Monday, March 13, 2023

1 Shot of interferon lambda Might Boost Immunity and Fight COVID Across Variants. Review of a potential novel treatment for COVID-19

Yet another COVID-19 treatment has emerged, but is interferon lambda the miracle cure the world has been waiting for?

Summary of Key Points

* Currently available COVID-19 treatments have limitations and concerns.

* A new clinical trial shows promise for interferon lambda, effective against all variants and drops viral loads faster than other COVID-19 treatments.

* Interferon lambda is a “one-and-done” treatment.

* Interferon lambda has little interaction with other drugs, making it a safer treatment option for many individuals.

* The Food and Drug Administration has not approved interferon lambda as a COVID-19 treatment; emergency use authorization is still pending.

Limitations and Concerns With Current COVID-19 Treatments

The currently available treatments for COVID-19 have been far from perfect, with each presenting its limitations and concerns.

For instance, questions have been raised about the safety and effectiveness of Molnupiravir, while Paxlovid is associated with a high number of cross-drug interactions, and there are concerns about managing rebound syndrome.

On the other hand, three days of intravenous remdesivir is cumbersome to set up, requiring a visit to an infusion center or dedicated home care service. More importantly, the drug has caused potentially fatal side effects, including kidney failure.

Additionally, Omicron and its subsequent mutations have made all previously available monoclonals ineffective.

In this context, a recent clinical trial has shown promising results for pegylated interferon lambda, a naturally occurring protein produced by the immune system in response to viral infections. The study showed interferon lambda could reduce COVID-19 risk by up to 50 percent.

What Is Interferon Lambda?

Interferons (IFNs) are a group of proteins produced by the immune system in response to viral infections. These proteins have antiviral, anti-tumor, and immunomodulatory effects and regulate the immune system. There are three types of interferons: type I, type II, and type III.

All types of IFNs have similar effects on the body but activate different sets of genes.

Interferons work by “interfering” with viral replication and infection. This is done by activating pro-inflammatory pathways, recruiting immune cells, or targeting viral replication by breaking down its proteins, enzymes, and RNA.

Type I and type II interferons launch a systemic antiviral response throughout the body. On the other hand, type III interferons are limited to epithelial cells and specific immune cells like neutrophils.

This indicates that type III interferons provide targeted protection for skin, gut, and lung surfaces while minimizing the side effects.

Given the characteristics of interferons, especially considering the specificity of type III interferons, they are useful for treating acute and chronic viral infections.

Previously, type I IFNs have been used to treat chronic hepatitis C and B viral infections. Although effective, they have significant side effects, such as flu-like symptoms, nausea, and fatigue, as they can theoretically affect almost all cells in the body. In contrast, studies (1,2) in mice showed that type III interferon (IFN-λ) was more effective at preventing and treating influenza viral infections with fewer side effects. Additionally, in treating hepatitis C, interferon lambda was equally as effective as type I IFNs, with milder side effects.

Regarding the timing of infection and host defense, IFNλs are the first IFNs that defend at the epithelial barrier to inhibit the initial spread of viruses without triggering inflammation.

In the context of COVID-19, type III interferons are more appropriate for development as a treatment for three reasons.

Firstly, interferon lambda works on the same locations, namely the respiratory and gastrointestinal systems where COVID-19 primarily attacks, so as to result in greater inhibition of viral replication from the nasal epithelium to the upper respiratory tract.

Secondly, most severe COVID-19 patients experience cytokine storms. Avoiding systemic inflammation is essential to reduce the risk of a cytokine storm and prevent the exacerbation of COVID-19 symptoms.

Lastly, type III interferons are localized to epithelial cells and confer long-lasting antiviral effects in the upper respiratory tract and block virus transmission, according to a report from a German laboratory study.

Interferon Lambda Works Differently Than Other COVID-19 Treatments

While most COVID-19 treatments are exogenous, meaning they are produced outside the body and later introduced to the body, interferon lambda is endogenous, produced naturally by the body in response to viral infections.

This means that interferon lambda, even if administered exogenously, is less likely to cause adverse effects, and is less likely to interact with other medications.

Interferon lambda works with your natural immune system, not against it. This differs from other COVID-19 treatments, such as vaccines, that aim to “hack” your immune system into working for you. The beauty of interferons is that your immune system can immediately use them. The idea is that we are letting our immune system do the work with a little boost from outside.

Interferon lambda triumphs above other COVID-19 treatments due to the following:

* Effective against all virus variants, including the Delta and Omicron variants.

* Drops viral loads faster than other treatments, making it an effective way to limit the spread of the virus.

* Interferon lambda is a “one-and-done” treatment.

* Little interaction with other drugs makes it a safer treatment option for many individuals.

Interferon Lambda Clinical Trial Shows Promise for COVID-19 Treatment

Two studies (1, 2) have reported the results of phase 2 clinical trials on the impact of pegylated interferon lambda on the viral load of SARS-CoV-2. Phase 2 clinical trials are small studies designed to test the safety and effectiveness of new drugs, whereas phase 3 clinical trials involve hundreds to thousands of participants.

The breakthrough study published in the New England Journal of Medicine (NEJM), “Early Treatment With Pegylated Interferon Lambda for COVID-19,” was the phase 3 trial many people were waiting for, and the results are intriguing.

The phase 3 clinical trial recruited 2,617 participants, of whom 933 were randomly assigned the treatment of pegylated interferon lambda, while 1,018 received a placebo. The remaining 666 patients were assigned to other intervention groups.

The placebo group was given either a single subcutaneous injection or an oral placebo. The median age of all the patients was 43 years, ranging from 18 to 92.

Of the patients in the interferon group, 25 of 931 (2.7 percent) showed a primary-outcome event, meaning the patient suffered from hospitalization or emergency treatment, compared to 57 of the 1,018 (5.6 percent) placebo patients. The difference shows a reduction of 51 percent risk between the control and placebo.

Additionally, there were no differences in the incidence of adverse events between the control and placebo groups, showing that the interferon lambda therapy did not lead to, at least in the scope of this study, more side effects.

Overall, patients who received a single dose of pegylated interferon lambda were significantly less likely to require hospitalization or an emergency department visit due to COVID-19 than those who received a placebo.

Our Genes Decide the Response to Interferon
It’s important to note that there are limitations to using interferon lambda injections. First, the COVID-19 patients were treated early—within 7 days after the onset of symptoms as defined in the NEJM clinical trial.

Secondly, only non-hospitalized patients were included in the study. Patients requiring hospitalization or who exhibited signs of severe COVID-19 symptoms were excluded from the trial.

Thirdly, not everyone responds to interferon therapy. Some intrinsic factors predetermine our response to interferons, such as our genes.

For example, a 2022 study published in Nature examined the OAS1 gene, which is activated by interferons to produce an important enzyme that helps the body fight viral infections.

The study discovered that a common gene pattern of OAS1, called a haplotype, was linked to an increased risk of severe illness and reduced clearance of the COVID-19 virus.

Evaluation of the prevalence of this haplotype is warranted, yet the interplay between COVID-19 and specific genes raises a bigger question regarding the impact of our genes on disease.

Let’s take approaches to happiness as an example. Hedonic lifestyles prioritize pleasure and positive emotions, such as joy, excitement, and satisfaction, and may involve activities such as indulging in good food, entertainment, or material possessions.

In contrast, eudaimonic lifestyles prioritize meaning, purpose, and personal growth and may involve pursuing challenging goals, contributing to the greater good, and cultivating meaningful relationships. While both approaches can bring about positive feelings and experiences, eudaimonic well-being tends to be more sustainable and satisfying over the long term, as it is rooted in the sense of purpose and deeper fulfillment beyond the pursuit of immediate pleasure.

In a study published in PNAS, researchers found that individuals who lived a eudaimonic lifestyle had higher interferon gene expression and significantly lower expression of pro-inflammatory genes.

On the other hand, individuals living a hedonistic lifestyle showed higher expression of pro-inflammatory genes and downregulation of interferon gene expression.

The study suggests that the interconnectedness between mind and body is powerful and should be taken into account when trying to prevent or treat illness.




No comments: