Thursday, June 3, 2021

Our Wonderful Natural Immune System vs. Drugs and Vaccines Defenses Against Covid and Other Infections

I received a short comment by a retired architect last night (3 June, 2021) inside my WhatApp chat group. 

 Here’s what he wrote:


 “It is so sad that most people nowadays depend on vaccines to solve their health problems and generally ignore or forget that they have such a great protector called the immune system right inside their bodies to fight diseases for them. Of course we have to bolster our immune system by exercises, eating nutritious foods, having a positive mindset, blah, blah, blah” 


 I could not help thinking how correct he was. He immediately prompted me to write this essay to elaborate. 



Our Wonderful Natural Immunity vs Drugs and Vaccines Defenses
 

" Iwill praise thee; for I am fearfully and wonderfully made: marvelous are thy works; and that my soul knoweth right well." (Psalm 139:14. KJV)

 Many drugs have since been suggested for the treatment of Covid, starting with anti-malarials like chloroquine and its derivatives, hydroxychloroquine that is also used for the treatment of autoimmune disorders like rheumatoid arthritis and lupus. 


Chloroquine and hydroxychloroquine have since shown no notable antiviral effect against infections with SARS-CoV-2 in macaques or human lung cells according to two studies published online in Nature. Hydroxychloroquine and chloroquine — drugs that are generally used for the treatment of malaria have been investigated for their prospective treatment for COVID-19 in more than 80 registered clinical trials. 


They have been shown to inhibit SARS-CoV-2 infection in cell cultures, but their efficacy for the management of patients with COVID-19 has been debated. 


 Roger Le Grand and colleagues investigated the effects of hydroxychloroquine action on cynomolgus macaques, a non-human primate model of SARS-CoV-2 infection in humans. Hydroxychloroquine was shown to have no substantial antiviral activity, regardless of the timing of treatment initiation, either before infection, soon after infection or late after infection. 


In addition, using this antimalarial drug in combination with azithromycin, an antibiotic, had also no significant effect on virus levels in the macaques either. https://www.scimex.org/newsfeed/chloroquine-and-hydroxychloroquine-shown-ineffective-against-covid-19 



A Megadose of vitamin C to be given intravenously has also been tried and claimed to be ‘successful’ but no extensive studies have been done except in some hospitals in the UK. 



 Others then came out with the antiviral drug remdesivir that targets a range of viruses. It was originally developed over a decade ago to treat hepatitis C. Remdesivir, a nucleotide drug originally developed for the treatment of Ebola when it was found to inhibit the replication of a wide range of human and animal coronaviruses in vitro and in preclinical studies. 



 However a study by Wang, Yeming et al published in April 2020, was the first double-blinded, placebo-controlled, randomized clinical trial (RCT). It was also a multicentre trial with ten hospitals in China with 237 patients. 158 of them were given Remdesivir, and the rest were given a placebo, while they were on other forms of COVID-19 protocol treatments. 



 Despite a low sample size, the study found no significant differences in patients treated with Remdesivir in comparison with the placebo treatment. Source: Wang, Yeming, et al. on “Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.” The Lancet 395.10236 (2020): 1569-1578. 



 It was therefore not surprising when the SARS-CoV-2 coronavirus emerged in late 2019 in China, remdesivir was tried When remdesivir was found to be ineffective, though initially ‘promising’, the antiparasitic drug ivermectin was suggested despite heavy criticism and warnings by WHO Ivermectin is an FDA-approved drug for the treatment of parasitic diseases in animals that was found to inhibit the replication of SARS-CoV-2 in vitro. 



 In one claim, it was said that ivermectin was able to effect approximately a 5,000-fold reduction in virus at 48 hr in cell culture. Hence this drug is now been repurposed for the treatment of SARS-Covid-2? 



In a setting where the number of COVID-19 patients is rapidly escalating resulting in increasing mortality worldwide, hydroxychloroquine, doxycycline, azithromycin, and other drugs shown to be futile, an effective drug has to be considered. 



 Ivermectin is the candidate to be tried. It was reported to be able to suppress SARS-CoV-2 replication. At least this was shown in a vitro experiment by an Australian group. Ivermectin is an anti-parasitic drug used since 1987 for the control of river blindness and lymphatic filariasis, as well as in the treatment of scabies in humans. 



 Ivermectin has very low toxicity and is a cheap drug. It was then tried out for as a prophylaxis as well as for the treatment of COVID-19 in Central and South American countries. One month after the declaration of the pandemic, countries such as Iraq, Egypt, Iran, and India began clinical trials with it with mixed results. 



 Many other small trials elsewhere have also not shown convincing results, and currently WHO and the Ministry of Health Malaysia has not recommended ivermectin to be used for Covid either despite lobbying its use by some quarters. 


 Then came an anti-inflammatory drug baricitinib originally meant for the treatment of mild to moderate rheumatoid arthritis due to its ability to reduce inflammatory cytokines. Baricitinib is an oral Janus kinase (JAK) inhibitor that is selective for JAK1 and JAK2. 



It is being assessed for the treatment of COVID-19 as it may check cellular immune activation and inflammation. It is approved by the Food and Drug Administration (FDA) to treat moderate to severe rheumatoid arthritis. However on November 19, 2020, the FDA issued an Emergency Use Authorization (EUA) for the use of baricitinib in combination with remdesivir in hospitalized adults and children aged ≥2 years with COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. 



 A study was conducted in a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients in the study received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). 



The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. This study on the efficacy of baricitinib together with remdesivir was carried out byAndre C. Kalil and his colleagues who concluded baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. 



The combination was associated with fewer serious adverse events. As already mentioned, baricitinib binds to JAK1/2, which inhibits JAK1/2 activation and leads to the inhibition of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This decreases the production of inflammatory cytokines and may prevent an inflammatory response. However my own feeling is, baricitinib role in managing Covid-19 may not be very satisfactory other than it inhibits the intracellular signalling pathway of cytokines such as IL-2, IL-6, IL-10, interferon-γ, and granulocyte macrophage colony-stimulating factor. 



 Nevertheless, it has been also shown to improve the lymphocyte count and probably may prevent entry of the virus into the cell? The next agent to be considered was another antiviral drug - nelfinavir that is used along with other medications to treat human immunodeficiency virus (HIV) infection. Nelfinavir belongs to a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood.



 Scientists then thought since nelfinavir is a protease inhibitor that competes for the active cleavage site on the protease enzyme, it would be able to block the cleavage of the poly-proteins of SARS-Covid-2 virus and thus the maturation of new viral particles. But unfortunately it failed to be.



 Another alternative researchers have in view is famotidine. This is an antiviral that was believed to be able to bind a papain-like protease that is encoded by the SARS-CoV-2 genome and would be able to block the entry of SARS-CoV-2? When it did not work as well as anticipated, they then came out with the ideas of using monoclonal antibodies together with lopinavir and ritonavir that are also virus protease inhibitors that were used in the treatment of human immunodeficiency. 



But we are not sure the outcome of the idea Initially researchers also thought that chloroquine and hydroxychloroquine may work as polymerase inhibitors. In some ways they may work as a polymerase inhibitor by blocking out RNA duplication since a polymerase is an enzyme that synthesizes long chains of nucleic acids to assemble themselves as the RNA of SARS-Covid-2 virus. 



The virus uses base-pairing template strand for replication. Initial results were encouraging, but after a period of trials, both chloroquine and hydroxychloroquine lost their effect probably by blocking out the inhibitor of polymerase on which they build up their RNA strands It looks like the virus was able to circumnavigate that by erasing the polymerase inhibitors as part of their evolutionary process to be more adaptable and resilient. 



This is just my personal view that needs to be investigated Other scientists and researchers then suggested using umifenovir, a small indole-derivative molecule that is used in Russia and China or tocilizumab and also sarilumab that is used as a prophylaxis against influenza virus A and B Despite all the efforts of scientists and researchers the virus is still ahead of them in defiance. 



 Then they came out with another idea of using bevacizumab (Avastin) which is actually a cancer drug that is also used to treat certain eye diseases This drug like baricitinib is a Janus kinase inhibitor with potential anti-inflammatory, immunomodulating and antineoplastic activities. 



Other than this pharmacodynamics, I am unsure in what other ways this drug is going to work against SARS-Covid-2 virus? In desperation when all drugs failed, other workers suggested an antidepressant drug fluvoxamine which is an immunomodulatory agent. Again, I am unsure how immunomodulation per se would work.



Going through the literature other scientists suggested using a combination of antiviral lopinavir and ritonavir. Several small studies have been conducted on all these drugs, but none has been shown satisfactory within expectations. They all require large-scale well-designed randomized studies against placebos. 



 In a video sent to me lately of a doctor in the UK who even suggested using antihistamines and mast cells inhibitors to suppress cytokine storms in a hyperactive immune reaction for Covid-19, while other doctors claimed they have ‘successfully’ treated Covid patients with bronchodilators and steroids? But these two are just examples of isolated ideas that holds no water to the consensus of a scientific community.


Now they have thrown out hydroxychloroquine previously thought would be the answer, they have brought back the anti-parasitic drug ivermectin once again. 



 Whether it was chloroquine, hydroxychloroquine or ivermectin, to my mind the initial results may be hopeful, but as with all organisms, they are able to fly round a threat for their inherent survival as prescribed in the laws of survival of the fittest. This phenomenon has always been observed since 4,000 million years ago and there is no possibility for us to defy Nature in her well-designed and unyielding evolutionary process 



 As I see it, this virus is here to stay along with their entire families from SARS, MERS, to Covid-19, and I think they are much more mutagenic strains yet to come to confront our human race who is unable to live in harmony with them and with other creatures of evolution.



 Our Immune System:



 Having everything now have failed us, let us discuss how our own immune system may be our sole hope. It is outside the scope of this short essay to discuss immunology or the immunological system of our body. The immunological role of the body in combating this coronavirus would take chapters, and this is necessary for this short review. 



 Furthermore, this short article as with all other articles in this blog is meant only for the general reader. It is not a research paper where all the references need to be cited. A general simple essay like this for the general readers does not require these or technical details that would be lost in transition. 



 Let’s now see how the immune system works for most people during this pandemic Briefly to be explained in simple language, one of the components of the immune system is composed of lymphocytes in the white blood cells. A lymphocyte consists of many components, among them, natural killer cells that are responsible for cell-mediated, cytotoxic natural immunity, T cells responsible for cell-mediated, cytotoxic adaptive immunity, and the B cells that produces the humoral antibodies for adaptive immunity. These are the main type of cells found in lymph and plasma of blood, hence the name "lymphocyte" Lymphocytes make up between 18% and 42% of circulating white blood cells, or WBC which are also called the leukocytes. 


 CD Cells: 


 There are actually many more types of lymphocytes such as NK cells, T-helper cells, T-regulatory cells, cytotoxic T- cells…all responsible for the defense system. They are classified as CD cells under the immunophenotyping system. But we shall not go into all that. 


 Collectively, the white blood cells, the antibodies, the lymphatic system, spleen, bone marrow and the thymus together make up the immune system. We shall also not go into these sub-systems either except briefly mentioned here. 



 Although the detailed mechanisms of the immune response are beyond the scope of this article, we shall have a brief look at how antibodies are produced by the immune system. When our body immune system encounters a foreign molecule such as a protein of the spike protein of the SARS-Covid-2 virus for the first time, specialized cells such as macrophages and dendritic cells arrest these foreign molecules to present them as antigens to the B cell lymphocytes. 


 As scientists and medical researchers, we called this an ‘antigen presentation’


 Once an antigen presentation to the B cell lymphocytes is effected, a process known as somatic hypermutation allows the B cell to begin coding for a new antibody that will contain a unique antigen binding site in the variable region that is capable of binding specifically to part of an antigen molecule to which an antibody attaches itself. We called this an epitope from the antigen. Each B cell lymphocyte produces one unique antibody against one unique epitope. 



 Once antibodies with sufficient specificity to the epitope can be encoded, the B cell begins to discharge antibodies into the bloodstream. These antibodies then bind explicitly with the foreign molecule and allow the immune system to eliminate the foreign molecule from the system. 



 In some cases, these antibodies can disable pathogens such as viruses directly due to the binding action When antibodies produced by the B lymphocytes (B cells) bind to the antigen (SARS-Covid-2 virus for example) it stimulates the B cell to divide and mature into a group of identical cells called a clone. They then make many copies of them as memory cells 



 The immune system keeps a record of every microbe or viruses that was previously encountered by its B- and T-lymphocytes. They then keep them in the memory as memory cells. In the next encounter with the same virus or with any foreign protein or pathogenic organism previously presented, it immediately recognizes them and destroys them. 


 Some infections, like the flu and the common cold, or Covid-19 where the virus has mutated into other variants or strains they may not be recognized by the memory cells and will not confer immunity. 



 In other words, vaccines against one strain or variant virus may not confer immunity to the same virus if it has mutated into another strain or another variant.


 Antibodies (Immunoglobulins): 



 Let’s now briefly look at some of the antibodies or immunoglobulins. In short, they are designated as ‘Ig’ produced by the B cells of the lymphocytes There are five major classes of antibodies, namely, Immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin D (IgD), immunoglobulin M (IgM), and immunoglobulin E (IgE). 



 In humans these can be sub-grouped into IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) based on additional small differences in the amino acid heavy chain sequences. Based on differences in the amino acid sequence in the regular regions of the light chain, immunoglobulins can then be further sub-classified by determination of the type of light chain (kappa light chain or lambda light chain). A light chain has two successive domains, one constant domain and one variable domain. 


 The immunoglobulins are specific for different types of infections or may change even for the same infection For instance in one study by Yanan Wang and his colleagues they showed virus-specific IgM for Covid-19 patients reached up to over 80% from the second week to the eighth week after symptom of onset, then declined quickly to below 30% in the twelfth week. In another paper by Rhea Veda Nugraha et al here:


 https://www.hindawi.com/journals/ecam/2020/2560645/ 



 They found “the serology information about SARS-CoV-2 also remains unclear. Most patients with COVID-19 showed a peak increase of immunoglobulin M (IgM) nine days after disease onset and shifted to immunoglobulin G (IgG) in the second week. Other data showed that viral load increases mostly during the first week of the disease but decreases in the second week. Then, IgM and IgG begin to increase on day 10” 


A Shift in the Immunological Tune:


Somewhere on the 9th day of the infection the IgM shifted to IgG for reason unclear. I suspect the vaccine containing the synthetic isolate or the attenuated virus may have mutated in the body to present a different pathogenic behavior requiring different types of immunoglobulins. 



 I suggest this needs further investigation, without which we will not be able to predict the vaccines long-term effect that has been hotly debated over and over again by many immunologists, molecular biologists, researchers, clinicians and ordinary man-in-the-street who were all very skeptical and cautious of these vaccines 



 In their study, concentrations of IgG remained high for at least 3 months before subsequently declining. As compared with the non-severe group, serum IgM level from week 3 to week 8 was significantly higher among the patients with severe clinical symptoms What all this means in a nut-shell there may be already a lot of people with of SARS-Covid-2-specific IgM and IgG circulating in their blood through cross infections without them knowing it, or showing any symptom of the infection. We can call this as “herd immunity” 



 Most people survived this pandemic on their own without any drugs or previous vaccines given to them except perhaps a minority of them were given supplemental oxygen to help them breathe, or an acute cases if they are unable to breathe on their own they were being ventilated by endotracheal intubation.



Statistics on Mortality: 



 If we now look at the statistics as on Wednesday, 2 June, 2021 there were 171.196,260 cases recorded worldwide with only 3,565,444 deaths. This amounts to just 2.1 %. No data is given for total recovery In Malaysia yesterday on June 2, 2021 at 8 pm (1200 hrs GMT), there was a total of 587,165 confirmed cases, 82,274 total active cases (14.0 %), 501,898 total recovery (85.47 %) and only 2,993 death (0.5 %) since the pandemic started in December, 2019. 



 We can clearly see how beautifully our own immune system has been designed to work for us without any drugs, vaccines except hospitalization


 “Our body is a temple of the Holy Spirit (God)” (1 Corinthians 6:19), and 



 "I praise you because I am fearfully and wonderfully made; your works are wonderful, I know that full well” (Psalm 139:14). 



Unfortunately, most people have not realized this wonderful work of Nature with some even giving praises to certain medications they took on their own instead of giving this well-deserved glory to their own body and to the Intelligent Designer who has naturally protected them. 


I think we should be thankful for this gift of our immune system that did most of the job for us that has healed most people instead of believing in some other treatment except with some help of supplemental oxygen given to them in a hospital. 



I hope others will join me to see how wonderfully our body and our immune system has been designed to work for us in an infection to heal itself eventually with just 2.0 % mortality worldwide from this pandemic so far.



 A few thought it was the antimalarial drug chloroquine and hydroxychloroquine, and the antiviral drug remdesivir that helped them that they labeled as ‘miracle drugs’ 



Now they found the virus is smarter than us by causing these antiviral agents to be resistant by their ability to express enzymes on their own to block out the action of the inhibitor of polymerase that synthesizes long chains of RNA nucleic acids for replications. 



It is so apparent to us, or at least to me, that this humble teeny-tiny virus not endowed with any brain are far more smarter and intelligent than our combined smartest and brainiest scientists on Earth attempting to encounter them Initially our drugs were found encouraging, but now this virus has become much smarter and resistant to them just as the malarial parasites are now resistant to chloroquine due to evolution of better and hardier strains. 



 Now they revert to ivermectin that now seems maybe promising, but in the long term when this coronavirus is confronted by any agent that threatens their continuing existence, ivermectin may too fail like chloroquine, hydroxychloroquine, remdesivir, and the rest of the other antiviral agents.



 In the final scenario it is still our own immune system that is living to protect us. No vaccine can work without our immune system 



War of the Worlds:


On this note, may I divert you to an article I wrote soon after the outbreak of this pandemic in the late December 2019 where I compared a story HG Wells wrote: “War of the Worlds” where he paid tribute to our microbes, the bacteria that eventually fought for us against the Martians who did not have that immune systems as we do 


In that scenario, HG Wells wrote it was not our combined world armies, nor our nuclear weapons just like our drugs and vaccines that that finally won the battle for us, but it was our humble bacteria for which the Martians have no immune system against our bacteria This article called “War of the Worlds; Earthlings vs. the Coronavirus” was published on May, 2020 in Ir. Lau Tai Onn blog here: 




All vaccines still require our immune system to produce all those antibodies to confront our made-made virus antigen in the vaccines. Without our immune system that produces these antibodies as our sole savior to challenge this virus, or the modified virus as in vaccine we will be doomed. 



 In fact we can clearly see if a virus or the antigen in the vaccine is injected and presented into our body without the immune system as our natural defenses, we will just let this pathogen go right through with any defenses. 



In short, the vaccine kills us straight away in one sentence If not for our living body, but as a dead body without any more immune system operative anymore, then absolutely nothing, whether drugs or vaccines can elicit response anymore. Just be very thankful how our body has been designed by an Intelligent Designer for us. 


Don’t we think so? 


 I hope I have explained, and thank you for encouraging me to write this essay.

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