Table 2

Comparison of the 2020 and 2021 points to consider on the use of immunomodulatory treatment in SARS-CoV-2 infection

2021 (current) versionChanges performed2020 (previous) version
Overarching principles
 The phenotype of SARS-CoV-2 infection is heterogeneous ranging from asymptomatic to lethal disease due to multiorgan damage.UnchangedThe phenotype of SARS-CoV-2 infection is heterogeneous ranging from asymptomatic to lethal disease due to multiorgan damage.
 SARS-CoV-2 infection may need different treatment approaches, including antiviral, oxygen therapy, anticoagulation and/or immunomodulatory treatment at different stages of the disease.UnchangedSARS-CoV-2 infection may need different treatment approaches, including antiviral, oxygen therapy, anticoagulation and/or immunomodulatory treatment at different stages of the disease.
Points to consider
 In non-hospitalised patients with SARS-CoV-2 infection there is currently no evidence to support the initiation of immunomodulatory therapy (LoE 2/3/4).UnchangedIn non-hospitalised patients with SARS-CoV-2 infection there is currently no evidence to support the initiation of immunomodulatory therapy (LoE 2/3/4).
 In hospitalised patients with SARS-CoV-
 2 infection that do not need oxygen therapy there is currently no evidence to support the initiation of immunomodulatory therapy to treat their COVID-19 (LoE 2/3/4).
UnchangedIn hospitalised patients with SARS-CoV-2 infection that do not need oxygen therapy there is currently no evidence to support the initiation of immunomodulatory therapy to treat their COVID-19 (LoE 2/3/4).
 Hydroxychloroquine should be avoided for treating any stage of SARS-CoV-2 infection since it does not provide any additional benefit to the standard of care, and could worsen the prognosis in more severe patients particularly if coprescribed with azithromycin (LoE 2).UnchangedHydroxychloroquine should be avoided for treating any stage of SARS-CoV-2 infection since it does not provide any additional benefit to the standard of care, and could worsen the prognosis in more severe patients particularly if coprescribed with azithromycin (LoE 2).
 In patients with COVID-19 requiring supplemental oxygen, non-invasive or mechanical ventilation, systemic glucocorticoids should be used since they can decrease mortality; most evidence concerns the use of dexamethasone (LoE 2/3).UnchangedIn patients with COVID-19 requiring supplemental oxygen, non-invasive or mechanical ventilation, systemic glucocorticoids should be used since they can decrease mortality; most evidence concerns the use of dexamethasone (LoE 2/3).
 In patients with COVID-19 requiring supplemental oxygen, non-invasive or mechanical ventilation combination of glucocorticoids and tocilizumab should be considered since it reduces disease progression and mortality (LoE 2). More data are needed to fully appreciate the effect of other IL-6R inhibitors (LoE 2/3).ModifiedAn evolving RCT landscape cannot yet allow formal recommendation of the routine use of tocilizumab in patients with COVID-19 requiring oxygen therapy, non-invasive or invasive ventilation (LoE 2).
 In COVID-19 there is no robust evidence to support the use of anakinra at any disease stage (LoE 2/4).ModifiesIn COVID-19 there is no robust evidence to support the use of anakinra or canakinumab at any disease stage (LoE 2).
 In COVID-19 there is no robust evidence to support the use of low-dose colchicine at any disease stage (LoE 2)NewNot applicable
 In patients with COVID-19 requiring oxygen therapy, non-invasive ventilation or high-flow oxygen, the combination of glucocorticoids and baricitinib or tofacitinib could be considered since it might decrease disease progression and mortality (LoE 2).ModifiedIn patients with COVID-19 requiring non-invasive ventilation or high-flow oxygen, the combination of remdesivir plus baricitinib could be considered since it can decrease time to recovery and accelerate improvement in clinical status (LoE 2).
 An evolving RCT landscape cannot yet allow formal recommendation of the use of GM-CSF inhibitors (mavrilimumab, otilimab, lenzilumab) in COVID-19 (LoE 2)NewNot applicable
 In patients without hypogammaglobulinaemia and with symptom onset >5 days there is robust evidence against the use of convalescent plasma (LoE 2)NewNot applicable
 In patients at risk of severe COVID-19 course, symptom onset <5 days or still seronegative, monoclonal antibodies against antispike protein should be considered (LoE 2)NewNot applicable
 In patients with COVID-19 there is currently insufficient evidence to recommend the use of other immunomodulatory drugs, including interferon alpha, interferon beta, interferon kappa, interferon lambda, leflunomide, non-SARS CoV-2 IVIg (LoE 2), eculizumab and cyclosporine (LoE 3)ModifiedIn COVID-19 there is currently insufficient evidence to recommend the use of other immunomodulators, including ruxolitinib, intravenous immunoglobin, convalescent plasma therapy except in Ig-deficient patients, interferon kappa, interferon beta, leflunomide, colchicine (LoE 2), sarilumab, lenzilumab, eculizumab, cyclosporine, interferon alpha (LoE 3), canakinumab (LoE 4).
  • GM-CSF, Granulocyte-Macrophage Colony-Stimulating Factor; IL-6R, Interleukin-6 receptor; LoE, lovel of evidence; ; RCT, randomised controlled trial.