose is inversely related to the pre-booster level. In other words, if you start with very high levels of antibody before the dose (as you would have 2 months after your most recent booster) then you don’t get much of an increase. You can almost hear the conversation in the lymph nodes with T cell saying to B cell, “Bob let’s not waste a lot of effort with this one, I think last month’s inventory is more than sufficient, but if we get a really novel order from China right before the holidays we might need to really crank it out”. Memory B cells and T cells, (which have a great deal to do with both how sick we get from the disease, and how well our immune system can recognize invaders that are similar to but different from the initial virus in the vaccine) both continue to mature in their response repertoire over six months. Remember being told over and over, “You might catch COVID but your vaccinations will still be working to protect you from severe disease and hospitalization”? Well, that is largely true, assuming you have an intact immune system, and are not in extremely tenuous health for other reasons. Beyond this evidence favoring a longer interval between boosters than the new CDC recommendation, is the theoretical concern of overdosing the immune system and creating tolerance to the protein of interest. That is what immunotherapy for allergies accomplishes. Frequent administration of the allergen causes your immune system to ignore the foreign substance. It’s going to be a long cold winter with lots of indoor gathering, especially around the holiday period at the beginning of the new year. It’s also a good bet that another variant will supplant BA.5 in the next few months (BA.7 and BA.2.75.2 are contenders to watch). Shooting at a moving target with the variant specific RNA spike vaccine approach is not a logical or sustainable approach with a virus that has shown such rapid evolutionary adaptation.

I mentioned BA.2.75.2 in my last post and this variant is being looked at closely with expansion noted in several countries currently. It is of concern because of very extensive escape from vaccine and prior natural immunity. Below is a link to a preprint appearing last week demonstrating this variant’s high level resistance to Evushield (that is the monoclonal antibody combination which has been available for prophylactic use in people with compromised immune systems). In addition, this variant is significantly less neutralized than BA.5 by serum from recovered people (6.5x less sensitive). There is absolutely no predicting the evolutionary path of COVID with certainty, but a variant with an enhanced ability to evade the immunity of the masses of people recovered from BA.4/.5, and a Spike protein with the highest affinity for the human ACE2 receptor of any variant thus far seems like a contender in the race for next “Bad Boy”.

Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies

Daniel J. Sheward, et al.

doi: https://doi.org/10.1101/2022.09.16.508299

During the Pandemic, the UK has been a fairly reliable canary in the coal mine for what’s about to happen in the US three to four weeks later. The ZOE health Project is an app based tool following 500,000 Brit’s symptoms and home administered COVID tests. In the last 2 weeks they are detecting a 30% increase in new cases. The official tally from the NHS is only a 13% case increase, but a 17% increase in hospitalizations last week. ZOE data is reported to be a leading indicator of what is recorded by the National Health Service, so this may be the start of the next cold weather wave. For more on this see the link below. It’s worth noting here that the UK decided to go with a new vaccine formula which targets original Wuhan and BA.1, the first Omicron variant, and not BA.4/.5 as ordered by the CDC. Also, the UK is recommending the new booster only for people over 65, pregnant, front line HCWs and some other very high risk persons. But then again the Brits like warm beer—how could they be right about anything important?

https://www.cnn.com/2022/09/27/health/uk-fall-wave-covid-us/index.html

Finally I’d like to discuss a fairly disturbing report from Germany published in Radiology. Using a low intensity MRI scanner they were able to evaluate the lungs of children recovered from COVID over variable time intervals, and a group, average age 11, with ‘Long COVID” syndrome. They looked at the match up of areas of the lung which are being ventilated and perfused with blood simultaneously (V/Q match). They found that compared to normal control patients both the COVID recovered children and the “Long COVID” patients had a significant reduction in V/Q match. That suggests a measurable reduction in the pulmonary function of gas exchange even in the children with no lingering post COVID complaints. One would think that given the tens of millions of children who have been infected, we would have had an avalanche of reports of a sudden decline in student athlete performance if these MRI findings were functionally significant. This is however, uncharted territory and we will need further confirmatory studies. Are these changes something that may take years to manifest as reduced pulmonary reserve, and accelerated “aging” of lung function? It is anybody’s guess right now. Here is the link below.

Pulmonary Dysfunction after Pediatric COVID-19 Published Online:Sep 20 2022https://doi.org/10.1148/radiol.221250

I generally have avoided the subject of long COVID, there is so much pure speculation about: how common it is, how to even define it for study, how much economic impact it will have, is it fundamentally different from chronic fatigue states that can follow a variety of severe viral infections. I will just reiterate my belief that it will fall into three broad categories: damage done, to blood vessels and organs, ongoing inflammation from persistent immune dys-regulation or persistent viral antigens, and somatic complaints of psychological origin.

The holidays are fast approaching and with the meteoric rise in the dollar this might be a good time to lock in some toys made in China. Popular items this year are a Trump doll that has nice hair and reminds you every few minutes what a great toy it is. Then there is Papa Joe Big Guy doll that wanders around asking what day it is and recommends ice cream flavors. Finally, there is a Putin doll which comes with its own bunker and dispenses cyanide capsules to the trick or treaters.

Thanks for your interest and attention.