Evaluation of botanicals as potential COVID-19 symptoms terminator

Table 2 Human clinical studies showing the effect of plants on respiratory infections

Plant	Disease state	Participant	Dosage	Study design	Results
Aged garlic extract[107]	Cold andflu illness	120 healthy subjects, 2 groups (21-50 yr)	4 capsules/d (2.56 g); 90 d	Double-blind, randomized, placebo-controlled parallel intervention	Increase in γδ-T cell and NK cell. Reduction in cold and flu severity; decrease in symptom days
E. purpurea and E. angustifolia root[108]	New-onset common cold	719 patients, 4 parallel groups (12-80 yr)	First 24 h: Equivalent of 10.2 g of root. Next 4 d: 5.1 g	Randomized, controlled trial	Disease duration and severity are not statistically significantly changed
Echinacea purpurea alcohol extract (Echinaforce®)[109]	Common cold	755 healthy subjects, 2 groups (≥ 18 yr)	Illness prevention: 3 × 0.9 mL. Acute stages of colds: 5 × 0.9 mL	Randomized, double-blind, placebo-controlled trial	Reduction of the total number of cold episodes, cumulated episode days, and pain-killer medicated episodes. Inhibited virally confirmed colds and especially prevented enveloped virus infections. Maximal effects on recurrent infections. Prophylactic intake of E. purpurea over a period of 4 mo to provide a positive risk/benefit ratio
Echinacea root extract[110]	Respiratory symptoms	175 adults, 2 groups (18–65 yr)	Tablets: 112.5 mg E. purpurea 6:1 extract (equivalent to 675 mg dry root) and 150 mg E. angustifolia 4:1 extract (equivalent to 600 mg dry root) 3 × 1 tablet, if required: 3 × 2 tablets	Randomized, double blind, placebo-controlled trial	Lower respiratory symptom scores. Preventive effect against the development of respiratory symptoms during travel, including long-haul flights
Green tea catechins and theanine[111]	Influenza	200 healthcare workers, 2 groups	Capsules: Green tea catechins (378 mg/d) and theanine (210 mg/d). 5 m	Randomized, double-blind, placebo-controlled trial	Lower incidence of influenza infection in the catechin/theanine group
Ivy leaf extract[112]	Acute or chronic bronchial inflammatory disease	9657 patients (5181 children)	Ivy leaves extract [drug-to-extract ratio: 5-7.5:1; extraction solvent: ethanol 30% (w/w)]. 0–5 yr: 3 × 2.5 mL; 6–12 yr: 3 × 5 mL; 12 yr and adults: 3 × 5–7.5 mL. 7 d	Prospective, open, multicenter post marketing study	Healing or improvement in 95% of symptoms. Effective and well tolerated
Ivy extract (Hedelix®)[113]	Acute respiratory catarrh and/or chronic recidivating inflammatory bronchial disease	268 children, 2 groups (syrup and drops groups) (0-12 yr)	0-1 yr: 1 × 2.5 mL syrup or 3 × 5 drops, 1-4 yr: 3 × 2.5 mL syrup or 3 × 16 drops, 4-10 yr: 4 × 2.5 mL syrup or 3 × 21 drops, 10-12 yr: 3 × 5 mL syrup or 3 × 31 drops. 14 d	Independent open, non-interventional studies	Effective and safe treatment of cough. Reduction in symptoms (especially rhinitis, cough and viscous mucus)
Ivy leaves dry extract (Prospan ®)[114]	Bronchial asthma	30 children (suffering from partial or uncontrolled mild persistent allergic asthma despite long-term treatment with 400 μg budesonide equivalent), 2 groups (6–11 yr)	2 × 5 mL (corresponding to 70 mg extract) 28–30 d	Randomized, double blind, placebo-controlled, cross-over study	Improvement of MEF75-25, MEF25 and VC
Korean red ginseng extract[115]	Influenza-like illness	100 healthy adults, 2 groups (30-70 yr)	9 capsules/d. 3 m	Placebo-controlled trial	Reduced the incidence of influenza-like illness
Modified ginseng extracts (GS-3K8 and GINST)[116]	Acute respiratory illness	45 healthy applicants, 3 groups (39-65 yr)	Capsules: 500 mg; 6 capsules/d; 8 wk	Randomized, double-blind, placebo-controlled pilot study	Reduction in acute respiratory illness development and symptom duration
Panax quinquefolius extract CVT-E002[117]	Acute respiratory illness and Chronic Lymphocytic Leukemia	293 patients, 2 groups (≥ 18 yr)	2 × 200 mg extract. 3 m	Randomized, double-blind, placebo-controlled study	Reduction intense acute respiratory illness and moderately-severe sore throat. Increased antibody responses.
Panax ginseng[118]	Chronic obstructive pulmonary disease	14 participants, 2 groups (57–73 yr)	2 × 200 mg 4 wk	Clinical trial protocol and pilot study	One participant in P. ginseng group reported events of sore throat, cough and fever
Panax ginseng root extract[119]	Chronic obstructive pulmonary disease	168 participants, 2 groups	2 × 100 mg capsules. 24 wk	Randomized, multi-center, double-blind, placebo controlled	Reduction in symptoms
Pelargonium sidoides extract EPs® 7630[120]	Chronic obstructive pulmonary disease	199 adults, 2 groups (18 yr and older)	30 drops. 24 wk	Randomized, double-blind, placebo-controlled, parallel group trial	Improvement in HRQoL (health-related quality-of-life) and PRO (Patient-reported outcomes)
Pelargonium sidoides extract EPs® 7630[121]	Acute bronchitis	220 patients (1-18 yr)	1-6 yr: 3 × 10 drops; 6–12 yr: 3 × 20 drops; 12-18 yr: 3 × 30 drops; 7 d	Randomized, double-blind, placebo-controlled clinical trial	Reduction in the total score of bronchitis-specific symptoms (especially cough and rales at auscultation)
Pelargonium sidoides extract EPs® 7630[122]	Upper respiratory tract infections	28 children with a diagnosed transient hypogammaglobulinemia of infancy (1-5 yr)	3 × 10 drops; 7 d	Randomized, placebo controlled, prospective, monocentric pilot study	Increased appetite. Reduction of nasal congestion
Pelargonium sidoides root extract EPs® 7630[123]	Upper respiratory tract- asthma attacks	61 children (1–14 yr)	1–5 yr: 3 × 10 drops; 6–12 yr: 3 × 20 drops; 12 yr and above: 3 × 30 drops; 5 d	Randomized, placebo controlled	Reduction the severity of symptoms (especially cough and nasal congestion). Shortening of the duration of upper respiratory viral infections. Reduction asthma attack frequency
Pelargonium sidoides preparation EPs® 7630[124]	Acute non-streptococcal tonsillopharyngitis	126 children, 2 groups (6–10 yr)	3 × 20 drops. 6 d	Double-blind, placebo-controlled clinical trial	Decrease in tonsillitis severity score compared to placebo in the EPs® 7630 group after 4 d of treatment
Pelargonium sidoides extract EPs® 7630[125]	Common cold	207 adults (18-55 yr)	SD: 3 × 30 drops; HD: 3 × 60 drops; 10 d	Prospective, double-blind, parallel-group, placebo-controlled, phase 3, 2 parts, 2-arm, clinical trial	After 10 d, clinical treatment in 90.4% of the active drug group. Reduction the severity of symptoms and short the duration of the disease. Higher full recovery rates or greater recovery for HD treatment on day 5
Sambucus nigra extract[126]	Influenza	64 patients (16-60 yr)	Lozenge: 175 mg extract; 4 lozenges/d; 2 d	Randomized, double-blind, placebo-controlled, pilot clinical trials	Significant improvement in most symptoms within 24 h (fever, headache, muscle aches and nasal congestion). Significant improvement in all investigated symptoms within 48 h (cough and mucus discharge)
Sambucus nigra extract[127]	Respiratory health	312 adults, 2 groups	Capsules: 300 mg. Before travel: 2 capsules/d. During travel and after arrival: 3 capsules/d. 14 d	Randomized, double-blind placebo-controlled clinical trial	Reduction of cold duration and severity in air travelers. Low symptom score

SD: Standard dose; HD: High dose.