Interferon COVID-19 Treatment

Interferons are naturally-occurring proteins secreted by immune system cells. Three classes of interferons exist:

Each class has overlapping effects. Commercially available interferons are human interferons produced using recombinant DNA technology. The mechanism of action of interferons is complex and not fully understood. Interferons regulate the immune system’s response to viruses, bacteria, cancer, and other foreign substances by modulating gene activity that controls the secretion of proteins affecting cell growth.

Interferon alfa and beta may be used in hospitalized or unhospitalized COVID-19 patients, typically in clinical trials only.

Available Interferons

• interferon alfa-2a (Roferon-A)
• interferon alfa-2b (Intron-A)
• interferon alfa-n3 (Alferon-N)
• peginterferon alfa-2b (PegIntron, Sylatron)
• interferon beta-1a (Avonex)
• interferon beta-1a (Rebif)
• interferon beta-1b (Betaseron)
• interferon beta-1b (Extavia)
• interferon gamma-1b (Actimmune)
• peginterferon alfa-2a (Pegasys ProClick)
• peginterferon alfa-2a and ribavirin (Peginterferon)
• peginterferon alfa-2b and ribavirin (PegIntron/Rebetol Combo Pack)
• peginterferon beta-1a (Plegridy)
• interferon alfacon-1 (Infergen has been discontinued in the US)

Interferons as COVID-19 Treatment

Interferon beta-1a, currently used for multiple sclerosis, and interferon alfa-2b are being investigated as potential COVID-19 treatments. When a cell encounters a virus, it releases interferon to activate immune defenses. Interferon Beta 1a activates macrophages and natural killer cells, strengthening the innate immune system. Interferon therapy boosts dormant immune components to fight SARS-nCoV-2.

However, interferons can worsen flu-like symptoms caused by COVID-19 initially, as natural interferon in the body is responsible for these symptoms in viral infections. Administering interferon-based medicines to ventilated patients with overwhelming symptoms can be hazardous. Interferon therapies are typically a last resort due to their potential for severe side effects.

Clinical trials around the world, including a significant WHO study, are exploring interferons as possible COVID-19 treatments. However, interferons were previously used for Hepatitis C treatment in the US, leading to severe side effects and low cure rates, which may explain the hesitance in using them for COVID-19.

Data for COVID-19 section provided by Dominic Chan, Pharm.D., infectious disease specialist at Legacy Health System in Oregon.

Interferon Side Effects

Common side effects of interferons (may occur with all types) include flu-like symptoms after each injection, such as:

These side effects range from mild to severe and affect up to 50% of patients. Symptoms tend to decrease with repeated injections and can be managed with acetaminophen and antihistamines. Injection sites may experience tissue damage, more commonly with specific interferon types.

Other side effects that may occur with all interferons, especially at higher doses, include:

• Fatigue
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Joint aches
• Back pain
• Dizziness
• Anorexia
• Congestion
• Increased heart rate
• Confusion
• Low white blood cell count
• Low platelet count (thrombocytopenia)
• Low red blood cell count
• Elevated liver enzymes
• Increased triglycerides
• Skin rashes
• Mild hair loss or thinning
• Swelling (edema)
• Cough
• Difficulty breathing
• Allergic or anaphylactic reaction

Some interferons may be associated with liver failure, requiring periodic liver function tests during therapy. Depression and suicidal thoughts have been reported in patients receiving interferon treatment, but it is unclear whether they are caused by the diseases being treated or the interferons themselves.

Interferons for Various Conditions

Interferons enhance the immune system and are used to treat various immune-related diseases:

• interferon alfa-2a (Roferon-A) is FDA-approved for hairy cell leukemia, AIDS-related Kaposi’s sarcoma, and chronic myelogenous leukemia
• interferon alfa-2b is approved for hairy cell leukemia, malignant melanoma, condylomata acuminata, AIDS-related Kaposi’s sarcoma, chronic hepatitis C, and chronic hepatitis B
• Ribavirin combined with interferon alfa-2b, interferon alfacon-1 (Infergen), pegylated interferon alfa-2b, or pegylated interferon alpha-2a are approved for chronic hepatitis C
• interferon beta-1b (Betaseron) and interferon beta-1a (Avonex) are approved for multiple sclerosis
• interferon alfa-n3 (Alferon-N) is approved for genital and perianal warts caused by human papillomavirus (HPV)
• interferon gamma-1B (Actimmune) is approved for chronic granulomatous disease and severe, malignant osteopetrosis
• peginterferon beta-1a (Plegridy) is used for multiple sclerosis (MS)

Differences Among Interferon Types

Although interferons are similar, they affect the body differently, resulting in different uses:

• Interferon alphas are used for treating cancers and viral infections
• Interferon betas are used for treating multiple sclerosis
• Interferon gamma is used for treating chronic granulomatous disease

Interactions with Other Drugs

Interferon alfa-2a, interferon alfa-2b, peginterferon beta-1a, and interferon beta-1b may increase blood levels of zidovudine (AZT, Retrovir). This may improve zidovudine’s effectiveness but also raise the risk of blood and liver toxicity. Therefore, zidovudine doses may need to be reduced by up to 75%.

Interferon alfa-2a and interferon alfa-2b may prolong the elimination time of theophylline (for example, Theo-Dur) from the body, necessitating a reduction in theophylline dosage.

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Summary

Interferons are naturally occurring proteins used to treat various immune-related diseases, such as cancers, hepatitis, AIDS, multiple sclerosis (MS), genital and perianal warts, and granulomatous disease. Two types of interferons are being investigated for severe COVID-19 cases caused by the SARS-nCoV-2 virus.