Midsummer Night’s Viral Update

Are we living in a Golden Age for viruses? It sure might seem that way, with COVID on its now yearly summer binge, and Avian Influenza H5N1 continuing its rampage through the dairy herds of the US, and decimating the domestic poultry industry. We will start with a quick look at COVID, since you likely either had it recently or know someone with infection right now. Although the CDC no longer keeps track of absolute hospitalization numbers, this summer’s viral burden looks higher than last year. I’ve added some dashed lines to the usual CDC graphs so you can easily see that test % positivity, emergency room visits for COVID, and episodes of severe disease are running well above the same time last summer. The early expectation that this virus would settle down into a seasonal pattern of a single cold weather peak each year, like Influenza, is getting less likely with each passing year. As a friend of mine with expertise in molecular biology and infectious diseases summed it up, “Thanks COVID, now we can get a flu like illness year round”.

A couple of posts ago I discussed the fact that Paxlovid has lost a great bit of its utility in this later era of the Pandemic, and now I can add yet another failure, as a randomized trial has demonstrated that Paxlovid, when given prophylactically as either a 5 or 10 day course, failed to prevent COVID in the household contacts of infected patients. I’d be willing to accept an advisory board position and 3 months of Paxlovid sales receipts to stop reporting the facts about Paxlovid’s current performance—but I haven’t heard a word back from all the emails I have sent Pfizer. Here is the link where you can examine the data.

Oral Nirmatrelvir–Ritonavir as Postexposure Prophylaxis for Covid-19 DOI: 10.1056/NEJMoa2309002 NEJM: VOL. 391 NO. 3

This week Colorado became the first state to mandate the testing of bulk milk from every dairy producer in the state. This is a desperate attempt to stem the spread of H5N1 within the state dairy herds. I suppose I applaud the move, but realistically it’s futile. The virus has exploded across the state, and within a couple of weeks we went from 25% of herds infected to 45%. The sad truth—which government officials should recognize by now—is it’s too late; and in fact it might never have been early enough, to stem the spread of this uber virus, which has traveled to every corner of the world with gold medal speed, and infected hundreds of millions (if not billions) of birds and all sorts of mammals. Colorado right now is ground zero for H5N1, but the virus will continue to move on. As of yesterday 7/25/24, the state has identified 10 cases in people involved in the culling operation of infected chickens. Two weeks ago I passed on the information that Colorado authorities were planning to destroy 1.8 million chickens—that number is now up to 3.2 million, and likely to go higher. We are no more able to stop the spread of H5N1 than the fiction that any location on earth could insulate itself from SARS2. The Chinese tried harder than anyone; with people locked in their apartment buildings burning to death as a result, and the totalitarian communist government rocked to its core by the normal human reaction to the lockdowns. But the virus just bided its time, awaiting the moment when the exhausted, frustrated, and now enraged humans finally gave up. We should at this point be collecting as much information as possible on infection rates in humans with close contact to the infected animals, whether they are symptomatic or not; and through contact tracing providing antiviral prophylaxis to the household contacts of any infected farm workers. What we should be striving to avoid is infection of severely immunocompromised individuals, who presumably are at higher risk of severe disease, and whose infection may offer the virus a ready milieu for accelerated mutation. Oh, and they should be checking the piggies regularly for infection (you know by now that I love the piggies) and my bet is on serious trouble to potentially come from that direction.

A couple more thoughts on Avian Influenza (if you haven’t already moved onto the weekend funnies and political memes). Viruses of course don’t “want” to do anything, but evolution will increase the odds of the virus becoming both more transmissible between humans, and more severe. Random mutations are occurring all the time as the virus replicates, and most are dead-end changes, which either reduce that particular mutant’s ability to compete or have no effect, and consequently don’t get amplified and disappear. Any mutation that enhances the transmissibility between humans has the obvious consequence of opening up a whole new species of mammals to viral replication; triggering a mutational arms race as the virus competes against our immune response, and further improvements in viral fitness are selected for. Less obvious perhaps is the fact that mutations which increase disease severity are very likely to be selected for, since a sicker person is generally prone to be spreading much higher amounts of virus for longer, causing that mutant to quickly becomes the only game in town. Early on in the SARS2 Pandemic, when few people had any pre-existing immunity, we saw examples of evolution selecting for more severe variants, including Delta. As the Pandemic progressed, and more and more people had some baseline immunity, evolutionary selection for increased severity faded in favor of the advantage conferred by increasing ability to spread by outflanking protective antibodies.

I started out by alluding to a Golden Age for viruses. That was just a bit of click bait, but I’m fairly certain that the whole history of life of earth has been quite a picnic for the viruses. They will undoubtedly be around as hitchhikers until the last non-viral life form expires. We can find them everywhere we look, including ancient viruses intercalated into our DNA. The true Golden Age has been the explosion of our ability to find and accurately describe the viruses. The increasing ability to measure something always gives the illusion that it’s becoming more prevalent over time. I will highlight some recent “new” viruses, which of course aren’t necessarily new at all, but our ability to identify and measure them is.

An old and common malady in European domestic cats called Staggering Disease, has just been proven to be due to a fairly recently discovered virus named Rustrela virus (RusV), which is in the same family as the Rubella virus. RusV has been shown to cause serious meningoencephalitis (brain infection) in a variety of mammals, and a recent paper in Nature Communications proves that it is the cause of the fatal Staggering Disease in kitties. Almost simultaneous with the paper in Nature is the report of the first known case of Staggering Disease in a Colorado mountain lion, which had to he euthanized, and at autopsy showed the characteristic brain pathology.

Mystery of fatal ‘staggering disease’ unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats. Published: 04 February 2023. https://doi.org/10.1038/s41467-023-36204-w

Moving on to India and bringing it closer to home with a severe human disease is the Chandapura virus. It was initially described in 1965, but not felt to be a significant human pathogen until an outbreak in India in 2004, when over 300 cases occurred in one state with a mortality rate of 50%. The disease is almost exclusively severe in children and teenagers, with rapidly progressive, often fatal encephalitis, and is spread by the bite of sandflies. India is now having another outbreak of this poorly understood virus, which is in the same family as the Rabies virus, with 28 deaths this month in the state of Gujerat linked to the infection. A virus in the rabies family with a horrible mortality rate for children, no treatment, and spread by the common biting sandfly, is not a good combination.

Next up is the Oz virus, not named after the famous doctor friend of Oprah and purveyor of all sorts of weight loss “super foods”, or even after the famous realm of ruby red slippers I’d wager. This virus was first isolated from ticks in Japan in 2018. Surveys of a small number of hunters suggested that they might have had prior infection, since they had antibodies which reacted with the virus, but the first known human case, which was fatal, was identified last year. Like many recently discovered viruses, it’s quite likely doctors have encountered other very sick patients in the past with this same pathogen, but at the end of the day shrugged their shoulders and said, “Maybe it was some virus”. Guanarito, Junin, Sabia, SFTS (Severe Fever Thrombocytopenia Syndrome Virus), I could go on naming viruses which cause severe disease, but “didn’t exist” when I was in training; doing my best to become at least familiar with the names of the known pathogens of humans. The point is many of them have always been around, only our ability to identify then has grown exponentially in recent years.

Some time back I had a post entitled, “How Safe is the Food Chain”. I’d like to draw attention to the fact that the exact same question can be asked of supplements and recreational extra-curricular goodies. My first awareness of this issue dates back to the late 1980’s when I had a young female patient with a bizarre debilitating illness of thickening and stiffness of her subcutaneous tissues, shortness of breath and elevated eosinophils (a type of white blood cell). I think she might have been referred to me because the high eosinophils can be suggestive of a parasitic infection. Eventually I diagnosed her with eosinophilia-myalgia syndrome—which was a newly recognized complication of taking the over the counter supplement L-tryptophan. The CDC estimates that in addition to hundreds of episodes of severe disease this “supplement” caused 37 deaths. In 1989 the FDA recalled a variety of products containing L-tryptophan—the response of the supplement industry was then to market a very similar molecule 5 hydroxytryptophan , with the same completely unsubstantiated claims of its health benefits. Next stop was a patient with unexplained hepatitis—unexplained until we discovered she was taking red yeast rice, and failed to list it as one of her medications, since it was “a safe and natural OTC supplement”. Red yeast rice does in fact lower your cholesterol, but it does that because it contains several chemical compounds closely related to the first generation cholesterol medications. In red yeast rice those chemicals are present in totally unregulated amounts, and with related compounds which have never been systematically studied in humans. That patient’s illness I published as the first reported case of chemical hepatitis due to red yeast rice. Red yeast rice remains a highly popular supplement around the world, especially in Japan, where it is considered a traditional Eastern medicine. Currently in Japan and Taiwan there is a massive multi-month outbreak of severe disease directly related to Kobayashi red yeast rice. Thousands of people have sought medical care for illness, over 500 have been hospitalized and at least 80 have died with severe kidney and liver injury. This product is produced by letting a particular type of red yeast ferment rice, which is then collected and ground up into various supplements. If the strain of yeast changes, (mutates?) or perhaps there is a change in a wide number of other environmental variables, then the mix of chemicals produced changes in amount and composition. Some of those chemicals may be toxic—but nobody is checking. The quality control on these non-regulated “supplements” is how many folks get sick and die when something goes wrong. Right now the CDC is investigating an outbreak of illness in eight states related to Diamond Shruumz brand edibles, with 10 hospitalizations. The products are purported to include a “proprietary mix” of mushrooms, but of course nobody, including the people selling them have the foggiest idea what is actually in them. The 10 people hospitalized weren’t admitted because they were a little too stoned to go home—they had severe neurologic and metabolic toxicity, including respiratory failure requiring intubation in some cases, and kidney injury.

Not So Happy Birthday

That’s it from me this week. The political season, which seems to be perpetual now, is in full swing. Be skeptical of all the hyperbole, and viscous personal attacks that are now the sum of our political discourse. Whichever side of the non-existent debate (for debate would suggest the considered exchange of rational arguments and facts) you might be on, be skeptical of things told to you with solemn authority by people who have lied to you in the past. Also be skeptical of products marketed to you with meaningless words like: micro-dosing (a tiny bit of some poisons will kill you); neuro-enhancing; eco-friendly; self-actualizing; all natural (Amanita plalloides the “Death Cap mushroom” is extremely natural). I thank those of you who think of a new person to foreword this post to.