Living With COVID

Is There a POX Upon This House?

Living with COVID is turning out to seem very similar to the Pandemic phase, which we were recently informed had ended in the United States. I wasn’t quite sure what Fauci was talking about when he made that statement, after all cases in the US were already on the upswing again. The definition of a pandemic has nothing to do with the mortality rate of the disease in question, it could be anywhere from apocalyptic to simply makes everyone sick enough to skip dinner with the in-laws. A pandemic is the unrestrained spread of infection on a world wide basis, and we are certainly still having the rapid spread of COVID here and around the world. US daily cases continue to increase, and now are approaching the peak of numbers we saw during last summer’s Delta wave. Given our lack of accurate data, I would guess daily cases may well be even higher at this point. The New York City Health Department has just issued an “advisory” to begin masking again in indoor settings, as have other locales around the country. Portugal is having an extraordinary surge in cases, that has eclipsed their Omicron wave, and shows no sign of letting up. Experts on North Korea are predicting an unprecedented mass death event, the true magnitude of which we will likely never know. On the bright side, there has now been ten days of slowly declining cases in South Africa, suggesting to me that BA.4/BA.5 will not have sufficient escape from Omicron immunity to cause a massive wave in the short term. For anyone who thinks we will deal with BA.2.12.1 as a one and done — I have a time share in Kyiv I’d be willing to let you have a bargain price.

Why should we be concerned about getting COVID at this point with our vaccinated and boosted, or double boosted status? In the last post we looked at how short lived and incomplete is the bump in protection from infection offered by booster doses. Beyond the risk of acute disease, and even severe disease or death, what we know and don’t know about Post Acute Sequelae of COVID Syndrome should be on your radar for risk assessment. You are probably familiar with the long list of symptoms which have been reported. Many symptoms of course are subjective in nature, but now we have published research showing a variety of hard, measurable endpoints most of us would like to avoid. Studies have shown an increased rate of cardiovascular events, stroke, MI and heart failure, persisting for months after recovery from acute COVID. MRI imaging has revealed a reduction in brain grey matter in patients recovered from COVID versus matched controls. I’m reminded of Woody Allen’s quip, “The brain? It’s my second favorite organ”. Early in the Pandemic, doctors observed that soon after hospitalization a significant number of patients experienced a metabolic derangement with elevated glucose levels and insulin resistance. This was seen both in patients with a prior history, and de novo in others with no history of diabetes or pre-diabetes. Later studies confirmed an unexpectedly high rate of new diabetes developing in both children and adult convalescents during the months following the acute infection. There has been controversy about whether the SARS2-Cov19 virus directly infects pancreatic B cells (the source of insulin production and excretion) but this appears to be settled by two recent papers in Nature and Cell Metabolism.

https://doi.org/10.1016/j.cmet.2021.05.013 Wu, et al. https://www.nature.com/articles/s42255-021-00347-1 Muller, et al.

Taken together, these researchers demonstrate that the virus infects human pancreatic cells and replicates in B cells. It impairs their response to glucose and triggers activity in cellular pathways of programed cell death or apoptosis. For a broader summary of the issues which have been identified so far in Long COVID, I’d refer you to Ezekiel Emanuel’s article in the Washington Post of 4/12/22: Stop dismissing the risk of Long COVID.

It has been difficult to get a handle on how much risk of developing long COVID one actually faces, and who is even at risk. Now a White Paper, put forth by Fair Health on May 18th, seems to provide some of the most comprehensive analysis to date. Their data is based on all US private insurance claims from October 1, 2021 to January 31, 2022 which included a newly introduced diagnostic code that captures symptoms related to Long COVID. The results are striking. 75.6% of patients with a Long COVID diagnosis had not been hospitalized. The elderly (or at least the 50-65 yo group since Medicare was not included) were not the most frequently affected; 35% of patients were in the 36-50 yo age group. Since only 8.4% of patients with a COVID diagnosis were hospitalized and 24.2% of Long COVID diagnosis occurred in the hospitalized cohort, it is obvious that the risk of persistent symptoms is highest in the group with severe initial disease. The fact remains however, that the majority of people who will suffer long term symptoms have had mild to moderate initial disease.

This week the FDA approved booster doses of the Pfizer COVID vaccine for the 5-12 yo group. This was based solely on demonstrated increases in neutralizing antibody levels, (which we now know decay rapidly over an 8-10 week interval) and not on any demonstration of vaccine efficacy in reducing infection rates, or any impact on the more rare occurrence of severe disease. In my prior post, I suggested I thought this would be a hard sell to parents with only 28% of the young demographic primarily vaccinated so far—let’s see how that goes. Last week the Los Angeles County public school board announced that they are “delaying” the implementation of their vaccine mandate for students 12 and older until summer 2023. Also, the Louisiana Department of Health just announced they are scrapping the COVID vaccine mandate for all students K-12, which was scheduled to go into effect for the 2022 summer school session. This of course is not because we have vanquished COVID, but an acknowledgment that only in the Looking Glass World can you mandate a vaccine which during the Omicron era produced an efficacy in disease prevention, and therefore transmission, of about 14% in the younger age group at only a few months after the last dose. Back on February 18th I wrote ,“The Disappearing Vaccine Mandate”— that one has aged pretty well.

On the therapeutics side, I was intrigued by a STAT article by Dr. Paul Fenyves of Weil-Cornell Medicine, “Does Paxlovid work in people vaccinated against COVID-19?”. After all, the trial demonstrating the impressive 89% advantage in preventing hospitalization was conducted on non-immunized people. Mechanistically of course, there is no reason to think the drug would not exert a similar or better antiviral effect in an immunized person, but the question becomes how necessary is it? What is the N needed to treat to prevent one hospitalization or death? There is a Pfizer trial ongoing now that might answer the question.

Finally I will end today with the Monkey business. I am going to assume everybody has been devouring the news this week about the outbreak of Monkey Pox in Europe; and with cases now in the US, Canada and Australia, so far there are about 100 cases and growing. I will also assume that if you have been reading the news you currently know more about Monkey Pox than 95% of physicians did 2 weeks ago. I will limit my comments primarily to some speculation. This is not going to be the next Pandemic, nor even much of a big deal for the the vast majority of people. There have been limited outbreaks of Monkey Pox outside West Africa in the past. What is unusual now, is the pattern of sexual transmission being observed. Clusters of infection have been seen in groups of sexually active bisexual and homosexual men. Of course it would come as no surprise that a disease which is spread by contact with pustular skin lesions, or droplet to mucous membrane, can be transmitted sexually. The point is they have not previously seen such efficient sexual transmission and clusters of sex related cases in Africa, and I’m guessing there is a healthy amount of sex there too. The logical assumption is that this Orthopox virus, a relative of Smallpox, has acquired some novel mutation which is allowing a bit more efficient transmission. It also appears from early reports that the typical clinical presentation is a bit different than the classic disease. A CDC alert informs us that the rash may appear in atypical genital locations without the usual prodromal period of fever and lymph node swelling. A preliminary sequence of the viral genome has just been released yesterday in preprint, suggesting that no major changes are noted from a reference strain that has been prevalent in recent years. A more in depth analysis should follow quickly, and as we know from Zika, minor genetic changes can have a vast impact on the pathogenicity. The Pox is readily identifiable by skin lesions when the person is contagious, and this is an acute illness, not a Trojan Horse like HIV, where a person can remain well for years unknowingly spreading the virus. These outbreaks should be rapidly controlled despite the somewhat novel clinical course. The US government has ordered $119 million worth of Monkey Pox vaccine, reasonable under the circumstances I guess, but I really didn’t need that to sleep at night.