Table 3b. Characteristics of Immune-Based Therapy Under Evaluation for the Treatment of COVID-19

Last Updated: August 27, 2020

Table 3b. Characteristics of Immune-Based Therapy Under Evaluation for Treatment of COVID-19
Drug Name Dosing Regimen
There are no approved doses for the treatment of COVID-19. The doses listed here are for approved indications or from reported experiences or clinical trials.
Adverse Effects Monitoring Parameters Drug-Drug Interaction Potential Panel Recommendations, Comments, and Links to Clinical Trials
Blood-Derived Products
COVID-19 Convalescent Plasma

1 or more transfusions based on patient response

  • TRALI
  • TACO
  • Allergic reactions
  • Antibody-mediated enhancement of infection
  • Red cell alloimmunization
  • Transmission of infectious pathogens1
  • Thrombotic events
  • Monitor for transfusion-related reactions.
  • Vital signs at baseline and during and after transfusion
Drug products should not be added to the IV infusion line for the blood product.
  • There are insufficient data for the Panel to recommend either for or against the use of COVID-19 convalescent plasma or SARS-CoV-2 immunoglobulins for the treatment of COVID-19.
  • A list of clinical trials is available: Convalescent Plasma
Immunoglobulins: SARS-CoV-2 Specific Doses vary by clinical trial.
  • TRALI
  • TACO
  • Allergic reactions
  • Antibody-mediated enhancement of infection
  • Red cell alloimmunization
  • Transmission of infectious pathogens
  • Monitor for transfusion-related reactions.
  • Vital signs at baseline and during and after transfusion
Drug products should not be added to the IV infusion line for the blood product.
  • There are insufficient data for the Panel to recommend either for or against the use of SARS-CoV-2 immunoglobulins for the treatment of COVID-19.
  • A list of clinical trials is available: Immunoglobulin
Immunoglobulins: Non-SARS-CoV-2 Specific Doses vary based on indication and formulation.
  • Allergic reactions including anaphylaxis
  • Renal failure
  • Thrombotic events
  • Aseptic meningitis syndrome
  • Hemolysis
  • TRALI
  • Transmission of infectious pathogens
  • Monitor for transfusion-related reactions.
  • Vital signs at baseline and during and after infusion
  • Discontinue if renal function deteriorates during treatment.
IVIG may interfere with immune response to certain vaccines.
  • The Panel recommends against the use of non-SARS-CoV-2 specific IVIG for the treatment of COVID-19, except in a clinical trial (AIII). This recommendation should not preclude the use of IVIG when otherwise indicated for treatment of complications that arise during COVID-19.
  • AEs may vary by formulation.
  • AEs may be precipitated by high-dose, rapid infusion, or underlying conditions.
  • A list of clinical trials is available: Intravenous Immunoglobulin
Mesenchymal Stem Cells
  • Doses vary by clinical trial.
  • In the United States, mesenchymal stem cells should not be used for the treatment of COVID-19 outside of an FDA-approved clinical trial, expanded access protocol, or EIND process.
  • Failure of the cells to work as expected2
  • Potential for mesenchymal stem cells to multiply or change into inappropriate cell types
  • Product contamination
  • Growth of tumors
  • Infections
  • Thrombus formation3
  • Administration site reactions4,5
  • Monitor for administration site reactions.
Drug products should not be added to the IV infusion line for the mesenchymal stem cell product.
  • The Panel recommends against the use of mesenchymal stem cells for the treatment of COVID-19, except in a clinical trial (AII).
  • The FDA has issued several warnings about patients being potentially vulnerable to stem cell treatments that are illegal and potentially harmful.4 A number of cord blood-derived products are currently licensed by the FDA for various indications, such as the treatment of cancer (stem cell transplant) and rare genetic diseases. These products are not FDA approved for the treatment of COVID-19.
  • A list of clinical trials is available: Mesenchymal Stem Cells
Immunomodulators
Corticosteroids
Dexamethasone For COVID-19:
  • Dexamethasone 6 mg daily IV or PO, for up to 10 days6
  • Dexamethasone should be continued for up to 10 days or until hospital discharge, whichever comes first.
  • Hyperglycemia
  • Secondary infections
  • Reactivation of latent infections (e.g., HBV, HSV, strongyloidiasis, TB)
  • Psychiatric disturbances
  • Avascular necrosis
  • Adrenal insufficiency
  • Increased blood pressure
  • Peripheral edema
  • Myopathy (particularly if used with neuromuscular blocking agents)
  • When used during outbreaks of other novel coronavirus infections (i.e., MERS and SARS), corticosteroid therapy was associated with delayed virus clearance.7,8
  • Blood glucose
  • Blood pressure
  • Sign and symptoms of new infection
  • When initiating dexamethasone, appropriate screening and treatment to reduce the risk of Strongyloides hyperinfection in patients at high risk of strongyloidiasis (e.g., patients from tropical, subtropical, or warm temperate regions or who engage in agricultural activities) or fulminant reactivations of HBV should be considered.9-11
  • Moderate CYP3A4 inducer
  • CYP3A4 substrate
  • Although coadministration of RDV and dexamethasone has not been formally studied, a clinically significant PK interaction is not predicted (Gilead, written communication, August 2020).
  • On the basis of the preliminary report from the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, the Panel recommends using dexamethasone 6 mg per day for up to 10 days or until hospital discharge, whichever comes first, for the treatment of COVID-19 in hospitalized patients who are mechanically ventilated (AI) and in hospitalized patients who require supplemental oxygen but who are not mechanically ventilated (BI).
  • The Panel recommends against using dexamethasone for the treatment of COVID-19 in patients who do not require supplemental oxygen (AI).
  • If dexamethasone is not available, the Panel recommends using alternative glucocorticoids such as prednisone, methylprednisolone, or hydrocortisone (AIII).
  • The approximate daily dose equivalencies for these glucocorticoids to dexamethasone 6 mg (PO or IV) are: prednisone 40 mg, methylprednisolone 32 mg, and hydrocortisone 160 mg.
  • In the RECOVERY trial, only 5 patients received RDV; therefore, the safety and efficacy of coadministering RDV and dexamethasone are not known.
  • In the United States, dexamethasone is available in the following formulations: oral tablet, oral solution, oral elixir, and IV solution.
  • A list of clinical trials is available: Dexamethasone
Interferons
Interferon Alfa
  • Peginterferon alfa-2a 180 mcg SQ once weekly for 2 weeks for MERS12,13
IFN Alfa-2b
  • COVID-19 Clinical Trial Dosing: Nebulized IFN alfa-2b 5 million international units twice daily (no duration listed in the study)14
  • Flu-like symptoms (e.g., fever, fatigue, myalgia)15
  • Injection site reactions
  • Liver function abnormalities
  • Decreased blood counts
  • Worsening depression
  • Insomnia
  • Irritability
  • Nausea
  • Vomiting
  • Hypertension
  • Induction of autoimmunity
  • CBC with differential
  • Liver enzymes; avoid if Child-Pugh Score >6
  • Depression, psychiatric symptoms
  • Reduce dose in patients with CrCl <30 mL/min.
  • Low potential for drug interactions
  • Inhibition of CYP1A2
  • The Panel recommends against the use of IFNs for the treatment of patients with severe and critical COVID-19, except in a clinical trial (AIII).
  • For COVID-19, IFN alfa has primarily been used as nebulization and usually as part of a combination regimen.
  • Nebulized IFN alfa-2b is not approved by the FDA for use in the United States.
  • IFN alfa-1b is not approved by the FDA for use in the United States.
  • Use with caution with other hepatotoxic agents.
  • Reduce dose if ALT >5 times ULN; discontinue if accompanied by increase in bilirubin.
  • Reduce dose or discontinue if neutropenia or thrombocytopenia occur
  • A list of clinical trials is available: Interferon
Interferon Beta

IFN Beta-1a:

  • IFN beta-1a 44 mcg SQ 3 times weekly for MERS13
  • Duration for COVID-19 unknown

IFN Beta-1b:

  • IFN beta-1b 8 million international units SQ, every other day, up to 7 days total for COVID-1916
  • Flu-like symptoms (e.g., fever, fatigue, myalgia)17
  • Leukopenia, neutropenia, thrombocytopenia, lymphopenia
  • Liver function abnormalities (ALT > AST)
  • Injection site reactions
  • Headache
  • Hypertonia
  • Pain
  • Rash
  • Worsening depression
  • Induction of autoimmunity
  • Liver enzymes
  • CBC with differential
  • Worsening CHF
  • Depression, suicidal ideation
Low potential for drug interactions
  • The Panel recommends against use of IFNs for the treatment of patients with severe and critical COVID-19, except in a clinical trial (AIII).
  • There are insufficient data to recommend either for or against the use of IFN beta for the treatment of early (i.e., <7 days from symptom onset) mild and moderate COVID-19.
  • Use with caution with other hepatotoxic agents.
  • Reduce dose if ALT >5 times ULN.
  • A list of clinical trials is available: Interferon
Availability:
  • Several products are available in the United States; product doses differ.

IFN Beta-1a Products:

  • Avonex, Rebif

IFN Beta-1b Products:

  • Betaseron, Extavia
Interleukin-1 Inhibitor
Anakinra
  • Standard adult dose is anakinra 100 mg SQ once daily
  • Has also been used IV
  • Duration unknown
  • Neutropenia (particularly in combination with other agents that can cause neutropenia)
  • Anaphylaxis
  • Headache, nausea, diarrhea, sinusitis, arthralgia, flu-like symptoms, and abdominal pain
  • Injection site reactions
  • Liver enzyme elevations
  • CBC with differential
  • Renal function (reduce dose in patients with CrCl <30 mL/min
  • Liver enzymes
Use with TNF-blocking agents is not recommended due to increased risk of infection.
  • There are insufficient data for the Panel to recommend either for or against the use of IL-1 inhibitors (e.g., anakinra) for the treatment of COVID-19.
  • A list of clinical trials is available: Anakinra
Interleukin-6 Inhibitors
Anti-Interleukin-6 Receptor Monoclonal Antibodies
Sarilumab18

Clinical Trial Dosing (See ClinicalTrials.gov Identifier NCT04315298):

  • Sarilumab 400 mg IV (single dose)19

Note: The only FDA-approved sarilumab product is an SQ formulation.

  • Neutropenia, thrombocytopenia
  • Gastrointestinal perforation
  • HSR
  • Increased liver enzymes
  • HBV reactivation
  • Infusion reaction possible
  • Monitor for HSR
  • Monitor for infusion reaction
  • Neutrophils
  • Platelets
  • Liver enzymes
  • Elevated IL-6 may downregulate CYP enzymes; use of sarilumab may lead to increased metabolism of drugs that are CYP450 substrates.
  • Effects on CYP450 may persist for weeks after therapy.
  • The Panel recommends against the use of sarilumab for the treatment of COVID-19, except in a clinical trial (BI).
  • May mask signs of acute inflammation or infection (i.e., suppression of fever and CRP)
  • A list of clinical trials is available: Sarilumab
Tocilizumab20

Clinical Trial Dosing:

  • Tocilizumab 8 mg/kg IV once
  • Dose should not exceed tocilizumab 800 mg
  • Dose may be repeated once, 12 hours later, if clinical symptoms worsen or show no improvement (see NCT04320615).
  • Infusion-related reactions
  • HSR
  • Gastrointestinal perforation
  • Hepatotoxicity
  • Treatment-related changes in neutrophils, platelets, lipids, and liver enzymes
  • HBV reactivation
  • Monitor for HSR
  • Monitor for infusion reactions
  • Neutrophils
  • Platelets
  • Liver enzymes
  • Elevated IL-6 may downregulate CYP enzymes; use of tocilizumab may lead to increased metabolism of drugs that are CYP450 substrates.
  • Effects on CYP450 may persist for weeks after therapy.
  • The Panel recommends against the use of tocilizumab for the treatment of COVID-19, except in a clinical trial (BI).
  • May mask signs of acute inflammation or infection (i.e., suppression of fever and CRP)
  • The SQ formulation is not intended for IV administration.
  • A list of clinical trials is available: Tocilizumab
Anti-Interleukin-6 Monoclonal Antibody
Siltuximab
  • Siltuximab 11 mg/kg IV over 1 hour every 3 weeks for multicentric Castleman disease21
  • Dose and duration for COVID-19 unknown
  • Infusion-related reaction
  • HSR
  • Gastrointestinal perforation
  • Neutropenia
  • Hypertension
  • Dizziness
  • Rash
  • Pruritus
  • Hyperuricemia
  • Monitor for HSR
  • Monitor for infusion reaction
  • Neutrophils
  • Elevated IL-6 may downregulate CYP enzymes; use of siltuximab may lead to increased metabolism of drugs that are CYP450 substrates.
  • Effects on CYP450 may persist for weeks after therapy.
  • The Panel recommends against the use of siltuximab for the treatment of COVID-19, except in a clinical trial (BI).
  • May mask signs of acute inflammation or infection (i.e., suppression of fever and CRP)
  • A list of clinical trials is available: Siltuximab
Kinase Inhibitors
Bruton's Tyrosine Kinase Inhibitors
Acalabrutinib Doses for FDA-Approved Indications:
  • Acalabrutinib 100 mg PO every 12 hours
  • Dose and duration for COVID-19 unknown
  • Hemorrhage
  • Cytopenias (neutropenia, anemia, thrombocytopenia, lymphopenia)
  • Atrial fibrillation and flutter
  • Infection
  • Headache
  • Diarrhea
  • Fatigue
  • Myalgia
  • CBC with differential
  • Signs and symptoms of bleeding (particularly when coadministered with anticoagulant or antiplatelet therapy)
  • Monitor for cardiac arrhythmias
  • Monitor for new infections
  • Avoid concomitant use with strong CYP3A inhibitors or inducers.
  • Dose reduction may be necessary with moderate CYP3A4 inhibitors.
  • Avoid concomitant PPI use.
  • H2-receptor antagonist should be administered 2 hours after acalabrutinib.
  • The Panel recommends against the use of BTK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
  • Avoid use in patients with severe hepatic impairment.
  • Patients with underlying cardiac risk factors, hypertension, or acute infections may be predisposed to atrial fibrillation.
  • A list of clinical trials is available: Acalabrutinib
Ibrutinib Dose for FDA-Approved Indications:
  • Ibrutinib 420 mg or 560 mg PO once daily
  • Dose and duration for COVID-19 unknown
  • Hemorrhage
  • Cardiac arrhythmias
  • Serious infections
  • Cytopenias (thrombocytopenia, neutropenia, anemia)
  • Hypertension
  • Diarrhea
  • Musculoskeletal pain
  • Rash
  • CBC with differential
  • Blood pressure
  • Signs and symptoms of bleeding (particularly when coadministered with anticoagulant or antiplatelet therapy)
  • Monitor for cardiac arrhythmias
  • Monitor for new infections
  • Avoid concomitant use with strong CYP3A inhibitors or inducers.
  • Dose reduction may be necessary with moderate CYP3A4 inhibitors.
  • The Panel recommends against the use of BTK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
  • Avoid in patients with severe baseline hepatic impairment. Dose modifications required in patients with mild or moderate hepatic impairment.
  • Patients with underlying cardiac risk factors, hypertension, or acute infections may be predisposed to cardiac arrhythmias.
  • A list of clinical trials is available: Ibrutinib
Zanubrutinib Dose for FDA-Approved Indications:
  • Zanubrutinib 160 mg PO twice daily or 320 mg PO once daily
  • Dose and duration for COVID-19 unknown
  • Hemorrhage
  • Cytopenias (neutropenia, thrombocytopenia, anemia, leukopenia)
  • Atrial fibrillation and flutter
  • Infection
  • Rash
  • Bruising
  • Diarrhea
  • Cough
  • Musculoskeletal pain
  • CBC with differential
  • Signs and symptoms of bleeding
  • Monitor for cardiac arrhythmias
  • Monitor for new infections
  • Avoid concomitant use with moderate or strong CYP3A inducers.
  • Dose reduction required with moderate and strong CYP3A4 inhibitors.
  • The Panel recommends against the use of BTK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
  • Dose reduction required in patients with severe hepatic impairment.
  • A list of clinical trials is available: Zanubrutinib
Janus Kinase Inhibitors
Baricitinib22 For Rheumatoid Arthritis:
  • Baricitinib 2 mg PO once daily
Doses for COVID-19 in Clinical Trials:
  • Baricitinib 2-4 mg PO once daily for 7-14 days
  • Lymphoma and other malignancies
  • Thrombosis
  • Gastrointestinal perforation
  • Treatment-related changes in lymphocytes, neutrophils, hemoglobin, liver enzymes
  • Herpes simplex
  • Herpes zoster
  • CBC with differential   
  • Renal function
  • Liver enzymes
  • Monitor for new infections

Dose modification is recommended when concurrently administering with a strong OAT3 inhibitor.

  • The Panel recommends against the use of JAK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
  • Baricitinib is not recommended in patients with severe hepatic or renal impairment.
  • A list of clinical trials is available: Baricitinib
Ruxolitinib
  • Doses for FDA-approved indications range from ruxolitinib 5 mg PO twice daily to 20 mg PO twice daily.
  • Doses in COVID-19 clinical trials range from ruxolitinib 5 mg PO twice daily to 20 mg PO twice daily, for 14 days.
  • Thrombocytopenia
  • Anemia
  • Neutropenia
  • Liver enzyme elevations
  • Risk of infection
  • Dizziness
  • Headache
  • Diarrhea
  • CPK elevation
  • Herpes zoster
  • CBC with differential
  • Liver enzymes
  • Monitor for new infections
  • Dose modifications required when administered with strong CYP3A4 inhibitors.
  • Avoid use with fluconazole doses >200 mg.
  • The Panel recommends against the use of JAK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
  • Dose modification may be required in patients with moderate or severe renal impairment, hepatic impairment, or thrombocytopenia.
  • A list of clinical trials is available: Ruxolitinib
Tofacitinib Doses for FDA-Approved Indications:
  • Tofacitinib 5 mg PO twice daily (rheumatoid and psoriatic arthritis)
  • Tofacitinib 10 mg PO twice daily (ulcerative colitis)
  • Dose and duration for COVID-19 usunknown; a planned COVID-19 clinical trial will be evaluating tofacitinib 10 mg twice daily for 14 days.
  • Thrombotic events (pulmonary embolism, DVT, arterial thrombosis)
  • Anemia
  • Risk of infection
  • Gastrointestinal perforation
  • Diarrhea
  • Headache
  • Herpes zoster reactivation
  • Lipid elevations
  • Liver enzyme elevations
  • Lymphoma and other malignancies
  • CBC with differential
  • Liver enzymes
  • Monitor for new infections
  • Dose modifications required when administered with strong CYP3A4 inhibitors, or when used with a moderate CYP3A4 inhibitor coadministered with a strong CYP2C19 inhibitor.
  • Avoid live vaccines. 
  • The Panel recommends against the use of JAK inhibitors for the treatment of COVID-19, except in a clinical trial (AIII).
  • Avoid use in patients with ALC <500 cells/mm3, ANC <1,000 cells/mm3, or Hgb <9 grams/dL.
  • Dose modification may be required in patients with moderate or severe renal impairment or moderate hepatic impairment.
  • A list of clinical trials is available: Tofacitinib