Viruses, Bacteria and Fungi Never Rest

China’s second COVID wave is now underway

One certain thing all humans share is the regular need to take a rest. It might be our diurnal sleep cycle, or a rest from behavioral impositions which run counter to our cultural habits: wearing masks constantly in public, physically distancing from everyone and avoiding hugging and kissing friends and family, washing hands after touching basically anything in the environment other people might touch. We all understand now that wearing a mask to walk to your table in a crowded restaurant and then removing it for an hour and a half was absurd theater. But even if early on you apprehended this fact, and were otherwise the most compliant mask wearer—after six months or a year of preparing every meal at home, most people used to dining out several times a week were seduced into thinking—“OK this is safe I am following the rules”. You got tired and needed a rest, because you’re human, and like Anthony Fauci, Rochelle Walensky, Joe Biden etc., and you caught COVID. Maybe you think you’re a NOVID, chances are pretty high you had asymptomatic infection or just brushed off a froggy throat, a day of “low energy” or sore joints. Viruses, bacteria and fungi never get tired.

COVID in particular isn’t weary, and despite the memo announcing the end of the Pandemic, is unleashing its second wave on China right now. China delayed the inevitable reconning with the virus through the most draconian policies on the planet—well maybe North Korea beat them out for first place, we never know what goes on in that little communist lunatic asylum. When the Chinese got tired, and the regime sensed it might be loosing control of the beleaguered people, the COVID controls went from 110% to 0% overnight. That unleashed the massive wave of BF.7 and BA.5 there starting in December, and infecting an estimated 80% of the population in the country which bragged it had beaten COVID. The R value of the epidemic (a measure of how many forward cases are transmitted from each new infection) reached a staggering 16, with new cases doubling in less than 24 hours. The only problem was, these Omicron derivatives were already old news in most of the rest of the world. So while that virus swept through China crowding out anything different, the new and improved XBB family was spreading everywhere else in the world, and patiently biding its time to ricochet back for a Chinese tour. This week a top epidemiology official in Beijing announced that new XBB infections are estimated to be 40 million a week now, and modeling shows a projected peak at the end of June of 65 million a week. Let’s say for argument’s sake that they average 50 million cases/ week over the next month and that the virus now has a mortality rate of only 1/10th what is had been earlier in the Pandemic, or .1%. Those conservative estimates suggest that China could see 200,000 deaths over the next 6-8 weeks. Not too shabby for a virus whose Pandemic is over. The difference this time around is that the government has stopped telling everyone they are going to die if they don’t follow orders, and there will be no attempt to shut down the just recovering economy. Any hope that China’s approach to the Pandemic somehow allowed them to get away with a one and done COVID wave has just evaporated. Of course we will never know the truth, but it’s a certainty the Chinese government will not be exaggerating case and death numbers. China, like the CDC has slowed the pace of its COVID statistics collection and reporting.

This week’s update will be a potpourri of information, observations and advice—never loose sight of the fact that you get what you pay for. The Monkey Pox (MPOX) epidemic was controlled nicely but not eradicated. A recent spike in US cases, and low level persistence over the course of the last year suggests that we may not be able to eliminate this scourge, and it is on a path to endemnicity. A recent publication in the NEJM shows that the Jynneos smallpox vaccine, which was emergently pressed into service against Monkey Pox, and given intradermally at 1/5 the previously approved dose, had a vaccine efficacy of 36% following one dose and 66% after two doses. (For more information on that see my post “Monkey Business with the Pox Vaccine” 9/9/2022) My take home from this is that the rapid control of disease transmission was in large part due to behavioral changes in the population at risk. We can assume that since: transmission was rapidly abating while many folks at risk were not yet vaccinated, and now we have data showing the vaccine was mediocre in performance. This is a situation where the mode of transmission was clear from the beginning, and despite some minor false starts due to political correctness, the Public Health messaging and vaccination campaign was on target. Kudos to people at risk for their rapid acceptance of vaccination and other precautions.

https://www.nejm.org/doi/full/10.1056/NEJMoa2215201

Next is some advice about Mexico. Don’t go there for surgery. Don’t go there to buy drugs, and for God’s sake don’t go there to sell drugs, there are some locals who really frown on competition. This story started in Durango, Mexico with the occurrence of a severe form of fungal meningitis (Fusarium solani) caused by the injection of contaminated epidural anesthetic medication. This occurred at several clinics and ultimately 80 people were infected, of whom 39 died and some are still under treatment. Now an outbreak of the same infection has occurred under the similar circumstances in the northern Mexican town of Matamoras. The place is popular with Americans looking for discounted plastic surgery rates. So far 7 cases of this same infection have been identified with 4 in Americans, but the CDC just announced that more than 200 Americans are felt to be at risk after having had recent surgery in Matamoras. This is an extremely nasty infection with a high mortality and morbidity rate despite proper treatment. There are some things it’s just not worth trying to save money with—gas station sushi and condoms from North Korea come to mind.

Finally I’d like to discuss how prepared we are for the next Influenza pandemic, when (not if) it occurs. The problem is we don’t know which strain of Influenza A that will be. We will be in much better shape if it’s a typical human influenza, even one with a major antigenic shift, given our accumulated immunity from vaccinations, repeated infections, and in the developed world at least, the benefit of modern medical care and antibiotics to combat secondary bacterial infections. Only one of those weals, prior infection immunity, was operative during the 1918 Influenza Pandemic, and 80 million people died, nonetheless I put a lot of faith in the other advantages as long as we are dealing with a human Influenza strain. The picture is substantially different if the Influenza that comes knocking is an Avian virus, say H5N1, or an H7, or H9 strain which has adapted and jumped over to humans. As you know H5N1 is high on my radar given its spread around the world in hundreds of millions of birds and many mammalian species. Over the last two decades, the several hundred humans who have been infected with highly pathogenic strains of Avian Influenza have had mortality rates in the 50% range. That’s a big number considering COVID had a general mortality of perhaps 1%, and that figure was substantially pushed to that level by the virus’ efficiency in killing the old and infirm. Most of the people who have contracted Avian Influenza have been individuals working in the poultry industry or home farms, and a good bit younger and more fit than the majority of COVID victims. So an Avian Influenza pandemic could quite possibly have a mortality rate higher than 50% in the elderly or compromised. In that scenario, a shortage of ventilators would be quickly eclipsed by a shortage of refrigerator trucks.

The labor intensive method of traditional Influenza vaccine production depends on a ready supply of millions of chicken eggs—a dicey proposition in the middle of an Avian Influenza Pandemic.

Since our health care capacity was briefly overwhelmed by COVID with its 1% mortality, it seems clear that the advantages. of modern medical care would be nullified in the setting of a highly contagious respiratory virus with 50% mortality and no prior population immunity. That leaves vaccination as the only leg up we would have to avert a 1918 type outcome, or even worse. More than a a decade ago our government set up the NPIVS (National Pre-pandemic Influenza Stockpile). The strategy was to have about 20 million doses of various strains of Influenza vaccine which could be used to vaccinated the “critical members of society”: the healthcare workers, first responders, food chain workers (and I’ll bet your favorite Congress person)—while they set about producing a vaccine which more closely matches the new circulating virus. Those 20 million doses would disappear quickly (trust me there would be a lot less vaccine hesitancy if a virus with 50% mortality among the middle-aged and healthy started carving through the population. Remember that Warp Speed gave us the fastest vaccine development from genomic sequencing to clinical release in history, but that was still 9 months; if we have to rely on the traditional chicken embryo method of Influenza vaccine production it could be longer. Again, you are potentially looking at a lot of refrigerator trucks. What about expiration dates on all that stored vaccine? The H5N1 supply was formulated with a viral isolate from Vietnam in 2004, and in 2018 the government (BARDA) undertook a study to evaluate the immunogenicity (how well it works to produce antibodies) and safety of this vaccine which had been on the shelf for over 12 years—now of course 17 years. They tested the vaccine for antibody levels against 6 different H5N1 strains circulating around the world with the most recent being a 2014 virus.

Safety and immunogenicity of influenza A(H5N1) vaccine stored up to twelve years in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) https://doi.org/10.1016/j.vaccine.2018.11.069

While no individual or pooled group met the FDA Center for Biologics Evaluation and Research (CBER) accelerated approval license criterion [16] for post-immunization titer ≥40 (i.e., lower bound of the two-sided 95% CI for the percent of subjects achieving an HAI antibody titer ≥40 should be ≥70%), pooled group comparisons indicated that subjects receiving 7.5 µg HA + MF59 (Groups A + C) and 15 µg HA + MF59 (Groups B + D) showed significantly greater SPRs of HAI antibodies on D42 (65.9% and 64.0%, respectively) compared to subjects vaccinated with 90 µg HA alone (Groups E + F) (34.1%)

The study is a little complicated by the fact that the authors investigated whether they could improve the immunogenicity, also stretch the supply, by testing lower doses of the vaccine antigen mixed with an adjuvant (a substance which enhances the immune response to a vaccine antigen) as well as the original 90mcg dose. The good news is the stored vaccine remains safe with a typical short term side effect profile for approved vaccines. The less than good news is that overall only 58% of subjects reached what is considered a protective level of antibodies. (If this is your thing check the paper directly, some of the groups with adjuvant did a little better). Unlike COVID, decades of studying Influenza has given us a pretty solid understanding of the level of antibodies needed to protect against infection. If you’re thinking, “OK maybe the antibodies won’t be high enough to prevent infection, but the vaccine will turn on T cells to limit the severity of disease,” then you have a good understanding of the immunology at work. The problem as I see it is that a vaccine with this level of efficacy won’t do much to prevent wide spread community transmission, and most importantly the supply will be highly limited in distribution during the first year of the pandemic. Final point for today is that the modest activity of the stored H5N1 vaccine, 5 years ago, was measured against historical strains of H5N1 with the most recent from 2014. H5N1 has been mutating steadily since then and is now on a rampage around the world, with a significant new evolutionary adaptation allowing it to infect all sorts of mammals for the first time. How much that genetic change in the virus will affect the efficacy of the stored vaccine is anybody’s guess, but I wouldn’t bet on it being favorable.

Now that I have had an opportunity to get you into the holiday mood, be sure to enjoy the Memorial Day festivities. Remember our veterans, those serious people who made it possible for those of us who are Jewish to be here, and the rest of us to be speaking anything other than German. If you asked any of them for their pronoun, they would have said, “American”. Please share “Clear and Present Thinking” along with the hot dogs, hamburgers, potato salad, and corn—leave the chicken unless you’re sure it’s well done. Cole slaw is notorious for Listeria, ditto for any unpasteurized cheese, anything with Mayo and you’re risking certain Staph food poisoning. Forget the raw bar if your not immune to Hepatitis A, and think twice about swimming in the nice warm waters of the Gulf or our southern Atlantic coast, the range of flesh eating Vibrio species has been expanding. Be liberal with the insect repellant since Lyme Disease, Ehrlichiosis, Anaplasmosis, Heartland or Powasson Virus can ruin a good time—not to mention the pesky mosquitos carrying West Nile and a bunch of encephalitis virus surprises. In short have a terrific, care free holiday experience. The like button will ward off all these inconveniences.