Table 4.

Clinical trials on the evaluation of the administration of PCs or PCs-rich foods as a possible therapeutic management for patients with COVID-19.

Reference	Type of clinical trial	Sample (intervention group)	Severity of COVID-19	Treatment	Place and period	Main findings
PCs
Ahmadi et al. (2021)	Controlled, randomized, triple-blind.	30 patients. Mean age: 41.3 years, 66.7% male.	Mild or moderate.	Nano-curcumin: 40 mg/6 times daily for 7 days.	Imam Reza Hospital, Iran. April to July 2020.	Improvement of symptoms except sore throat. Decreased levels of inflammatory markers. Increased lymphocyte count.
Asadirad et al. (2022)	Controlled, randomized, open-label.	30 patients. Mean age: 56 years, 20% male.	Mild or moderate.	Nano-curcumin: 240 mg daily for 7 days.	Razi Hospital, Iran. June to July 2020.	Reduced expression of proinflammatory cytokines.
Di Pierro et al. (2021b)	Controlled, randomized, open-label, still-oingoing.	21 patients. Mean age: 42.5 years, 47.6% male.	Mild.	Quercetin: 200 mg/3 times daily for 7 days and 2 times daily for 7 more days.	Department of Medicine, King Edward University, Pakistan. December 2020 to March 2021.	Higher number of recoveries than in the cg (16 vs. 2 in the first week, 5 vs. 17 in the second week). Decreased levels of inflammatory markers. No deaths, except in the cg (4.8% of patients).
Saber-Moghaddam et al. (2021)	Controlled, nonrandomized, open-label.	21 patients. Mean age: 53,5 years, 31,3% male.	Mild or moderate.	Nano-curcumin: 40 mg/2 times daily for 2 weeks.	Imam Reza and Quaem Hospitals, Iran. April to July 2020.	Improvement of symptoms (fever, chills, cough, myalgia, and tachypnea). Increased lymphocyte count. Need for supplemental O2 was 1,75 days shorter. Hospitalization was 4,1 days shorter. No deterioration of symptoms, except in the cg (40% of patients).
Shohan et al. (2022)	Controlled, randomized, open-label.	30 patients. Age: 35–75 years, 56.7% male.	–	Quercetin: 1 g daily for 7 days.	Ahvaz Razi Teaching Hospital, Iran. December 2020 to January 2021.	Decreased levels of inflammatory markers. Increased hemoglobin level. Increased respiratory rate. No deaths, except in the cg (10% of patients).
Valizadeh et al. (2020)	Controlled, randomized, double-blind	20 patients. Mean age: 53,3 years, 77% male.	–	Nano-curcumin: 40 mg/4 times daily for 14 days.	Imam Reza Hospital, Iran. Period not specified.	Decreased expression and secretion of inflammatory cytokines.
Natural medicine rich in PCs (plants/substances/functional foods)
Al-haidari et al. (2021)	Controlled, randomized, open-label.	160 patients. Age: 13 to >65 years, 50% male.	–	Nigella sativa: 40 mg/kg daily for 13 days.	Kirkuk General Hospital, Irak. From September to November 2020.	Decrease in the severity of the infection. No deaths, except in the cg (5.4% of patients).
Ashraf et al. (2020)	Controlled, randomized, multicenter.	157 patients. Age: ≤ 40 to >80 years, 57.3% male.	Moderate or severe.	1 g/kg of honey plus 80 mg/kg of N. sativa daily for 13 days.	Four medical care facilities in Pakistan. April to July 2020.	Patients recovered with moderate (6 vs 10 days) and severe cases (8.6 vs 12 days) in less time than in the cg. No deaths, except in the cg (2,7% of patients).
Eskandarian et al. (2022)	Controlled, randomized.	34 patients Age: < 40 to >60 years, 67.6% male.	–	Chlorella vulgaris (300 mg/4 times daily) plus polyherbal brewb (6 g/3 times daily) for 2 days minimum until the end of hospitalization.	Not specified.	Decreased levels of inflammatory markers. Decrease in the prevalence of diarrhea. Hospitalization was 2 days shorter.
Hashem-Dabaghian et al. (2021)	Controlled, randomized.	23 patients. Mean age: 36.6 years, 73.9% male.	Mild, moderate or severe.	Lavender syrup (5% of lavender extract plus 66,5% of honey plus 28,5% of water):9 mL/2 times daily for 3 weeks.	clinic of the Gonbad-E-Kavoos Health center, Iran. In 2020.	Improvement of olfactory dysfunction. Improvement of symptoms not significant.
Huseini et al. (2022)	Controlled, randomized, double-blind.	21 patients. Mean age: 58 years, 63.3% male.	–	Imflunac (102.48 mg GAE/g dry extract): about 500 mg/3 times daily for 14 days.	Baqiyatallah Hospital, Iran. May 2020.	Improvement of symptoms (cough and dyspnea). Decreased levels of inflammatory markers. Non-significant improvement of lung lesions.
Kamalinejad et al. (2021)	Controlled, randomized, double-blind.	25 patients. Mean age: 53.5 years, 36% male.	Mild or moderate.	Tiband: 5 mL/3 times daily for 14 days.	Tertiary care center, Iran. April to May 2020.	Improvement of symptoms (dyspnea, fatigue, and appetite).
Karimi et al. (2021)	Controlled, randomized, open-label, multicenter.	182 patients. Mean age: 48.7 years, 58.1% male.	–	Polyherbal decoctione (35.57 GAE/g): about 900 mL daily for 7 days.	Three hospitals in Tehran and two hospitals Isfahan, Iran. March to July 2020.	Improvement of symptoms (vertigo, muscle pain, dry cough, sputum cough, runny nose, chills, headache, anorexia, and fatigue). Duration of dyspnea was 2.3 days shorter.
Kosari et al. (2021)	Controlled, randomized.	25 patients. Mean age: 41 years, 48.7% male.	–	30 mL of syrup (1,5 mg of Hyoscyamus niger L. extract plus 450 mg of propolis)/daily for 6 days.	Akhavan and Sepehri Clinics, Iran. May to June 2020.	Improvement of symptoms (headache, dry cough, abdominal pain, chest pain, sore throat, fever, dyspnea, dizziness, and diarrhea).
Koshak et al. (2021)	Controlled, randomized, open-label, two-arm, parallel-group.	91 patients. Mean age: 35 years, 53% male.	Mild.	N. sativa oil: 500 mg/2 times daily for 10 days.	King Abdulaziz University Hospital, Saudi Arabia. May to September 2020.	Higher percentage of recovered patients (62 vs 36%) and in less time (10.7 vs 12.3 days) than in the cg.
Sardari et al. (2021)	Controlled, randomized.	21 patients. Mean age: 45.2 years, 42.2% male.	–	Thyme essential oil: 5 mL/3 times daily for 7 days.	Vali-e Asr Hospital, Iran. In 2020.	Improvement of symptoms (cough, fever, dyspnea, dizziness, cough, muscular pain, chest wall pain, headache, weakness, lethargy, fatigue, and anorexia). Increased lymphocyte count and reduced neutrophil count.
Shiri et al. (2021)	Controlled, randomized, double-blind.	21 patients. Mean age: 41 years, 51.4% male.	–	3 g of herbal supplement (1,5 mg of Saccharum officinarum plus 1 g of Pistacia lentiscus, and 0,5 g Terminalia chebula plus)/2 times daily The days of treatment are not specified.	Peymaniyeh Hospital, Iran. May to July 2020.	Improvement of symptoms (dyspnea, fever, cough, and myalgia). Patients recovered in less time (4.12 vs 8.37 days) than in the cg. No deaths, except in the cg (8.6% of patients).
Silveira et al. (2021)	Controlled, randomized, single center, open-label.	40 and 42 patients for the lowest and highest dose, respectively. Mean age: 49.5 years, 28% men for the lowest dose, and 48.9 years, 30% men for the highest male.	–	Propolis: 100 mg/4 times daily or 200 mg/4 times daily for 7 days.	São Rafael Hospital, Brazil. June to August 2020.	Patients recovered in less time (7 (lower dose) and 6 (higher dose) vs. 12 days) than in the cg. Decrease in acute kidney injury with higher dose.
Takdehghan et al. (2021)	Controlled, randomized, double-blind.	116 patients. Mean age: 52.2 years, 47.64% male.a	Mild or moderate.	Phoenix dactylifera L. leaf extract (28.2 mg GAE/g): 5 mL in 30 mL of water/5 times daily for 14 days.	Ganjavian Hospital, Iran. October to November 2020.	Decreased levels of inflammatory markers. Increased partial pressure of oxygen in the blood.
Tavakoli et al. (2022)	Controlled, randomized, single-blind, two-arm, parallel-group.	50 patients. Mean age: 56.8 years, 37% male.	Moderate.	Persian barley water (72 mg GAE/100 g dry matter): 250 mL daily for 14 days.	Ali Asghar Hospital, Iran. January to March 2021.	Decrease in fever. Decreased levels of inflammatory markers. Hospitalization was 4,5 days shorter.
Varnasseri et al. (2022)	Controlled, randomized, double-blind.	30 patients. Mean age: 47.9 years, 40% male.	–	Phyllanthus emblica (39.56 g GAE/100 g extract): 2 g of powder or 100 mL daily for 10 days.	Razi and Sina Hospitals, Iran. May to June 2020.	Patients recovered in less time (4.44 vs 7.18 days) than in the cg. Improvement of symptoms (fever, severity of cough, dyspnea, and myalgia.). Decreased levels of inflammatory markers. Decreased lung involvement.
Zhao et al. (2021)	Controlled, randomized, single center, open-label,	204 patients. Mean age: 52 years, 43.1% male.	Mild.	Huashibaidu granulef: 10 g/2 times daily for 7 days.	Dongxihu FangCang hospital, China. February to March 2020.	Symptoms worsened in fewer patients (2.5 vs 7.8%) than in the cg.

Note: All treatments were complementary to standard medication. Although it is emphasized that the natural medicine used is rich in PCs, it should be considered that they contain other bioactive phytochemicals such as carotenoids, terpenoids, lecithins, alkaloids, etc.

^aage and percentage of male patients based on the total group (placebo and intervention).

^bMixture of Althaea rosea, Mentha longifolia, Malva sylvestris, and Matricaria recutita.

^cMixture of Echinacea angustifolia DC. aerial part, Stachys lavandulifolia Vahl aerial part, Artemisia annua L. aerial part, Hyssopus officinalis L. aerial part, Polypodium vulgare L. rhizome, Alpinia officinarum Hance rhizome, Zingiber officinale Roscoe rhizome, and Panax ginseng C.A.Mey root.

^dMixture of Ziziphus jujuba Mill and Trachyspermum ammi (L.) Sprague.

^eMixture of Urtica dioica L. leaf, Althaea officinalis L. flower, Matricaria chamomilla L. flower, Nepeta bracteata Benth. flower, Zataria multiflora Boiss. aerial part, Glycyrrhiza glabra L. root, Ficus carica L. fruit, and Ziziphus jujuba mill. fruit.

^fMixture of Herba Ephedrae, Armeniacae Semen Amarum, Gypsum Fibrosum, Glycyrrhizae Radix et Rhizoma, Pogostemonis Herba, Magnoliae Officinalis Cortex, Atractylodis Rhizoma, Tsaoko Fructus, Pinelliae Rhizoma Praeparatum, Poria, Rhei Radix et Rhizoma, Astragali Radix, Descurainiae Semen Lepidii Semen, and Paeoniae Radix Rubra.