Efficacy of the current investigational drugs for the treatment of COVID-19: a scoping review

Figures & data

Table 1. Quality assessment of the included studies.

Study ID	Score	Rate
Cao et al. [13]	8	Good
Tang et al. [14]	8	Good
Chen et al. [16]	9	Good
Cai et al. [18]	8	Good
Gautret et al. [5]	6	Good
Chen et al. [17]	10	Good
Runan et al. [15]	4	Poor
Leng et al. [11]	6	Poor
Ye et al. [12]	3	Poor
Jun et al. [19]	9	Good
Tang et al. [22]	8	Good
Jun et al. [21]	6	Good
Zha et al. [20]	8	Good
Wang et al. [28]	6	Good
Grein et al. [26]	7	Fair
Gautret et al. [27]	7	Good
Liu et al. [2]	4	Poor
Wang et al. [1]	6	Good
Dan et al. [33]	2	Poor
Shi et al. [34]	5	Fair
Luo et al. [31]	6	Poor
Zheng et al. [23]	4	Poor
Duan et al. [25]	4	Poor
Sun et al. [24]	7	Fair
Zhang et al. [29]	5	Poor
Shen et al. [30]	7	Fair
Chen et al. [32]	7	Fair
Wang et al. [35]	4	Poor

Figure 1. Flowchart describing the literature search process.

Table 2. Summary of the included studies.

Study ID	Study design	Population	Intervention	Sample size	Duration of treatment	Main findings
Cao et al. [13]	Randomized open-label clinical trial	Patients with severe COVID-19 infection	Lopinavir–ritonavir with standard care against standard care alone	199	28 d	Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. In hospitalized adult patients with severe COVID-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care
Tang et al. [14]	Randomized open-label clinical trial	Patients with COVID-19 infection	Hydroxychloroquine With standard care	150	28 d	The administration of hydroxychloroquine did not result in a higher negative conversion rate but it results in more alleviation of clinical symptoms of the patients
Chen et al. [15]	Randomized open-label clinical trial	Patients infected with COVID-19	Hydroxychloroquine and standard treatment	62	24 d	Hydroxychloroquine could significantly shorten time to clinical recovery and promote the absorption of pneumonia
Cai et al. [18]	Randomized open-label clinical trial	Patients infected with COVID-19	Favipiravir against Lopinavir and ritonavir with IFN-α by aerosol inhalation	80	15 d	Favipiravir showed a better treatment effects in terms of disease progression and viral clearance than lopinavir and ritonavir
Gautret et al. [5]	Non-randomized open-label clinical trial	Patients with COVID-19 infection	Hydroxychloroquine and azithromycin, was added to treatment depending on their clinical presentation	36	16 d	Hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance and its effect is reinforced by azithromycin
Chen et al. [17]	Pilot clinical trial	Patients with COVID-19 infection	Hydroxychloroquine sulphate treatment against control group	60	7 d	Moderate patients prognosis was good and future studies a better endpoint
Runan et al. [15]	Pilot clinical trial	Patients COVID-19 pneumonia	Triple treatment group: interferon a-2b, arbidol and, lopinavir/ritonavir against double treatment group: interferon a-2b and lopinavir/ritonavir	237	24 d	The earlier the three-drug combination antiviral treatment time, the faster the viral nucleic acid negative time
Leng et al. [11]	Pilot clinical trial	Patients with COVID-19 infection with no improvement signs were observed under the standard treatments.	Mesenchymal stem cells (MSCs) transplantation against placebo	10	25 d	The pulmonary function and symptoms of all patients were significantly improved in two days after MSC transplantation. Treatment was safe and effective
Ye et al. [12]	Pilot clinical trial	Patients with COVID-19 infection.	Lopinavir/ritonavir with adjuvant drugs against control patients that received adjuvant drugs only	47	14 d	Combination of LPV/ritonavir and adjuvant drugs has a more evident therapeutic effect than pneumonia-associated adjuvant drugs alone
Jun et al. [19]	Pilot clinical trial	Patients with common COVID-19 infection	Hydroxychloroquine sulphate along with standard treatment	30	20 d	It is difficult to determine the effect of the treatment plan in the study of the main endpoint of the virus conversion rate and the critical rate
Tang et al. [20]	Cohort study (retrospective)	Patients with coagulopathy combined with severe COVID-19 infection	Anticoagulant therapy using low molecular weight heparin	449	7–28 d	Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer
Jun et al. [21]	Cohort study (retrospective)	Patients with COVID-19 infection	First group: interferon α2b, lopinavir and ritonavir against Second group that received interferon α2b and abidor, third group: interferon α2b and any antiviral drugs	134	17 d	It has not been found that lopinavir ritonavir and abidor have the effect of improving symptoms or shortening the negative time of viral nucleic acid in respiratory specimens
Zha et al. [20]	Cohort study (retrospective)	Patients infected with the acute COVID-19 infection	Corticosteroid with standard care	31	26 d	No association between corticosteroid therapy and outcomes in patients without acute respiratory distress syndrome
Wang et al. [28]	Case series (retrospective)	Patients, two mild and two severe COVID-19 pneumonia	Lopinavir/ritonavir (Kaletra^®), arbidol and Shufeng Jiedu Capsule (SFJDC), a traditional Chinese medicine	4	6–15 d	All patients were improved. The efficacy of antiviral treatment including lopinavir/ritonavir, arbidol and SFJDC warrants further verification in future study
Grein et al. [26]	Case series (retrospective)	Patients with COVID-19	Remdesivir, 200 mg on day one then 100 mg daily in the following nine days	61	Median 18 d	Randomized clinical trials are required to measure the efficacy of remdesivir
Gautret et al. [27]	Case series (retrospective)	Patients with COVID-19 infection	Hydroxychloroquine and azithromycin combination	80	6–17 d	Hydroxychloroquine associated with azithromycin is effective in the treatment of COVID-19 infection
Liu et al. [2]	Case series (retrospective)	Patients with COVID-19 infection	Immunoglobulin G, corticosteroids with standard care	137	57 d	Systemic corticosteroid treatment did not show significant benefits
Wang et al. [1]	Case series (retrospective)	Patients with COVID-19 pneumonia	Arbidol with standard care	69	14 d	Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate
Dan et al. [33]	Case series (retrospective)	Patients mild and severe COVID-19 pneumonia	Respiratory support, lopinavir, ritonavir, and abidor, moxifloxacin, cefoperazone, linezolid, imipenem, cilastatin, moxifloxacin, glucocorticoids	30	–	Most of the patients were improved
Shi et al. [34]	Case series (retrospective)	Patients with mild or severe COVID-19 pneumonia	Abidor, peramivir, ribavirin, oseltamivir phosphate, glucocorticoid therapy, immunoglobulin and albumin therapy	109	–	Treatment can improve prognosis and reduce mortality
Luo et al. [31]	Case series (retrospective)	Patients with moderate and severe COVID-19 pneumonia	Tocilizumab therapy	15	39 d	Tocilizumab appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. For critically ill patients with elevated IL-6, repeated dose of the TCZ is recommended
Zheng et al. [23]	Case series (retrospective)	Paediatric patients with COVID-19 infection	Interferon, oseltamivir, cefoperazone/sulbactam, interferon, mechanical ventilation, systematic corticosteroids and intravenous immunoglobulin	25	–	The symptoms on admission were alleviated 96% of the patients
Duan et al. [25]	Case series (retrospective)	Paediatric patients with mild/asymptomatic COVID-19 pneumonia	Interferon, oseltamivir, ribavirin, lopinavir/ritonavir, gamma globulin antibiotics, Chinese medicine	31	–	Given general treatment, the overall prognosis is good in the near future
Sun et al. [24]	Case series (retrospective)	Severe or critically ill paediatric patients with COVID-19 pneumonia	Symptomatic treatment and respiratory support, (virazole, oseltamivir and interferon) to all patients. Depending on patients’ conditions, intravenous glucocorticoids and immunoglobulin, traditional Chinese medicine was given	8	32 d	Most of the patients were improved and discharged
Zhang et al. [29]	Case series (prospective)	Critically ill patients with COVID-19	Convalescent plasma transfusion with standard care	4	18–46 d	Plasma reduce the relative risk of mortality of patients
Shen et al. [30]	Case series (prospective)	Critically ill patients of COVID 19 infection with ARDS	Convalescent Plasma transfusion with standard care	5	10–22 d	Convalescent plasma containing neutralizing antibody was followed by improvement in the clinical status
Chen et al. [32]	Case series (prospective)	Patients with pulmonary fibrosis related to acute respiratory distress syndrome due to COVID-19	Lung transplantation	3	30 d	Lung transplantation can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis
Wang et al. [35]	Case series (prospective)	Patients with COVID-19 infection	Tissue plasminogen activator (tPA) treatment with standard care	3	–	The observed improvements were transient and lost over time after completion of their tPA infusion. Further studies needed to confirm the results

SFJDC: Shufeng Jiedu Capsule; TCZ: tocilizumab; tPA: tissue plasminogen activator; ARD: acute respiratory distress syndrome.

Table 3. Baseline characteristics of the included studies.

Study ID	Location	Group	Sample size	Age Median (IQR) Mean ± SD Range	Gender Male (%)	Primary clinical diagnosis
						Fever %	Cough%	Dyspnoea	WBC (10^9/L)	Lymph (10^9/L)	CRP (mg/dl)	IL-6 (ng/L)	Ct values	Chest CT score
Cao et al. [13]	China	Treatment	99	58.0 (50.0–68.0)	61.6%	89%	–	−	7.3 (5.3–9.6)	0.8 (0.6–1.4)	–	–	–	–
		Control	100	58.0 (48.0–68.0)	59.0%	93%	–	–	6.9 (4.9–9.1)	0.9 (0.5–1.2)	–	–	–	–
Tang et al. [14]	China	Treatment	75	48.0 ± 14.1	56.0%	59.70%	51.50%	22.10%	5.59 ± 1.90	1.46 ± 0.60	9.9 ± 13.30	12.90 ± 36.30	–	–
		Control	75	44.1 ± 15.0	53.3%	53.30%	38.20%	5.90%	5.60 ± 1.80	1.60 ± 0.50	7.4 ± 12.80	8.90 ± 13.00	–	–
Chen et al. [16]	China	Treatment	31	44.1 ± 16.1	45.2%	70.90%	70.10%		–	–	–	–	–	–
		Control	31	45.2 ± 14.7	48.3%	54.80%	48.40%	–	–	–	–	–	–	–
Cai et al [18]	China	Treatment	35	43 (35.5–59)	40.0%	62.9%	34.3%	–	8.1 (3.8–6.6)	1.5 (1.0–1.8)	15.0 (3.0–19.2)	14.0 (3.5–11.0)	30.7 (21.2–37.0)	12(4.0–14.0)
		Control	45	49 (36–61)	46.7%	82.2%	22.2%	–	4.3 (3.4–4.9)	1.2 (0.9–1.4)	21.4 (5.0–23.2)	12.9 (5.3–16.8)	29 (18.8–38.0)	10 (4.5–13.5)
Gautret et al. [5]	France	Treatment	20	51.2 ± 18.7	45.0%	–	–	–	–	–	–	–	–	–
		Control	16	37.3 ± 24.0	37.5%	–	–	–	–	–	–	–	–	–
Chen et al. [17]	China	Treatment	30	50.5 ± 3.8	60.0%	60.0%	–	–	5.20 (3.90–6.70)	1.11 ± 0.43	–	–	–	–
		Control	30	46.7 ± 3.6	40.0%	86.70%	–	−	4.90 (4.50–7.40)	1.18 ± 0.55	–	–	–	–
Runan et al. [15]	China	Treatment	196	45.7 ± 17	53.1%	–	–	−	5.1 (4.1–6.4.0)	−	11.8 (3.1–25.8)	–	–	–
		Control	41	45.1 ± 16.7	58.5%	–	−	4.2 (3.2–7.0)	−	8.1 (2.9–23.0)	–	–	–	–
Leng et al. [11]	China	Treatment	7	57.0 ± 7.70	57.1%	85.7%	71.5	71.4%	−	−	−	−	−	−
		Control	3	65.0 ± 16.47	0 %	33.3%	33.3	66.7%	−	−	−	−	−	−
Ye et al. [12]	China	Treatment	42	–	50.0 %	−	−	−	−	−	−	−	−	−
		Control	5	–	20.0%	−	−	−	−	−	−	−	−	−
Jun et al. [19]	China	Treatment	15	50.5 ± 3.8	60%	60%	–	−	1.11 ± 0.43	−	−	−	−	−
		Control	15	46.7 ± 3.6	80%	86.7%	–	−	1.18 ± 0.55	−	−	−	−	−
Tang et al. [22]	China	Survivors	315	63.7 ± 12.2	78.0%	−	−	−	−	−	−	−	−	−
		Non-survivors	134	68.7 ± 11.4	48.9%	−	−	−	−	−	−	−	−	−
Jun et al. [21]	China	Treatment	52	47 (35–60)	51.9%	92.3%	19.2%	1.9%	5.0 (3.7–5.66)	1.24 (0.93–1.56)	9.5 (0–26.8)	−	−	−
		Comparison	34	44 (34–62)	52.9%	91.1%	32.4%	0%	4.18 (3.44–5.19)	1.04 (0.72–1.33)	10.9 (4.0–25.2)	−	−	−
		control	48	55 (36–62)	50.0%	95.8%	22.9%	8.3%	5.09 (4.10–6.30)	1.23 (0.85–1.57)	19.5 (7.6 36.6)	−	−	−
Zha et al. [20]	China	Treatment	20	37 (27–52)	60%	70%	40%	5%	–	–	–	–	–	–
		Control	11	53 (36–57)	73%	100%	100%	27%	–	–	–	–	–	–
Wang et al. [28]	China	Treatment	4	44 (19–63)	75%	100%	75%	50%	−	6.17 (4.4–10.84)	–	–	–	50%
Grein et al. [26]	Data collected from different countries	Treatment	61	64 (48–71)	75%	–	–	–	–	–	–	–	–	–
Gautret et al. [27].	France	Treatment	80	52.5 (42–62)	52.5	15%	58.8%	–	–	–	−	–	23.6 ± 4.3	–
Liu et al. [2]	China	Treatment	137	57 (20–83)	44.5%	48.3%	48.2%	19%	43.8%	27.7%	83.9%	–	–	–
Wang et al. [1]	China	Treatment	69	42 (35–62)	46%	44.0%	55.0%	29.0%	3.82 (2.98–5.57)	1.15 (0.82–1.46)	13.2 (6.78–49)	8.54 (4.68–20.58)	9.0%	–
Dan et al. [33]	China	Treatment	30	43 (21–72)	60%	–	–	–	–	–	–	–	–	–
Shi et al. [34]	China	Treatment	109	52.5 ± 10.8	44%	95.5%	86.5%	21.3%	−	53.2%	79.8%	−	24.8%	–
Luo et al. [31]	China	Treatment	15	73 (62–80)	80%	–	–	–	–	–	–	–	–	–
Zheng et al. [23]	China	Treatment	25	3 (2–9)	56%	52.0%	44.0%	8.0%	6.2 (4.30–9.85)	2.19 (1.15–3.31)	14.5 (0.93–25.04)	−	68.0%	–
Duan et al. [25]	China	Treatment	31	7 (0.5–17)	–	65%	45%	–	−	6%	10%	–	–	–
Sun et al. [24]	China	Treatment	8	3 (0.6–15)	75%	75%	75%	–	−	8.10 (1.5–14.95)	25.8 (0.5 − 103)	10.07 (63.99–2.92)	–	–
Zhang et al. [29]	China	Treatment	4	57 (31–73)	50%	–	–	–	–	–	–	–	–	–
Shen et al. [30]	China	Treatment	5	54 (36–73)	60%	80%	–	–	–	−	130.62 (65–242.8)	−	25.52 (18.9–38.0)	–
Chen et al. [32]	China	Treatment	3	66 (58–73)	100%	–	–	−	–	0.56 (0.41–0.7)	–	–	–	–
Wang et al. [35]	China	Treatment	3	61 (49–75)	67%	100%	100%	67%	–	–	–	–	–	–

IQR: interquartile range; SD: standard range; WBCs: white blood cells; lymph: lymphocytes; CRP: C-reactive protein; IL-6: interleukin-6; CT: computed tomography.

Table

Drug	Nature	Mode of action	Ref.
Hydroxy chloroquine	Antimalarial drug	Inhibit viral replication	[5,14,16,17,27]
Favipiravir	Inhibitor of RNA polymerase	Inhibit RNA polymerase to inhibit the replication of viral RdRp gene	[41]
Immunoglobulin	Inhibitor of Fc receptor	Neutralize endogenous antibody especially for enteroviruses	[42,43]
Arbidol or umifenovir	Antiviral drug	Inhibit the fusion of haemagglutinin membrane	[1,12,21,23,28,44,45]
IFN-b1b	Cytokine	Inhibit mRNA synthesis and its translation to proteins	[46]
Remdesivir	Adenosine analogue	Inhibit viral replication through inhibition of RNA polymerase	[26,47,48]
Baloxavir marboxil	Cap-dependent endonuclease inhibitor	Inhibit viral Cap-dependant endonuclease	[49]
Lopinavir/ritonavir	Protease inhibitor	Inhibit the activity of 3CL^PRO and PL^PRO proteases of the COVID-19 virus	[17,28,29,50–52]
Nafamostat/mesilate	Serine protease and TMPRSS2-inhibitor	Inhibit coagulation, complement and kallikrein–kinin systems	[6]
Camostat/mesilate	TMPRSS2-inhibitor	Inhibit fusion and replication of COVID-19 virus	[53]
Jakotinib hydrochloride	JAK inhibitor	Inhibit AAK1 and JAK	[54]
Ruxolitinib	JAK inhibitor	Inhibit protein tyrosine kinases, JAK inflammation and cellular proliferation	[55]
Baricitinib	JAK inhibitor	Lowering COVID-19 endocytosis and inhibit JAK1/2 and AAK1	[56]
Meplazumab	Humanized multiple antibodies	Inhibit the activity of IL-5	[57]
Tocilizumab	IL-6 inhibitor	Has a role in the inhibition of cytokine syndrome	[31]
Corticosteroids	Glucocorticosteroid hormones	Cease inflammatory and fibrotic reactions	[2,6]

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