Several Questions Answered

Today we will take a quick look at all things COVID then move on to some other topics. In my post of October 26th I asked what would be on the COVID Holiday Menu this season? It looks like the special this year is something of a surprise dark horse. The variant BA.2.86 (Pirola) caused some sensation when it first appeared back in September due to a large number of mutations separating it from any other variant, but it failed to gain traction and percolated along as an obscure member of the viral pack. Now suddenly BA.2.86 and its close descendent JN.1 are quickly expanding at the expense of other variants both in Europe and the US. The latest CDC Nowcast data shows BA.2.86 tripled over a 2 week period, and as of last Friday was projected to be 9% of US COVID. While that is a still a small number, it’s the rate of change which suggests strongly that Pirola and JN.1 will soon be the major COVID strains around. Data from Yunloung Cao’s lab, also referenced on October 26th, showed JN.1 to have the highest degree of immune escape from prior infection or vaccination seen so far. This past week a pre-print out of David Ho’s lab at Columbia gives reassurance that NAB (neutralizing antibody titers) against all the major circulating COVID variants, including Pirola and JN.1 are boosted by this years XBB monovalent vaccine—although JN.1 NABS are significantly lower (by 2.9 - 4.3 fold) compared to the other variants.

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants

https://doi.org/10.1101/2023.11.26.568730

Since we know by now that vaccination against SARS-2 virus won’t prevent most infections (but WILL give added protection against critical disease) the advantage JN.1 and Pirola have from enhanced antibody escape will allow them to quickly take over from the currently dominant family of XBB variants. (So says yours truly). Does it matter what’s floating in the alphabet soup? These variants so far are not known to cause more severe disease, but if they manage to ramp up the number of infections substantially, (as the original Omicron did), that will be a problem. The most interesting question from my point of view is what caused BA.2.86 to take so long in gaining traction before finally taking off? The most likely answer is a change in the background immunity landscape. Vaccination with the new XBBB vaccine could be a factor to some extent. Given the very high mutation rate of this virus, any vaccine which does little to block infection will create immunologic pressure favoring the population wide expansion of variants even slightly less inhibited by the post vaccination antibodies. Given that only 16% of the US population has taken the fall XBB shot, a larger influence is likely the widespread infection with XBB derivative variants over the summer, finally giving an edge to Pirola’s slightly better antibody escape. And then there are plenty of things we just don’t understand about the ebb and flow of COVID.

Below is the latest CDC data showing the expected cold weather, post Thanksgiving jump in measured COVID disease. For reference the level of hospitalizations in October had slipped to 13,500/week and now we are back to almost 20,000, which was the peak of the late summer surge.

Two weeks ago we discussed the epidemic of pediatric respiratory disease in China. Shortly after, the WHO reported that China had provided information clarifying that thus far they have not identified any novel pathogens, and cases of pneumonia are being caused by Mycoplasma and other common pathogens. Several locales in the US have reported higher than average numbers of pediatric pneumonia cases (Ohio and Massachusetts), which unfortunately has been dubbed “White Lung syndrome”in the media. The CDC is stating that investigation so far shows these cases are simply a surge in usual respiratory pathogens including Mycoplasma, Influenza, adenoviruses and routine bacterial pneumonia. Given recent history, could any of us be blamed for being on high alert for “out of the ordinary” infectious disease epidemics first reported in China?

Next up for discussion is Mpox (aka. Monkey Pox), another gift that keeps on giving and apparently is here to stay. The world wide outbreak has continued to percolate along but has been especially bad in the Democratic Republic of Congo in 2023. Jynneos vaccine turned out to be less effective than initially predicted, and the major route of transmission, sex, seems to remain popular around the world even as other fads come and go. There are 2 main types of Mpox virus: Clade I which has caused most of the endemic cases in central Africa for years, and Clade II which sparked the world wide epidemic. Beyond the sheer numbers of cases this year in the DRC, 12,569, the WHO is reporting 581 deaths or a case fatality rate of 4.6%. This compares to a fatality rate of 0.2% during the 2021 epidemic, both in the DRC and world wide. What’s going on in the heart of Africa? Has the Mpox virus suddenly become 23 times more lethal? Let’s hope not—and there are other potential explanations. The current outbreak is caused by Clade I, which based on pretty flimsy evidence has been thought to be a bit more lethal than Clade II, but nothing approaching the level of case fatality currently being reported. The most likely possibility is that the public health authorities in the DRC have been under-prepared and overwhelmed by the current surge in disease. The WHO reports the test positivity rate in this current epidemic is 65%, and that is a pretty reliable indicator that they are testing only obviously ill and likely very ill people. Without more widespread testing (confirmed by a MUCH lower test positive rate) the vast majority of people with mild or nearly asymptomatic disease will not show up in the numerator of deaths/infections. Of course there is the unpalatable possibility that the virus has acquired some new virulence factor; our luck with viruses hasn’t been stellar lately. The following quote is from the WHO External Situation Report #30 of November 25th.

WHO has published a Disease Outbreak News outlining the ongoing and evolving epidemiology of mpox in the Democratic Republic of the Congo. This summary highlights the reporting since 1 January 2023, of 12 569 suspected (i.e. clinically-diagnosed) cases in the country, and among these, 581 deaths (case fatality ratio 4.6%). Newly identified outbreaks related to sexual transmission of clade I MPXV are also reported.

The last infectious disease item for today is a possible answer to a mystery about the 2015 Zika epidemic in Brazil and other countries in the Americas. As you probably recall there was a sudden explosion of Zika caused fetal neurologic injury, often with microcephaly, or fetal demise. Zika virus had been endemic in Africa and Asia for decades, and nothing like this epidemic of fetal pathology had been seen before. An epidemic of Zika had occurred following the virus’ first introduction to the islands of French Polyonesia in 2007, but without the terrible results of fetal involvement. The first introduction of Zika virus into Brazil was thought to have occurred as recently as 2013 with rapid spread across most of the country. The virus is transmitted by the same mosquitoes which transmit Dengue, Chikungunya and Yellow Fever, and causes a generally mild febrile illness with rash, headache, and myalgias.

Exacerbated Zika virus–induced neuropathology and microcephaly in fetuses of dengue-immune nonhuman primates

SCIENCE TRANSLATIONAL MEDICINE

25 Oct 2023 Vol 15, Issue 719

DOI: 10.1126/scitranslmed.add2420

This study in non-humane primates shows very dramatically that pregnant female monkeys with pre-existing Dengue antibodies transmit high levels of the Zika virus to the fetus, and that those infant monkeys are born with severe neurologic injury including microcephaly, or spontaneous abortion. The pregnant monkeys without Dengue antibodies don’t transmit the virus to their fetus. You may recognize this as a form of ADE (antibody dependent enhancement), where the presence of pre-existing antibodies in the individual leads to more severe disease upon infection with another pathogen. Dengue of course is very wide spread and frequent in Brazil; and the likely conclusion is that a huge population with no baseline immunity to Zika, but with high levels of Dengue antibodies was the perfect storm for this epidemic of fetal infection.

There is nothing quite as pernicious as the mosquito—you expect nothing good from it, and it never fails to live up to that reputation. This week however we had some challengers in the form of three elite Ivy League University presidents testifying before Congress. You have heard all the criticism by now, and the deafening silence from the three university’s Boards of Trustees. To sum up their testimony, they conclude that calls for genocide are indeed horrific, unless you are talking about eliminating Jews and the State of Israel—in which case it’s important to consider the context of the discussion. A very thoughtful and rigorous academic analysis from these pillars of the intellectual world. As dreadful as it sounds, their collective response didn’t surprise me in the least, such a world view is a direct result of the campus environment these women have had a hand in creating. When asked whether public calls for genocide against Jews violated the university’s Code of Conduct, by constituting intimidation and harassment, University of PA. president Magill made the important observation that Freedom of Speech is so sacrosanct, that for it to cross into the realm of conduct there would have to be actions. The message is: “If you’re out there calling for the elimination of the apartheid State of Israel and the Jews, we won’t discipline you unless you beat up or kill someone”. This position on the need to protect hateful language is of course coming from the very academics who have spent years lecturing us that words cause unbearable pain—and using that argument to silence anyone on campus expressing a position contrary to their Left-wing, Marxist world view. We live in a world where hypocrisy is so unexceptional and blatant we hardly notice it, but this trio has taken it to new levels of academic excellence. They are all unfit to run an ice cream truck let alone a University. Like the mosquito, I expect nothing less.

It’s the Holiday Season again and my editor and the entire staff want to wish you Joy and Peace, and a healthy New Year. Forwarding these pages to your friends or enemies is much appreciated. The button below will help the soon to be unemployed find temporary work over the holidays, so bang away.