Overarching principles and points to consider on the use of immunomodulatory treatment in COVID-19, with levels of evidence (LoE) and levels of agreement (LoA)
| LoA mean (SD); % of votes ≥8/10 | |
| Overarching principles | |
| The phenotype of SARS-CoV-2 infection is heterogeneous ranging from asymptomatic to lethal disease due to multiorgan damage. | 9.92 (0.3); 100 |
| SARS-CoV-2 infection may need different treatment approaches, including antiviral, oxygen therapy, anticoagulation and/or immunomodulatory treatment at different stages of the disease. | 9.92 (0.3); 100 |
| 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). | 9.58 (1.0); 96 |
| 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). | 9.04 (1.6); 88 |
| 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). | 9.92 (0.3) 100 |
| 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). | 9.75 (0.4) 100 |
| 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). | 9.17 (1.7) 87.5 |
| In COVID-19 there is no robust evidence to support the use of anakinra or canakinumab at any disease stage (LoE 2). | 9.16 (0.9) 96 |
| In COVID-19 there is no robust evidence to support the use of low-dose colchicine at any disease stage (LoE 2) | 9.5 (0.9) 96 |
| 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). | 8.92 (1.4) 87.5 |
| An evolving RCT landscape cannot yet allow formal recommendation of the use of GM-CSF inhibitors (mavrilimumab, otilimab, lenzilumab) in COVID-19 (LoE 2) | 9.13 (0.9) 92 |
| In patients without hypogammaglobulinaemia and with symptom onset >5 days there is robust evidence against the use of convalescent plasma (LoE 2) | 9.04 (1.9) 83.3 |
| In patients at risk of severe COVID-19 course, symptom onset <5 days or still seronegative, monoclonal antibodies against SARS-CoV-2 spike protein should be considered (LoE 2) | 9.29 (1.1) 92 |
| 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) | 9.79 (0.4) 100 |
GM-CSF, Granulocyte-Macrophage Colony-Stimulating Factor; IL-6R, Interleukin-6 receptor; RCT, randomised controlled trial.