ADE

I haven’t written about coronavirus for quite a while.  The sturm und drang over the vaxx has reached baroque levels.  Ample evidence is out there that it’s not providing much protection against whatever strains are floating around now, all multiply mutated beyond the original Wuhan variant.  Highest new infection rates are in states and countries with the highest vaccination rates (1).  Clinical courses may not run worse in those who have been vaccinated, so say mainstream outlets like Johns Hopkins (2), but ya still get sick!.  Even St. Anthony admits that the stab was never meant to protect against actual infection – meaning this vaxx can never be part of a strategy to eradicate this coronavirus – only to make the infection you get a little less worse (3).  Yet, the drumbeat to get the stab rolls on.  Those who decline, for whatever reason, become pariahs, selfishly and ignorantly refusing to help in the crisis of our time, even contributing to it’s perpetuation.  No wonder they should be denied medical care and be driven from their jobs.  High level people who opt out are pilloried.  Look how they turned college graduate, articulate and universally loved NFL championship quarterback Aaron Rogers into a selfish knuckle-dragger.   You’d think he voted for Donald Trump (probably did).  Mr. Rogers got to go back to work.  Not so for many who decline and work in a business or institution under a mandate.  While the 5th circuit court and OSHA might save us, there’s still a lot of businesses, from fire and police departments, hospitals, airlines, plants, and stores operating with severe manpower shortages, deprived of people who don’t see a future filled with spike proteins as a good option.  In what might be one of the bigger tragedies in this ongoing drama, little children are being brought into the fold.  The parents are the ones giving informed consent here, and anyone who has not read over the stats on consequences of COVID infection in children, and the zero chance the kids have of transmitting to an adult, and thereby refused the stab for their child, is guilty of child abuse (4).  Yet playing on a time out in the basketball game last Sunday, then again several times, was a black and white piece featuring smiling little children walking in a field toward the camera, saying how happy and healthy they were, with at least one saying “I’m happy to be vaccinated”, with an adult female voice over reminding us how important it was to get the little darlings stabbed.  Pure Soviet propaganda. Chilling.

Could it be worse?  In Australia and New Zealand riots are breaking out by those chafing under the tyrannical lockdowns both countries have been under since the get go.  New COVID cases from the Northern Territories will go to camps.  Demonstrations – many violent – arise across Europe protesting new winter restrictions.  In Austria, plans are afoot to confine the unvaxxed to a second class citizen status the likes of which have not been seen since the country called Herr Hitler a proud son.  Maybe they’ve still got some of those yellow stars laying around to slap on the unvaxxed.  Germany is not far behind, tapping into a spirit in their citizenry always below the surface and ready to institute uber alles.  German euthanasia clinics are refusing patients who are not vaccinated.

For translations: caption “the racer under the Christmas tree”.  The blaster in his chair “I’ll get you, refuse to vaccinate”.  On the box, “Covidstrike” is the “first person shoot game of the year”

Surely, there must be some hope on the horizon.  Those boys and girls in our labs have to be doing something besides ginning up booster shots.  The NIH has received almost $4.9 billion to date to fund important COVID-19 research on diagnostic tests, vaccines, and treatments.   DEVEX, an outfit tracking global development trends, found $21.7 trillion committed worldwide as of June 27, 2020.  Pfizer developed Paxlovid (PF-07321332 plus ritonavir, a protease inhibitor on its shelf (it’s an old unused AIDS pill) (5) while me-too Merck was more creative, coming up with Lagevrio (molnupiravir); by presenting false building blocks of RNA, it throttles RNA dependent RNA polymerase, the enzyme the virus uses to replicate itself (6) As such, it could be effective against other RNA viruses, including flu! Pfizer released preliminary data showing huge protection against hospitalization and death.  Reductions from Lagevrio weren’t quite a substantial.  “Emergency authorization” being sought for both.  Uncle has already committed $5.9 billion for 10 million doses of Paxlovid.  My, that’s an expensive pill!  But Pfizer will forego royalties.  Under the deal struck with the global Medicines Patent Pool (MPP), Pfizer — which also produces one of the most widely-used Covid vaccines with German lab BioNTech — will not receive royalties from the generic manufacturers, making the treatment cheaper.  Pfizer will sub-licence production of its promising Paxlovid pill to generic drug manufacturers for supply in 95 low- and middle-income nations covering around 53 percent of the world’s population.

But in the cheap seats, all is not well.  With unseemly glee, a group of bean counters has dissected last summers review of ivermectin for COVID, finding the two larger cited studies flawed by 1st world standards, leaving support for ivermectin much weaker. (7). Reports of grisly side effects from ivermectin have appeared, even though some dosing regimens included things like paste, with few employing a logical mg/kg dosing regime (8).  Plaquenil, after emerging from last year looking o.k. got slammed by the WHO in the spring.  Someone snuck a little trial into JAMA showing that a single azithromax pill taken once has no effect on evolution of symptoms 2 weeks later compared with placebo (9).  Original proponents of such regimens, like the heroic Dr. Zelenko, continue to prescribe such regimens, and his patients stay out of hospitals.  My wife and I follow an ivermectin prophylaxis regimen.

Complications of the vaxx continue to roll in. 1,742,488 adverse events, with a small fraction of people actually reporting. Hard to imaging what a lifetime teeming with spike protein might mean (10)

And something fishy is going on with the “variants”.  Remember when “delta” emerged last summer, coming out of the subcontinent where it had caused quite a bit of disease, the CDC had it on its radar as a “variant of concern”, all sequenced and characterized.  Whether those 13 mutations in its spike protein would make it less recognizable to any immune response primed for the Wuhan strain was never established.  But CDC scrutiny for variants seems to have ground to a halt.  All the strains isolated now are the delta (11) with 10 “Variants being monitored” as of October 4 (12).  Such a sloppily replicating virus (1 error per 10,000 nucleotides, or 3 mutations per replication) should be spewing out variants right and left.  There must be some tremendous selective pressures for delta.  One advantage of having delta still standing is that it can become the basis for the next round of vaccinations.

Nearly every door slammed by a mandate opens a little window with the chance to prove weekly that one is not harboring COVID.  At the University, there are multiple sites where you can sign up for an appointment for a test, walk in and answer some questions, spit into a little funnel, and hear within 24 hours that you’re still clean.  Such goes into your phone, and you can print it out if you want “papers” (I do), and you can flash these into the face of anyone at a restaurant or a concert venue seeking proof of your purity.  There’s a lot of this about.  Per ourworldindata.com 3.37 tests were performed per 1,000 people 11/15/21 nationwide.  With the current population of the United States of America is 333,691,290 as of Sunday, November 21, 2021, based on Worldometer elaboration of the latest United Nations data.  So that’s 1,124,539 tests in just one day.  With a median cost per test of about $150, that’s $16,680,947 per day.  While some have to pay for these tests or charge it to their insurance, most tests are “free” covered by some flow of government funds.  Into who’s pockets does all this case flow?   I’m still working on this, but some people are getting very rich.

Costs for these tests may be going up around here.  Campus has been hit by an alarming increase in influenza A cases.  Patients, like my wife, hit by a respiratory illness resembling COVID also have that test tube up the nose look for influenza A, which she had, and gave to me.  That test is about 3 times as expensive. What pans out here in AA will be interesting.  It might be a local flash in the pan, or a harbinger of a larger trend.  Remember, last season the flu numbers were way down, something the mask/lockdown crowd ascribed to the success of their maskings, forgetting the experience of the 1918 Spanish Flu epidemic that showed masks were worthless.  Ultimately, it was due to the isolation, with no one entering into the social arenas where virus exchange could take place.  Students are still out and about on campus, still masked.  But most have their immune systems focused on spike proteins.  How much can be left to take on another RNA virus?  I guess we’ll see.

But my impetus for writing this was to help my endocrinologist friend Dave understand Antibody Dependent Enhancement (ADE), a phenomemon invoked to explain why we’re still in this mess with COVID, 2 years after the boys and girls at the Wuhan Lab sprung it on us.  Ya’ think the masks, distancing, lockdowns and vaxx woulda let us move to something else.  But here we are.  So aren’t vaccines good?  Even Sabin’s sugar cubes spread a little polio.  In the late 60s, vaccination of neonates and the very young against Respiratory Syncytial Virus, and RNA respiratory virus, produced a vaccinated population that still could catch RSV, and get much sicker for it than those who had been left alone.  Thus was born the notion of ADE, whereby antibodies raised that do not neutralize virus facilitate other processes that augment the virulence of any ensuing infection (13).  Scientists saw this coming for COVID less than 6 months (14,15) after it sprung, as talk about vaccines was well underway (19,20).  Maybe they recalled the work of their Taiwainese colleagues at Kaohsiung who in 2014 looked at the first SARS outbreak and found ADE correlated with antibodies against spike protein (16).  Attempts at a vaccine broke when antibody dependent enhancement arose on in a monkey model (17). Everything old is new again.

Our immune system is an elegant, immensely complex tangle of processes that protect us from ourselves and the outside world (18).  That we deign to manipulate it to do our bidding is another bit of the hubris of Western medicine.  For COVID, we figure if we hijack our own ribosomes to crank out the Wuhan version of spike protein – action arm of the virus that hooks onto the ACE2 receptor – pushing that product in the face of all arms of our immune cells will make them take notice if something similar comes their way.  Since not all antibodies raised are neutralizing, chance for ADE mischief come afoot.  So what happens?  As the virus enters the vaxxed host (or one with natural immunity), non neutralizing antibody facilitates viral uptake , enhances replication, and helps evade intracellular innate immune receptors (the tickled arm of the immune system much more critical to fighting the virus than the antibody response).  More virus invades the host. The Chinese (Shenzen, not Wuhan) have it sorted out, with pictures, if you’re interested (19).  Curiously, the only article addressing this topic this year is out of Iran (20)).  It’s not something you can protective yourself against, except to avoid the vaxx altogether.  Maybe that’s something you can throw at your pro-vaxx “friends”.  “No ADE for me!”

Just one more thing to bolster the wisdom of the late, great Nancy Reagan

1.         Joodeph BC.  If the vaccines work, why aren’t the working?  American Thinker November 22, 2021 https://www.americanthinker.com/articles/2021/11/if_the_vaccines_work_why_arent_they_working.html

2.         Maragakis L, Kelen GB.  Breakthrough Infections: Coronavirus After Vaccination.  Johns Hopkins Medicine 11/13/21.  https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/breakthrough-infections-coronavirus-after-vaccination

3.         Coleman K.  Dr. Fauci Just Issued This Urgent Warning to Vaccinated People .  Yahoo!.  11/12/21 https://www.yahoo.com/now/dr-fauci-just-issued-urgent-201846228.html

4.         Kostoff RN, Calina D, Kanduc D, Briggs MB, Vlachoyiannopoulos P, Svistunov AA, Tsatsakis A. Why are we vaccinating children against COVID-19? Toxicol Rep. 2021;8:1665-1684. https://doi: 10.1016/j.toxrep.2021.08.0105.  . Epub 2021 Sep 14.

5.         Pfizer’s novel COVID-19 oral antiviral treatment candidate reduced risk of hospitalization or death by 89% in interim analysis of phase 2/3 epic HR study.  Pfizer.com 11/5/21. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

6.         Begley A.  EMA issues advice on use of Lagevrio for the treatment of COVID-19.   European Pharmaceutucal Review.  11/24/21. https://www.ema.europa.eu/en/news/ema-issues-advice-use-lagevrio-molnupiravir-treatment-covid-19

7.Reardin S.  Flawed ivermectin preprint highlights challenges of COVID drug studies.  https://www.nature.com/articles/d41586-021-02081-w 

8. Huizen J.   WHO ‘strongly’ against hydroxychloroquine use for COVID-19 prevention. News Today 3/3/21  https://www.medicalnewstoday.com/articles/who-strongly-against-hydroxychloroquine-use-for-covid-19-prevention#Dangers-outweigh-potential-health-benefits.Medical

8. Temple C, Hoang R, Hendrickson RG.  Toxic Effects from Ivermectin Use Associated with Prevention and Treatment of Covid-19.  NEJM.  October 20, 2021
DOI: 10.1056/NEJMc2114907.  https://www.nejm.org/doi/full/10.1056/NEJMc2114907

9.         Oldenburg CE, Pinsky BA, Brogdon J, et al. Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection: A Randomized Clinical Trial. JAMA. 2021;326(6):490–498. https://doi:10.1001/jama.2021.11517. https://jamanetwork.com/journals/jama/fullarticle/2782166

10. OpenVAERS. https://openvaers.com/

11.         COVID Data Tracker.  Variant Proportions.  COVID.  CDC. Gov.  https://covid.cdc.gov/covid-data-tracker/#variant-proportions

12.       SARS-CoV-2 Variant Classifications and Definitions.  CDC.  Gov.  https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html#anchor_1632150752495

11.       SARS-CoV-2 Variant Classifications and Definitions.  CDC.  Gov.  https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html#anchor_1632150752495

13. Arvin AM, Fink K, Schmid MA, Cathcart A, Spreafico R, Havenar-Daughton C, Lanzavecchia A, Corti D, Virgin HW. A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature. 2020 Aug;584(7821):353-363. https://doi: 10.1038/s41586-020-2538-8. Epub 2020 Jul 13.

14. Coish JM, MacNeil AJ. Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19. Microbes Infect. 2020 Oct;22(9):405-406. https://doi: 10.1016/j.micinf.2020.06.006. Epub 2020 Jun 24.

15.       Wen J, Cheng Y, Ling R, Dai Y, Huang B, Huang W, Zhang S, Jiang Y. Antibody-dependent enhancement of coronavirus. Int J Infect Dis. 2020 Nov;100:483-489. https://doi: 10.1016/j.ijid.2020.09.015. Epub 2020 Sep 11.

16.       Wang SF, Tseng SP, Yen CH, Yang JY, Tsao CH, Shen CW, Chen KH, Liu FT, Liu WT, Chen YM, Huang JC. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochem Biophys Res Commun. 2014 Aug 22;451(2):208-14. https://doi: 10.1016/j.bbrc.2014.07.090. Epub 2014 Jul 26.

17. Luo F, Liao FL, Wang H, Tang HB, Yang ZQ, Hou W. Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine. Virol Sin. 2018 Apr;33(2):201-204. https://doi: 10.1007/s12250-018-0009-2. Epub 2018 Mar 14..

19.       Wen J, Cheng Y, Ling R, Dai Y, Huang B, Huang W, Zhang S, Jiang Y. Antibody-dependent enhancement of coronavirus. Int J Infect Dis. 2020 Nov;100:483-489. https://doi: 10.1016/j.ijid.2020.09.015. Epub 2020 Sep 11.

20.       Farshadpour F, Taherkhani R. Antibody-Dependent Enhancement and the Critical Pattern of COVID-19: Possibilities and Considerations. Med Princ Pract. 2021;30(5):422-429. https://doi: 10.1159/000516693. Epub 2021 Apr 21.

Published by rike52

I retired from the Rheumatology division of Michigan Medicine end of June '19 after 36 years there. Upon hitting Ann Arbor for the second time (I went to school here) it took me almost 8 months to meet Kathy, 17 months to buy her a house (on Harbal, where we still live), and 37 months to marry her. Kids never came, but we've been blessed with a crowd of colleagues, friends, neighbors and family that continues to grow. Lots of them are going to show up in this log eventually. Stay tuned.

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