Global Biosurveillance

From: John Kiel
Sent: Tuesday, February 06, 2007 8:41 PM

Cc: Kiel, Johnathan L Civ AFRL/HEPC
Subject: Re: Pulse Article – Texas Tech University Health Sciences Center

 

Dr. Kiel,

 

I hope you enjoyed the previous issue of Pulse I mailed last week. I am looking forward to working with you!

 

Below you will find several questions regarding you, your job and how you arrived where you are in your life today. Please feel free to add any additional information you feel would be helpful. Once I have your answers if I don’t need further information I will draft the article and send it to you for your review. Our first draft deadline is February 19th.

 

Thank you again for your help!

 

Where are you from? I was born in Houston, TX and grew up there, although my Mother is British and I spent some summers as a child with my Grandparents in St Helens outside of Liverpool UK  (UK is kind of my second home).

 

What other degrees do you hold? BS (Texas A&M, veterinary science, 1973); DVM (Texas A&M School of Veterinary Medicine, veterinary medicine, 1974); PhD (TTUHSC, interdisciplinary in biochemistry and microbiology, 1981)

 

Why did you choose TTUHSC? Originally, because of a wound healing research program at TTUHSC that I saw in an advertisement on a bulletin board at Indiana University, Kokomo, Indiana, when I was taking classes there in calculus, during my duty as a USAF Base Veterinarian on Grissom AFB, Indiana, Peru, Indiana; when I got to TTUHSC, the program was no longer in effect, so I shifted to the anti-tumor effects of granulocyte and macrophage oxidase/peroxidase systems.

 

Who did you study under? Johannes Everse (Dept of Biochemistry) and Stanley S. Lefkowitz ( Dept of Microbiology; I believe he is now at University of South Florida, Tampa, FL, on the faculty of the Dept of Microbiology and Immunology).

 

Describe your experience here. It was very intense and stimulating. I was among the first of the PhD students at TTUHSC and maybe the very first inter-departmental interdisciplinary student. The USAF demanded that under the Civilian Institutions Air Force Institute of Technology Program that I complete my PhD in 3 years; I did so with a six month extension (in 3 ½ years); I believe this might be some kind of record of a single subject PhD, much less a double major PhD.

 

What did you like or not like about the university and or your experience? I didn’t like the hail, dust storms and the tornadoes; I did like the small town atmosphere for my wife and children and the flexibility of the university in accommodating my educational needs as a USAF military officer assigned to a civilian university; I especially liked the Chemistry Department courses on the main campus and the highly intellectually stimulating environment of the Dept of Biochemistry at TTUHSC; I also enjoyed working with the Dept of Surgery in the Medical School; we gave lectures together to local AMA branches on venomous snakebite treatment (another one of my avocations—venomous snake herpetology).

 

How did you come to choose medical biochemistry and what drove you to get your PhD? Although I had been on faculty, after my graduation from the Vet School at A&M, as an instructor of pathogenic bacteriology, before going into the military, I thought that pathogenic microbiology was on its way out in the late 70s early 80s; boy was I wrong, with the advent of AIDS (HIV), and other emerging infectious disease, this attitude completely changed (after I graduated from TTUHSC); so I decided to look at biochemistry as a way to unravel the mystery of why white blood cells would make free radicals to kill cancer cells (or infectious agents, but I focused on cancer because that was where the grant support was coming from for my graduate advisor in biochem), when such free radicals probably originally caused the genetic damage that led to the cancer in the first place (and aging as well). In the long run, my interdisciplinary education and approach has led to many opportunities within my military and scientific career to see interactions among many militarily and medically relevant “stressor” interactions—radiation, chemical and biological.

 

What is your rank and/or title? I am the Senior Scientist for Counterproliferation (a Brigadier General Civilian Equivalent in USAF) for the Human Effectiveness Directorate of the Air Force Research Laboratory

 

What do you do for the Air Force and why do you enjoy it? I mentor and lead a research team and serve as the USAF’s senior advisor on preventing and countering biological warfare and bioterrorism attacks through non-medical means (not vaccines or therapeutics, although we have spin-off research in this area). I like working with a team, like the conductor of an orchestra with very skilled, mature researchers being the concert masters or first violins. I prefer the group approach as opposed to the individual investigator approach, although I also enjoy having young people enter our group. They come as summer students, post docs, or in collaborative graduate study programs with various universities. I also enjoy “making a difference” in the defense of my country and its civilian population (especially in the case of preventing bioterrorist attacks).

 

I noticed that your research varies considerably in topic. Is that a result of your job role or are you interested in a myriad of topics? One of my patent attorneys once said that I was a “consummate scientist” ; I am really just a person with insatiable curiosity and interested in learning anything new in science—whether it is biochemistry, microbiology, physics, astronomy or engineering—I guess I am just a generalist or at worst a megalomaniac.

 

Are there any unique experiences that you’ve had in life you’d like to share? In 2005, I traveled around the world from West (from San Antonio) to East through Dublin, Ireland; the Netherlands; Hong Kong; Hanoi, Vietnam; Korea; San Francisco; and back to San Antonio in 2 weeks. In my last 10 years, I have traveled almost every month. My wife says I have learned to like every place I visit (and especially the one I visited last). These experiences have made me greatly appreciate, and respect other peoples, cultures, and countries, and has led to many gratifying professional international collaborations and interesting experiences abroad. Someday I will write a book about it.

Dr. Kiel,

 

Thank you for getting this back to me so quickly. I wanted to run something by you. It seems to me based on your answers that I have come across a diamond in the rough.

 

In this issue of Pulse I am also writing a four page feature story on alumni of the Health Sciences Center who are working in uncommon avenues of health care. I have already started contacting graduates who I knew fit in that category and I believe after what I just read you would be perfect to include in this feature as well.

 

If you are open to this, I would like to look for another Graduate School of Biomedical Sciences alum to feature in our alumni feature section (the one page features toward the back of the magazine) and move you to my uncommon occupations article instead.

 

I know you are busy and travel frequently but I will be happy to work with you in any way I can. Because the feature is much more in depth I may have some additional questions.

Let me know what you think. Thanks!

Associate Dean of Research Candidate, Johnathan Kiel, will have an interview with the Dean of the Texas Tech University School of Veterinary Medicine, 6/16/21:

8/21/21 Dear Johnathan,

Thank you for your interest in Texas Tech University and for the time you invested in applying for the position of Associate Academic Dean of Research 22120BR.

We appreciate the opportunity to speak with you and learn more about your qualifications. After careful consideration, we have selected another candidate for this position. We encourage you to continue to check our website for positions that interest you. To access submitted applications for other positions, please visit us at www.workattexastech.com.

Log-in using your username and password:

• Click Candidate Zone.
• Selected Dashboard.
• Applications submitted are listed under Submitted Applications.

We wish you the best of luck with your job search and your future professional endeavors.

Sincerely, Texas Tech Human Resources

 

The Antibody Dependent Enhancement (ADE) process is usually seen with antibody that is not against the primary receptor binding protein, non-neutralizing antibodies; like with whole virus inducing many different types of antibodies which do not neutralize the virus. The uptake by a cell is enhanced by the Fc portion of the antibody binding to a Fc receptor on the cell (macrophages where the virus replicates).This complement binding portion of antibody also activates the complement cascade that non-specifically destroys microbes. In viruses like SARS-CoV-2 which can induce anti-complement antibodies then the whole virus can induce Fc receptor activated inflammation without killing the virus. Dengue vaccines exacerbate disease when vaccinated for one strain followed by infection with another different strain, but not neutralized by the vaccine induced antibodies. The CMV virus is a herpes virus all of which are never cleared but only suppressed by the immune system. The current COVID vaccines are aimed at the RBP in the spike of the virus. Unlikely to cause the ADE but a whole attenuated CoV vaccine could possibly cause this as the actual viral infection followed by infection with a different strain (because of induction of non-neutralizing antibody).

ADE has been known for a long time. It was seen in animals with SARS-1 but overcome in vaccine development. The vaccine was never needed because SARS-1 disappeared in 6 months. We even developed enhanced uptake (infection) in our lab at Brooks of an intracellular bacterium Rickettsia artificially using aptamers in place of antibody:

Recent evidence has arisen, giving at least some insight, into how the immune system can reduce COVID-19 into a mild, unimpactful infection and then, in some cases, progress into a high mortality and morbidity form. Some hint was given by its early history of causing a mild phase progressing into a severe phase after 10-12 days of symptomatic infection, if including 2 days or more of asymptomatic infection, about the length of time (14 days or more) to develop a full humoral response. The most compelling case is for the development of humoral autoimmunity, autoantibody. Patients with life-threatening COVID-19 pneumonia have neutralizing IgG autoantibodies against Interferon-ω, the 13 types of interferon-α, or both, at the beginning of severe disease; a few also have autoantibodies against the other three type I Interferons. The autoantibodies neutralize the ability of the type I interferons to block SARS-CoV-2 infection in cell cultures. These autoantibodies are not found in those with asymptomatic or mild SARS-CoV-2 infection and only rarely in healthy individuals https://science.sciencemag.org/content/sci/early/2020/09/23/science.abd4585.full.pdf. This mechanism also explains the Kawasaki-like syndrome, the multisystem inflammatory syndrome (MIS-C), seen on rare occasion in young children and adolescents. The development of effective and lasting immunity appears to depend on cellular-mediated immunity (CMI; largely, T lymphocytes and production of gamma interferon) https://www.biorxiv.org/content/10.1101/2020.05.26.115832v1.full.pdf. The serum concentrations of IL-17A (a protein that recruits monocytes and neutrophils to an inflammatory site) and IFN-γ, but not TNF-α or IL-6, decrease with age of patients; therefore, gamma interferon’s ability to prevent viral replication but not induce oxidative damage to host cells, as with TNF-α, is more important in children’s responses. Recent evidence supports decline in soluble IL17A receptors, which block TNF-alpha and interferon gamma production by competing with the cellular T17 lymphocyte receptor, leads to more severe COVID19 https://science.sciencemag.org/content/sci/early/2020/10/14/science.abe9403.full.pdf. Adults show a more robust T cell response to the viral spike protein compared to pediatric patients shown by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+CD4+ T cells. Also, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis are higher in adults than in pediatric COVID-19 patients. The neutralizing antibody titer increases with age while the IL-17A and IFN-γ serum concentrations decrease. Therefore, neutralizing antibody levels alone are not sufficient to decrease severity of COVID. The first effective response to the SARS-CoV-2 virus is innate, involving the triggering of interferon 1 production (a complex of 13 proteins) leading to predominantly interferon omega, a form that recruits upregulation of the phagocytic activities of whole blood cells, macrophages and NK (Natural Killer) cell activities with decreased viral excretion https://www.karger.com/Article/Fulltext/495897#top. Type 1 interferons induce type III interferon (IFN-λ), which is primarily restricted to mucosal surfaces and is thought to confer antiviral protection without driving damaging proinflammatory responses. The interferon 1 released from infected cells prevents neighboring cells from replicating virus. The phagocytes produce NO, nitric oxide, that yields inhibition of viral replication and in greater amounts cell death, which may result in killing cells before virus can replicate, and damaging viral RNA. Greater amounts of NO can lead to swelling and further non-specific inflammation if it gets out of control. In children and those adults who recover from mild infection, the virus is eliminated by these innate and adaptive cellular immunity. If virus persists and disseminates in the lungs and other tissues, a strong humoral adaptive response may ensue. If with autoantibodies, phagocytes, with accompanying cytokine inflammation, will be directed against infected tissues, causing sepsis and perhaps death https://www.the-scientist.com/news-opinion/the-immune-hallmarks-of-severe-covid-19-67937. Antibody directed enhancement (ADE) may also ensue, wherein antibody increases viral uptake by white blood cells and endothelial cells by linking the viral bound antibody to the target cells through Fc receptors or complement component linkers/anti- ligands on the cells, and leading to more viral replication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165974/pdf/IMR-268-340.pdf.

There may be correlates in animals. Cats get an enteric coronavirus which has little or no signs, but, in certain young cats, it becomes disseminated, causing peritonitis with lethality usually 100%. CMI provides an effective immune response that resolves the infection in the enteric, intestinal form. If it does not, a strong humoral response kicks in and selects for a more pathogenic form of the virus which infects and replicates in macrophages https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112361/pdf/main.pdf. Also, autoantibodies form. There seems to be genetic predisposition toward this resulting in peritonitis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819880/. Peritonitis pathology involves severe systemic inflammatory damage of serosal membranes and widespread pyogranulomatous lesions in the lungs, liver, lymph tissue, and brain. The host immune system produces profound T-cell depletion from the peripheral and lymphatic tissues and changes cytokine expression. The clinical finding of hypergamma-globulinemia-associated feline infectious peritonitis is indicative of over production of antibody against an antigen which cannot be cleared, like a host cell-associated antigen. Therefore, like COVID-19, the feline coronavirus virus disease has this dichotomy, based on viral dissemination and autoantibody. The selection of the appropriate immune pathway with vaccination becomes very important to avoid adverse effects. Other viruses have had a similar warning due to overt responses, predominantly in children, resulting in hemorrhagic disease, when becoming immune (for life) to one strain but then becoming infected with another as in Dengue (4 strains), a mosquito-borne virus. The right antigen for the right vaccine must be selected to prevent such adverse effects. Another way that the viral replication and subsequent damage can be reduced is to stop or delay an overt response without altering it directly by using the anticoagulant heparin which blocks virus’ binding to the target cells https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2931230-7. (No longer a viable option because of the finding of anti-heparin antibodies in COVID: COVID-19 patients often show high-titer non-platelet-activating anti-PF4/heparin IgG antibodiesJ Thromb Haemost 1 May;19(5):1294-1298.doi: 10.1111/jth.15262. Epub 2021 Apr 7).

The 2003 outbreak of severe acute respiratory syndrome (SARS) may have left some survivors with pan coronavirus neutralizing antibodies. Former SARS patients who have been vaccinated against COVID-19 appear able to defend against all extant variants of SARS-CoV-2 (https://url2151.isid.org/ss/c/TLh_csrC34X_iXpbYoMam9jBwU6UUz6NJPZ04_cCUCL3644PNl-ALRgE0mFO6PwGe5X-VMh61_QdppWA_Rt5zQzaP0DvIIfJpW6Myagfu8XJSvXPtvEIYNwaJ89jkhOm2FatxVUPahWt0W2Y-bJ3esjVNEAmyKqtVA5l4Gv-740/3el/HxrT06euQNqqGKe7EBUHdw/h2/Jo2MuHI5q-FuEA-kMgKblceH5fHY6jN7au2pmKduPhI).

Stopping selecting the self-destructive immune pathway is what Dr Mullis’ chemically programmed immunity, mentioned in an earlier posting, sought to accomplish as well.

Whereas the following DNA vaccine technologies are no longer being pursued at this time for FDA licensure. India has granted emergency use authorization to a DNA COVID-19 vaccine that uses plasmids, to prime the immune system by synthesizing protein antigen in situ against SARS-CoV-2. The vaccine, ZyCoV-D, was developed by the Indian pharmaceutical firm Zydus Cadila; it is the first DNA vaccine for humans to receive authorization anywhere in the world.

Nov 16, 2020, 07:00 ET, it was announced that INOVIO received approval from the U.S. Food & Drug Administration (FDA) to proceed with Phase 2 of its Phase 2/3 clinical trial for INO-4800, its COVID-19 vaccine candidate. INO-4800 is the only nucleic-acid based vaccine that is stable at room temperature for more than a year and does not need to be frozen in transport, an important factor for implementing mass immunizations. INOVIO’s DNA vaccine plasmid is delivered directly into cells intramuscularly or intradermally using INOVIO’s proprietary hand-held device called CELLECTRA®. The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in cells to allow the plasmids to enter, overcoming a key limitation of other DNA vaccines and mRNA vaccines. Once inside cells, the DNA plasmids enable the cell to produce the targeted antigen. The antigen triggers the normal T cell and antibody-mediated immune responses. The CELLECTRA device ensures that the DNA plasmids are efficiently delivered directly into the body’s cells to drive the immune response. INOVIO’s DNA vaccine does not interfere with or change in any way an individual’s own DNA. The advantages of INOVIO’s DNA vaccine platform are how fast it was designed and manufactured; its stability, not requiring freezing for storage and transport; and the robust immune response, safety profile, and tolerability evident in clinical trials. The CELLECTRA® electroporation device developed by Inovio Pharmaceuticals, Inc., is currently being assessed in clinical studies for both prophylactic and therapeutic applications.

This device delivers square-wave electric pulses by applying an adaptive electric field based on constant current, rather than constant voltage. This system measures electrical parameters and adjusts appropriately for changes in tissue resistance in realtime to avoid tissue damage and diminished DNA cell entry. The device has been evaluated in animal models, including mice, pigs, and rhesus macaques, and demonstrated acceptable immune responses.

DNA vaccines have been criticized in the past because of the possible off-target effects in expression of protein, integration of foreign DNA into the host genome and difficulties in delivery to the right target cells. As noted above INOVIO has provided evidence that they have overcome these limitations by plasmid design and a proprietary electroporation device. The concern about plasmid in comparison to mRNA vaccines is that they must enter the nucleus to be converted into mRNA before being translated into protein in the ribosomes of the cytoplasm. mRNA vaccines do not require entry into the nucleus before this last step. I have spent a lot of time providing accounts and data of the Brooks Counterproliferation Team’s work on these problems for different military applications in previous posts. It is ironic that INOVIO has received a significant level of funding from the Department of Defense independent of our work: On June 23, 2020, INOVIO received a $71 million contract from the U.S. Department of Defense to scale up its manufacture of its CELLECTRA® 3PSP Smart Device and procurement of CELLECTRA® 2000 for COVID-19 DNA Vaccine delivery https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906411/pdf/hvi-9-2246.pdf.

Our work began with efforts to synthesize a microwave and radio frequency electromagnetic radiation interacting polymer starting in 1981. We succeeded (1 March 1988) in making one from the amino acid 3-amino-L-tyrosine which through diazotization ended up with the following structure:

This polymer demonstrates a number of interesting and very applicable physical and chemical properties. It is thermochemiluminescent while oxidizing, binds to DNA without damaging it functionally, and further interacts instantly with pulsed direct current electric fields, and those of pulsed radio frequency and microwave radiation. The classical explanation of its behavior is as an inductor, that it is a passive two-terminal electrical component that stores energy in a magnetic field when electric current flows through it. An inductor consists of an insulated wire wound into a coil around a core. When the current flowing through an inductor changes, the time-varying magnetic field induces an electromotive force (e.m.f.) (voltage) in the conductor, described by Faraday’s law of induction. According to Lenz’s law, the induced voltage has a polarity (direction) which opposes the change in current that created it. As a result, inductors oppose any changes in current through them. The coiled ground state structure of DALM may be responsible for its behaving as a molecular inductor. The discharge of luminescence and/or thermalization are related to the release and conversion of this stored energy.

The next step was to try to make DALM from feedstock chemicals fed to bacteria that have inducible nitrate reductase. When this process was not totally satisfactory, genetic modification with plasmids delivered by electroporation or calcium phosphate was tried and succeeded in enhancing the production of DALM. This even worked with mammalian and human cells harboring nitric oxide producing enzymes (nitric oxide synthase, NOS) which could integrate with a component of the barley plant nitrate reductase to enhance both their activities simultaneously.

Plasmids transferred to target cells with DALM nanoparticle vectors have demonstrated desired functional transfer such as antibiotic resistance for clonal selection, antimicrobial activity, and DALM nanoparticle biosynthetic capability, but also the less desirable transfer and off target effects of genome integration in mammalian and human cells (expected based on plasmid constructs used), and in bacteria, not only the clonal selection antibiotic resistance, but also the off target effects of bacteriophage resistance and hemolytic activity in a pathogen (Bacillus anthracis, anthrax). The DALM nanoparticle vector has demonstrated its broad utility as a potential plasmid DNA vaccine vector and also its ability to be manufactured by microbes’ making biosynthetic complete DALM, nanoparticle, plasmid DNA vectors for genetic transfer.

I have found it necessary to re-post this post. The only way vaccines have affected reproduction is when live attenuated vaccines are given to pregnant hosts, infect the fetus and cause defects or abortion—the mRNA vaccines in particular are not of this class and even the aforementioned effects do not result in sterility and should not be confused with it.

A recent popular article has suggested, that because the SARS-CoV-2 spike (fusion) protein has a homologous polypeptide to Syncytin 1, a protein that forms the syncytium of cells by fusion binding the fetus to the uterus through the placenta, the vaccines against the spike protein would develop antibodies against the placenta and cause sterility, but the data does not support this https://edwardnirenberg.medium.com/are-covid-19-vaccines-going-to-cause-infertility-939bbdb62b64. The fusogen proteins that allow enveloped viruses to fuse with their target host cells are related but not necessarily identical to the placenta protein. In fact, Syncytin 1 and 2 were originally viral proteins and are necessary to the development of placentas in mammals. This was accomplished by infection with a Type D retrovirus which became integrated into the mammalian and human genomes. HERV–W genome integrated into its host’s germ-line around 63 million years ago, spread into Old and New World monkeys and then evolved independently. The viral genes were incorporated into the germ cells and, therefore, for all subsequent generations. This endogenous retrovirus, HERV-W, is the source of Syncytin I. The env gene from HERV-W produced a functional class I fusion protein capable of merging cells into a syncytium. Such syncytia are at the placental interface between the embryo and mother; preferential expression of HERV-W occurs in embryo cells that become part of the placental interface. This virally derived fusion protein is syncytin, later called syncytin-1; a second such protein from HERV-FRD, is called syncytin-2.

“These ubiquitous endogenous retroviruses are permanently transmitted in germ cell genomes and almost all have lost their ability to replicate outside of their genome-integrated DNA and to infect other cells horizontally as complete infectious virions. They are associated with resistance to other exogenous retroviruses, the process of xenotropism, and with placental development in mammals.

Endogenous beta retroviruses (enJSRVs) are present in the genomes of sheep and goats. The enJSRVs are highly related to Jaagsiekte Sheep Retrovirus (JSRV) and the Enzootic Nasal Tumor Virus (ENTV), which cause naturally occurring carcinomas of the respiratory tract of sheep. The enJSRV blocks exogenous JSRV replication by a novel two-step interference mechanism acting both early and late during the virus replication cycle. The only retrovirus sequences that have been added to the human genome since humans became a separate species from their common primate ancestor are members of the Human Mouse Mammary Tumor Virus-like 2 (HML-2) group of the beta retrovirus-like viruses. This human endogenous retrovirus is HERV-K whose elements are integrated in all extant human genomes”— The Black Dragon Trilogy by JOHNATHAN KIEL
https://a.co/8OGjRRc

Mammals and humans have become immunotolerant to these viral placental proteins. Although it is possible for there to be cross reactivity between microbial antigens and self, the evolutionary adaptation to this essential viral appropriated protein has minimized the likelihood of this type of autoimmunity. Fusogenic proteins are so pervasive in enveloped viruses, that if this kind of autoimmunity were likely, we would see sterility with many types of viral infection and their developed vaccines. Normal births have occurred and been reported from SARS-CoV-2 infected mothers. Example viruses producing fusogens, including viral class I fusogens, are major human pathogens, including influenza A, Lassa virus, SARS-CoV, Ebola, human parainfluenza virus-3, HIV-1, and human T-lymphotropic virus-1. Class II fusogens come from Dengue fever virus, West Nile virus, Zika virus, and tick-borne encephalitis virus https://www.cell.com/current-biology/pdf/S0960-9822(20)30668-0.pdf. When viruses such as rubella and Zika cause birth defects it is because of the wild viral infection not autoimmunity to a host antigen https://www.ncbi.nlm.nih.gov/books/NBK507879/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140214/. Therefore, this extrapolation and extension of a evolutionary relationship between host and ancient viruses have not led to sterility but rather advanced fetal development.

Perhaps the most remarkable interaction of endogenous retrovirus is with HIV (Human Immunodeficiency Virus):

“Recently, it has been shown that the expression of HERV-K proteins suppresses HIV replication, perhaps through tuftsin, an inflammatory macrophage cytokine. Decline in tuftsin and increased expression of HERV-K is associated with advancing AIDS. Activation of HERV-K expression has correlated with the level of HIV-1 production. Studies of autoimmune neurological demyelinating disease (experimental autoimmune encephalomyelitis (EAE)) in rodents indicates that tuftsin administration upregulates immunosuppressive Helper-2 T cell (Th2) cytokine transcription factor and that tuftsin-mediated microglial cell activation results in shifting microglia to an anti-inflammatory phenotype. In return, the T cell phenotype is shifted towards immunoprotection after exposure to tuftsin-treated activated microglia, that is, downregulation of pro-inflammatory Th1 responses triggered in conjunction with upregulation of Th2-specific responses and expansion of immunosuppressive regulatory T cell clones. Macrophages with activated HERV-K expression were more resistant to HIV infection, perhaps in part by its Gag protein being expressed and interfering with the assembly of the HIV virions, and cells expressing HERV-K and infected with HIV were more susceptible to destruction by cellular immunity. Infection of CD4 + T cells with HIV-1 was shown to result in transcription of the HML-2 lineage of HERV-K [HERV-K( HML-2)] and to express the Gag and Env proteins of this virus. HERV-K( HML-2)–specific CD8 + T cells obtained from HIV-1–infected human subjects responded to HIV-1–infected cells in a Viral infectivity factor (Vif)-dependent manner in vitro. HERV-K( HML-2)–specific CD8 + T cells (cytotoxic T cells) eliminated cells infected with globally diverse HIV-1, HIV-2, and SIV isolates in vitro. A second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K( HML-2)-Pol has raised the possibility that similarities between HIV-1 and HERV-K play a role in forming, triggering, and perhaps enhancing, the T cell response to HIV-1. There is even some suspicion, because of the association with HERV-K expression with certain tumor cell lines, that its expression can lead to cancer triggered by HIV infection as was perhaps my brother’s brain lymphosarcoma. HERV-K is both protective, initially through triggering the innate immune system and later specific T cell cytotoxicity, and detrimental by perhaps triggering the formation of cancer. The dilemma with HERV-K and the human immune system is that the initial innate response producing reactive oxygen species could protect against both HERV-K and HIV, simultaneously, but the switch to the inadequate nitric oxide response in human macrophages encourages the replication and release of HIV to infect other recruited and susceptibly activated macrophages to carry the HIV to lymphoid tissue. Evolutionarily, HERV-K’s advantages have outweighed its disadvantages and has led to resistance to such coming plagues as that could result from Viper Plague Virus, at least for now.”— The Black Dragon Trilogy by JOHNATHAN KIEL
https://a.co/57tGvuL

The anti-mask, anti-vaccine clamor is destroying the United States. We need not repeat the disastrous cataclysms of the past.

Although pseudoscience may be literally defined as “false” science, it is much more. It grows out of the need to promote and popularize a myth which is accepted based on some authoritarian view or bias, religious, political, or philosophical, and the need to justify that view with “facts” which are carefully selected to support the view and presented in a way to mimic the scientific method.”— The Black Dragon Trilogy by JOHNATHAN KIEL https://a.co/hnHWBsg. This kind of propaganda now depends on the internet and social media full of testimonials and posting unsubstantiated reports supporting the emotional assertions. Testimonials are not science and neither are uncontrolled observations leading to causal conclusions based on association, especially time related causality. This is not science. It is not based on the scientific method. People also confuse the unedited collection of adverse reactions data by the FDA on medicines and vaccines as causal proof, but it is only to consider all possible adverse reactions for future rigorous scientific investigation using the scientific method (https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Understanding-the-Vaccine-Adverse-Event-Reporting-System-(VAERS).pdf. and https://www.nature.com/articles/d41586-021-00290-x?utm_source=Nature+Briefing&utm_campaign=5eb3714930-briefing-dy-20210217&utm_medium=email&utm_term=0_c9dfd39373-5eb3714930-43804265).

The most notorious example of pseudoscience perpetrated by a scientist involved AIDS in South Africa. UC Berkeley professor Dr. Peter Duesberg, a University of California at Berkeley, tenured professor in the Department of Molecular and Cell Biology, believed that HIV does not cause AIDS. In 1987, he first questioned the link between HIV and AIDS in the journal Cancer Research (“Retroviruses as carcinogens and pathogens: Expectations and reality”. Cancer Research 47 (5): 1199–220, 1987).” In 2000, Duesberg was a prominent member of the panel which advised President Thabo Mbeki of South Africa on the cause of the AIDS epidemic which was exploding out of control in South Africa. This “scientific support” led President Mbeki to deny AIDS was caused by a virus and denied anti-viral treatments in his country. Between 2000 and 2005, more than 330,000 deaths and an estimated 35,000 infant HIV infections occurred. Nicoli Nattrass of the University of Cape Town estimated 343,000 additional AIDS-related deaths and 171,000 infections occurred because of President Mbeki’s administration’s policies. According to Peter Mandelson in 2002, a British Labour Party politician and President of the international think tank Policy Network, it was a “genocide by sloth”. Duesberg recently still asserted his views in a paper first published in 2009, then withdrawn and republished in a revised form, in the peer-reviewed journal The Italian Journal of Anatomy and Embryology (IJAE) in December 2011. This example shows that scientists can also be lured into supporting pseudoscience if they do not manage their biases and remain true to the scientific method even when it contradicts their most favorite hypotheses (I did not say “theories”, which are often confused with the term “theoretical”). Scientific hypotheses are just that, they remain to be tested with well-designed experimentation, while scientific theories, like evolution, or the theory of relativity, are supported by many generations of observations and experimentation and predictive science before being generally accepted as a scientific consensus.

In respect to vaccination hesitancy and resistance, the consequences can be swift and devastating, with diseases almost never seen anymore, erupting abruptly seemingly out of nowhere. From 2011 to date, measles has become a problem for public health officials in the US. There were 220 cases in 2011, just 55 in 2012 and 186 in 2013. The illnesses have appeared in clusters for the most part, although single cases have also appeared in many states. In 2014, there have been three large measles outbreaks. Southern California saw an outbreak from January through May 2014 at 59 cases. New York City had an outbreak that stopped at 26 cases. Ohio has had an outbreak through 16 May 2014, with 83 people infected In 2013 through 2014, in the US, three outbreaks accounted for most of the measles cases. These included clusters of measles cases: in Texas tied to the Kenneth Copeland televangelism ministry and his mega-church; in North Carolina linked to a Hindu religious community and shrine; and in New York City, in 2014, in the Hasidic Orthodox Jewish community in Brooklyn. The national measles report from the Centers for Disease Control 1 Jan through 9 May 2014, released 12 May 2014, showed 187 measles cases from 17 states. Since that report, Ohio reported an additional 23 cases, with new cases in Tennessee, Pennsylvania, Massachusetts, and other states. The measles cases in both Ohio and California, in 2014, were linked to an ongoing measles epidemic in the Philippines. Both outbreaks in the States were results of travelers returning from the Philippines who had not been vaccinated and who brought back incubating measles. Six cases in Washington State were in patients without immunizations with ties to the Dutch Reformed Church, in British Columbia, which was the center of a 400-case outbreak of measles. The church opposes the use of all vaccines, including the measles vaccine. These examples illustrate the effects of misinformation, particularly on the internet and social media, where its removal is problematic, and perhaps, where it remains eternal. A study of the correlation of the dissemination of such information, the decline of vaccination, and the occurrence of cases should be made. My hypothesis is that the correlation would be high, and the pattern would resemble the spread of an infectious disease itself, with the computer being the vector and the electronic misinformation being the infectious agent (at least a surrogate for measles). Now imagine the consequences of anti-vaccination campaigns against SARS-CoV-2 and the devastation which has already occurred at this writing to date, continuing indefinitely because herd immunity can never be reached through “natural means” and large populations of unfettered virus allows for probable continuous emergence and “ natural selection” of resistant variants. This is, as I have posted earlier, the common nature of coronaviruses. Finally, as noted in a previous post, development of immunity after widespread dissemination of the virus in organs and tissues sets them up for devastating immune mediated complement interactions and innate immune cell (neutrophil and other granulocyte) mediated collateral destruction of blood vessels and other tissues.

All this being said, potential detrimental effects as well as beneficial ones of treatments and vaccines must be reported and investigated by the scientific method with even handedness. This includes herbal and indigenous peoples’ remedies. Historically, pharmaceuticals and pharmacology are deeply rooted in botany of medicinal plants; many which originated in folk remedies but which stood scientific scrutiny. Examples include Belladona (resulted in atropine and scopolamine), digitalis (digoxin), quinine, and lastly, the very important antimalarial drug Artemisinin (Chinese remedy). Belladonna (Atropa belladonna) is a plant which has been used as a medicine since ancient times. “Belladonna” means “beautiful women” used by the ladies of Renaissance Italy to enlarge their pupils, which they found alluring. But because it can be a lethal poison, the plant of origin also goes by the more sinister name deadly nightshade. Digoxin and digitalis are cardiac glycosides derived from the plant, foxglove, used to treat mild to moderate congestive heart failure and abnormally rapid atrial rhythms (atrial fibrillation, atrial flutter, and atrial tachycardia). The quinine mentioned above, and its present day Chinese successor, Artemisinin (from Wormwood), are actually very old remedies. Quinine, from the bark of the cinchona tree, and which can now be made synthetically, was originally discovered by the Quechua, indigenous people of Peru and Bolivia. Jesuit Missionaries were the first to introduce cinchona to Europe in the 17th century. Chinese herbalist’s use of Artemisia annua (Wormwood), which predated quinine, was first described in a 4th-century Chinese text, the source of the modern day antimalarial drug arteminisin. Quinine was commonly used for treatment of malaria until the 1940s, when chloroquine and other drugs were developed because they had fewer side effects. Except for vitamin D3 (addressed in a previous post) and some ongoing studies on the microbiome, I know of no other natural remedies being scientifically examined for prevention or treatment of COVID at this time. However, recent studies don’t support the expectations for Vitamin D3. In a study of hospitalized COVID-19 patients, a single high dose of vitamin D3 did not significantly shorten hospital lengths of stay. These findings do not support the use of high dose vitamin D3 for treatment of moderate to severe COVID-19. Criticism of this study suggesting that it did not look at subpopulations of different severity independently or early treatment suggests that the treatment should not be rejected before it has been further studied and then found effective or not (https://jamanetwork.com/journals/jama/articlepdf/2776738/jama_murai_2021_oi_200145_1613509376.92008.pdf and https://jamanetwork.com/journals/jama/articlepdf/2776736/to jama_leaf_2021_ed_200126_1613509372.9982.pdf). Vaccination, in spite of variants, (https://www.researchsquare.com/article/rs-226857/v1 and https://jamanetwork.com/journals/jama/articlepdf/2776739/jama_walensky_2021_vp_210031_1613509382.71695.pdf.) and sanitary precautions are still our best defense against COVID. What is certain, COVID can be lethal and can have persistent long term debilitating effects which are lacking with vaccination and can be prevented by it.

With the reported rise of mutants with increased transmissibility and potential immune escape supported by epidemiological and clinical data, the search for a panacea which will cover all strains of SARS-CoV-2 has become a frenzied pursuit. Such haste and grasping any favorable observations, no matter how tenuous, have inundated social media, the press, and placed undue pressure on medical institutions to modify and scale back their warnings about such unsubstantiated treatments and prophylactics, https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html. The problem is balancing the specific with the non-specific. The former decreases adverse side effects, such as anaphylaxis and Guillain-Barré syndrome (GBS; neurological weakness and paralysis), but is subject to mutation leading to neutralization of effectiveness. The 1976 flu vaccine, I took while in the military and which was falsely associated with GBS, rose public concern and misconceptions and fears because of a historic small increase in GBS risk associated with the vaccine, which was later found to be lower than initially thought. Concerns about vaccine-related GBS risk persist despite comprehensive surveillance of influenza vaccine-related increases showing only one additional case of GBS per million flu vaccinations. In contrast, the risk of flu-related complications is 17 per million cases. A recent study showed no link between COVID-19 and Guillain-Barré syndrome https://www.cidrap.umn.edu/news-perspective/2020/12/study-finds-no-link-between-covid-19-guillain-barr-syndrome and https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awaa433/6031905. The most common trigger for GBS is infection with Campylobacter jejuni, a bacterium that causes gastroenteritis, or infection of the digestive tract, the most common cause of food borne illness. Therefore, benefits of vaccination far outweigh the risks. The use of broad spectrum, non-specific potential treatments have more adverse side effects associated with them, and diluted effectiveness.

What are we up against? Three mutants V367F, W436R, and D364Y, have arisen in Wuhan, Shenzhen, Hong Kong, and France, which have demonstrated higher human ACE2 affinity. This is because of enhanced stabilization of the receptor binding protein (receptor binding domain, RBD). High frequencies of RBD mutations have been identified: V367F with five mutations from France and one Hong Kong mutant, V483A, and G476S mutant from the USA. Lineage B.1.1.7 (also called 501Y.V1) is rapidly spreading in southeastern England. It has 17 mutations which developed prior to its detection in early September 2020, which indicates prior evolution, possibly in a chronically infected patient. B.1.1.7 expanded when SARS-CoV-2 cases were widespread and achieved dominance by outcompeting an existing population of circulating virus, natural selection of virus more transmissible. Dr. Joel Ernst, an infectious disease expert at UCSF, has stated the B.1.1.7 UK variant has been found in 22 states so far, including 72 cases in California, according to the Centers for Disease Control and Prevention.

The variant in South Africa was first detected in Nelson Mandela Bay in samples dating back to the beginning of October 2020. South Africa showed a sharp rise in the number of infected during November 2020, and reported 501Y.V2 to the World Health Organization on 18 Dec 2020. More than 1.3 million people have been infected with the virus in South Africa, highest of any African nation, more than 37,000 South Africans have died from COVID-19. Most new infections are caused by the 501Y.V2 variant.

Mutations have significantly changed the South African virus’ spike protein; the spike protein has now rotated about twenty degrees and can therefore get more deeply into the binding site on cells; thus, the virus can bind better to human cells, enabling it to become a more efficient virus for transmission. The South Africa variant is about 50% more contagious than the original strain. The Western Cape region took 107 days to reach 100,000 cases in the first wave compared to 54 days in the second wave, when the variant appeared. The South African variant has spread to 14 countries. The director of the Centers for Disease Control and Prevention said, 29 Jan 2021, that the South African Covid-19 variant, which was just detected in two people in South Carolina, had already reached the point of community spread in the U.S. On 9 Jan 2021, Japan notified WHO of a new SARS-CoV-2 variant B.1.1.28 detected in 4 travelers from Brazil. This variant has 12 mutations to the spike protein, including 3 mutations in common with 501Y.V2, ie, K417N/T, E484K and N501Y, which potentially can change transmissibility and host immune responses. Brazil has also reported emergence of a similar variant, with E484K mutation, which evolved independently of the variant from the travelers.

By mid January 2021, Dr. Charles Chiu, director of the UCSF-Abbott Viral Diagnostics and Discovery Center, from sequencing results from his lab at UCSF, found a rare variant, that Chiu had only seen in a handful of samples, suddenly jump up to 25% in his samples. Chiu’s team was the first to report the new variant, now called L452R, but within days, diagnosticians at Cedars-Sinai reported the same variant was now making up more than a third of cases in Los Angeles.

Now Delta (B.1.617.2) variant is currently the most prevalent variant in the United States. New data indicate that the Delta variant spreads almost twice as fast as the original SARS-CoV-2 virus.

These variants suggest specific antiviral measures may be sidestepped by their changes if the measures are targeted too specifically to an antigen. I stated this in an earlier post about monoclonal antibody driving escape mutations by selection pressure. This has been borne out by recent clinical studies. Treatment with bamlanivimab and etesevimab, monoclonal anti-spike antibodies to different epitope targets, of nonhospitalized patients with mild to moderate COVID-19 illness, compared with placebo, showed statistically significant decrease in SARS-CoV-2 viral load at day 11; however, no significant reduction in viral load was seen with bamlanivimab monotherapy. The South African strain has also demonstrated escape from such treatment. It has been observed to completely escape from three monoclonal antibodies, reported by scientists from three South African universities, with the National Institute for Communicable Diseases (NICD), in a paper published on the bioRxiv website (https://bit.ly/2Y0lHEt). In addition, 501Y.V2 showed substantial or complete escape from neutralizing antibodies from COVID-19 convalescent plasma. They concluded reinfection could occur, and the differences in the variant may lead to reduced efficacy of current spike-based vaccines (New COVID-19 Variant Defeats Plasma Treatment, MABs, May Reduce Vaccine Efficacy – Medscape – Jan 20, 2021). Such dire predictions, have led individuals and physicians to pursue broad-spectrum treatments which make such variations irrelevant.

Didier Raoult’s tarnished claim hydroxychloroquine and azithromycin were effective against COVID-19 has not completely died because of this need for a generalized treatment, even in the scientific community. In a recent ACS paper, the investigators used hydroxychloroquine (HCQ) as a reference template to screen for structural similarity against a library of approximately 4000 approved drugs. The top-ranked drugs, based on structural similarity to HCQ, selected for in vitro antiviral assessment, were zuclopenthixol and nebivolol, which blocked SARS-CoV-2 in vitro infection with EC₅₀ values in the low micromolar range. The anti-SARS-CoV-2 potential of ambroxol, amodiaquine, and its active metabolite (N-monodesethyl amodiaquine) were discussed. They concluded both the pK_a (acidity) and the HCQ aromatic core play a role in antiviral activity. These are such broad mechanisms that such studies are academic and may have too many in vivo variable interactions to be clinically relevant (Giovanni Bocci et al. ACS Pharmacol. Transl. Sci. 2020, 3, 6, 1278–1292; publication date: October 14, 2020, https://doi.org/10.1021/acsptsci.0c00131). Unfortunately, another anti-parasitic drug, Ivermectin, has been revisited as a general antiviral after 50 years of study that have not translated into such clinical use https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251046/pdf/210_2020_Article_1902.pdf and https://www.nature.com/articles/s41429-020-0336-z.pdf. Among the many mechanisms of action of Ivermectin, the most relevant to antiviral activity is as an inhibitor of nuclear transport mediated by the importin α/β1 heterodimer, responsible for the translocation of various viral species proteins. Unfortunately, most of the viruses it is supposed to effect are not inhibited in replication or infection, or at least consistently. For HIV type 1, a study showed that Ivermectin failed to control the nuclear accumulation of telomer repeat factor-1 (GFP-TRF) which can only be transferred by IMPβ1 to the cell nucleus disputing the proposed mechanism. Researchers concluded that Ivermectin is not a specific inhibitor for IN-IMP α/β interaction, but it appears to be a specific inhibitor of cargos that are dependent on the heterodimer, making its predicted antiviral activity in a host even more suspicious. Law of diminishing returns seems to come into play with Ivermectin treatment. Virus out runs capacity. In pigs with circovirus 2, in the first 24 hrs, Ivermectin reduced viral load by 41% and 28.2%, However, in 48 hrs, it reduced viral load 28.8% and 15.7%, at the same treatment concentrations. Evidently, it decreases in drug efficacy at later time points of infection. In a recent study among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings did not support the use of ivermectin for treatment of mild COVID-19 https://jamanetwork.com/journals/jama/articlepdf/2777389/jama_lpezmedina_2021_oi_210022_1614808764.76432.pdf. In spite of all its years of use in Veterinary Medicine, to prevent heartworms in dogs and other worms in livestock, I have never heard of a veterinarian using it to treat viral infections. Also, I don’t see Ivermectin listed in the Overview of Antiviral Agents, Pharmacology, in the Merck Veterinary Manual. For Ivermectin to be effective against SARS-CoV-2, in cell culture, the concentrations had to be in the microgram per ml range, blood levels of Ivermectin are at safe therapeutic doses in the 20–80 ng/ml range.

The National Institutes of Health (NIH), under pressure from clinicians, has dropped its recommendation against the inexpensive antiparasitic drug Ivermectin for treatment of COVID-19, and the agency now states it can’t recommend for or against its use, leaving the decision to physicians and their patients. “Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19,” according to new NIH guidance released recently. Some clinical studies showed no benefits or worsening of disease after its use; however, others reported shorter time to resolution of disease. This may be tied to viral load or just an unreliable, unpredictable response.

Some have already failed clinical trials (such as hydroxychloroquine) and some seem counterintuitive (like the immunosuppressant cyclosporine) so caution must be taken in extrapolating these results and they only be considered for suggesting possible clinical testing candidates. They found nine drugs with antiviral activity in lung epithelial cells: 7 of the drugs have been used in humans, 3 FDA approved in the United States (cyclosporine, dacomitinib, and salinomycin), and ebastine (an anti-histamine) approved outside the United States (https://www.cell.com/action/showPdf?pii=S2211-1247%2821%2900273-4). Some of the immunosuppressive and ant-histamine anti-SARS-CoV-2 activities may be explained by the linkage of the host response to the virus to the peculiar anti-parasite, anti-tumor immunity and its adverse effects in COVID.

Other non-immune-mediated drugs are being considered. The government is paying Merck & Co about 356 million USD to fast-track production of one of its potential treatments under Operation Warp Speed. The funding will allow the company to deliver up to 100,000 doses by 30 June 2021, if successful and FDA clears the treatment for emergency use. It is called MK-7110, designed to minimize damaging effects of an overactive immune response to COVID-19. Another promising drug is plitidepsin (aplidin), 27.5 times more potent than remdesivir in cell culture. The mechanism of action against SARS-CoV-2 is through inhibiting eEF1A, a key cellular protein in proliferation and growth (the eukaryotic elongation factor 1 α, eEF1A). During protein translation, eEF1A recruits aminoacyl t-RNA to the ribosome and translocates the growing polypeptide from the ribosomal A site to the P site. Therefore, the drug inhibits viral protein production and, subsequently, viral replication. It’s potential toxicity, because of this non-specificity, is on protein synthesis, growth and healing. The viral production was inhibited at 8-12 hours but was not significant after 24 hours of infection. Therefore, it must be used early in infection based on these in vitro and animal studies https://science.sciencemag.org/content/sci/early/2021/01/22/science.abf4058.full.pdf. Recently modeling efforts and in vitro cell culture studies have examined repurposing other FDA approved drugs as antivirals to treat COVID. These include the old anti-tapeworm drug niclosamide. It has shown broad efficacy against viruses including SARS-CoV-2. This salicylanilide’s antiviral activity is based on its ability to prevent acidification of endocytotic compartments, blocking membrane fusion and infection of the host cell. Early viral studies showed that the efficacy of salicylanilides was derived from the anilide ring, the important role of the N− H group in shuttling protons into the endosome. Niclosamide’s reduction of infection in cells without interacting directly with any viral components presents the possibility of anti-COVID-19 therapeutics with broad activity against current and future variants of the virus, but also may dilute out its effectiveness as seen with antihelmintics like ivermectin and increase the possibility of side effects (Steven Blake et al., Salicylanilides Reduce SARS-CoV‐2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model, https://doi.org/10.1021/acsinfecdis.1c00253
A, ACS Infect. Dis.).

How do we reconcile broad-spectrum, non-specific treatments to counter natural selection of viruses resistant to specific antibody or cellular immunity against requirements to avoid off-target and diluted-out effects of non-specific treatments ? First, the current vaccines may induce broader coverage immunity than illustrated by monoclonal antibody or convalescent plasma responses to infection. Even the difference between male and female immune responses, females having more effective T cell cellular immune responses than males’ B cell dominated antibody response, indicates broader immune coverage from the same SARS-CoV-2 antigens https://science.sciencemag.org/content/sci/371/6527/347.full.pdf. The Th17 response to COVID-19 also indicates a more generalized polyclonal immune response. So don’t write off the current vaccines yet. Second, I have alluded to, in earlier posts, that aptamers which can be selected synthetically to many targets on the virus and be changed rapidly, can also link these anti-ligands to specific pre-existing antibody or immune cells to rapidly mobilize the immune system against the virus and even convert the pathogenic virus into an autogenous endogenous vaccine after directly neutralizing it. The original route of administration was by inhalation to enable self-application of the treatment/prevention. However, these approaches are yet to get out of the basic research laboratory.

HeLa-NR1cells producing and extruding biosynthetic clusters of polymer nanoparticles (white) capable of carrying cell-synthesized RNA

You are probably sick of me saying this over and over again, but ignoring these facts and principles does not end the pandemic only makes it worse:

My book Pathogenic Ecology points out in detail how we get into such a mess and why we can’t ignore it:

Re-posting this post because of its prophetic content: The viruses, including SARS-CoV-2, continue to evolve by mutation and selection toward being more efficient at infection and transmission within close, tight social groups but falling off quickly when vaccination and moderate barriers, like masks and good ventilation, and social distancing are implemented.

Vaccination does NOT guarantee protection from infection by Delta variant or transient release of virus from asymptomatic vaccinated individuals. Vaccination is NOT for elimination of all possible virus but to reduce infection level below the point of symptoms of disease in immunized people (varies from person to person somewhat, but is more likely to be overcome with higher circulating viral loads). It is the circulating of more infectious particles over and over so there can be accumulation and increased probability of developing more mutants, therefore, variants, that is problematic. Also, we have no way of screening or asking the vaccine status, health status or contact status of those entering a high density environment. Therefore, I recommend wearing a mask as well, regardless of vaccine status, and for others with any immunocompromizing condition or respiratory illness, especially with fever in the last 10 days, not to attend such event locations. The more people present, knowingly or unknowingly infected, the more virus circulating and the more likely to overcome vaccination,

This post is a summary in lay, non-technical terms, of what we know about COVID and the virus that causes it, amongst its kind. I will couch this description in military terms and as if the virus enemy is a sentient being because of my military background. The analogy is only for illustration and not proof of what I say. Our story, in late 2019, early 2020, began with a foreboding of the consequences of our happy hurried ignorance of larger life and the cost of practicing ignorance of it when confronting it head on : “Violent Delights, Violent Ends: Fire and Powder, Kiss and Consume”, “I fear too early, for my mind misgives some consequence yet hanging in the stars shall bitterly begin this fearful date with this night’s revels, and expire the term of ….. life ….. by some vile forfeit of untimely death….” William Shakespeare, Romeo and Juliet, Act 1, Scene 4”. There is an elegance in design in what we have faced and experienced when we look past the undeniable tragedy, which should never be forgotten as a great battle is remembered, which we must admit we have lost to learn from it, in our ongoing war with microbes, and the missteps that led to it. We started with underestimating our enemy. After all, most physicians’ experience with coronaviruses is the cold-causing, self-limiting, take-an-aspirin-and-call-me-in-morning ones successfully treated by benign neglect. Even the serious ones like SARS 1 (Severe Acute Respiratory Syndrome Virus, from civet cats, originally from bats), which appeared in 2003 and disappeared in 6 months, and MERS (Middle East Respiratory Syndrome Virus, from camels, originally from bats), which has only spread slowly in the Middle East and Northern Africa, were largely ignored as harbingers of something worse to come. In our arrogance and ignorance, we thought they disappeared or were restricted because of expert human interference; we ignored the warning of “some consequence yet hanging in the stars” of something much worse. Not only physicians fed this false security (besides the inevitable politicians at the top), but also veterinarians, who thought coronaviruses were under control. We have seen coronaviruses pervasively in dogs, cats, cattle and birds, but largely of the young, from self-limiting, and diminishing as agents necessitating prevention by vaccination, especially in dogs, to vaccination effective, but not fully optimal control (focusing on the pregnant females or newborns to produce immunity even if transient or against disease but not infection), in preventing large economic losses in intensive bovine, porcine, and poultry production. This requirement makes their use routine and necessary in agriculture, especially in preventing respiratory disease losses in poultry, and losses in calves and pigs from hemorrhagic diarrhea and shipping fever complex in finishing out beef cattle. However, in birds, live attenuated vaccine viruses have been detected circulating in wild bird populations, leading to potential recombination with or mutation to pathogenic strains. Only in the virus that causes Feline Infectious Peritonitis (FIP), which is usually 100% fatal in young cats showing signs but showing few signs, if any, and self-limiting when the kittens are infected with a less lethal strain of the virus (most often), was there evidence of something persistent and on occasion much more lethal. Presently, veterinarians are attempting to treat FIP with the same antiviral drugs as COVID over very protracted times, prolonging life but struggling to get cures. Not even this foreshadowing of the enemy becoming capable of new more insidious and dangerous strategies was heeded. One health appeared to learn nothing from these experiences until the stealthy tragedy of COVID was upon the world. The FIP lesson of a virus that is highly infectious and widespread in close collections of cats, which could largely be ignored and not even worth vaccination, could on occasion, when symptomatic, kill with such lethality, was attributed solely to a rare emergence of a selected highly lethal strain. However, although it appears again and again, it never seems to get an epizootic foot hold, killing only a few or one cat in a close knit group. Where does it go? Why does it keep coming back in such a limited way? No very satisfactory answers. But it surely appears to have an uncanny, but not as well developed, resemblance to the COVID modus operandi—myth of a largely non-symptomatic disease, low overall mortality, until in reality it becomes severely symptomatic and then lethality jumps sky high. These characteristics feed the denial and false claims of inflated lethality for COVID. Unfortunately, this feeds more careless spread of the virus. Could this be its evolutionary “intent” ?

Since it’s discovery in 2006, ferret systemic coronavirosis has been an emerging fatal disease of ferrets caused by ferret systemic coronavirus (FRSCV) which shares clinical-pathological characteristics with the dry form of feline infectious peritonitis (FIP) in cats. Because of the vulnerability of mustelidae (a family of carnivorous mammals, including weasels, badgers, otters, ferrets, martens, minks and wolverines, among others, a diverse group which forms the largest family in the order Carnivora, suborder Caniformia, comprising about 56–60 species across eight subfamilies) to both FIP (ferret coronavirus) and SARS-CoV-2, these animals potentially link the pathology of FIP to SARS-CoV-2, at least deserving further study.

The major strategy change of the COVID virus from the others, especially animal ones (although all coronaviruses are zoonotic, the cold ones appearing to have originated in rodents, cattle and some unknown animal eons ago), has been to sparing the young of disease, although still being asymptomatic in most age groups, except the old and infirm. Its infectivity in cats, minks and ferrets, says SARS-CoV-2 (originating in bats) is still very much an animal virus. It still holds in common with all coronaviruses the goal of not burning through a host population so as to prevent herd immunity and always to have susceptible individuals in that population to maintain them indefinitely. Even in the most densely populated and numerous mammals in nature, perhaps only second to humans, bats, coronaviruses only infect about 10% of a given group at a time. Pathogenicity and lethality tend to be held in check except in individuals in a population that do not contribute to maintenance of the virus in the population, like the elderly and infirm who do not reproduce individuals vulnerable to infection and transmission. Why is COVID different from animals in these respects of populations? The answer may lie in that animal viruses establish carriers by preferring gastrointestinal infections that are not easily cleared and chronically shed transmissible virus. In other viruses, like influenza, especially in migratory birds and water fowl, it is predominantly a GI rather than respiratory virus, which most effectively maintains the birds as a reservoir rather than incapacitating or killing the birds, which would limit their ability to spread the viruses. The COVID virus has chosen a more unorthodox method to assure maintenance and transmission in the human population, although with time I believe we will find more and more asymptomatic GI shedders (by monitoring sewage which has begun) https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25825 and https://www.medrxiv.org/content/10.1101/2021.01.08.21249379v1. It has chosen to enhance anti-parasite immunity like that used by the hosts to control parasitic worm, pathogenic protozoan and fungal infestations and infections. This response often controls the number of parasites to a tolerable, but not immediately lethal, level and prevents further infestation (a process called premunition), but does not totally eliminate the parasite. In children, this form of innate non-specific immunity often rapidly clears an infection without inducing long term immunity. Therefore, they are allowed to survive, grow and reproduce more naive vulnerable individuals after spreading the virus in the population. They are also vulnerable to re-infection as they grow older. Adults can mount this type of immunity but then develop specific adaptive long term immunity, but unfortunately also “memory” of the initial innate response with a vengeance. If this “remembered” non-specific response becomes overt or is activated, as it is highly vulnerable to do, by non-viral stimuli, it can lead to autoimmunity and pro-inflammatory nonspecific disease, which has been observed in “long haulers”. The fatal severe COVID is a continuum of the infection from inapparent widespread tissue infection to a late activation of this parasite immunity to the extreme, death, without a break. This type of incomplete immunity is beneficial for resisting parasites and in tumor immunology because it is highly effective locally, but suppressed systemically to avoid collateral damage to normal self tissues.

I have observed an artificial reproduction, perhaps enhancement, or at least a mimic, of this type of reactive oxygen species innate immunity early in my research career. I described it in my first book . “Even though weaker, nonspecific cytotoxicity was expected with glucose oxidase and horseradish peroxidase, they were used. Very malignant Novikoff hepatocarcinoma (including metastases) in rats, spontaneous mammary adenocarcinomas in rats, L1210 leukemia in mice, B16 melanomas in mice, and carcinogen-induced squamous cell carcinomas in hamster cheek pouches all responded to regional or local injections of the cross-linked enzymes in saline and glucose solution. The Novikoff hepatocarcinoma responses were 50 to 100% cures in animals treated. Lactoperoxidase could be substituted for horseradish peroxidase, and similar results were obtained. However, galactose oxidase substitution or the absence of either the glucose oxidase or the respective peroxidase in the preparation failed to bring about tumor regression. L1210 leukemia in outbred white mice showed 50% cures. Treatment of B16 melanoma prolonged life from 23 days postinoculation of controls to 37 days with treatment. However, no simple dose-response curve was demonstrated..Also, smaller squamous cell carcinoma tumors responded better (some with cures) than did larger cheek pouch tumors, which did not respond at all..No direct injury to normal tissue was observed in histopathological sections of treated animals. However, some animals with heavy tumor loads (P388 lymphoma, L1210 leukemia, some with Novikoff hepatocarcinoma) died more quickly when treated than did untreated controls due to an apparent “necrotic crisis” from dying tumor tissue.”— Type-B Cytochromes: Sensors and Switches by J.L. Kiel. https://a.co/aJEAVsl. I was acutely aware of the relationship between oxidase/peroxidase innate non-specific immunity and resistance to parasites and cancer because I entered Texas Tech University Health Science Center, School of Medicine, Graduate School, in the Departments of Biochemistry and Microbiology, as one of their first PhD students, in the summer of 1977 at Lubbock, Texas, with the intent to study this anti-parasitic mechanism. My dissertation research was on the cytotoxic mechanisms of peroxidases, a principle antimicrobial and anti-parasitic enzyme in granulocytes and macrophages of animals and humans. I wanted to study the effects of eosinophilic peroxidase on blood flukes (an animal counterpart of Schistosoma called Heterobilharzia americana) but my graduate committee and the safety officer would not approve of my keeping my infected snails in an aquarium in the laboratory. Therefore, I turned to peroxidase killing of cancer cells.

This highly localized approach is necessary because parasites and cancers disguise themselves as normal host tissue and this type of immunity must attack them without confusing them with normal tissue, which could be fatal or at least highly damaging to normal tissues and organs. It is a very delicate balance that could go either way. Therefore, any treatments or vaccines must direct a response that limits early replication of the virus and do not trigger an overt systemic parasite immune response. Hopefully, the current vaccines and treatments currently being evaluated will do this.

As a final personal note, I dealt, in my professional lifetime, with trying to address these mechanisms in other infectious zoonotic diseases and where infectious agents come from, go to between outbreaks, and how to stop them from re-emerging and spreading. By my measure, what has happened with COVID-19 would have been a total failure if it had been in my purview of investigative and applied functions and responsibilities. I spent the first third of my career investigating the non-specific responses to chemical, biological, and radiation insults, especially non-ionizing electromagnetic radiation, microwaves and radiowaves, and the second two thirds investigating means to detect hidden infectious agents and to stop re-emergence of infectious agents from between outbreaks. You may question my authority and knowledge in this area and assume I should have some honored and respected position in academia or industry after my retirement from serving the military and nation. I do not. It appears the arts and sciences of attribution and Counterproliferation of biological agents, natural or nefarious, are so specialized that there is no venerable honored academic or industrial positions or no longer governmental positions that meet with my qualifications. Since my retirement in 2011 and being turned down many times for academic positions, I have only been called on by the federal government when emergency situations required my services and was summarily dismissed when the crisis passed. However, when the crisis occurs, as with COVID, is when my talents are least but albeit still critically effective if heeded. I thought that even at 71, I might be valuable in sharing my experience, knowledge and insights with those who need to follow me in these pursuits, which I did in the military, but am not allowed to do now except by my books, past publications and currently this blog. I will continue as long as one person reads this blog and am able to continue.

You are probably sick of me saying this over and over again, but ignoring these facts and principles does not end the pandemic only makes it worse:

My book Pathogenic Ecology points out in detail how we get into such a mess and why we can’t ignore it:

Re-posting this post because of its prophetic content: The viruses, including SARS-CoV-2, continue to evolve by mutation and selection toward being more efficient at infection and transmission within close, tight social groups but falling off quickly when vaccination and moderate barriers, like masks and good ventilation, and social distancing are implemented.

Vaccination does NOT guarantee protection from infection by Delta variant or transient release of virus from asymptomatic vaccinated individuals. Vaccination is NOT for elimination of all possible virus but to reduce infection level below the point of symptoms of disease in immunized people (varies from person to person somewhat, but is more likely to be overcome with higher circulating viral loads). It is the circulating of more infectious particles over and over so there can be accumulation and increased probability of developing more mutants, therefore, variants, that is problematic. Also, we have no way of screening or asking the vaccine status, health status or contact status of those entering a high density environment. Therefore, I recommend wearing a mask as well, regardless of vaccine status, and for others with any immunocompromizing condition or respiratory illness, especially with fever in the last 10 days, not to attend such event locations. The more people present, knowingly or unknowingly infected, the more virus circulating and the more likely to overcome vaccination,

This post is a summary in lay, non-technical terms, of what we know about COVID and the virus that causes it, amongst its kind. I will couch this description in military terms and as if the virus enemy is a sentient being because of my military background. The analogy is only for illustration and not proof of what I say. Our story, in late 2019, early 2020, began with a foreboding of the consequences of our happy hurried ignorance of larger life and the cost of practicing ignorance of it when confronting it head on : “Violent Delights, Violent Ends: Fire and Powder, Kiss and Consume”, “I fear too early, for my mind misgives some consequence yet hanging in the stars shall bitterly begin this fearful date with this night’s revels, and expire the term of ….. life ….. by some vile forfeit of untimely death….” William Shakespeare, Romeo and Juliet, Act 1, Scene 4”. There is an elegance in design in what we have faced and experienced when we look past the undeniable tragedy, which should never be forgotten as a great battle is remembered, which we must admit we have lost to learn from it, in our ongoing war with microbes, and the missteps that led to it. We started with underestimating our enemy. After all, most physicians’ experience with coronaviruses is the cold-causing, self-limiting, take-an-aspirin-and-call-me-in-morning ones successfully treated by benign neglect. Even the serious ones like SARS 1 (Severe Acute Respiratory Syndrome Virus, from civet cats, originally from bats), which appeared in 2003 and disappeared in 6 months, and MERS (Middle East Respiratory Syndrome Virus, from camels, originally from bats), which has only spread slowly in the Middle East and Northern Africa, were largely ignored as harbingers of something worse to come. In our arrogance and ignorance, we thought they disappeared or were restricted because of expert human interference; we ignored the warning of “some consequence yet hanging in the stars” of something much worse. Not only physicians fed this false security (besides the inevitable politicians at the top), but also veterinarians, who thought coronaviruses were under control. We have seen coronaviruses pervasively in dogs, cats, cattle and birds, but largely of the young, from self-limiting, and diminishing as agents necessitating prevention by vaccination, especially in dogs, to vaccination effective, but not fully optimal control (focusing on the pregnant females or newborns to produce immunity even if transient or against disease but not infection), in preventing large economic losses in intensive bovine, porcine, and poultry production. This requirement makes their use routine and necessary in agriculture, especially in preventing respiratory disease losses in poultry, and losses in calves and pigs from hemorrhagic diarrhea and shipping fever complex in finishing out beef cattle. However, in birds, live attenuated vaccine viruses have been detected circulating in wild bird populations, leading to potential recombination with or mutation to pathogenic strains. Only in the virus that causes Feline Infectious Peritonitis (FIP), which is usually 100% fatal in young cats showing signs but showing few signs, if any, and self-limiting when the kittens are infected with a less lethal strain of the virus (most often), was there evidence of something persistent and on occasion much more lethal. Presently, veterinarians are attempting to treat FIP with the same antiviral drugs as COVID over very protracted times, prolonging life but struggling to get cures. Not even this foreshadowing of the enemy becoming capable of new more insidious and dangerous strategies was heeded. One health appeared to learn nothing from these experiences until the stealthy tragedy of COVID was upon the world. The FIP lesson of a virus that is highly infectious and widespread in close collections of cats, which could largely be ignored and not even worth vaccination, could on occasion, when symptomatic, kill with such lethality, was attributed solely to a rare emergence of a selected highly lethal strain. However, although it appears again and again, it never seems to get an epizootic foot hold, killing only a few or one cat in a close knit group. Where does it go? Why does it keep coming back in such a limited way? No very satisfactory answers. But it surely appears to have an uncanny, but not as well developed, resemblance to the COVID modus operandi—myth of a largely non-symptomatic disease, low overall mortality, until in reality it becomes severely symptomatic and then lethality jumps sky high. These characteristics feed the denial and false claims of inflated lethality for COVID. Unfortunately, this feeds more careless spread of the virus. Could this be its evolutionary “intent” ?

Since it’s discovery in 2006, ferret systemic coronavirosis has been an emerging fatal disease of ferrets caused by ferret systemic coronavirus (FRSCV) which shares clinical-pathological characteristics with the dry form of feline infectious peritonitis (FIP) in cats. Because of the vulnerability of mustelidae (a family of carnivorous mammals, including weasels, badgers, otters, ferrets, martens, minks and wolverines, among others, a diverse group which forms the largest family in the order Carnivora, suborder Caniformia, comprising about 56–60 species across eight subfamilies) to both FIP (ferret coronavirus) and SARS-CoV-2, these animals potentially link the pathology of FIP to SARS-CoV-2, at least deserving further study.

The major strategy change of the COVID virus from the others, especially animal ones (although all coronaviruses are zoonotic, the cold ones appearing to have originated in rodents, cattle and some unknown animal eons ago), has been to sparing the young of disease, although still being asymptomatic in most age groups, except the old and infirm. Its infectivity in cats, minks and ferrets, says SARS-CoV-2 (originating in bats) is still very much an animal virus. It still holds in common with all coronaviruses the goal of not burning through a host population so as to prevent herd immunity and always to have susceptible individuals in that population to maintain them indefinitely. Even in the most densely populated and numerous mammals in nature, perhaps only second to humans, bats, coronaviruses only infect about 10% of a given group at a time. Pathogenicity and lethality tend to be held in check except in individuals in a population that do not contribute to maintenance of the virus in the population, like the elderly and infirm who do not reproduce individuals vulnerable to infection and transmission. Why is COVID different from animals in these respects of populations? The answer may lie in that animal viruses establish carriers by preferring gastrointestinal infections that are not easily cleared and chronically shed transmissible virus. In other viruses, like influenza, especially in migratory birds and water fowl, it is predominantly a GI rather than respiratory virus, which most effectively maintains the birds as a reservoir rather than incapacitating or killing the birds, which would limit their ability to spread the viruses. The COVID virus has chosen a more unorthodox method to assure maintenance and transmission in the human population, although with time I believe we will find more and more asymptomatic GI shedders (by monitoring sewage which has begun) https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25825 and https://www.medrxiv.org/content/10.1101/2021.01.08.21249379v1. It has chosen to enhance anti-parasite immunity like that used by the hosts to control parasitic worm, pathogenic protozoan and fungal infestations and infections. This response often controls the number of parasites to a tolerable, but not immediately lethal, level and prevents further infestation (a process called premunition), but does not totally eliminate the parasite. In children, this form of innate non-specific immunity often rapidly clears an infection without inducing long term immunity. Therefore, they are allowed to survive, grow and reproduce more naive vulnerable individuals after spreading the virus in the population. They are also vulnerable to re-infection as they grow older. Adults can mount this type of immunity but then develop specific adaptive long term immunity, but unfortunately also “memory” of the initial innate response with a vengeance. If this “remembered” non-specific response becomes overt or is activated, as it is highly vulnerable to do, by non-viral stimuli, it can lead to autoimmunity and pro-inflammatory nonspecific disease, which has been observed in “long haulers”. The fatal severe COVID is a continuum of the infection from inapparent widespread tissue infection to a late activation of this parasite immunity to the extreme, death, without a break. This type of incomplete immunity is beneficial for resisting parasites and in tumor immunology because it is highly effective locally, but suppressed systemically to avoid collateral damage to normal self tissues.

I have observed an artificial reproduction, perhaps enhancement, or at least a mimic, of this type of reactive oxygen species innate immunity early in my research career. I described it in my first book . “Even though weaker, nonspecific cytotoxicity was expected with glucose oxidase and horseradish peroxidase, they were used. Very malignant Novikoff hepatocarcinoma (including metastases) in rats, spontaneous mammary adenocarcinomas in rats, L1210 leukemia in mice, B16 melanomas in mice, and carcinogen-induced squamous cell carcinomas in hamster cheek pouches all responded to regional or local injections of the cross-linked enzymes in saline and glucose solution. The Novikoff hepatocarcinoma responses were 50 to 100% cures in animals treated. Lactoperoxidase could be substituted for horseradish peroxidase, and similar results were obtained. However, galactose oxidase substitution or the absence of either the glucose oxidase or the respective peroxidase in the preparation failed to bring about tumor regression. L1210 leukemia in outbred white mice showed 50% cures. Treatment of B16 melanoma prolonged life from 23 days postinoculation of controls to 37 days with treatment. However, no simple dose-response curve was demonstrated..Also, smaller squamous cell carcinoma tumors responded better (some with cures) than did larger cheek pouch tumors, which did not respond at all..No direct injury to normal tissue was observed in histopathological sections of treated animals. However, some animals with heavy tumor loads (P388 lymphoma, L1210 leukemia, some with Novikoff hepatocarcinoma) died more quickly when treated than did untreated controls due to an apparent “necrotic crisis” from dying tumor tissue.”— Type-B Cytochromes: Sensors and Switches by J.L. Kiel. https://a.co/aJEAVsl. I was acutely aware of the relationship between oxidase/peroxidase innate non-specific immunity and resistance to parasites and cancer because I entered Texas Tech University Health Science Center, School of Medicine, Graduate School, in the Departments of Biochemistry and Microbiology, as one of their first PhD students, in the summer of 1977 at Lubbock, Texas, with the intent to study this anti-parasitic mechanism. My dissertation research was on the cytotoxic mechanisms of peroxidases, a principle antimicrobial and anti-parasitic enzyme in granulocytes and macrophages of animals and humans. I wanted to study the effects of eosinophilic peroxidase on blood flukes (an animal counterpart of Schistosoma called Heterobilharzia americana) but my graduate committee and the safety officer would not approve of my keeping my infected snails in an aquarium in the laboratory. Therefore, I turned to peroxidase killing of cancer cells.

This highly localized approach is necessary because parasites and cancers disguise themselves as normal host tissue and this type of immunity must attack them without confusing them with normal tissue, which could be fatal or at least highly damaging to normal tissues and organs. It is a very delicate balance that could go either way. Therefore, any treatments or vaccines must direct a response that limits early replication of the virus and do not trigger an overt systemic parasite immune response. Hopefully, the current vaccines and treatments currently being evaluated will do this.

As a final personal note, I dealt, in my professional lifetime, with trying to address these mechanisms in other infectious zoonotic diseases and where infectious agents come from, go to between outbreaks, and how to stop them from re-emerging and spreading. By my measure, what has happened with COVID-19 would have been a total failure if it had been in my purview of investigative and applied functions and responsibilities. I spent the first third of my career investigating the non-specific responses to chemical, biological, and radiation insults, especially non-ionizing electromagnetic radiation, microwaves and radiowaves, and the second two thirds investigating means to detect hidden infectious agents and to stop re-emergence of infectious agents from between outbreaks. You may question my authority and knowledge in this area and assume I should have some honored and respected position in academia or industry after my retirement from serving the military and nation. I do not. It appears the arts and sciences of attribution and Counterproliferation of biological agents, natural or nefarious, are so specialized that there is no venerable honored academic or industrial positions or no longer governmental positions that meet with my qualifications. Since my retirement in 2011 and being turned down many times for academic positions, I have only been called on by the federal government when emergency situations required my services and was summarily dismissed when the crisis passed. However, when the crisis occurs, as with COVID, is when my talents are least but albeit still critically effective if heeded. I thought that even at 71, I might be valuable in sharing my experience, knowledge and insights with those who need to follow me in these pursuits, which I did in the military, but am not allowed to do now except by my books, past publications and currently this blog. I will continue as long as one person reads this blog and am able to continue.

My book Pathogenic Ecology points out in detail how we get into such a mess and why we can’t ignore it:

Re-posting this post because of its prophetic content: The viruses, including SARS-CoV-2, continue to evolve by mutation and selection toward being more efficient at infection and transmission within close, tight social groups but falling off quickly when vaccination and moderate barriers, like masks and good ventilation, and social distancing are implemented.

Vaccination does NOT guarantee protection from infection by Delta variant or transient release of virus from asymptomatic vaccinated individuals. Vaccination is NOT for elimination of all possible virus but to reduce infection level below the point of symptoms of disease in immunized people (varies from person to person somewhat, but is more likely to be overcome with higher circulating viral loads). It is the circulating of more infectious particles over and over so there can be accumulation and increased probability of developing more mutants, therefore, variants, that is problematic. Also, we have no way of screening or asking the vaccine status, health status or contact status of those entering a high density environment. Therefore, I recommend wearing a mask as well, regardless of vaccine status, and for others with any immunocompromizing condition or respiratory illness, especially with fever in the last 10 days, not to attend such event locations. The more people present, knowingly or unknowingly infected, the more virus circulating and the more likely to overcome vaccination,

This post is a summary in lay, non-technical terms, of what we know about COVID and the virus that causes it, amongst its kind. I will couch this description in military terms and as if the virus enemy is a sentient being because of my military background. The analogy is only for illustration and not proof of what I say. Our story, in late 2019, early 2020, began with a foreboding of the consequences of our happy hurried ignorance of larger life and the cost of practicing ignorance of it when confronting it head on : “Violent Delights, Violent Ends: Fire and Powder, Kiss and Consume”, “I fear too early, for my mind misgives some consequence yet hanging in the stars shall bitterly begin this fearful date with this night’s revels, and expire the term of ….. life ….. by some vile forfeit of untimely death….” William Shakespeare, Romeo and Juliet, Act 1, Scene 4”. There is an elegance in design in what we have faced and experienced when we look past the undeniable tragedy, which should never be forgotten as a great battle is remembered, which we must admit we have lost to learn from it, in our ongoing war with microbes, and the missteps that led to it. We started with underestimating our enemy. After all, most physicians’ experience with coronaviruses is the cold-causing, self-limiting, take-an-aspirin-and-call-me-in-morning ones successfully treated by benign neglect. Even the serious ones like SARS 1 (Severe Acute Respiratory Syndrome Virus, from civet cats, originally from bats), which appeared in 2003 and disappeared in 6 months, and MERS (Middle East Respiratory Syndrome Virus, from camels, originally from bats), which has only spread slowly in the Middle East and Northern Africa, were largely ignored as harbingers of something worse to come. In our arrogance and ignorance, we thought they disappeared or were restricted because of expert human interference; we ignored the warning of “some consequence yet hanging in the stars” of something much worse. Not only physicians fed this false security (besides the inevitable politicians at the top), but also veterinarians, who thought coronaviruses were under control. We have seen coronaviruses pervasively in dogs, cats, cattle and birds, but largely of the young, from self-limiting, and diminishing as agents necessitating prevention by vaccination, especially in dogs, to vaccination effective, but not fully optimal control (focusing on the pregnant females or newborns to produce immunity even if transient or against disease but not infection), in preventing large economic losses in intensive bovine, porcine, and poultry production. This requirement makes their use routine and necessary in agriculture, especially in preventing respiratory disease losses in poultry, and losses in calves and pigs from hemorrhagic diarrhea and shipping fever complex in finishing out beef cattle. However, in birds, live attenuated vaccine viruses have been detected circulating in wild bird populations, leading to potential recombination with or mutation to pathogenic strains. Only in the virus that causes Feline Infectious Peritonitis (FIP), which is usually 100% fatal in young cats showing signs but showing few signs, if any, and self-limiting when the kittens are infected with a less lethal strain of the virus (most often), was there evidence of something persistent and on occasion much more lethal. Presently, veterinarians are attempting to treat FIP with the same antiviral drugs as COVID over very protracted times, prolonging life but struggling to get cures. Not even this foreshadowing of the enemy becoming capable of new more insidious and dangerous strategies was heeded. One health appeared to learn nothing from these experiences until the stealthy tragedy of COVID was upon the world. The FIP lesson of a virus that is highly infectious and widespread in close collections of cats, which could largely be ignored and not even worth vaccination, could on occasion, when symptomatic, kill with such lethality, was attributed solely to a rare emergence of a selected highly lethal strain. However, although it appears again and again, it never seems to get an epizootic foot hold, killing only a few or one cat in a close knit group. Where does it go? Why does it keep coming back in such a limited way? No very satisfactory answers. But it surely appears to have an uncanny, but not as well developed, resemblance to the COVID modus operandi—myth of a largely non-symptomatic disease, low overall mortality, until in reality it becomes severely symptomatic and then lethality jumps sky high. These characteristics feed the denial and false claims of inflated lethality for COVID. Unfortunately, this feeds more careless spread of the virus. Could this be its evolutionary “intent” ? The major strategy change of the COVID virus from the others, especially animal ones (although all coronaviruses are zoonotic, the cold ones appearing to have originated in rodents, cattle and some unknown animal eons ago), has been to sparing the young of disease, although still being asymptomatic in most age groups, except the old and infirm. Its infectivity in cats, minks and ferrets, says SARS-CoV-2 (originating in bats) is still very much an animal virus. It still holds in common with all coronaviruses the goal of not burning through a host population so as to prevent herd immunity and always to have susceptible individuals in that population to maintain them indefinitely. Even in the most densely populated and numerous mammals in nature, perhaps only second to humans, bats, coronaviruses only infect about 10% of a given group at a time. Pathogenicity and lethality tend to be held in check except in individuals in a population that do not contribute to maintenance of the virus in the population, like the elderly and infirm who do not reproduce individuals vulnerable to infection and transmission. Why is COVID different from animals in these respects of populations? The answer may lie in that animal viruses establish carriers by preferring gastrointestinal infections that are not easily cleared and chronically shed transmissible virus. In other viruses, like influenza, especially in migratory birds and water fowl, it is predominantly a GI rather than respiratory virus, which most effectively maintains the birds as a reservoir rather than incapacitating or killing the birds, which would limit their ability to spread the viruses. The COVID virus has chosen a more unorthodox method to assure maintenance and transmission in the human population, although with time I believe we will find more and more asymptomatic GI shedders (by monitoring sewage which has begun) https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25825 and https://www.medrxiv.org/content/10.1101/2021.01.08.21249379v1. It has chosen to enhance anti-parasite immunity like that used by the hosts to control parasitic worm, pathogenic protozoan and fungal infestations and infections. This response often controls the number of parasites to a tolerable, but not immediately lethal, level and prevents further infestation (a process called premunition), but does not totally eliminate the parasite. In children, this form of innate non-specific immunity often rapidly clears an infection without inducing long term immunity. Therefore, they are allowed to survive, grow and reproduce more naive vulnerable individuals after spreading the virus in the population. They are also vulnerable to re-infection as they grow older. Adults can mount this type of immunity but then develop specific adaptive long term immunity, but unfortunately also “memory” of the initial innate response with a vengeance. If this “remembered” non-specific response becomes overt or is activated, as it is highly vulnerable to do, by non-viral stimuli, it can lead to autoimmunity and pro-inflammatory nonspecific disease, which has been observed in “long haulers”. The fatal severe COVID is a continuum of the infection from inapparent widespread tissue infection to a late activation of this parasite immunity to the extreme, death, without a break. This type of incomplete immunity is beneficial for resisting parasites and in tumor immunology because it is highly effective locally, but suppressed systemically to avoid collateral damage to normal self tissues.

I have observed an artificial reproduction, perhaps enhancement, or at least a mimic, of this type of reactive oxygen species innate immunity early in my research career. I described it in my first book . “Even though weaker, nonspecific cytotoxicity was expected with glucose oxidase and horseradish peroxidase, they were used. Very malignant Novikoff hepatocarcinoma (including metastases) in rats, spontaneous mammary adenocarcinomas in rats, L1210 leukemia in mice, B16 melanomas in mice, and carcinogen-induced squamous cell carcinomas in hamster cheek pouches all responded to regional or local injections of the cross-linked enzymes in saline and glucose solution. The Novikoff hepatocarcinoma responses were 50 to 100% cures in animals treated. Lactoperoxidase could be substituted for horseradish peroxidase, and similar results were obtained. However, galactose oxidase substitution or the absence of either the glucose oxidase or the respective peroxidase in the preparation failed to bring about tumor regression. L1210 leukemia in outbred white mice showed 50% cures. Treatment of B16 melanoma prolonged life from 23 days postinoculation of controls to 37 days with treatment. However, no simple dose-response curve was demonstrated..Also, smaller squamous cell carcinoma tumors responded better (some with cures) than did larger cheek pouch tumors, which did not respond at all..No direct injury to normal tissue was observed in histopathological sections of treated animals. However, some animals with heavy tumor loads (P388 lymphoma, L1210 leukemia, some with Novikoff hepatocarcinoma) died more quickly when treated than did untreated controls due to an apparent “necrotic crisis” from dying tumor tissue.”— Type-B Cytochromes: Sensors and Switches by J.L. Kiel. https://a.co/aJEAVsl. I was acutely aware of the relationship between oxidase/peroxidase innate non-specific immunity and resistance to parasites and cancer because I entered Texas Tech University Health Science Center, School of Medicine, Graduate School, in the Departments of Biochemistry and Microbiology, as one of their first PhD students, in the summer of 1977 at Lubbock, Texas, with the intent to study this anti-parasitic mechanism. My dissertation research was on the cytotoxic mechanisms of peroxidases, a principle antimicrobial and anti-parasitic enzyme in granulocytes and macrophages of animals and humans. I wanted to study the effects of eosinophilic peroxidase on blood flukes (an animal counterpart of Schistosoma called Heterobilharzia americana) but my graduate committee and the safety officer would not approve of my keeping my infected snails in an aquarium in the laboratory. Therefore, I turned to peroxidase killing of cancer cells.

This highly localized approach is necessary because parasites and cancers disguise themselves as normal host tissue and this type of immunity must attack them without confusing them with normal tissue, which could be fatal or at least highly damaging to normal tissues and organs. It is a very delicate balance that could go either way. Therefore, any treatments or vaccines must direct a response that limits early replication of the virus and do not trigger an overt systemic parasite immune response. Hopefully, the current vaccines and treatments currently being evaluated will do this.

As a final personal note, I dealt, in my professional lifetime, with trying to address these mechanisms in other infectious zoonotic diseases and where infectious agents come from, go to between outbreaks, and how to stop them from re-emerging and spreading. By my measure, what has happened with COVID-19 would have been a total failure if it had been in my purview of investigative and applied functions and responsibilities. I spent the first third of my career investigating the non-specific responses to chemical, biological, and radiation insults, especially non-ionizing electromagnetic radiation, microwaves and radiowaves, and the second two thirds investigating means to detect hidden infectious agents and to stop re-emergence of infectious agents from between outbreaks. You may question my authority and knowledge in this area and assume I should have some honored and respected position in academia or industry after my retirement from serving the military and nation. I do not. It appears the arts and sciences of attribution and Counterproliferation of biological agents, natural or nefarious, are so specialized that there is no venerable honored academic or industrial positions or no longer governmental positions that meet with my qualifications. Since my retirement in 2011 and being turned down many times for academic positions, I have only been called on by the federal government when emergency situations required my services and was summarily dismissed when the crisis passed. However, when the crisis occurs, as with COVID, is when my talents are least but albeit still critically effective if heeded. I thought that even at 71, I might be valuable in sharing my experience, knowledge and insights with those who need to follow me in these pursuits, which I did in the military, but am not allowed to do now except by my books, past publications and currently this blog. I will continue as long as one person reads this blog and am able to continue.

With the rise of many mutations and variants, the questions arise: 1) will the current vaccines protect and stem the tide of the pandemic? 2) Will the vaccines drive, by selection pressure, the establishment of new more resistant, transmissible and/or pathogenic variants? 3) Will masks and social distancing still be required after vaccination? Variants which emerged in Brazil (known as P.1.), Britain (known as 20I/501Y.V1 or B.1.1.7) and South Africa (known as 20I/501Y.V2 or B.1.351) are now the globally dominant strains because of their apparently enhanced infectivity and transmissibility.

Current vaccines work against the UK B.1.1.7 variant without the E484K mutation. However, recent clinical trials by Novavax and Johnson & Johnson showed that their new vaccines were less effective in South Africa compared with the UK or US, probably because of the high level of virus carrying the E484K mutation. However, Novavax vaccine was reported to have a 60% efficacy in South Africa which is a good response, when compared to influenza vaccine responses of from 40-60 %. Studies have shown that people who have been infected with SARS-CoV-2 generate T cells that target at least 15–20 different fragments of coronavirus proteins. Because of natural variability, a population will generate a large variety of T cells that could attack the virus (https://reader.elsevier.com/reader/sd/pii/S1074761320305379?token=3775A68CFC8B8609E4A6753EF03F560FAF6F4B30D3B821B81F3A1CBF077E6DB8C53232C5B16ACCA1E569F0AE6C5368F3). As I mentioned in an earlier post, it is very hard for the CoVID variant viruses to mutate to escape cell recognition because of this T cell variation, The specificity of antibodies works in favor of variants. A recent pre-print shows a single mutation can defeat monoclonal antibodies against the spike protein of the virus and increased cell receptor binding, unfortunately a rare converging of properties in a single mutation. The mutation has been observed in a recent variant in California, CAL.20C viral variant from clade 20C, lineage B.1.429, that since November 2020 has generated multiple outbreaks and is undergoing massive expansion in California. This L452R mutation allows SARS-CoV-2 positive selection toward strong viral adaptation against containment measures that work on less contagious variants and against increasing population immunity against previous forms. The L452R mutation is at the leucine-452 position in the receptor-binding area of RBD (receptor binding domain) at the interface with the ACE2 receptor. Replacing it with arginine is anticipated to result in both a much stronger receptor binding and escape from neutralizing antibodies https://www.biorxiv.org/content/10.1101/2021.02.22.432189v1.full.pdf. Escape from two monoclonal antibodies has been predicted in a recent Science article https://science.sciencemag.org/content/sci/371/6531/850.full.pdf.

In a preprint published on 9 February, researchers found most T-cell responses to coronavirus vaccination or previous infection do not target regions mutated in two recently discovered variants, including 501Y.V2 (https://www.researchsquare.com/article/rs-226857/v1). Also, the vaccine made by Novavax of Gaithersburg, Maryland, a single-shot vaccine made by Johnson & Johnson of New Brunswick, New Jersey, and a vaccine made by AstraZeneca of Cambridge, UK, and the University of Oxford, UK are less effective at protecting against mild COVID-19 in South Africa, where the 501Y.V2 variant dominates, than in countries where it is now less common. AstraZeneca’s vaccine was only 22% effective against mild COVID-19 in a study of 2,000 people in South Africa, but the trial was too small and participants too young to draw any conclusions about any loss of benefit in protecting against severe disease. However, another recent paper compared the vaccine – induced neutralization of a less contagious version of the SARS-CoV-2 virus from last year (USA-WA1/2020), to the new variants Brazilian P1 and UK variant B.1.1.7 which gave results “roughly equivalent.” Geometric mean titers (GMT) of neutralizing antibodies against the USA-WA1/2020 virus, the UK B.1.1.7 variant, and the P1 variant were 532, 633, and 437, respectively. The GMT against three versions of the South African B.1.3.5 variant were less at 195, 485, and 331, respectively (https://www.medscape.com/viewarticle/947064).

A recent, yet to be peer-reviewed, study of men from 70-84 years of age, who died from COVID-19, increased from 5% of those who tested positive for the older variant, to more than 6%, if confirmed positive for variant B.1.1.7. For men 85 years or older, the risk of dying increased from 17% to 22% of those confirmed positive for the new variant. Therefore, the apparent increase in severity of this new variant has been limited in scope. It may reflect an increased viral load rather than a normalized increase in pathogenicity. There is little evolutionary advantage for a virus to become more pathogenic in a host in preference to transmissibility. This may happen only if there is a maintenance reservoir host in which the pathogenicity is less and from which the virus periodically emerges entering the host more vulnerable to lethality.

As to the third question, until the pandemic has subsided, even vaccinated people, including those who may have gotten upgraded vaccine for new variants, should continue to use masks, social distance, and, of course, continue to use good hand washing practices. Another early treatment to block viral replication has been discovered; a single pill of the investigational drug molnupiravir, when taken twice a day for 5 days, has been shown to eliminate SARS-CoV-2 from the nasopharynx of 49 participants in a new study (https://www.medscape.com/viewarticle/947061). Phase 2/3 efficacy and safety studies of the drug have started. The drug creates viral error catastrophe by inducing replication and mutations until the virus can’t effectively produce viable copies. This new early treatment and the non-pharmaceutical practices are necessary to decrease the total number of viruses in circulation, to greatly decrease the probability of establishing new variants even if they are more transmissible, and especially if those infected shed larger amounts of virus asymptomatically or symptomatically.

“No Apology for the Truth I apologize for any errors you may find in this collection; like all human endeavors, it is subject to revision, but do not let that deter you from finding Truth within.” What we did will echo in history, but not remembered for the bioattacks, epidemics, pandemics that never occurred,