Table 1:

Potential treatments

Therapy	Target	Mechanism	Reference
Monalizumab	NKG2A	As upregulation of NKG2A is associated with reduced lymphocyte to neutrophil balance, inhibition of NKG2A may improve lymphocyte numbers and therefore virus control.	van Hall et al. [13]   Antonioli et al. [14]
Sarilumab and Tocilizumab	IL-6	Higher blood concentrations of IL-6 were reported to be predictive of fatal outcome in COVID-19 patients therefore blocking IL-6 using antibodies may be effective.	Ruan et al. [15]   Guaraldi et al. [16]   Tomasiewicz et al. [17]   ClinicalTrials.gov Identifier: NCT04320615 (no statistically significant differences in ventilator-free days between the drug and placebo)
Adalimumab	TNF	Proven to reduce inflammation in many diseases and thus promising for severe COVID-19	Mahase [18]
Anakinra	IL-1 receptor (agonist)	Competitively inhibits IL-1 binding to the IL-1 type I receptor. Increased IL-1 concentrations have been reported in COVID-19 patients. IL-1a and IL-1b have been implicated in severe COVID-19 disease.	Giamarellos-Bourboulis et al. [19]   Huang C et al. [20]   Ong et al. [21]   Huet et al. [22]   Cavalli et al. [23]
IFN I and IFN II targeting drugs	IFN blocking	Late IFN responses are associated with hyperinflammation in severe COVID-19 disease. Due to potential off-target effects, blocking IFN I responses may be more effective than blocking IFN II responses.	Hemann et al. [24]   Sallard et al. [25]   Prokunina-Olsson et al. [26]
IFN I supplementation	IFN-β,   IFN-α2b,   IFN-α1b	Severe COVID-19 patients have shown reduced IFN I responses. IFN I supplementation reduced the duration of inflammatory markers in mild disease and prevented COVID-19 infection in highly exposed individuals.	Hung et al. [27]   Zhou et al. [28]   Meng et al. [29] (prevented infection in highly exposed individuals)
Baricitinib, Ruxolitinib	JAK 1 and JAK 2	May prevent virus entry into cells as well as beneficial anti-inflammatory activity. Inhibits NK cell activity, DC development and function which could suppress antigen-specific T cell responses.	Stebbing et al. [30]   Elli et al. [31]
Gimsilumab, mavrilimumab, Sargramostim (Human recombinant GM-CSF)	GM-CSF replacement	GM-CSF promotes proinflammatory responses. GM-CSF expression increases T helper 1 cells and monocytes in COVID-19 patients, particularly those in intensive care. GM-CSF also plays a role in alveolar macrophage physiology and might protect against viral related injury in early stages.	Zhou et al. [32]   De Luca et al. [33]   Clinicaltrials.gov identifier: NCT 04326920
Monoclonal antibodies	Immune checkpoint blockade e.g. PD-1, NKG2A and CD39.	Immune checkpoint therapy, approved for melanoma, has been shown to upregulate effective immune responses by blocking inhibitory markers on immune cells and infected cells. In COVID-19 disease it was shown that NK cell responses could be enhanced using immune checkpoint blockade.	Demaria et al. [34]
Dexamethasone	Glucocorticoid receptor	Increases anti-inflammatory genes (e.g. IκB-α), reduces pro-inflammatory genes (e.g. COX2)	Johnson and Vinetz [35]
Hydrocortisone	Glucocorticoid receptor	Increases anti-inflammatory genes (e.g. IκB-α), reduces pro-inflammatory genes (e.g. COX2)	Mahase [36]
Anti-coagulants	Coagulation cascade	E.g. Warfarin, apixaban, betrixaban, dabigatran, edoxaban and rivaroxaban	Nadkarni et al. [37]
Ecluzimab	C5a	Inactivates C5a, removing anaphylatoxin activity	Cugno et al. [10]   Campbell and Kahwash [12]
High-dose IV immunoglobulin	C3b	Sequesters C3b stops both MAC activity and C5a production	Cugno et al. [10]