Rats and Humans Have a Long and Sordid History

Open your windows

There are a number of items I plan to cover this week, and not spend a great deal of time on each, but supply links for further reading. Paxlovid when it first debuted was extremely effective in preventing COVID hospitalization and death, but it seems everything has changed rapidly during the Pandemic, and Paxlovid hasn’t been spared. Although the original drug trial showed an 85% efficacy in reducing hospitalization and death, in a large community study between December 2021 and December 2022 the efficacy was found to be 65%

Effect of Nirmatrelvir/Ritonavir (Paxlovid) on Hospitalization among Adults with rrrCOVID-19: an EHR-based Target Trial Emulation from N3C

https://doi.org/10.1101%2F2023.05.03.23289084

Now it’s not unusual for drug efficacy to be lower in the real world than in clinical trials, and 65% was still impressive. That brings up the question of how the quite expensive Paxlovid is performing currently. The most recent data on this issue is a UK medrx preprint study from late May (a part of the huge UK-RECOVERY trial) which was a randomized comparison of antivirals to usual treatment alone. Paxlovid was found to have absolutely to effect on improving the outcome of hospitalized patients with COVID pneumonia. Molnupiravir, a drug I never thought was worth much, also failed.

Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, trial.

What exactly has changed? This trial was conducted during the Omicron era from March 2022 through May 2023, but the Omicron mutants all seem to have retained sensitivity to the drug. The biggest change is likely to be that Paxlovid was extremely effective in early 2021 when nobody was vaccinated, and were naive to infection. Now that the population is highly vaccinated and multiply infected, our cumulative immunity appears to have rendered Paxlovid superfluous. Caveat: this was a relatively small study and looked only people already sick enough to already be hospitalized with COVID pneumonia, so it’s possible the drug might still have a role in protecting very compromised people, but only earlier in their disease course. For quite a long time now I have advised against taking Paxlovid, unless you are at significant risk for critical disease or death, it does not have any significant role in reducing duration of symptoms, and you are already aware of the familiar the story on increased viral rebound.

While the finding of zero efficacy for Paxlovid in COVID pneumonia was surprising to me, the next entry into the ledger of Paxlovid’s demise is not. A large trial of 15 days of Paxlovid for Long COVID has failed, and was stopped early because it worked no better than placebo. When trials of this nature were first announced, I predicted Paxlovid would fail. Only a tiny percentage of Long COVID sufferers have been shown to have definite ongoing replication of the virus many months or years after infection, and that’s the only logical instance where Paxlovid might conceivably be helpful. The current crop of trials has enrolled patients based on the non-specific cluster of patient reported symptoms, so the chances of success were miniscule. I’m not anti-science, in fact I quite like it; but scientists should stop wasting our tax dollars and time on extremely low reward, high cost research. Predictably, researchers involved in this study and others working in the field, responded to the results with comments along the lines of: “Well this is disappointing but we need more studies to see if longer courses of Paxlovid might work, or if certain subgroups of patients with particular symptoms might benefit, or perhaps we should have treated people whose symptoms had existed for only 8 weeks instead of 16 weeks.” When you’ve got a hammer and get paid to use it, everything looks like a nail. Recently I discussed the blizzard of fake scientific articles flooding the academic world; there is also a problem with silly or superfluous research proposed almost exclusively for the purpose of padding academic bibliographies and funded, in the case of social studies grants by bureaucrats with highly biased social agendas, or in the case of medical research by bureaucrats overwhelmed with grant proposals. In 2022, the NIH funded 58,300 extra-mural grant proposals, a 3% increase over the previous year, for a total of 33.5 billion dollars. No less an authority on funding grant proposals than Dr. (I’ll stick with the title thank you Marjorie) Anthony Fauci said during his most recent testimony to Congress that, “It would be impossible to look into all the details of every grant we fund”.

Mice in New Mexico are the latest mammalian species found to be infected with highly pathogenic Avian Influenza H5N1. Rats will not be far behind in the advance of what I’m touting as the “Most Successful Virus” in history. Most people, especially in dense urban environments, which are ground zero for pandemic pathogen spread, don’t have contact with poultry, cows or pigs—but like it or not they have an intimate relationship with mice and rats. New York City has a Rat Tzar, so little imagination is required to appreciate that H5N1 infection of these vermin will provide astronomically increased contacts of the virus with humans compared to dairy cows in Michigan. Besides the “‘Black Death” that killed perhaps 30% of Europeans in the 5 year interval from 1347 to 1352, Bubonic Plague had repeated waves over 500 years with the last occurring in India in the late 19th century. Besides the bacterial agent of Bubonic plague, Yersinia pestis, rats and mice also transmit to humans: Salmonella, hantaviruses, Toxoplasmosis, Leptospiosis, lymphocytic choriomeningitis virus, Tularemia, Rat Bite Fever, Lassa Fever and no doubt others I have forgotten. More infections of humans gives the virus the mathematical edge to randomly hit upon mutations which will allow its more efficient transmission between humans.

It’s official now, the CDC has published their recommendations that people take doxycycline 200 mg the morning (and up to 48 hrs after) unprotected sex to reduce the incidence of chlamydia, gonorrhea (GC) and syphilis, which have skyrocketed in the last few years. This applies only to men who have sex with men, plus a prior STD in the last year, as studies have found this post-exposure prophylaxis effective in this group, but not in women. Short term follow up studies showed efficacy in the 87% range for preventing Syphilis and Chlamydia, but only 65% for GC. No surprise there, as GC has far greater ability to develop antibiotic resistance. Small numbers (not statistically significant) of GC cultures obtained after treatment showed at least low level doxycycline resistance had developed. The folks pushing this treatment to stem the tide of STDs are suggesting that concerns about increasing doxycycline resistance are exaggerated, but if you ask me, I’d bet that throwing that much antibiotic around when there are already significant numbers of low level doxycycline-resistant GC strains in the country has a predictable outcome. Too bad, doxycycline was always one of my favorite antibiotics—a broad spectrum oral drug that would be my first choice to have if stranded on a deserted island, after nuclear war, zombie apocalypse or disputed election. Here is a throw back to the “Just Say No” era.

Fresh air is good for you; the designers of early 20th century hospitals and clinics knew this, and they laid out large hospital wards with huge windows to create cross ventilation. Our obsession with thermal efficiency caused this fairly simple knowledge to fall by the historical wayside, and long before the SARS2 Pandemic people were suffering from symptoms of “sick building syndrome” due to ghastly inadequate ventilation. Some of us, (not the CDC or WHO) picked up on the scientific evidence for aerosol spread of the virus quite early in the Pandemic, and the importance of increasing fresh air ventilation of indoor spaces. Some of us took to carrying around small CO2 meters (the surrogate marker for how many times the air in the room had already been breathed out by humans) and avoiding locations with outrageously high levels. With the support of the local Public Health Department and San Miguel County, I made surveys of local schools, pre-schools, restaurants and other businesses who were interested in measuring their indoor ventilation, and finding ways of improving that. So we knew, or should have known, that the more the air was rebreathed (higher CO2) the more COVID (and other aerosolized viruses) you would be exposed to. Your N95 mask, which is very efficient at filtering out viruses and protecting you when properly worn, was of zero use when removed for 98% of the time you were in a restaurant, or the time in the tiny unventilated break room of the hospital where you ate a meal and relaxed for a few minutes. Recently there is excellent experimental evidence that higher CO2 levels not only are a marker for poor ventilation, but also dramatically enhance the survival of the SARS2 viruses inside the microscopic exhaled respiratory droplets. Other factors once considered to be major determinants of virus survival, like temperature and humidity, are likely completely eclipsed by the effect of CO2. I won’t go into the details of the science other than to indicate that equilibrium between atmospheric CO2 and bicarbonate ion in the respiratory secretions profoundly affects the droplet’s ph, which in turn has profound effects on the surface proteins of the virus and determine its viability. For detailed information the link is provided below. Poor ventilation is a double whammy, exposing you to higher levels of viable respiratory pathogens, and all the noxious volatile chemicals found in modern construction. A plethora of people are writing today about, “What have we learned and how can we do better next time”; I thought I would skip that in today’s title for an increased chance you would be tempted to continue reading! Yes there is a powerful anti-vax trend, disinformation mills, a failure of trust in the government, Public Health and Science—at least some part of which is due to gross failures by our institutions. Human nature is hard to change, and people’s opinions once they feel they have been deceived (genuinely or simply by poor communication) can be fairly inflexible. Our society is missing the boat by failing to address this issue of improved indoor ventilation. It won’t be a one trick pony working only to mitigate COVID—that is certain. It is a non-pharmacologic, non-vaccine, non-mask, non-mandate, common sense approach; validated by experimental evidence and without political toxicity. I don’t think there are many people out there who would object to increased fresh air. On second thought there is the cost issue—but the savings in terms of reduced job loss hours and reduced medical care expenditures would probably mollify the bean counters.

Ambient carbon dioxide concentration correlates with SARS-CoV-2 aerostability and infection risk | Nature Communications https://www.nature.com/articles/s41467-024-47777-5

The editorial department was challenged to discuss the myriad ways in which the government wastes taxpayer money, but they couldn’t come up with a single example and told me I exaggerate. A floating pier constructed in open seas at the Gaza coast, which coast $320 million to build and operated for only one week before being destroyed by waves I suggested, but the editors replied,”Chicken feed”. (Rough seas in the Mediterranean—who could have foreseen that). How about the $7.5 billion the administration requested and Congress approved in 2021 to create thousands of electric vehicle charging stations—7 have been built so far. “You are much too impatient,” they scoffed. But what about the California High Speed Rail system which taxpayers approved a bond and funded the estimated $33 billion project to build the 500 mile system in 2008? Currently 119 miles are partially under construction 16 years later, but the Transportation Authority now estimates the cost to complete the first 171 mile segment at $35 billion, more than the original cost for the entire 500 mile system. The Transit Authority is also estimating 25% less ridership than when they sold their project to the voters. “You are just so anti-progress”, the whole department chimed in. Most of them have now decamped anyway, taking jobs at the FDA, CDC, FDIC, Pharma and Defense companies or acting as non-registered foreign agents. Please forward this post to your friends and colleagues, it’s free as long as they don’t work for the government, and pound the like button. The first 10 readers sharing this post will receive their choice of a Donald Trump autographed copy of “How to Win Friends and Influence People” or an original Hunter Biden painting.