Table 4.
Efficacy and safety of propolis or bee products to treat or prevent COVID-19 and related clinical outcomes.
| Study | Outcome | Duration of assessment | Comparator group | Intervention group | P value |
|---|---|---|---|---|---|
| Case report | |||||
| Fiorini et al. [31] | Clinical symptom improvement and RT-PCR | 12 days | Not applicable | After 12 days of treatment, the patient’s general clinical symptoms improved significantly, and the patient recovered with negative RT-PCR. | Not available |
| Zorlu et al. [32] | Clinical symptom improvement | 1 month | Not applicable | The patient’s clinical symptoms improved at day 7 and the patient was discharged at day 10. At the health check-up visit 1 month later, the patient had no complaint except the forced exertion dyspnea. Normal blood test was observed and abnormal thorax computed tomography completely regressed | Not available |
| Case series | |||||
| El Sayed et al. [18] | Treatment: clinical symptom improvement and RT-PCR | > 9 days | Not applicable | Clinical symptom improvement: 14 patients (70%) improved within 4 days; 5 patients (25%) improved in 5–10 days; 1 patient (5%) improved in > 10 days; all patients had negative RT-PCR after the treatment. | < 0.01 |
| Prevention: SARS-CoV2 infection | 14 days | Not applicable | 14 patients (70%) did not get infected; 6 patients (30%) got infected | NR | |
| Safety data | 3 patients (18.8%) reported non-serious side effects including sweating, hyperglycemia and diarrhea | ||||
| Randomized controlled trial | |||||
| Ashraf et al. [17] | Time taken for alleviation of symptoms (d, median [IQR]) | 13 days | Moderate: 7 (7–8) | Moderate: 4 (3–4) | < 0.0001 |
| Severe: 13 (9–15) | Severe: 6 (5–7) | < 0.0001 | |||
| Time taken for SARS-CoV-2 RT-PCR clearance (d, median [IQR]) | Moderate: 10 (9–12) | Moderate: 6 (6–7) | < 0.0001 | ||
| Severe: 12 (11–17) | Severe: 8.5 (8–9) | < 0.0001 | |||
| Clinical grading score at day 6 (median [IQR]) | Moderate: 1 (1–2) | Moderate: 0 (0–1) | < 0.0001 | ||
| Severe: 3 (3–4) | Severe: 1.5 (0–2) | < 0.0001 | |||
| Degree of fever at day 4 (median [IQR]) | Moderate: 2 (1–2) | Moderate: 0 (0–1) | < 0.0001 | ||
| Severe: 2 (1–3) | Severe: 2 (1–2) | 0.0001 | |||
| CRP level at day 6 (mg/L, mean ± SD) | Moderate: 9.44 ± 4.94 | Moderate: 6.15 ± 2.45 | < 0.0001 | ||
| Severe: 23.32 ± 8.73 | Severe: 15.83 ± 7.17 | < 0.0001 | |||
| Severity of symptoms at day 8 (median [IQR]) | Moderate: 0 (0–2) | Moderate: 0 (0–0) | < 0.0001 | ||
| Severe: 2 (1–3) | Severe: 0 (0–1) | < 0.0001 | |||
| Clinical grading score at day 10 (median [IQR]) | Moderate: 1 (1–2) | Moderate: 1 (1–2) | < 0.0001 | ||
| Severe: 4 (2–4) | Severe: 1 (1–1) | < 0.0001 | |||
| 30-day mortality (n) | Moderate: 1 | Moderate: 0 | 0.49 | ||
| Severe: 10 | Severe: 2 | 0.029 | |||
| Safety data | No adverse event was noted with intervention groups | ||||
| Kosari et al. [33] | Dry cough score (mean ± SD) | 2–6 day | Day 2: 1.0 | Day 2: 0.5 | < 0.05 |
| Day 4: 0.7 | Day 4: 0.2 | < 0.001 | |||
| Day 6: 0.4 | Day 6: 0.1 | < 0.01 | |||
| Shortness of breath score (mean ± SD) | Day 2: 0.7 | Day 2: 0.3 | < 0.05 | ||
| Day 4: 0.5 | Day 4: 0.0 | < 0.001 | |||
| Day 6: 0.2 | Day 6: 0.0 | < 0.01 | |||
| Sore throat score (mean ± SD) | Day 2: 0.5 | Day 2: 0.2 | < 0.05 | ||
| Day 4: 0.3 | Day 4: 0.1 | < 0.05 | |||
| Day 6: 0.3 | Day 6: 0.0 | < 0.01 | |||
| Chest pain score (mean ± SD) | Day 2: 0.5 | Day 2: 0.2 | NR | ||
| Day 4: 0.3 | Day 4: 0.1 | < 0.05 | |||
| Day 6: 0.2 | Day 6: 0.0 | < 0.05 | |||
| Fever score (mean ± SD) | Day 2: 0.2 ± 0.4 | Day 2: 0.0 | < 0.05 | ||
| Day 4: 0.0 | Day 4: 0.0 | NR | |||
| Day 6: 0.0 | Day 6: 0.0 | NR | |||
| Headache score (mean ± SD) | Day 2: 0.52 ± 0.7 | Day 2: 0.04 ± 0.2 | NR | ||
| Day 4: 0.5 ± 0.6 | Day 4: 0.0 | NR | |||
| Day 6: 0.2 ± 0.4 | Day 6: 0.0 | NR | |||
| Muscular pain score (mean ± SD) | Day 2: 0.7 ± 0.8 | Day 2: 0.4 ± 0.2 | NR | ||
| Day 4: 0.6 ± 0.7 | Day 4: 0.1 ± 0.3 | < 0.01 | |||
| Day 6: 0.4 ± 0.6 | Day 6: 0.0 | < 0.01 | |||
| Diarrhea score (mean ± SD) | Day 2: 0.2 ± 0.5 | Day 2: 0.0 | NR | ||
| Day 4: 0.1 ± 0.3 | Day 4: 0.0 | NR | |||
| Day 6: 0.1 ± 0.3 | Day 6: 0.0 | NR | |||
| Runny nose score (mean ± SD) | Day 2: 0.2 ± 0.4 | Day 2: 0.0 | < 0.05 | ||
| Day 4: 0.2 ± 0.4 | Day 4: 0.0 | < 0.05 | |||
| Day 6: 0.1 ± 0.3 | Day 6: 0.0 | NR | |||
| Sore throat and larynx score (mean ± SD) | Day 2: 0.5 ± 0.7 | Day 2: 0.2 ± 0.5 | < 0.05 | ||
| Day 4: 0.3 ± 0.6 | Day 4: 0.1 ± 0.2 | < 0.05 | |||
| Day 6: 0.2 ± 0.5 | Day 6: 0.0 | NR | |||
| Fatigue score (mean ± SD) | Day 2: 1.0 ± 0.9 | Day 2: 0.7 ± 0.6 | NR | ||
| Day 4: 0.9 ± 0.8 | Day 4: 0.4 ± 0.5 | < 0.05 | |||
| Day 6: 0.7 ± 0.8 | Day 6: 0.1 ± 0.3 | < 0.001 | |||
| Anorexia score (mean ± SD) | Day 2: 0.6 ± 0.7 | Day 2: 0.1 ± 0.2 | NR | ||
| Day 4: 0.4 ± 0.5 | Day 4: 0.0 | NR | |||
| Day 6: 0.2 ± 0.4 | Day 6: 0.0 | NR | |||
| Trembling score (mean ± SD) | Day 2: 0.2 ± 0.4 | Day 2: 0.0 | NR | ||
| Day 4: 0.1 ± 0.2 | Day 4: 0.0 | NR | |||
| Day 6: 0.1 ± 0.2 | Day 6: 0.0 | NR | |||
| Nausea score (mean ± SD) | Day 2: 0.1 ± 0.3 | Day 2: 0.0 | NR | ||
| Day 4: 0.1 ± 0.3 | Day 4: 0.0 | NR | |||
| Day 6: 0.1 ± 0.2 | Day 6: 0.0 | NR | |||
| Vomit score (mean ± SD) | Day 2: 0.0 | Day 2: 0.0 | NR | ||
| Day 4: 0.0 | Day 4: 0.0 | NR | |||
| Day 6: 0.0 | Day 6: 0.0 | NR | |||
| Dizziness score (mean ± SD) | Day 2: 0.2 ± 0.4 | Day 2: 0.1 ± 0.2 | NR | ||
| Day 4: 0.2 ± 0.4 | Day 4: 0.0 | < 0.05 | |||
| Day 6: 0.1 ± 0.2 | Day 6: 0.0 | NR | |||
| Abdominal pain score (mean ± SD) | Day 2: 0.4 ± 0.6 | Day 2: 0.0 | < 0.001 | ||
| Day 4: 0.3 ± 0.6 | Day 4: 0.0 | < 0.01 | |||
| Day 6: 0.2 ± 0.4 | Day 6: 0.0 | < 0.01 | |||
| Safety data | Not available | One patient reported hot flashes | |||
| Silveira et al. [34] | Length of hospital stay (d, median [IQR]) | 28 days | 12 (8–16) | 400 mg/d: 7 (5–12) | 0.049 |
| 800 mg/d: 6 (5–11) | 0.009 | ||||
| Oxygen therapy dependency time (d, median [IQR]) | 5 (3–11) | 400 mg/d: 3 (1–6) | 0.470 | ||
| 800 mg/d: 2 (1–5) | 0.710 | ||||
| Acute kidney injury (n) | 10 | 400 mg/d: 5 | 0.305 | ||
| 800 mg/d: 2 | 0.048 | ||||
| Renal replacement therapy (n) | 3 | 400 mg/d: 1 | 0.415 | ||
| 800 mg/d: 0 | 0.994 | ||||
| Invasive ventilation after randomization (n) | 8 | 400 mg/d: 2 | 0.065 | ||
| 800 mg/d: 3 | 0.107 | ||||
| Vasoactive agent (n) | 10 | 400 mg/d: 4 | 0.161 | ||
| 800 mg/d: 3 | 0.098 | ||||
| ICU after randomization (n) | 6 | 400 mg/d: 0 | 0.993 | ||
| 800 mg/d: 5 | 0.601 | ||||
| Safety data | No patient had propolis treatment discontinued due to side effects. The percentages of patients experiencing adverse events were not different significantly among the three groups. The most severe adverse event overall was shock/need for vasoactive drugs and acute respiratory failure | ||||
CRP: C-reactive protein; ICU: intensive care unit; IQR: inter-quartile range; NR: not reported; RT-PCR: real-time polymerase chain reaction; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SD: standard deviation.