Things You Might Want To Know About New Vaccines, COVID, and Cancer Detection.

Sorry just couldn’t think of a catchy title

Let’s start with some good news. I’ll be highlighting COVID for the first couple items; if you couldn’t care less at this point skip ahead and read about RSV or a new approach to colorectal cancer detection. On Friday the FDA approved Moderna’s new mRNA Covid vaccine mNEXSPIKE for use in people over age 65 and for certain high risk individuals ages 12-64. This isn’t just the yearly tinkering with the current vaccine to attempt fine tuning to the newest variant, but a significant change in approach. The new vaccine targets the two critical functional regions of the viral spike protein, the RBD (receptor binding domain) and the NTD (the portion of the spike which facilitates cell entry after attachment to our ACE2 receptors). These are the regions of the spike protein which mutate rapidly, while the remainder of spike is pretty highly conserved. The theoretical advantage prompting development of this new vaccine is that it will focus the attention of the immune system on the critically important functional areas of the spike, whereas the existing vaccines have all used the entire protein. It is known that when our immune system is challenged with a new target, very similar to a prior invader that we have already mounted a response to, the immunologic cells will focus very substantially on producing antibodies to the previously recognized regions, at the expense of responding to the novel changes. That is one of several reasons why we keep getting infected with new mutant strains of COVID, even though the changes in the virus are fairly minimal.

The trial leading to approval was the kind of randomized, blinded, controlled trial to warm the cockles of RFK Jr.’s heart—comparing the new vaccine’s efficacy against the old Moderna staple. The trial was designed to demonstrate non-inferiority of the new formulation, which it did, and further showed a 9.3% superiority in the 12-64 age group and 13.5% superiority in the older age group. I can’t find published details regarding any other end point than infection, such as: ED visits, hospitalization, ICU admission or death—likely because in this era of substantial natural and prior vaccine immunity these would be very rare in a trial group of 14,000 participants. Before you yawn, the new vaccine achieved these results with a dose of 10 mcg compared to the current vaccine’s 50 mcg. Local injection site reactions were less, and mild systemic side effects similar. You might not be thinking about COVID much these days, but 47,000 Americans died with a primary diagnosis of COVID last year. If there are any takers for the bet that Moderna will lower the price of the new vaccine by 80%, given the reduced dosing, I’ll take the other side of that, and give you 3 to 1 odds.

The virulence of COVID has been steadily dropping since the initial huge wave of the first Omicron variant, which became dominant in December of 2021. All subsequent variants have been in this same lineage, and that has allowed our accumulated immunity to have a very large impact on reducing the severity of illness, even though the subtle changes of new variants continue to reinfect us. What about those people at highest risk, the elderly with co-morbidities? A new study published in Open Forum Infectious Diseases looked at this question in American Veterans during the 2023-2024 period. The results are surprisingly good. The study looked at 130,200 veterans diagnosed with COVID, and found that among the 2% (2690) that were hospitalized, the in-hospital mortality rate was 0.03%. The average age of this not particularly healthy cohort was 67, with many veterans much older. This very high risk group had a COVID related hospitalization rate of 2%, but it likely was truly much lower, since some of them were undoubtedly hospitalized for unrelated medical reasons and found to have incidental COVID infection by universal testing, while others certainly had asymptomatic COVID were never tested. Remarkably, of those sick enough to be hospitalized the mortality rate was as noted only 0.03%. The overall population mortality rate for COVID is obviously incredibly low at this point. Nothing says that some major mutational shift in the virus will not occur increasing its morbidity, but for now we can expect the usual summer wave of almost universally mild disease in normal people, followed by the similar winter wave.

Severe COVID-19 Outcomes Declined Among US Veterans From 2023 to 2024

Along the same lines a CDC study published January 2024 in Infectious Diseases Open Forum (which I missed when it appeared) found that as early as the 2021-2022 period (beginning of the Omicron era) the in hospital mortality for COVID had dropped and was EQUIVALENT TO INFLUENZA for all age groups except young adults, 18-49. [Those with COVID did require more advanced medical care on average.]

Open Forum Infectious Diseases, Volume 11, Issue 1, January 2024, ofad702, https://doi.org/10.1093/ofid/ofad702

Comparing clinical outcomes between people who were hospitalized with COVID-19 Omicron BA.5 versus people who were hospitalized with flu during the 2021–2022 season, a similar percentage of patients were admitted to the ICU and received invasive and noninvasive respiratory support. A higher percentage of patients hospitalized with Omicron BA.5 compared with flu received medication to increase blood pressure, received treatment to support function during kidney failure, and, among people 18 to 49, died in the hospital. For all other age groups, there was no difference in deaths of adults hospitalized with Omicron BA.5 and flu, including among older adults.

I frequently get asked about the RSV vaccine for adults over age 60. I reported on the registration trial data when the vaccine was approved in May 2023, but performance in the real world can be substantially different. A huge test negative case controlled study was published May 9th in JAMA Network Open, and showed that the vaccine had a 75% overall efficacy rate for prevention of the composite end points of symptomatic RSV upper respiratory infection, ED visit for RSV, hospitalization, ICU admission or death. Confidence intervals were very narrow with 787,000 cases tested across the country. During pre-approval testing there was a safety signal for Guillain-Barre syndrome, and this trial demonstrated 18 excess cases for every 1 million persons vaccinated. Healthy robust people age 60 to 70 are not frequently hospitalized and rarely die from RSV, and severe disease in the healthy is most frequent as age advances beyond 75 years. Also to consider is the near certainty that protection from this one time vaccine will fade with time, (although it looks pretty good out to 2 years so far). It doesn’t make sense in my opinion to take the vaccine at age 60 when your risk of disease is very low, knowing that it’s highly likely the protective effect will be substantially diminished a decade or more later when you will be at much greater risk. I’m not your doctor, and you should ask for his or her recommendation, but my plan is to delay getting this vaccine until about age 75. I’ll roll the dice balancing the low risk of serious disease for me personally, against the low risk of GB syndrome. This reasoning of course applies only to the healthy between ages 60 and 75. There are currently three RSV vaccines available; Moderna’s is an mRNA platform, as is Pfizer’s Abrysvo, while GSK’s Arexvy is a recombinant protein subunit. The current study did not distinguish which vaccine the person had received, only vaccinated versus unvaccinated, so comparison of the relative risk of this rare but very serious side effect is not possible from this data.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2833776

Effectiveness and Safety of Respiratory Syncytial Virus Vaccine for US Adults Aged 60 Years or Older

The next item today are potential newer means of screening for colorectal cancer. You might be aware that cancer cells shed genetic material into the blood stream referred to as “circulating tumor DNA” (ctDNA). This can be measured in a blood sample and used as a diagnostic tool to predict the presence of colorectal cancer or pre-malignant polyps. The first blood test like this, Shield, was approved by the FDA last July. Before you say, “Wow, a blood test instead of taking a day off to become a sock puppet”, realize that the sensitivity of the test for the presence of cancer is reported to be 83%, but only 13% for precancerous lesions, which we would like to identify and remove simply by colonoscopy before they become fully malignant. A second test of this type of system using AI analysis of the genetic findings to predict CRC (colorectal) malignancy from blood has just been been published, and the results look pretty similar to the already approved Shield test, with detection of cancer sensitivity 79.2%, but still very low sensitivity for advanced precancerous lesions at 12.5% (failing to meet a pre-specified acceptance criteria). Then there is the old standby poop in the bucket Cologuard Test, which looks for genetic material with the signature changes of malignancy. Cologuard has a reported CRC cancer detection rate of 92% and significantly higher detection rates for pre-malignant lesions (with rates dependent on the size of the polyp), then the blood test. No surprise, I guess that more cancer cell DNA (or RNA measured by yet a different test) is shed in the feces than makes its way into the blood. These tests are only for people at standard risk of cancer and never for those at high risk. For my money (or Medicare’s as the case may be), if you’re looking to avoid a colonoscopy the delightful bucket challenge is the way to go until the technology for blood diagnosis is improved. I feel it would be very unwise to avoid colonoscopy for several screenings in a row; if you have an advanced pre-malignant polyp there is an 85% chance (in the case of the blood tests) that it will be missed the first time around and presumably a similar or only slightly lower chance at your next screening—that's a long interval to allow such a lesion to potentially progress to cancer. The most logical way to use either of the noninvasive test types for the low risk person is to have one or more negative colonoscopies, and then slip in the non-invasive testing on the next go round. You may know that in 2021 the USPTF (US. Preventative Services Task Force)) lowered the recommendation for CRC cancer screening to 45 years from 50 years in response to the rising incidence of this cancer in younger people. That was a logical but unproven recommendation. This month a study from the Kaiser-Permanente Health Network in California, published in JAMA Network provided the first evidence that the incidence of both pre-malignant and malignant lesions was almost identical in sequential colonoscope screening groups in the 45-49 year and 50-54 year age groups. The data is very clear that “normal risk individuals should begin CRC screening by age 45”.

Colonoscope screening findings in the 45-49 and 50-54 year age groups:

• Advanced adenoma (3.8% vs 4.1%; aRR 0.90, 95% CI 0.75-1.09)

• Advanced serrated lesion (1.5% vs 1.8%; aRR 0.85, 95% CI 0.63-1.14)

• Any sessile serrated lesion (10.2% vs 10.4%; aRR 0.98, 95% CI 0.88-1.10)

• Colorectal cancer (0.1% vs 0.1%; aRR 0.56, 95% CI 0.15-2.07)

Other brief items of good news, not necessarily health or science related: 1. Fentanyl seizures are down very substantially at the southern border compared to the last two years—overdose deaths should now dramatically decrease, but statistics take several months to be reported. That is a gigantic win for the country—fentanyl killed far more otherwise healthy young people than COVID, with nearly 250,000 Americans dying from drug overdose since 2019.

2 The S&P 500 index had its best May since 1990, the job market remains strong based on today’s numbers, the Atlanta Federal Reserve increased their prediction For GDP growth next quarter to 4.8% from 3.6%, and J.P. Morgan Research has dropped their odds of a recession from 60% to 40%.

3 Ukraine kicked the living “stuff seen on colonoscopy” out of Russia with a drone attack causing incredible damage to Russian airpower. It was a replay of the old Trojan Horse strategy. Putin of course will respond by killing more Ukrainian civilians, but the message is clear—Russia has third rate military capabilities (other than their nukes) at this point.

4 Two Chinese scientists were caught by Customs and Immigration bringing a dangerous and banned fungus into the United States. Fusarium graninearum is a virulent multi-crop destroyer, listed as a potential Agroterrorism agent. One of these scientists is a member of and reportedly has worked for the CCP, and currently does research at the University of Michigan. The other scientist, who allegedly does research on this pathogen at a University in China, went to great lengths to hide this material in his luggage, and lied to Customs agents. The argument over the origin of the SARS2-COV19 virus should be laid to rest (barring new information which is unlikely). But one thing which became clear during the Pandemic event, was that American scientists who totally discounted the Lab leak hypothesis placed great trust in what they were being told by Chinese scientists. The Chinese blocked WHO access to primary research data books (says the WHO), and destroyed information; yet some of our leading scientists included in their argument against a Lab leak the attestations of Dr. Shi Zhengli about exactly what they were working on in the Wuhan Lab. The level of credulousness to believe the tales of Chinese scientists, who owe their entire careers to the CCP and can be cancelled or disappeared at the whim of the party, is truly hard to fathom. Even though we will in all likelihood never know the origin of COVID for certain, everyone who matters will hopefully come away from the Pandemic with an understanding that gain of function research is too dangerous to justify the risks, and that you can trust what a Chinese scientist tells you about as much as the spy balloon crossing the US was a just a weather balloon.

The recent attacks against our Jewish citizens are horrific. The execution style murder of the two young people in Washington, and the attack in Boulder where the terrorist attempted to burn Jews alive, are so far beyond the bounds of a decent society and humanity that it should laser focus everyone’s attention on the larger picture of what is happening. Jew hatred and calls for the destruction of Israel have been tolerated and normalized at some of our Universities for years. My initial assumption was the Boulder attack was carried out by a homegrown, deranged Left Wing lunatic, as was the case in Washington DC; but I was of course wrong, this was a genuine Muslim Jihadi who admits to have been planning the attack for over a year. He is in the country illegally after entering with a short stay visa in 2022, and failing to leave as required by law at the beginning of 2023–with no consequence for him, but dire consequences for some of his victims. The media is playing the obfuscation game, apparently not realizing that the brief era when a make-believe world could be conjured by their adventures with twisting the language to suit their agenda, is essentially over. CNN immediately had their panties in a bunch when the FBI called a terror attack a terror attack. The New York Times avoided calling the victims Jewish, referring to them as, “GAZA Hostage Awareness Supporters”. Do they think for one second that these people were attacked because they support the release of hostages? Would the victims have been fire bombed if they were say a group of mixed race devout Christians meeting to pray for the release of the hostages, or a group of women with hajibs calling for the release of the hostages because they believed it would help bring an end to the war and reduce suffering and death. Of course not—they were murdered and burned because they are Jewish. MSNBC described this terrorist with an already clearly identified Muslim name as a “white man”, quite an absurdity since in any other circumstance they would have referred to this Egyptian as a brown skinned person for the purpose of their divisive narrative. Mass rioting in France yesterday, over a soccer game, of course presented an opportunity to attack two synagogues and desecrate them with green paint (as in the color of Islam). Islamic Jihadis continue to slaughter thousands of Christian Africans in Nigeria, DRC, Kenya and Coptic Christians in Egypt. You don’t seem to hear much outrage about that on network or cable news. The world of make-believe needs to go away. There will be more of these attacks in America, because of the legion of antisemites trained in our “elite” colleges, plus the thousands of unvetted individuals, from societies where the destruction of Israel and Jews is dear to the hearts of many, who were allowed to flow freely across our borders. If we are to prevent any of these atrocities on American soil we need a very clear grip on reality—not pandering to political correctness.