Breaking! Study Shows That COVID-19 Triggers Immunoparalysis, Autoimmune Diseases, Neoplastic Transformation And Latent Infectious Diseases!

A new comprehensive study by researchers from University of São Paulo-Brazila and the Hospital do Servidor Público Estadual –Brazil has uncovered more concerning details about the COVID-19 disease. The researchers warn that COVID-19 is a chronic disease that can trigger immunoparalysis , autoimmune diseases, neoplastic transformation and latent infectious diseases! The Long COVID-19 prospects are even more alarming as a variety of conditions can arise including the promotion of tumors and cancers.

The study findings are a must for every clinician and researcher involved in COVID-19 treatments.
 
According to the study abstract, “The novel SARS-CoV-2 coronavirus triggers numerous physiologic changes in humans, with potentially fatal evolution.”
 
The study team says that COVID-19 can trigger immunoparalysis with deep and silent immunosuppression and a state of tolerance that may elicit opportunities for neoplastic transformation or latent infectious diseases.
 
Furthermore neurologic or psychiatric symptoms have been observed, some clinically present in usual diseases, but behind these phenomena, there is often the chronic phase of COVID-19 as a background, mediated by intense platelet activation.
 
Symptoms may vary greatly as they depend on subjacent comorbidities but reflect a unique wide-spectrum syndrome ranging between absent or mild autoimmune undetermined disease and two classical diseases: Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Granulomatosis with Polyangiitis (GPA).
 
Interestingly, deviations in tryptophan catabolism cause neutrophilia with variable eosinophilia and apparently, tryptophan metabolism is altered both due to inflammation and niacin depletion. Lack of tryptophan causes sustained anaemia due to insufficient stimulation of the bone marrow.
 
These study findings were based on articles reviewing, clinical observations, and high-intensity routine studies and in-hospital COVID-19 patients practice over 8 months.
 
The main conclusion of this study is that the whole process starts among neutrophils and then is perpetuated by sustained platelet activation.
 
The study findings were published in the peer reviewed Journal of Infectious Diseases and Epidemiology.
https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-195.php?jid=jide
 
 The key takeaways of the study are:
 
 -That COVID-19 is a chronic disease.
 
- The acute phase of the disease is viral and inflammatory, with the inflammatory component being responsible for severe acute respiratory failure.
 
- The chronic disease is due to changes in the metabolism of tryptophan and the lack of niacin (NAD/NADH+). Tryptophan has its metabolism altered by the lack of intestinal absorption due to internalization of ACE-2 and hypoxemia and inflammation, diverting its products to the formation of toxic Kynurenine metabolites.
 
- cHIS is pan-syndromic, the most evident b eing IL-6-mediated inflammatory syndrome, immunoparalysis syndrome, variable hypereosinophilic syndrome.
 
- The chronic phase (cHIS) can present multiple systemic changes such as muscle pain, skin lesions, changes in the central nervous system due to the presence of mastocytosis and eosinophilia, and the toxic component of tryptophan products.
 
- The formation of antibodies does not follow a pattern of formation since the disease is specific to each person and dependent on the immunosuppression that the virus determined for each individual.
 
- In the immunoparalysis phase, COVID-19 can reactivate latent infectious diseases such as fungal and bacterial infections such as mycobacteriosis.
 
- The pneumonia pattern in the chronic phase is an inflammatory component and is a disease already described called acute fibrinous organization pneumonia (AFOP) secondary to IL-6 and sustained inflammation.
 
- COVID-19 is a viral disease and, like other viral infections, can also cause diseases of autoimmune origin. Perhaps its propensity for autoimmunity to occur is that the virus triggers autoantibodies' formation while endothelial damage occurs.
 
- That COVID-19 causes a tolerance profile facilitating the appearance of autoimmune diseases and neoplasms.
 
- That the inflammatory component is dependent, among other factors, on the length of hypoxemia to which a person has been subjected in the acute phase of the disease with consequent consumption of NAD/NADH+ and stimulation of neovasogenesis.
 
- That there is a concomitance of immunological forces of Treg and Th17 profile.
 
- Persistent anaemia is due to the continuous activation of neutrophils in the subacute and chronic phases and dependent on the serotonin/tryptophan pathways.
 
- That COVID-19 in the cHIS phase presents an oscillating (almost sinusoidal) pattern of laboratory behaviour indicating periods with an increase followed by a sudden decrease in cell types/proteins always marked by hypocalcaemia.
 
- That Ca2+ is necessary for activation of neutrophils, cellular apoptosis and many other cellular metabolic systems is very consumed.
 
- Bone metabolism is greatly affected by serotonin and mastocytosis, which is why fractures and osteoporosis may increase after COVID-19.
 
- That both the first and second phases respond to corticosteroids.
 
The study team warns that COVID-19 is more than an infectious disease. It is an infectious, metabolic and deficiency disease, related to comorbidities especially those with inflammatory characters, previously present.
 
It can evolve more severely in patients with inflammatory conditions than compared to malnourished patients, for example.
 
Malnutrition can be corrected throughout hospitalisation stay, while the genetic settings leading to inflammatory conditions are much more challenging to manage.
 
The study team noted common severe disease predictors among those patients whose profiles were pronated to a worse evolution. They show an intracellular aerobic respiratory chain cycle that is completely shaken by lack of essential vitamin B3, which originated from the tryptophan cycle.
 
This explains some studies findings for a positive outcome found in the replacement of complex B vitamins in critically ill patients, not found for other vitamins.
 
COVID-19 patients are under high-intensity metabolic stress, with depleted NAD/NADH+ to connect aerobic metabolism to anaerobic respiration. Also, in this highly intense stress period, blood cortisol is found in high concentrations.
 
COVID-19 is a complex combination of viral action and metabolic deficits triggered by infection and internalisation of ACE-2, modifying the RASS axis to inflammatory vasospasm and thrombotic pathway, and reaches its maximum when immunoparalysis and tolerance allow the development of neoplasms, which the immune system should contain.
 
The basal IL-6 is already polarised in chronic inflammatory conditions. When there is increasing pressure to reassure this deviation, these patients develop massive and catastrophic immunosuppression.
 
This can explain the reactivation of latent infectious diseases observed in COVID-19 patients.
 
Further to this context, an inflamed bowel represents a significant and continuous supplier for Gram-negative bacteria and enterococci, leading to prolonged hospital stays and several antimicrobials' cycles, which show no effect on these bacteria. This condition is expected, given the phagocytosis capacity loss by polymorphonuclear cells under a permanent inflammatory state combined with exposed intestinal mucosae.
 
In this phase, the observed neurological findings are bizarre and intriguing and have not been explained or accepted.
 
It shouldbe noted that platelets secrete IL-6 by multiple mechanisms, stimulating mast cells and this cytokine is overexpressed in people who have chronic inflammatory diseases.
 
 With SARS-CoV-2 infection, a recrudescence provided a more intense mast cell, basophils and finally eosinophils mainly by IL-5 chemoattraction. There is a tendency towards neutropenia developing. Nevertheless, intense recruitment by bacterial translocation, systemic endothelial aggregation (motivated by low cellular respiration), autoantibodies, the complement cascade, and the tryptophan pathway make neutrophilia common; however, this finding is related to a poorer prognosis.
 
The chronic inflammatory process mimics a sinusoidal shaped curve, with inflammation peaks followed by a nadir with a decrease in inflammatory laboratory markers such as C-reactive protein, D-Dimer, oxaloacetic transaminase, and lactic dehydrogenase (DHL). Notwithstanding, after 5 to 7 days, there is a progressive neutrophilic march with repeating patterns: Worsening of laboratory markers, respiratory performance worsens, D-Dimer and HDL rise and new anguish permeates everyone who is caring for the patient.
 
Many facts were associated with the severe form of the disease, and the study team says among them are several genetic conditions (HLA-DR with high expression, for example), lifestyle and the environmental conditions, viral load to which it was exposed, the type of inflammatory comorbidity - with particular importance for fat metabolism and immunosenescence.
 
The team says that clinical experience has taught us that the first point to think about is that obese and diabetic patients should never have delayed intubation and that all intubation for this patient profile should be performed in a "golden time".
 
Since the beginning of the pandemic, physicians have been performing it, and efforts were made to define the main predictors for orotracheal intubation.
 
However, all results have shown very controversial information and based on the doubt of prolonging hypoxemia; physicians should chose to perform intubation by rigorous criteria: Pulse oximetry oxygen saturation (SatO₂) equals to 93% or less - with an oxygen offer of at most 50%; breathing rate (BR) = 30 inspirations per minute or more, dyspnoea, choppy speech, Glasgow Coma Scale score 8 points or less. Current studies have proven that ongoing hypoxemia is the major endothelium inflammation factor leading to a bad prognosis. The tryptophan pathway is impaired both by the infection and hypoxemia, and its consequences will rely on the individual Trp reserve and present comorbidities. When there is an intense gastrointestinal infection by SARS-CoV-2, Trp absorption is deficient, explained by internalisation and downregulation of ACE-2 by inflammation.
 
The study team also warns that individuals who are asymptomatic should also be monitored closely. Some followed outpatients who never had symptoms of COVID-19 have been reported to show odd symptoms, like diarrhoea, bone pain or neuropathic pain and some presenting mastocytosis and mood disorders. Subsequent examinations revealed monocytosis with leukopenia found in the blood cell count, with normal eosinophil counting and mild laminar atelectasis and bronchial thickening visible at chest CT scan.
 
These study findings are a must for every clinician and researcher involved in COVID-19 treatments. (Please also peruse through the lengthy appendix of the study)
 
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