COVID-19 Pandemic: Its Origin, Implications and Treatments

This is a succinct and current review of pertinent literature to guide developing serum therapy as an emergent treatment to save human lives at times of natural or genetically engineered viral/bacterial pandemics. The origin of 2019-nCoV and implications of COVID-19 are discussed using direct quotes of published scientific literature to avoid misinterpretation on this very important event that has caused great loss of human lives and international social economy. It is the goal of this review to warn against and to correct international misunderstanding created by deliberate falsification of scientific documentations and events. This misunderstanding may lead to further destruction of life, economy, and political relations. People should not be blind-sighted when making life decisions.

called myoblasts. There were numerous deficiencies associated with the use of the single gene transduction technology [9]. Much of the hurdles that were 18 years ago [16] [17] remain unresolved today.
Grandstands over the Human Genome Project (HGP) [18]- [23] and somatic gene therapies [10] [11] [16] [24] [25] [26] in the last three decades fueled enthusiasm that most human diseases would eventually be cured with molecular medicine [27] [28]. In his position as the Director of the National Institutes of Health (NIH), and in his "Language of God" [23], Collins not only did not provide any genetic treatment for COVID-19, he presented "evidence of make-beliefs" and misled the world with the natural origin of 2019-nCoV [29].
Amidst all the "if's", "but's", "possibly", and "almost certainly", Collins recorded, "So, what is the natural origin of the novel coronavirus responsible for the COVID-19 pandemic? The researchers [30] don't yet have a precise answer." People in Collins' position were often put in ugly situations of having to give up their scientific aptitude and choosing, because of political pressure from their immediate employer, the US Congress. I was once at the receiving end, or rather, non-receiving end of such malice [31].
Collins continued, "Existing computer models predicted that the new coronavirus would not bind to angiotensin converting enzyme II (ACE2) as well as the SARS virus. However, to their surprise, the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions." After presenting two scenarios of circumstantial evidence of genomic modeling, Collins concluded, "Either way, this study leaves little room to refute a natural origin for COVID-19." [29] Collins continued, "The researchers [30] went on to analyze genomic data related to the overall molecular structure, or backbone, of the new coronavirus.
Their analysis showed that the backbone of the new coronavirus's genome most closely resembles that of a bat coronavirus discovered after the COVID-19 pandemic began. However, the region that binds ACE2 resembles a novel virus found in pangolins, a strange-looking animal sometimes called a scaly anteater.
This provides additional evidence that the coronavirus that causes COVID-19 almost certainly originated in nature. If the new coronavirus had been manufactured in a lab, scientists most likely would have used the backbones of coronaviruses already known to cause serious diseases in humans." Was Collins talking about biological weapon in this last sentence? What kind of scientists were Collins referring to who would intentionally cause serious diseases in humans? In his tax-payers' entrusted position of NIH Director, Collins cited a non-committal reference [30] and presented a deliberate falsification of published scientific literature of studies described below that were supported by at least three Institutes of NIH, to mislead the world that COVID-19 originated from a natural course of viral evolution of the Hubei bats.
I hereby present below the direct, unequivocal evidence that 2019-nCoV is a P. K. Law Open Journal of Regenerative Medicine biological warfare weapon originally produced in the USA, and that COVID-19 is a pre-meditated event designed for the USA to consolidate and to sustain political and economic supremacy internationally.
In 2008, a group of SARS-like CoVs (SL-CoVs) isolated from horseshoe bats had their N terminus of the spike protein (S) combined with a human immunodeficiency virus (HIV)-based pseudovirus system, together with cell lines expressing the angiotensin-converting enzyme 2 (ACE2) molecules of human, civet, or horseshoe bat. Ren et al. reported, "in addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone." This was a Guided Natural Selection, a process designed to select a lethal, transmissible virus by serially infecting cells of an animal model that had ACE2 receptors similar to human. The chimeric S (spike) covering the receptor-binding domain (RBD) gained its ability to enter cells via human ACE2 receptor sites.
The Chinese authors demonstrated that "after replacement of a small segment (aa 310 to 518) of Rp3-S by the cognate sequence of BJ01-S, the chimeric spike protein mimics the function of BJ01-S in regard to receptor usage in the HIV pseudovirus assay system." That was sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function [32]. The CoV spike glycoproteins were responsible for cellular receptor recognition [32] [33], cell tropism [34] [35], and host specificity [36].
Ren et al. also reported failure of SARS-CoV S protein to use bat RpACE2 as a receptor, suggesting that despite the presence of a diverse group of SL-CoVs in horseshoe bats, they were unlikely to be the natural reservoir of the immediate progenitor virus for SARS-CoV [32]. That was a non-committal way of saying that SARS-CoV did not have a natural origin. Hou et al. (2010) [37] extended the above study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. Live SARS-CoV infection was carried out with help from Gary Crameri and Jennifer Barr, under BioDefense Level 4 (BSL4) conditions at the Australian Animal Health Laboratory (AAHL) [38] [39]. The results, as reported by a group of Chinese scientists funded by the Chinese government, showed that "ACE2 of Myotis daubentoni and Rhinolophus sinicus from Hubei province supported viral entry mediated by the SARS-CoV S protein, albeit with different efficiency in comparison to that of the human ACE2." Further, "the alteration of several key residues either decreased or enhanced bat ACE2 receptor efficiency" [39].
How effective was this genetically engineered construct that was capable of transmission cross-species from bat to human, and within the same species from human to human? Gain of function (GOF) by which the efficiency of viral spreading in human population was engineered and tested in an international collaborative study in 2015 as reported by Menachery

Implications of COVID-19
Menachery et al.'s 2015 [41] publication deserved every attention because it described the success of an international collaboration to genetically engineered a prototype of 2019-nCoV, confirmed its epidemic destructive capacity, demonstrated no effective medicament, vaccine, or any therapeutic or prophylactic modality, and predicted that COVID-19 would be preeminent. It described, "In addition to offering preparation against future emerging viruses, this approach must be considered in the context of the US government-mandated pause on gain-of-function (GOF) studies." A moratorium was called to end risky virology studies at 14 American institutions, but such effort was in vain [42]. From the 1998 viral P-shuttle SN Vector to the present clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology, SHC014CoV, the prototype of 2019-nCoV, was the prime of viral genetic engineering, and a deadly one. It was biological weapon at its best. It was scientifically carried out with vision and passion, and the inventors given due credits in P. K. Law funding and publications for their inventions. However, this invention was to benefit no human beings or bats; it would kill them by the millions if left uncontrolled. It revolutionized military warfare, killing enemies without deploying troops, without demarcating boundary, without war declaration, and usually without knowledge or evidence of attack. This invention enabled its owner to kill any mammals having human ACE2 receptors.
The 2015 publication of Menachery et al. alerted a potential pandemic if uncurbed [41]. In the title of the original article published in Nature Medicine, it used the phrase of "pose threat to human emergence". That was five years before COVID-19, in the land of technologic totalism of USA, where two Chinese scientists shared their academic advances and were given the middle and the second-last placement in the long 15-author list. It was for the American technology of GOF that they collaborated with UNC. The latter was close to Fort Detrick, a key BioDefense Laboratory of the 4 th level (BSL4) for biologic weapon production and testing. The GOF "turbo-charged" the SARS-CoV/HIV recombinant and, for the first time, transformed it to become the world's most power biological weapon of pandemic caliber. This is the origin of the 2019-nCoV. To a business mind, why spent the money to make a man-killing chimeric virus, and found a vaccine against it, unless the vaccine could be sold at a good profit.
However, it is extremely hard if not impossible to develop such vaccine, even by the UNC team itself [43]. Due to the tremendous random recombination of the chimeric viral RNA with different DNA repertoires from different patients by nature, no vaccine can be completely effective in principle, not even manufactured by Baric's team from UNC for Americans [43]. The only scientifically valid vaccine can only be derived from pooled antisera of rehabilitated patients of the same blood type [44] [45]. Immediately available therapy for the critically-ill and dying patients could only be from serum therapy as previously described [44] [45]. One's own immune system is the number one protection. Failing that, passive immunogens [44] [45] have to be implemented immediately to save lives. "Strikingly, the 2019-nCoV S-protein sequence contains 12 additional nucleotides" [4]. These are the "insertions" of genetic engineering. It is the goal of this review to warn against and to correct international misunderstanding created by deliberate falsification of scientific documentations and events. This misunderstanding may lead to war and further destruction of life, economy, and political relations. People should not be blind-sighted when making life decisions. It is my social responsibility, as a scientist, to inform the world of the scientific origins of 2019-nCoV and COVID-19. It is time for scientists to form alliance to speak up and to protect everything that belongs to human society. Left unchecked, COVID-19 will leave us with death, destruction, and grief, only second to the last world war.

Treatment of COVID-19
I had previously published the emergent serum therapy and antibody medicine to counteract sudden attacks of COVID-19 and other pathogenic epidemics [44] [45]. This is to provide background development leading to such.  The diverse and potent neutralizing antibodies identified recently appeared to be promising candidates for prophylactic and therapeutic interventions for the 2019-nCoV [62]. The safety and efficacy of Remdesivir usage is doubtful for lack of statistics [63].

Regulatory and Compassionate Drug Usage
Without a compassionate use approval from the FDA/EMA/CFDA, drug discoveries had never been timely enough to gain regulatory approval to save lives, and may never will in a safe and efficacious manner.

Evolutionary Antidote
It is not only scientifically valid but also logical to deem convalescent serum therapy be the treatment of choice because the antiserum contains the antiviral  [45]. We do not have any other immunotherapy or medicament with virus-specific antibodies that works on the same mechanism and principle. Beating bacterial or viral infections can give "acquired immunity" where the immune system recognizes the infectious agent the next time it is encountered. This is done by antibodies that label or neutralize the infectious agent.
I could not have emphasized more that although the antiviral antibodies were contained in the lymph, serum, plasma and whole blood of the rehabilitated subject, transfusion of each component delivered different consequences for what each contained. A formal evaluation [44] [45] and a systematic review and exploratory meta-analysis [64] argued against the contention that the use of convalescent plasma as a treatment could be without the occurrence of severe adverse events [65]. Without properly-designed control studies, many patients who died of acute respiratory distress syndrome (ARDS) and/or multiple organ failure were counted as died of natural course of the diseases rather than serious adverse reactions triggered by non-scientific use of convalescent plasmas [66].

Historic Development
In Medieval times, death was often associated with blood loss, and blood transfusion for revitalizing wounded soldiers became a norm to save lives in the battle field. Without the knowledge of ABO-blood type matching, or how to control infections, most of these blood recipients died with few exceptions.
With the discovery of microscopy in 1665, scientists could distinguish various cell types including the non-nucleated platelets. However, there were still question as to whether a dying man should have the whole blood of the donor, or the latter's plasma, or serum alone.  [81].
The use of convalescent human serum in treating 37 influenza pneumonia patients in 1918 demonstrated that thirty were rehabilitated; six were continuing treatment; one had died; all but one of these had a favorable outlook [82]. Blood to the amount of about 800 cc. was taken from each donor, under sterile precautions; 400 cc. at a time on two successive days. Thus, each donor yielded about 300 cc. of serum. The blood was allowed to clot at room temperature for about an hour, then plate cultures were made, and the containers placed on ice. over night. The separated serum was cleared by centrifugalizing at high speed; then bottled, and in most cases given the same day.
Attempt was made to test the potency of the serum of the donors in the old days by complement fixation and by gross agglutination, using isolated influenza bacillus as an antigen. However, without PCR technology to assess the antibody content of the serum, efficacy can only be determined by its clinical action on recipients [83].
Serum therapies were successfully used to treat many infectious diseases (anthrax, plague, scarlet fever, measles, tularemia, diphtheria, dysentery, meningococcal meningitis, rabies, pneumococcal pneumonia) for half a century af- 2) Stop any scientific development toward biological warfare, especially funding. Set up surveillance systems to destroy and ban biological warfare weapons.
3) Implement serum therapy and research for vaccine in the correct way [44] [45] with haste and precision. Everyday counts; watch the death toll board.

Conclusion
These are COVID-19's treatment, origin and implications; the good, the bad, and the ugly. Gina Kolata or others may use this platform for me to discuss gene therapies with William French Anderson and Francis Collins 30 years after we created and established this very important field of biomedicine.