An Experimental Model for Systemic Organ Fibrosis after SARS-CoV-2 Coronavirus Infection

Part I: General Principles and Idiopathic Pulmonary Fibrosis

Above Image: An Oncological Example of Disseminated Intravascular Coagulopathy. A Striking Similarity to COVID/Long COVID

I will now begin to lay out my case arguing that SARS-CoV-2 is a continuation of Coronavirus GOF “research” done to induce slow, fatal outcomes. This “research” has its roots in the work of Ralph Baric, who developed models decades ago for Coronaviruses that could induce Congestive Heart Failure after infection. I believe this work was continued. A study was done, but apparently not published, researching the effects of MERS-CoV on the Human Microvascular Endothelium. Please see my recent posts documenting these events.

To begin with, I would like to discuss the unique problem SARS-CoV-2 and its Spike Protein pose as an endothelial threat. I will quote extensively from a masterful paper which I suggest all read.

Similarly, we discuss common therapeutic interventions for various conditions, noting that in many cases of microvascular thrombosis associated with an underlying disease, the standard of care in therapy consists of treatment of the underlying disease.

Microvascular thrombosis: experimental and clinical implications
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245314/

The problem is that, as I have stated repeatedly for a long time, the Spike Protein IS the underlying disease, as it induces what I have called Spike Protein Endothelial Disease, which I believe is the primary pathogenic engine of SARS-CoV-2.

Let us look at a marker for microvascular destruction and thrombosis. That is the presence of schistocytes.

A hallmark of TMA (Thrombotic Microangiopathies) is the presence of mechanically damaged red blood cells (RBCs) in circulating blood, termed schistocytes, deemed to result during passage of highly deformable RBC through porous microthrombi and/or interactions with fibrin strands in the microthrombi.

Microvascular thrombosis: experimental and clinical implications

These are present in COVID

The causes of coagulopathy associated with COVID-19 disease are poorly understood. We aimed to investigate the relationship between markers of endothelial activation, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with equal distribution of survivors and non-survivors. Patients who died had significantly lower ADAMTS13 activity, significantly higher LDH, schistocytes and von Willebrand Factor levels compared to patients discharged alive. Only 30% of patients with an initial ADAMTS13 activity <43% survived vs. 60% with ADAMTS13 ≥43% who survived. In conclusion, COVID-19 may manifest as a TMA-like illness in a subset of hospitalized patients. Presence of schistocytes on admission may warrant a work-up for TMA. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of TMA treatments in COVID-19.

Evidence for secondary thrombotic microangiopathy in COVID-19
https://www.medrxiv.org/content/10.1101/2020.10.20.20215608v1.full

They are also present in Long COVID.

Given that our patient had an elevated D-dimer and rare schistocytes on the peripheral blood smear during her initial episode of thrombocytopenia, there may have been an early microangiopathic component to her thrombocytopenia. She then developed a prolonged disease course with recurrent ITP relapses, which may have been due to an autoimmune-mediated mechanism and/or a decrease in platelet production as a result of bone marrow infection and suppression. Chronic COVID syndrome (i.e., “long COVID”) is a well-recognized potential complication of COVID-19 infection and is believed to develop as a result of insufficient viral clearance. Chronic COVID syndrome can damage multiple organ systems, and it is possible that it may have perpetuated our patient’s ITP relapses through episodic viral attacks.

Persistent Relapsing Immune Thrombocytopenia Following COVID-19 Infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392851/

Yet another condition with endothelial damage that causes the occurrence of schistocytes is Disseminated Intravascular Coagulation (DIC).

DIC is a different, but not mutually exclusive, category of microvascular occlusion than TMA. The fibrin-rich microvascular occlusions in DIC111 are presumed to not allow for a significant percentage of RBCs to extrude through the occlusions resulting in anemia from characteristic mechanical damage.124 Although schistocytes may be present in DIC, they tend to occur at a much lower frequency than in TMA.199 Additionally, DIC is differentiated from TMA by widespread fibrin deposition resulting in low fibrinogen and coagulation cascade factor consumption leading to coagulopathy.

Microvascular thrombosis: experimental and clinical implications

Again, this is present in COVID

The pathology of coronavirus disease 2019 (COVID-19) is exacerbated by the progression of thrombosis, and disseminated intravascular coagulation (DIC), and cytokine storms.

COVID-19-associated coagulopathy and disseminated intravascular coagulation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664/

And also, Long COVID.

A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage.

The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases
https://pubmed.ncbi.nlm.nih.gov/34696334/

Given that the definition of DIC is:

Disseminated intravascular coagulation can be defined is a widespread hypercoagulable state that can lead to both microvascular and macrovascular clotting and compromised blood flow, ultimately resulting in multiple organ dysfunction syndrome.

Disseminated Intravascular Coagulation
https://www.ncbi.nlm.nih.gov/books/NBK441834/

It is certain, I believe, that this is central to Long COVID.

To investigate the role of amyloid microclots in Long COVID, Drs Pretorius and Kell and colleagues evaluated blood samples from 80 patients included in the South African Long COVID/Post-Acute Sequelae of COVID-19 (PASC) registry. All patients were experiencing lingering symptoms of shortness of breath, low oxygen levels, heart palpitations, constant fatigue, joint and muscle pain, brain fog, sleep disturbances, digestive problems, or kidney problems.

Analysis of patient blood samples found that microclots and platelet pathologies were present in all 80 patients. Using a spreading, clumping, and microclot scoring system, 30 of the 80 patients were found to have moderate activation.

Are Amyloid Fibrin Microclots Central to Long COVID?
https://www.endocrinologyadvisor.com/home/topics/general-medicine/covid-amyloid-fibrin-micro-clots-central-treatment-risk/

I am stunned by the COVID-19 analysis in the Microvascular thrombosis article.

COVID-19 manifestations further demonstrate the connection between inflammation and thrombosis in the microvasculature. The mechanisms responsible for microvascular thrombosis in COVID-19 are unclear; one intriguing possibility involves NETs.

Unclear? UNCLEAR? NETs? Of course it involves NETs. It’s like the authors are looking at the last piece of a jigsaw puzzle and wondering where it belongs… (SMH)

To me this is as clear as day. Additionally, NETs are central to DIC! How can this be UNCLEAR? Especially since NETs are mentioned in association with DIC in the very same article.

So, as my readers know (and if you are new, please search my stack for an explanation of SPED) I believe the Spike Protein’s interaction with the endothelium causes damage and destruction to the endothelium – especially the endothelium of the microvasculature. We know the spike is present in Acute COVID. However, the Spike is also present in Long COVID.

And, make no mistake, JUST the SPIKE PROTEIN.

They found that one particular SARS-CoV-2 antigen—the spike protein—was present in the blood of a majority of long COVID patients, up to a year after they were first diagnosed with COVID-19.

Long COVID: 'Viral reservoir' of spike protein may explain long-term symptoms
https://www.medicalnewstoday.com/articles/long-covid-viral-reservoir-of-spike-protein-may-explain-long-term-symptoms

Now. What is the point of explaining these general principles of my proposed “Experimintal Model?” The point is that this is all, perhaps, preamble. The ultimate result of this extended, chronic assault on the microvasculature – is organ fibrosis. One can theoretically trace the steps from coronavirus induced heart failure, to coronavirus induced endothelial damage, to systemic organ fibrosis.

Over the next several posts I will detail the mechanism in each major organ. For now, let’s start with the lungs.

Interstitial lung disease compatible with idiopathic pulmonary fibrosis (IPF) developed in 19 previously healthy patients. Although interstitial and/or honeycomb parenchymal fibrosis was present in all, there were patchy areas of paucicellular septal capillary injury along with corroborative direct immunofluorescent evidence of a humorally mediated microvascular injury syndrome.

The Role of Microvascular Injury in the Evolution of Idiopathic Pulmonary Fibrosis
https://pubmed.ncbi.nlm.nih.gov/12710128/

Except, remember. The underlying disease here is not humorally mediated. It is the Spike Protein.

We must learn from those who have had COVID and who, unfortunately, have Long COVID. We must search and discover if this is happening. Also, we must learn if repeated infections and exposures to the Spike Protein inexorably lead to this condition. I have also worked on discovering therapeutics which also need to be trialed.

As always, thank you for your continued support. I will keep working for us all.