TABLE 4.

Immunotherapy in clinical trials of COVID‐19 treatment

Study	Drug	Mechanism (s)	Medical indication
1. Monoclonal antibodies
N = 9 N = 1 N = 1	Tocilizumab Tocilizumab + Pembrolizumab Tocilizumab + Favipiravir	IL6R antagonist Anti‐PD‐1 humanized IgG4 Anti‐viral	Patients with COVID‐19 pneumonia and acute hypoxic respiratory failure and systemic cytokine release syndrome Adult patients with COVID‐19 pneumonia and bad prognostic factors who are nonresponsive to frontline therapy within 48 hours from treatment initiation Patient with coronavirus disease 2019
N = 1	Anti‐Human C5 Therapeutic Antibody (IFX‐1)	Anti‐human complement factor C5a	Severe COVID‐19 pneumonia
N = 3	Sarilumab	IL6R antagonist	Adult patients hospitalized with severe or critical COVID‐19
N = 1	Meplazumab	Humanized anti‐CD147 antibody	Patients with 2019‐nCoVs infection pneumonia
N = 1	Anti‐GM‐CSF Monoclonal Antibody (TJ003234)	Anti‐GM‐CSF monoclonal antibody	Subjects with severe COVID‐19 under supportive care, and to assess the effect of the drug on the levels of cytokines
N = 2	Bevacizumab	Anti VEGF recombinant humanized monoclonal antibody	Severe and critical COVID‐19 patients
Total = 19
2.Janus kinase inhibitors
N = 2	Baricitinib	Anti‐Janus kinase inhibitor (anti‐JAK) acting against JAK1 and JAK2 Capable to reduce or interrupt the passage of the virus into target cells, and to inhibit the JAK1‐ and JAK2‐mediated cytokine release May lower the hyperinflammation caused by the virus, then, prevent damage to the lungs and possibly other organs	Patients with mild to moderate COVID‐19 infection Patients with COVID‐19
N = 1	Tofacitinib	JAK1/3 inhibitor and could mitigate alveolar inflammation by blocking IL‐6 signal	Patients with early‐onset SARS‐CoV2 interstitial pneumonia
N = 4	Ruxolitinib	Inhibits the protein kinase activities of Jak1/2 which is responsible for proinflammatory signals such as IL‐6 Immunomodulator and decreased the cytotoxic T lymphocytes and increasing the Treg cells	Patients with severe/very severe COVID‐19 illness Patients with severe acute respiratory syndrome caused by COVID‐19
Total = 7
3. Immunosuppressants
3.1 Glucocorticoids
N = 2	Dexamethasone	The potent anti‐inflammatory and antifibrotic properties	Pulmonary and systemic damage in ARDS patients
N = 4	Methylprednisolone		Severe acute respiratory failure
N = 1	Methylprednisolone vs. Siltuximab	IL6R antagonist	Hospitalized patients with pneumonia
N = 1	Methylprednisolone +Tacrolimus	Tacrolimus: inhibit both pro‐inflammatory cytokines and, also, human coronavirus SARS‐Cov replication	Severe lung injury
N = 1	Levamisole with Inhaler Budesonide/Formoterol Lopinavir/Ritonavir + hydoxychloroquine	Levamisole: Immunostimulator Budesonide can suppress the immune reaction locally in the respiratory system	Positive COVID‐19 patients
N = 1	Ciclesonide metered dose inhaler Ciclesonide metered dose inhaler and hydroxychloroquine	Eradicates SARS‐CoV‐2 from respiratory tract earlier in patients with mild COVID‐19	Adults with mild COVID‐19
Total = 10
3.2 Other immunosuppressive drugs
N = 1	CD24Fc human IgG Fc fusion protein	CD24 is an innate checkpoint against the inflammatory response to tissue injuries	Hospitalized adult subjects who are diagnosed with severe COVID 19
N = 1	Fingolimod	Sphingosine‐1‐phosphate receptor regulators	Severe patients with SARS‐CoV‐2 pneumonia to prevent ARDS development
N = 1	Sirolimus		Hospitalized patients with COVID‐19 pneumonia
N = 2	Thalidomide	Anti‐inflammatory, anti‐fibrotic, anti‐angiogenesis, and immune regulation effects	Pneumonia patients with new coronavirus (COVID‐19) pneumonia Severe COVID‐19 Patient
N = 1	PD‐1 blocking antibody + Thymosin	Blocking PD‐1 could prevent T cell death, regulate cytokine production, reduce organ dysfunction and reduce death in sepsis in animal models Thymosin: regulate cellular immunity in sepsis patients	Patients with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection
N = 1	Anakinra or tocilizumab	Anakinra: IL‐1R antagonist Tocilizumab: IL‐6R antagonist	In case of diagnosis of macrophage activation syndrome (MAS) treatment with anakinra In case of diagnosis of immune dysregulation treatment with tocilizumab
N = 1	Anakinra or emapalumab	Anakinra: IL‐1 receptor antagonist Emapalumab: Anti‐interferon gamma (Anti‐IFNγ) monoclonal antibody	Patients with COVID‐19 infection that have hyper‐inflammation and respiratory distress
N = 1	Tocilizumab Tocilizumab + Anakinra Siltuximab Siltuximab + Anakinra	IL‐6R antagonist IL‐6R antagonist+ IL‐1R antagonist IL‐6R antagonist IL‐6R antagonist+ IL‐1R antagonist	Patients with COVID‐19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome
N = 1	Anakinra	Blocks IL‐1α and IL‐1β	Adult patients hospitalized with COVID‐19 either diagnosed with moderate or severe pneumonia
N = 10
4. Immunoglobulins
N = 1	Intravenous Immunoglobulin	Provides passive immunity and anti‐inflammatory, the immunomodulatory effect	Patient with severe 2019‐nCoV infected pneumonia
N = 1	Immunoglobulin of cured patients		Acute severe 2019‐nCoV pneumonia
Total = 2
5. Interferons
N = 1	Recombinant human interferon α1β	Inhibits MERS‐CoV and closely related coronavirus severe acute respiratory syndrome (SARS)‐CoV	Patients with a new type of coronavirus infection
N = 1	Peginterferon Lambda‐1a		Patients with uncomplicated COVID‐19 disease
N = 1	Lopinavir/ritonavir, Ribavirin and INF Beta 1b combination versus Lopinavir/ritonavir alone		Patients with 2019‐n‐CoV infection
5.1 Inhaler IFN
N = 1	Recombinant human interferon alpha‐1b (nasal drop) or Recombinant humaninterferon‐alpha‐1b + Thymosin alpha 1 (s.c.)		In medical staff in the epidemic area
N = 1	Umifenovir (Abidol) hydrochloride or Umifenovir (Abidol) hydrochloride+Interferon (PegIFN‐α‐2b) atomization		Patient with 2019‐nCoV pneumonia
N = 1	Danoprevir+ritonavir with or without interferon nebulization		Patient with SARS‐CoV‐2 infection
Total = 6