With the Vaccinated Dying, Allopathy is Ready for Early Treatment: A Single Dose of PEG-IFNLambda (IL-29) Reduces Hospitalization and Death Due to COVID19 by Over 50%
In a NEJM study from Brazil, a single subcutaneous dose of Interleukin 29 (aka IFN1-lambda) showed amazing results: >50% reduction in hospitalization and death.
This is not an endorsement, and this article contains neither medical nor investing advice. I have no conflicts of interest to report. Just the facts, ma’am. I am interested in your comments!
The first large, Phase III clinical trial of a single subcutaneous dose of IL-29 shows efficacy against hospitalization and death in COVID-19. The study, conducted in Brazil, involved 1951 patients randomized to receive the dose upon diagnosis vs. placebo. All of the patients had an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms, a positive rapid antigen test for SARS-CoV-2, and at least one high-risk criterion for the progression of Covid-19.
Of the 1951 patients, a total of 931 patients received a dose of a “pegylated” analog of IL-29 and 1018 (2 patients did not complete the trial). Pegylation is the addition of polyethylene glycol to a biological compound to be protected from destruction by the immune system. Most (83%) of the patients in the study had been vaccinated.
The risk of a primary-outcome event was markedly reduced; only 25 of 931 patients (2.7%) in the IL-29 group were hospitalized or had to go to the ER, compared to 57 of 1018 (5.6%) in the placebo group. The authors reported a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%).
Other measured outcomes were much improved as well, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19–related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). Even patients with a high viral load at baseline who received pegylated interferon lambda had lower viral loads by day 7 than those who received a placebo.
Vaccinated outpatients with Covid-19 treated with IL-29 experience significantly reduced incidence of hospitalization or an emergency department visit (observation for >6 hours) compared to placebo.
Interestingly, during the trial, multiple SARS-CoV-2 variants emerged, and the study authors noted higher efficacy of IL-29 across the predominant variants.
About IL-29
From Wolk et al., (2010):
“The skin forms an essential barrier between the inside of an organism and the environment. In addition to its function in insulation, temperature regulation, and sensation, it protects the body against physical trauma, pathogens, UV radiation, and excessive water loss. Many processes necessary for maintaining skin integrity, including antimicrobial/antiviral defense, wound healing, and removal of tumors, are regulated by cytokines. Accumulating results lead us to assume that interleukin (IL)-28 and IL-29, 2 novel members of the IL-10-interferon cytokine family, are important regulators of some of these processes. In the skin, IL-28 and IL-29 can be produced by virus-infected cells, maturing dendritic cells (DCs), and regulatory T-cells and they mainly influence keratinocytes and melanocytes. In keratinocytes, IL-28 and IL-29 induce growth inhibition. Simultaneously, these cytokines increase the cellular synthesis of proteins that directly hinder virus replication and enhance the readiness to present viral antigens to immune cells. Further, IL-28 and IL-29 upregulate the expression of viral and microbial sensing cellular receptors, including toll-like receptor (TLR)3, TLR2, and melanoma differentiation-associated gene 5, and strengthen the cellular response to these receptors' ligands. Thereby, in the noninfected skin IL-28 and IL-29 enhance the capacity of keratinocytes to react to viral and microbial products and at least indirectly upregulate their inflammatory potential and innate immunity. IL-28 and IL-29 can act synergistically with other mediators secreted during DC maturation (eg, IL-20). In summary, IL-28/IL-29 may play an important role in the skin in the clearance of viral and microbial infections and the removal of tumors.”
IL-29 activates the expression of tissue inhibitor of metalloproteinase 1 in macrophages via toll‑like receptor 2 (there’s the TLR2 connection everyone has been talking about). It is IL-29 is among several immune signaling molecules that are reduced in Chikungunya virus infection. It also exhibits multiple immune regulatory activities, including antiviral, antiproliferation, and antitumor properties.
Stimulation of immune cells with SARS-CoV-2 causes higher IL-29 expression immune cells from females than in males (Agrawal et al., 2021):
“(P)eripheral blood mononuclear cells (PBMCs) from healthy young individuals were stimulated in vitro with the virus. Our results indicate that PBMCs from females upregulated the expression of HLA-DR and CD86 on pDCs and mDCs after stimulation with the virus, while the activation of these cells was not significant in males. Monocytes from females also displayed increased activation than males. In addition, females secreted significantly higher levels of IFN-α and IL-29 compared with males at 24 h. However, the situation was reversed at 1-week post-stimulation and males displayed high levels of IFN-α production compared with females. Further investigations revealed that the secretion of CXCL-10, a chemokine associated with lung complications, was higher in males than females at 24 h. The PBMCs from females also displayed increased induction of CTLs.”
BCG vaccination results in a general (non-specific) stimulation of the innate immune response, including an increase in IL-29 (just being complete, not promoting off-label BCG vaccination!).
Better than Paxlovid?
To see any treatment result in a greater than 50% reduction in the risk of a primary-outcome event is a welcome development. Better yet, the results were consistent across the SARS-CoV-2 variants of concern and were independent of vaccination status.
From the NEJM study: “To place the findings in the context of available oral therapies for outpatient treatments, we examined the effect of pegylated interferon lambda on the composite outcome of Covid-19–related hospitalization or death. Our trial showed a 41% reduction in time to death or hospitalization due to Covid-19 (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). Among patients who had begun to receive interferon within 3 days after symptom onset, this reduction increased to 65% (relative risk, 0.42; 95% Bayesian credible interval, 0.21 to 0.80).”
Eiger Pharmaceuticals’s Product
Eiger Pharmaceuticals owns the “PEGInterferonLambda” treatment, which is patented for herpes delta virus infection, and provided the product for the study at no cost.
I also found that Nanogen Pharmaceutical Biotechnology (the maker of the aluminum-adjuvanted COVID-19 vaccine, Novavax), owns a patent on a process related to pegylated interferon lambda.
The Downside: Not Safe for Everyone?
The rate of any adverse event was 15.1% in the treatment group vs. 16.9% in the placebo group. The rate of serious adverse events in the two groups was 3.4% and 4.8%, respectively.
IL-29 is found to be increased in the serum of several chronic illnesses, including osteoarthritis as well as in obesity-induced inflammation and insulin resistance. Whether this is the result of viral infections or autoimmunity-related processes driving the inflammation response is not clear.
The history of commercialization of interferon-based medicine is fraught with controversy (see Royalty payments to staff researchers cause new NIH troubles and NIH Scientists Caught Concealing Millions in Royalties for Experimental Treatments – AP).
The NEJM Study: Early Treatment with Pegylated Interferon Lambda for Covid-19 | NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2209760
Other Early COVID-19 Treatments
Sounds promising. For me, I have a child whose development was delayed and never seemed to recover after a GI doc had us give him PEG everyday for a year. I personally do not trust that compound and have out off having a colonoscopy because of the requirement to consume a bunch of PEG.
Also, I’m curious: for this new subcutaneous injection in the article, does the manufacturers get liability release like vaccine makers or do they stand behind the safety of their product like every other manufacturer?
What about profits? That is the key factor on whether a treatment like this can move forward. IF Pharma can make a lot of money from it then it might move forward, but if not, then the future is pretty bleak for interleukin 29 treatment.