Current status of COVID-19 treatment: An opinion review

Table 1 Summary of the most investigated drugs for the treatment of coronavirus disease 2019

Therapeutic agent	Mechanism of action	Ongoing trials, n	Associations	Suggested dosage	Route of administration	Principal side effects	Ref.	NCT identifier
Hydroxychloroquine	Changes the pH of endosomes, prevents viral entry, transport and post-entry replication	224	Azithromycin, tocilizumab, lopinavir-ritonavir	200 mg BID or TID (10 d)	Oral-intravenous	Retinal toxicity, QT prolongation, nausea	[6-10]	NCT04315948
Chloroquine	Increases the endosomal pH interfering with the process of virus/cell fusion	225	Remdesivir, tocilizumab	2.5 g (3 d)	Oral-intravenous	Retinal toxicity, QT prolongation, nausea	[11]	NCT04303507
Convalescent plasma	Adaptive immunotherapy (neutralizing antibody tiers above 1:640)	129	Remdesivir, Interferon-alpha, oseltamivir, antibacterial and antifungal frugal drugs, methylprednisolone	200 ml single dose	Intravenous	Evanescent facial red spot	[37-41]	NCT04321421
Lopinavir/Ritonavir	Inhibition of the HIV protease/inhibition of CitP450-iso3A4 and augmented plasmatic concentration of lopinavir	67	Hydroxychloroquine, azithromycin, dexamethasone	200 mg/50 mg BID	Oral	Gastrointestinal upset, augmented plasmatic concentration of colchicine	[25-28]	NCT02735707
						And HGAM-CoA reductase inhibitors
Azithromycin	Prophylaxis of bacterial super-infection	59	Hydroxychloroquine, tocilizumab, atovaquone	500 mg	Oral-intravenous	QT prolongation	[19-24]	NCT04332107
Tocilizumab	Monoclonal antibody which targets the IL-6 receptor	50	lopinavir-ritonavir, remdesivir, chloroquine, hydroxychloroquine	Dosing according to weight range	Intravenous	Runny or stuffy nose, sinus pain, sore throat, headache, gastrointestinal upset, urinary tract infection	[30]	NCT04320615
Ivermectin	Suppression of SARS-CoV-2 viral replication in cell cultures (in vitro)	30	Hydroxychloroquine	600 mcg/kg	Oral	Tiredness, loss of energy, stomach pain, loss of appetite, nausea, vomiting, diarrhea, dizziness	[48]	NCT04381884
			Dutasteride
			Azithromycin
			Proxalutamide
Statin	Reduces chemokine release, adhesion molecules, and modulating T cell activity	23	Standard of care; colchicine + rosuvastatin	20 mg/d atorvastatin Rosuvastatin 40 mg/d or equivalent	Oral	rabdomiolisis	[12]	NCT04472611
Remdesivir	Nucleotide analogue that is incorporated into the nascent viral RNA chain resulting in its premature termination	20	Hydroxychloroquine, chloroquine, tocilizumab, convalescent plasma	200 mg 1st day – 100 mg (10 d)	Intravenous	Phlebitis, constipation, headache, ecchymosis, nausea, pain in extremities	[13-18]	NCT04292899
Methylprednisolone	Immunosuppression against cytokine storm	17	Siltuximab, tacrolimus	40 mg BID (5 d) - f 1-2 mg/kg/d (5-7 d)	Oral-intravenous	Headache, nausea, weight gain, excitement, infections	[35]	NCT04323592
Sarilumab	Monoclonal antibody which targets the IL-6 receptor	17	Not available	400 mg or 200mg single dose	Intravenous	Neutropenia, increased ALT, injection site redness, upper respiratory infections, nasal congestion, sore throat, urinary tract infections, thrombocytopenia	[29]	NCT04315298
Colchicine	Non-selective inhibitor of NLRP3 inflammasome, inhibitor of microtubule polymerization and leukocyte infiltration	17	Not available	0.5 mg per os (BID) for 3 d - then once daily for the last 27 d	Oral-intravenous	Gastrointestinal upset, low blood cells count and rhabdomyolysis	[33-34]	NCT04322682
Heparin	Inhibition of Xa factor and thrombin	15	Methylprednisolone	Dosed to target activated partial thromboplastin time (aPTT) between 1.5-2.0 times the normal value	Subcutaneous injection	Reduced creatinine clearance	[45]	NCT04485429
Anakinra	Monoclonal antibody which targets the IL-1 receptor	11	Siltuximab or tocilizumab (single i.v. injection)	1 injection a day (max 28 d)	Subcutaneous injection	Gastrointestinal upset, headache, joint pain, flu symptoms, redness-bruising-pain in the injection site	[30,31]	NCT04330638
Dexamethasone	Immunosuppression against cytokine storm	10	Not available	20 mg/d (5 d) then 10 mg/d (5 d)	Intravenous	Headache, weight gain, excitement, infections	[36]	NCT04325061
Enoxaparin	Inhibition of Xa factor and thrombin	5	Not available	4000 UI/d or 100 UI/kg	Subcutaneous injection	Skin irritation in injection site, bleeding, heparin-induced thrombocytopenia, fatigue, fever	[45]	NCT04367831
Eculizumab	Monoclonal antibody which targets C5 inhibiting its cleavage in C5a and C5b	3	Hydroxychloroquine, lopinavir-ritonavir, ceftriaxone, vitamin C	3600 mg/wk (8-22 wk)	Intravenous	Fever, headache, nausea and vomiting, body aches, confusion, increased sensitivity to light, stiffness	[32]	NCT04288713
Vitamin C	Antioxidant, increases the synthesis of norepinephrine and vasopressin, attenuate increases in cytokine levels	3	All mentioned drugs	12 g/12 h (7 d) or 50 mg/kg/6 h (4 d)	Oral-intravenous	Gastrointestinal upset	[42-44]	NCT04264533

In this table are the most utilized and investigated drugs for the treatment of coronavirus disease 2019. It provides the name of the therapeutic agent, mechanism of action, number of ongoing trials, drug association if available, suggested dosage and maximum period of time the drug should be administered, route of administration, principal side effects, a reference on the drug, and an example of randomized clinical trial (RCT) identified by the national clinical trial number. Drugs investigated in less than three RCTs have been excluded. BID: Bis in die; IL-1: Interleukin 1; NCT: National clinical trial; RCT: Randomized clinical trial; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; TID: Tris in die.