Skip to main content
. 2022 Feb 12:1–20. doi: 10.1080/00325481.2022.2033563

Table 1.

Summary of guidance and evidence on the use of immunomodulators in the management of COVID-19

Intervention FDA EUA NIH recommendation Potentially optimal use/efficacy Potential benefit
Convalescent plasma Yes, high-titer plasma only

  • No recommendation for or against in non-hospitalized patients, with or without impaired humoral immunity

  • Recommendation against use in hospitalized patients without impaired humoral immunity.

  • Early disease.

  • High-titer

  • Hospitalized patients with impaired humoral immunity.

  • Increase in anti-SARS-CoV-2 neutralizing antibodies.

  • Reduction in immune system exhaustion.

  • Activation of memory B and T cells.

  • Reduction in pro-inflammatory cytokines and mediators (e.g. IL-6 and IFN-γ).

  • Improvement in clinical outcomes (e.g. inflammation, pulmonary function, length of hospitalization, need for intubation, progression to severe disease).

  • Decrease in mortality risk.
IVIGs        
  SARS-CoV-2-specific IVIG No. No recommendation for or against. N/A N/A
  Non-SARS-CoV-2-specific IVIG No.
  • Recommendation against, except:
    • In a clinical trial.
    • When indicated for COVID-19 complications.

  • Early disease.

  • Severe disease.

  • Hospitalized patients.

  • Indicated COVID-19 complications

  • Increase in clinical improvement (e.g. reduced hospital length of stay, reduced need for mechanical ventilation, improvement in hypoxia).

  • Decrease in mortality.
Anti-SARS-CoV-2 monoclonal antibodies        
  Bamlanivimab/ etesivimab Yes. Recommended in non-hospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression in regions where the combined frequency of potentially resistant SARS-CoV-2 variants is low

  • Non-hospitalized.

  • Adults and pediatric (>12 years and >40Kgs).

  • Mild-to-moderate disease.

  • Confirmed SARS-CoV-2 infection.

  • High risk of progression to severe COVID-19 and/or hospitalization.

  • Infection with susceptible variant of interest.

  • Reduction of viral load.

  • Decreased hospitalizations.

  • Decreased mortality.
  Casirivimab/imdevimab Yes. Recommended for non-hospitalized
patients with mild to moderate COVID-19 who are at high risk of clinical progression.

  • Non-hospitalized

  • Adults and pediatric (>12 years and >40Kgs).

  • Mild-to-moderate disease.

  • Confirmed SARS-CoV-2 infection.

  • High risk of progression to severe COVID-19 and/or hospitalization.

  • Reduction of viral load.

  • Decreased hospitalizations.

  • Decreased mortality.
  Sotrovimab Yes. Recommended for non-hospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression.

  • Non-hospitalized

  • Adults and pediatric (>12 years and >40Kgs).

  • Mild-to-moderate disease.

  • Confirmed SARS-CoV-2 infection.

  • High risk of progression to severe COVID-19 and/or hospitalization.

  • Reduction of progression in patients with mild-to-moderate disease.

  • Safe and tolerable.
IFNs        
  IFN-α No.

  • Recommendation against in non-hospitalized patients.

  • Recommendation against in hospitalized patients outside of a clinical trial.

  • Early disease.

  • Hospitalized patients.

  • Increase in viral clearance.

  • Decrease in inflammatory markers.

  • Decrease in length of hospitalization.

  • Improvement in clinical outcomes.

  • Decrease in mortality.
  IFN β (1a and 1b) No. Recommendation against

  • Early disease.

  • Mild-to-moderate disease.

  • Hospitalized and non-hospitalized patients.

  • Faster clinical improvement

  • Increase in virological clearance rates.

  • Reduction in hospitalizations.

  • Decrease in mortality.
IL Inhibitors        
  IL-1 inhibitors:
Anakinra		 No. No recommendation for or against.

  • Severe to critical disease.

  • Hospitalized patients.

  • Decrease in severe respiratory failure and the need for mechanical ventilation and oxygen supplementation.

  • Management of the cytokine storm syndrome and alleviation of hyperinflammation.

  • Decrease in mortality.

  • Decrease in hospital stay
  Canakinumab No. Recommendation against, except in a clinical trial.

  • N/A

  • N/A
IL-6 inhibitors        
  Sarilumab No. Can be used instead of tocilizumab if it is not available in the same recommended categories.

  • Early disease.

  • Severe disease.

  • Hospitalized.

  • Need for oxygen supplementation.

  • Need for oxygen through high-flow. device or non-invasive ventilation.

  • Need for mechanical ventilation or extracorporeal membrane oxygenation.

  • Increase in clinical improvement.

  • Improvement in prognosis.

  • Reduced mortality.

  • Reduced time to ICU discharge.

  • Increased number of organ support-free days.
  Tocilizumab No.
  • Recommendation for the addition of tocilizumab to dexamethasone and/or remdesivir, only specific cases when rapid respiratory decompensation and systemic inflammation due to COVID-19 is seen:
    • Hospitalized patients with requirement for oxygen supplementation:
    • Hospitalized patients with requirement of oxygen through a high-flow device or non-invasive ventilation
  • Recommendation for the combination of IV tocilizumab with dexamethasone for:
    • Hospitalized patients requiring mechanical ventilation or extracorporeal membrane oxygenation who are within 24 hours of hospital admission.

  • Early disease

  • Severe disease

  • Hospitalized.

  • Need for oxygen supplementation.

  • Need for oxygen through high-flow. device or non-invasive ventilation.

  • Need for mechanical ventilation or extracorporeal membrane oxygenation.

  • Resolution of inflammation.

  • Decrease in invasive ventilation risk.

  • Decrease in mortality.

  • Reduced time to ICU discharge.

  • Increased number of organ support-free days.
  Siltuximab No.
  • Recommendation against, except:
    • In a clinical trial.
 N/A N/A
  TNF inhibitors No. N/A N/A

  • Decrease in invasive ventilation risk.

  • Decrease in hospitalization risk.

  • Decrease in mortality.
Kinase Inhibitors        
  JAK inhibitors:
Baricitinib		 Yes.
in combination with remdesivir in hospitalized patients ≥2 years of age requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.		 Baricitinib is recommended only in combination with dexamethasone, with or without remdesivir, in hospitalized patients who require oxygen supplementation through a high flow device or non-invasive therapy.

  • Hospitalized patients.

  • Requiring non-invasive oxygen support.

  • Increase in clinical improvement.

  • Improvement of pulmonary function.

  • Decrease in hospital admission.

  • Decrease in mortality.
  Tofacitinib No.
  • Recommendation to use instead of baricitinib in case:
    • Baricitinib is not available.
    • Baricitinib cannot be used.

  • Hospitalized.

  • Requiring non-invasive oxygen support.

  • Decrease in mortality

  • Decrease in respiratory failure.
  BTK inhibitors No.
  • Recommendation against, except:
    • In a clinical trial.
 N/A

  • Improvement in oxygenation.

  • Improvement in inflammation.
Corticosteroids        
  Dexamethasone
(or equivalent prednisone, methylprednisolone, or hydrocortisone)		 No.

  • Recommendation against in mild-to-moderate non-hospitalized

  • Recommendation for dexamethasone:
    • Orally for patients with increasing oxygen needs that were discharged due to scarce resources. Recommended only for the duration of oxygen supplementation, not to exceed 10 days.
    • Alone or in combination with other drugs (remdesivir and/or baricitinib or IV tocilizumab) in hospitalized patients requiring supplemental oxygen or oxygen delivery through a high-flow device or non-invasive ventilation.
    • Alone for hospitalized patients requiring invasive mechanical ventilation or extracorporeal membrane oxygenation or in combination with IV tocilizumab in patients within 24 hours of admission.

  • Hospitalized and requiring oxygen support (oxygen supplementation, oxygen through high-flow device or non-invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation).

  • Non-hospitalized due to scarce resources but unstable and requiring oxygen supplementation

  • Decreased time on ventilators.

  • Decreased mortality.
Colchicine No.
  • Recommendation against for:
    • Non-hospitalized patients.
    • Hospitalized patients

  • Moderate-to-severe disease.

  • Hospitalized patients.

  • Non-hospitalized patients.

  • Decrease in need for oxygen supplementation and invasive ventilation.

  • Decrease in inflammation.

  • Prevention of disease progression.

  • Increase in clinical improvement.

  • Decrease in mortality.

  • Decrease in duration of hospitalization.

BTK: Bruton’s kinase; COVID-19: coronavirus disease 2019; EUA: Emergency Use Authorization; FDA: Food and Drug Administration; ICU: Intensive Care Unit; IL: Interleukin; INF: Interferon; IV: Intravenous; IVIG: Intravenous Immunoglobulin; JAK: Janus kinase; NIH: National Institutes of Health; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; TNF: Tumor Necrosis Factor