Covid-19 End Game – Prospects for Herd Immunity – Severity of (re)Infection

So we now have moderate restrictions in place in many western countries. Some hints that it might progress to total lockdown for some undefined period of time if the infection rate does not slow down.

How does this end? Even if we slowed the infection rate and stopped community spread, what would happen if we then all just went back to normal?

It is likely we would have merely turned back the clock and the infection rate would pick up again where it left off. The number of cases would again increase until we have to shut everything down again.

If you listen to any media outlet there are basically two end games here.
1.) Natural Herd Immunity built from enough people contracting the virus, recovering and becoming immune.
2.) A Vaccine is developed, proven effective, mass produced, and then mass deployed.

Either route is dependent upon the efficacy of antibodies and other Immune memory cells to prevent reinfection. What if this proves unreliable?

They have been working on a vaccine for the original SARS-CoV 1 Virus for 16 years now with no success. This current strain is different but behaves similarly enough to question why we would have any better success with the new SARS-CoV 2 version?

The antibodies from survivors of SARS maintained at relatively high levels in their systems for roughly 2 years before precipitously dropping off in the 3rd year.

In the present, with this new strain, there is some evidence that people may be getting either re-infected or have experienced a relapse within weeks of recovery and negative lab tests.

Reinfection
14% reinfection rate

“About 14% of patients who recovered from the novel coronavirus and were discharged from hospitals in southern China’s Guangdong province were tested positive again in later check-ups”

Confirmed infected, disease progression, multiple negative tests, recovered, then positive test again.

“All 4 patients were exposed to the novel 2019 coronavirus through work as medical professionals. Two were male and the age range was 30 to 36 years. Among 3 of the patients, fever, cough, or both occurred at onset. One patient was initially asymptomatic and underwent thin-section CT due to exposure to infected patients.
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All 4 patients had 2 consecutive negative RT-PCR test results. The time from symptom onset to recovery ranged from 12 to 32 days.
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After hospital discharge or discontinuation of quarantine, the patients were asked to continue the quarantine protocol at home for 5 days. The RT-PCR tests were repeated 5 to 13 days later and all were positive. All patients had 3 repeat RT-PCR tests performed over the next 4 to 5 days and all were positive. An additional RT-PCR test was performed using a kit from a different manufacturer and the results were also positive for all patients. The patients continued to be asymptomatic by clinician examination and chest CT findings showed no change from previous images. They did not report contact with any person with respiratory symptoms. No family member was infected.”

This is concerning, even if it does not indicate a lack of developed immunity, it will make containment measures that much more difficult. This Virus is presenting widely different disease progressions amongst the masses. It makes it difficult to predict and difficult to treat.
While the clinical data on SARS-CoV 2 is sparse at this point. We can look at some of the extensive research done on original SARS Virus to see some of the ways it might potentially be impacting our immune systems.

One of the things that many people do not grasp is how pervasive a SARS disease can be. It is NOT merely a respiratory tract infection.


SARS-CoV can infect multiple cell types

“SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury.
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Immune Cells
Most of the infected cells were T cells. Some B cells and NK cells also were infected by the virus.
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Spleen and Lymph nodes
In situ hybridization identified the SARS viral sequence in the enlarged macrophages and in the isolated and sometimes clustered T lymphocytes, which were distributed mostly at the periphery of the germinal centers of the splenic white pulp, lymph nodes, and peripheral blood
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GI Tract
The lymphoid component of the intestine showed widespread degenerative changes. The lymphoid follicles (Peyer's patches) showed markedly decreased lymphocytes (Fig. 3 A), and in severe cases only the depleted stromal framework of the structure remained.
In addition, the epithelial cells of mucosa of the small and large intestines were found to be infected by the virus by in situ hybridization and EM
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Kidneys
The kidneys were focally hemorrhagic.
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Brain
SARS genome sequences were detected in the brain of all SARS autopsies with LM, EM, and with real-time RT-PCR. The signals were confined to the cytoplasm of numerous neurons in the hypothalamus and cortex (Fig. 3 O). Edema and scattered red degeneration of the neurons were present in the brains of six of the eight confirmed cases of SARS.
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Testes
The testes of the seven male patients displayed focal atrophy.
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It is evident that infection by the SARS virus is not confined to the lungs, but also involves other parts of the respiratory tract and other organ systems, most importantly immune cells, particularly the T lymphocytes, monocytes, and macrophages. The finding of early and consistent decreases of T lymphocytes in 65 patients who had SARS, but not in the 35 misdiagnosed patients, further suggests that lymphocyte damage is the hallmark of SARS. Administration of glucocorticoids contributed to a decrease in lymphocyte counts in both groups of patients; however, the difference in counts between the two groups persisted after glucocorticoid therapy. It was reported that lymphopenia is one of the earliest changes, and is a reliable prognostic predictor in SARS (13–18). An extensive literature search has not revealed a report of any other type of pneumonitis producing such severe lymphopenia. As the only logical explanation for the early and consistent lymphopenia that is demonstrated in patients who have SARS, we suggest that lymphocytes—particularly T lymphocytes—are infected and destroyed by the virus or by other immune cells.
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The observation of virus in neurons may provide an explanation for the higher than usual incidence of neuronal and psychologic abnormalities that are seen in patients who have late-stage SARS
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The damage to the immune system, more than damage to the lungs, determines whether a patient recovers or dies from the infection. In a way, the name “sudden acute respiratory syndrome” is inappropriate because it diverts attention from the primary pathologic changes that result from SARS virus infection. It must be emphasized that immune damage most likely is the primary determinant of clinical outcome.”

The impact on the Immune system itself and the Central Nervous System are two areas of major concern for anyone infected with a SARS variant coronavirus. This Virus is a slippery yet potent operator and gives the immune system all it can handle. Some of these impacts have been largely overlooked by many.

The following article outlines some of the ways it can drastically alter the immune response.
- Inhibition of Cytokines
- Initiation and propagation of T-Cell Death
- Suppressed interferon response
- Infection of Dendrite Cells

Immune Suppression and Evasion

“While MHV proteins are generally restricted to the cytoplasm, the nucleocapisd proteins of coronaviruses representing groups I, II, and III were shown to localize to the nucleolus as well as to the cytoplasm (343). This report suggests that N protein induces a cell cycle delay or arrest, most likely in the G2/M phase, possibly by inhibition of cytokines.
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the E protein of SARS-CoV has been shown to induce apoptosis when expressed in Jurkat T cells, and this activity is inhibited by expression of the antiapoptotic protein Bcl-xL (348). Those authors suggest that T-cell apoptosis may contribute to the SARS-CoV-induced lymphopenia that is observed in most SARS patients.
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Like other RNA viruses, all coronaviruses encode, in addition to structural proteins and replicase proteins, small nonessential proteins of unknown function. There are many examples of such proteins, encoded by RNA viruses, which interact with and compromise the alpha/beta interferon response
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Analysis of gene expression of PBMCs of SARS patients by using a microarray platform that includes more than 8,000 gene sequences suggests that the response of SARS patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection. Those authors did not find significant upregulation of major histocompatibility complex class I genes or major cytokines, including IFNs (IFN-α, IFN-β, and IFN-γ), or genes involved in complement-mediated cytolysis. They concluded that the immune response against the SARS-CoV may be different from that in other viral infections or that the virus may be using an unusual strategy to evade the host immune system and cause the pathogenesis and mortality.
Lymphopenia and increasing viral load in the first 10 days of SARS suggest immune evasion by SARS-CoV. The lack of an IFN-β response in SARS-CoV-infected cells has been reported in vitro, using human primary myeloid-derived dendritic cells (176) and the epithelial 293 cell line (291). Law et al. (176) proposed a mechanism of immune evasion by SARS-CoV in DCs, based on their findings of low expression of antiviral cytokines (IFN-α, IFN-β, IFN-γ, and IL-12p40), moderate upregulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and IL-6), and significant upregulation of proinflammatory cytokines (MIP-1α, RANTES, IP-10, and MCP-1). Spiegel et al. (291) demonstrated that SARS-CoV escapes interferon-mediated growth inhibition by preventing the induction of IFN-β through interfering with the activation of IFN regulatory factor 3. The mechanism of lymphopenia remains unclear. The rapid decrease in both CD4 and CD8 T cells may be associated with an adverse outcome (185, 338). Due to the absence of ACE2 expression in T- and B-cell lymphocytes (126), it seems unlikely that SARS-CoV-induced lymphopenia may be caused by direct viral infection. Rather it has been suggested that apoptosis of uninfected lymphocytes may lead to the acute lymphopenia observed in SARS patients. In this sense, various SARS-CoV proteins have been suggested to induce apoptosis in vitro. These include ORF 7a (305), ORF 3a (177), and ORF 3b (366), in addition to E protein (see above) and N protein”

In addition to suppressing and evading the immune system it also seems to have a novel way to shift its tropism and attack immune cells directly. Once the immune system has gotten on top of the virus, created antibodies and blocked its preferred infection pathway of the Spike Protein binding to the ACE 2 receptors in the body, the virus appears to be able to upregulate a completely different cell entry pathway, not using ACE 2.


SARS-CoV infects Immune Cells

“We previously reported that a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers triggered infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents
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SARS-CoV-induced pathology is not confined to the respiratory tract but also involves other tissues and organs, most importantly cells of the gastrointestinal tract and the immune system
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The outcome of infection with SARS-CoVpp in the presence of anti-Spike immune-serum depended on the target cell type. Although heat-inactivated serum inhibited SARS-CoVpp entry into the permissive VeroE6 cell line in a dose-dependent fashion, as demonstrated by a dramatic drop in the intensity of luminescence (Fig. 1A and B, hatched bars), it facilitated infection of the human monocytic cell line THP-1 and of the B cell lines Daudi and Raji. In contrast, no infection of these cell lines was noticed when SARS-CoVpp were preincubated with control serum
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Taken together, these experiments indicate that anti-Spike serum can trigger infection of immune cells by live SARS-CoV, similarly to that observed with the pseudotyped viral particles.
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Altogether, these results indicate that despite the ability of SARS-CoV to exploit antiviral antibodies to invade Raji B cells, only abortive replication occurs upon infection, and no infectious virus is released from the ADE-infected Raji cells.
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We demonstrate here that anti-Spike antibody potentiates infection of immune cells by SARS Spike-pseudotyped lentiviral particles and replication-competent SARS-coronavirus.
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Our experiments conclusively demonstrate with several lines of evidence that both SARS-CoVpp and replication-competent SARS-coronavirus infect certain immune cells only in the presence of anti-Spike immune serum and not in its absence.
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The observation of a change of tropism of SARS-CoV in the presence of antiviral immune serum distinguishes the ADE of SARS-CoV infection from many other examples of antibody-mediated viral infection
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Altogether, our results report a novel mechanism by which SARS-CoV can enter into target cells that do not express the conventional virus receptor and are otherwise refractory to the virus. This may have implications for understanding the tropism and pathogenesis of the virus and highlight potential pitfalls associated with immunization against this coronavirus. These findings should prompt further investigations for a better understanding of the molecular and cellular mechanisms underlying ADE of SARS-CoV infection. The consequences of this alternative infection pathway on the functionality and/or homeostasis of the target cells also need to be resolved.”

This explains partially why a SARS Vaccine has been so difficult to develop. This immune cell attack ONLY happens in the presence of anti-Spike protein Antibodies. It is an Antibody Dependent Enhancement of the SARS infection. This condition is specifically induced by a typical Vaccine response in the body, bypassing the innate system and triggering only the adaptive system to create antibodies. We may have overlooked the value of the innate system with our vaccine approach. Here is some evidence the innate system is quite robust in its own right.

Innate Immune response can clear the virus without Antibody or T-cell assistance.
SARS generates multiple waves of inflammatory immune response in the lungs.

Innate Immune Response

“Mice depleted of both CD4+ and CD8+ T cells, which therefore lacked both T-cell and Ab responses to the virus, were able to control SARS-CoV replication in the lungs by day 12 p.i., suggesting an immune mechanism independent of Abs and T cells.

The activation of the innate defense system at the early phase of infection appears to play an important role in the control of SARS-CoV replication. A second wave of inflammatory mediators noted on day 7 p.i. involved an increase of the cytokines TNF-α and IL-6 and chemokines CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL9/MIG, and CXCL10/IP-10 and an increase of T-cell-mediated inflammatory cytokines IFN-γ, IL-2, and IL-5.”

The key is to have the entire immune system operating in balance and according to its own natural progression. Cytokine storms only happen when the immune system gets imbalanced and dysfunctional. Vaccine induced ADE can set the immune system off kilter from the get go when eventually challenged with the live, replicating virus.

The damage to the lungs or other organs of the body can be catastrophic. The Central Nervous System in particular is sensitive to immune induced inflammation. SARS has an advanced stealth mode when impacting the brain. It is able to access the CNS and cause significant neural cell death without triggering a massive inflammatory immune response.

SARS NINJA MODE

CNS infection and cell death without inflammation

“While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae

No evidence of inflammation was detected in the brains of any infected K18-hACE2 mice even when infection was widespread

GFAP expression by astrocytes was detected in limited areas in SARS-CoV-infected animals with a distribution and intensity of staining similar to that observed in naïve animals (Fig. 6A). In contrast, JHMV-infected brains displayed upregulation of GFAP, and the GFAP-positive cells were found throughout the brain. These findings suggest that astrocytes in SARS-CoV-infected mice were not activated, despite extensive neuronal infection.

In all studies that examined brain sections from Human SARS patients, virus was detected almost exclusively in neurons.

Our results suggest that SARS-CoV primarily entered the brain via the olfactory nerve. However, the rate at which SARS-CoV spread within the brain was striking. Viral antigen was not detected until 60 to 66 h p.i. and, by this time, was already present in the olfactory bulb and several brain regions connected to this structure. Furthermore, 6 to 12 h later, viral antigen was detected throughout the brain and had spread to first- and second-order structures connected with the olfactory bulb as well as structures only remotely connected with the olfactory system.

SARS-CoV infects dendritic cells… may be one mechanism that would result in a diminished inflammatory response. It is also striking that we detected no evidence of apoptosis (Fig. 5B). Cells that die by necrosis would be expected to induce an immune response, but this was not detected in the SARS-CoV-infected CNS”

The end result, SARS patients can begin to show symptoms of neurological impairment, yet a brain scan will show little to no inflammation despite widespread infection. The damage that a SARS infection can inflict on the lungs and brain in particular can be permanent and debilitating.

With SARS operating in stealth mode, it can do significant damage even in patients who exhibit very mild symptoms throughout the early stages of disease progression. This can lead to rapid deterioration in a matter of days, 2-3 weeks into the infection.

Lets say you survive, your immune system successfully clears the disease and your antibodies and memory cells are successful at preventing reinfection of the current strain. When/If this particularly infectious SARS variant mutates again, those left over immune cells can actually increase your risk of a serious outcome the second time around. The first infection can “prime” your immune system to facilitate the speed of infection of the second mutated variant.

The following video shows how reinfection with a slightly different strain of the same virus can cause enhanced infection leading to Cytokine Storm. This video is specific to Hemorrhagic fevers such as Ebola or Dengue Fever, but the concept transfers to SARS-CoV 2 just with different receptors and cell targets.




We need to consider that this virus may not ever go away, but rather be endemic to our population. We need to focus on systemic healthy diet, exercise, sleep patterns and nutrition to bolster our immune systems and prepare ourselves to go multiple rounds with this pesky invader.

There is some good news coming out about drug therapies that seem to be helping. This will hopefully save many lives globally. Even with emerging drug therapies and potential vaccines, it is still best to conquer SARS-CoV 2 with a healthy, balanced, and complete immune system response that does not require drug support or modulation.

Stay positive,
Support each other,
Stay informed.

Soul

I think, or sense that there are also non-medical reasons for lockdowns. TPTB use this opportunity for getting further on the road for Orwell society and beyond..


The demented slow reactions of using natural and pharmaceutical remedys for covid-19 speaks to me that there is a desire for exploit the
situation for getting countrys to more Orwellian society.


I dont much believe vaccine , and it can be too dangerous. Even if vaccine would help with this covid-19...it might destroy ,harm immune system too much ,and so people who had the vaccines might die on next disease, or get serious disease . Is it worth it ?


Good information and i agree that balanced, and complete immune system is best weapon. Problem with vaccines are, that the adjuvants cause immuno system to go off from balance and start greating too powerfull immuno response, aluminium is adjuvant that does that and mercury also ..so with overactive immuno system and a new novel virus the responce can go to really crazy level fast making cytokine storm .

a reply to: [post=25034435]SoulReaper[/post
What about using the plasma of those who have a strong immune response?

a reply to: SoulReaper

I honestly think we should stop worrying about the virus and focus on the power the government has granted itself.

That power move is much scarier than any virus imo.

a reply to: Kenzo

Vaccines may be an acceptable risk with some disease prevention, although the Aluminum adjuncts are troublesome. But this particular virus is a tricky one to combat with the vaccine approach. I have my doubts they will succeed.

Soul

a reply to: 5senses

Hey I am all for research into any alternative treatments. If they can provide proof of clinical improvement without over offsetting negative side effects. I'm on board. I wonder if using plasma from recovered patients could potentiate an ADE response similar to that observed above with SARS. Where it triggered immune cell targeting that was not happening before.

The immune response is complicated and delicately balanced. We just need to be careful not to interfere in the wrong ways and make things worse.

Soul

originally posted by: scraedtosleep
a reply to: SoulReaper

I honestly think we should stop worrying about the virus and focus on the power the government has granted itself.

That power move is much scarier than any virus imo.

We can consider both at the same time. The Virus is a clear risk to society, higher risk for some demographics then others, yet in reality if the hospitals are overrun, overwhelmed, and high risk of disease spread. Then it effects all of us, because even young healthy people need medical care sometimes.

My Wife is pregnant and has a due date of June 7th. What if there is no hospital bed or safe sterile place available for child birth? What if she has complications in child birth that would require urgent care?

The government actions can be addressed and rolled back when the threat has passed.

Soul

a reply to: SoulReaper

Very strong thread Soul ... great work, and thanks so much. There is a lot of information that you just provided that I didn't know, especially the molecular stuff. I really appreciate your time and effort on this. Go go go

a reply to: Fowlerstoad

Thanks, to be honest I mostly put this together in response to a bunch of my extended family members who kept claiming one of two things.
1.) This virus doesn't even exist, it's just a big manufactured hoax to cause panic.
2.) This virus is way less serious then the flu, what's the big deal.

I wanted to show the unique qualities of a SARS variant disease progression. There is a reason event 201 choose a highly infectious coronavirus as the antigen to model a pandemic that could stress and overwhelm the world medical infrastructure. IT IS NOT A FLU!!

Soul