Interferon therapy for COVID-19 and emerging infections: Prospects and concerns

Leonard H. Calabrese; Tiphaine Lenfant; Cassandra Calabrese

doi:10.3949/ccjm.87a.ccc066

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Figure 1
Three stages of COVID-19 disease.

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TABLE 1

Currently available interferons

Drug(s) by type	Indications and dosage	Contraindications	Safety and warnings
Type I
Interferon alpha-2a (Roferon-A) Peg-interferon alpha-2a (Pegasys)	CHC, hairy cell leukemia, chronic myelogenous leukemia; dose depends on indication, SC CHC, cirrhosis, CHC-HIV coinfection, chronic hepatitis B; 180 µg/week SC

Peg-interferon alpha-2b (Pegintron) Peg-interferon alpha-2b (Sylatron) Interferon alpha-2b (Intron-A)	CHC (in adults 1.5 µg/kg/week SC), polycythemia vera, essential thrombocytopenia Adjuvant treatment of melanoma; 6 µg/kg/week for 8 doses followed by 3 µg/kg/week SC Infectious (chronic hepatitis B and C, AIDS-related Kaposi sarcoma), hematologic (hairy cell leukemia, polycythemia vera, essential thrombocythemia, follicular lymphoma), condylomata acuminate, malignancies (melanoma); dose depends on indication, IM, SC, IV, intralesional	Autoimmune hepatitis Hepatic decompensation in patients with cirrhosis, neonates and infants Hypersensitivity	May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders Monitor closely and withdraw therapy with persistently severe or worsening signs or symptoms of the above disorders

Peg-interferon beta-1a (Plegridy) Interferon beta-1a (Avonex) Interferon beta-1a (Rebif)	Multiple sclerosis; 125 µg every 14 days SC Multiple sclerosis; 30 µg once a week IM Multiple sclerosis; 22 or 44 µg 3 times a week SC	Hypersensitivity	Hepatic injury, depression and suicide, seizures, anaphylaxis, injection site reactions, congestive heart failure, decreased peripheral blood counts, thrombotic microangiopathy, autoimmune disorders

Interferon beta-1b (Betaseron) Interferon beta-1b (Extavia)	Multiple sclerosis; 0.25 mg every other day SC Multiple sclerosis; 0.25 mg every other day SC	Hypersensitivity	Hepatic injury, anaphylaxis, depression, suicide, injection site necrosis, injection site reaction

Type II
Interferon gamma-1b (Actimmune)	Chronic granulomatous disease, severe malignant osteopetrosis; 50 µg/m2 to 1.5 µg/kg/dose, 3 times weekly SC	Hypersensitivity	Cardiovascular disorders

Type III
Peg-interferon lambda-1a (Lambda)	Not yet approved (in trial for hepatitis B, C, and D)	Although no synthetic interferon lambda is yet FDA-approved, preliminary results in a clinical trial in hepatitis D patients show that it has the same antiviral potency as type I interferon but is much safer and better tolerated.

AIDS = acquired immunodeficiency syndrome; CHC = chronic hepatitis C; FDA = U.S. Food and Drug Administration; HIV = human immunodeficiency virus; IM = intramuscular; IV = intravenous; SC = subcutaneous

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TABLE 2

Clinical trials involving type I and III interferons in COVID-19

Interferon	Phase 1	Phase 2	Phase 3	Phase 4
Interferon alpha	–	NCT04379518 NCT04480138	NCT04349410 NCT04320238 NCT04534725	NCT04254874
Interferon beta	NCT04293887	NCT04449380 NCT04343768 NCT04469491 NCT04276688 NCT04521400 NCT04385095 NCT04465695 NCT04350281 NCT04494399	NCT04324463 NCT04315948 NCT04492475 NCT04552379	NCT04350671 NCT04350684 NCT02735707
Interferon lambda	–	NCT04343976 NCT04388709 NCT04534673 NCT04354259 NCT04344600	–	–