Characteristics of the included studies
| Reference | Dosage and administration | Study design | Country | Participant population | No. of participants | Age, mean ± SD* | Percentage of population who were male | Percentage of population with severe disease | |
|---|---|---|---|---|---|---|---|---|---|
| Study intervention | Antiviral agent comparison | ||||||||
| Favipiravir v. lopinavir/ritonavir | |||||||||
| Cai et al., 2020 (14) | Favipiravir 1600 mg po b.i.d. on day 1 and 600 mg po b.i.d. on days 2–14 plus interferon-α (60 μg b.i.d.) by aerosol inhalation | Lopinavir/ritonavir (200 mg/50 mg) 500 mg po b.i.d. on days 1–14 plus interferon-α 60 μg b.i.d. by aerosol inhalation | Cohort | China | Nonsevere COVID-19 | 80 | 47.0 (35.8–61.0)† | 43.8 | 0 |
| Favipiravir versus umifenovir | |||||||||
| Chen et al., 2020 (15)‡ | Favipiravir 1600 mg po b.i.d. on day 1 and 600 mg po b.i.d. for 7–10 d§ | Umifenovir (200 mg) po t.i.d. for 7–10 d | RCT | China | COVID-19 with mixed severity | 236 | NR | 46.6 | 11.4 |
| Favipiravir versus no favipiravir | |||||||||
| MDVI (16) | Favipiravir 1200 mg po b.i.d. for 1 d, followed by 800 mg po b.i.d. for 4 d | Placebo | RCT | Multiple countries | Influenza with unspecified severity | 386 | 42.7 (20.0–80.0)¶ | 45.3 | NR |
| Hydroxychloroquine versus no hydroxychloroquine | |||||||||
| Chen et al., 2020 (17)‡ | Hydroxychloroquine (200 mg) po b.i.d. for 5 d | No hydroxychloroquine | RCT | China | Nonsevere COVID-19 | 62 | 44.7 ± 15.3 | 46.8 | 0 |
| Tang et al., 2020 (18)‡ | Hydroxychloroquine: loading dose of 1200 mg daily for 3 d followed by a maintainence dose of 800 mg daily for remaining treatment days (total treatment duration: 2 wk for patients with mild/moderate disease or 3 wk for patients with severe disease) | No hydroxychloroquine | RCT | China | COVID-19 with mixed severity | 150 | 46.1 ± 14.7 | 54.7 | 1.3 |
| Magagnoli et al., 2020 (19)‡ | Hydroxychloroquine dose not mentioned | No hydroxychloroquine | Cohort | US | COVID-19 with mixed severity | 255 | NR | 100.0 | NR |
| Mahevas et al., 2020 (20)‡ | Hydroxychloroquine 600 mg/d | No hydroxychloroquine | Cohort | France | COVID-19 with mixed severity | 181 | 60.0 (52.0–68.0)† | 71.1 | NR |
| Hydroxychloroquine plus interferon versus interferon alone | |||||||||
| Chen et al., 2020 (21) | Hydroxychloroquine (400 mg) po daily for 5 d plus interferon-α by aerosol inhalation (80.0% of patients used umifenovir) | Interferon-α by aerosol inhalation (66.7% of patients used umifenovir and 13.3% used lopinavir/ritonavir) | RCT | China | Nonsevere COVID-19 | 30 | 48.6 ± 4.1 | 70.0 | 0 |
| Interferon versus no interferon, ribavirin versus no ribavirin | |||||||||
| Al Ghamdi et al., 2016 (22) | A: interferon-α B: interferon-β C: ribavirin | A: no interferon-α B: no interferon-β C: no ribavirin | Case–control | Saudi Arabia | MERS with mixed severity | 51 | 54.0 (36.5–58.0)† | 78.4 | 37.3 |
| Interferon plus ribavirin versus ribavirin alone | |||||||||
| Shalhoub et al., 2015 (23) | Interferon-α2a (180 μg) by sc injection weekly; interferon-β1a (44 μg) by sc injection 3 times per week plus ribavirin (2 g loading dose) po followed by 600 mg q.12h | Ribavirin (2 g loading dose) po followed by 600 mg q.12h | Cohort | Saudi Arabia | MERS with mixed severity | 32 | 60.0 (42.0–73.0)† | 56.0 | NR |
| Interferon plus umifenovir versus umifenovir alone | |||||||||
| Zhou et al., 2020 (24)‡ | Interferon-α2b (5 mIU) by aerosol inhalation twice daily plus umifenovir (200 mg) po 3 times daily | Umifenovir 200 mg po 3 times daily | Cohort | China | COVID-19 with mixed severity | 70 | 48.7 ± 18.1 | 44.3 | NR |
| Interferon v. no interferon | |||||||||
| Li et al., 2005 (25) | Interferon-α (1 mIU/d) by im or sc injection for 6–10 d | No interferon | Cohort | China | SARS with mixed severity | 87 | 28.1 ± 9.5 | 18.4 | 71.3 |
| Lopinavir/ritonavir versus no lopinavir/ritonavir | |||||||||
| Cao et al., 2020 (26) | Lopinavir/ritonavir (400/100 mg) po b.i.d. for 14 d | No lopinavir/ritonavir | RCT | China | Severe COVID-19 | 199 | 58.0 (49.0–68.0)† | 60.3 | 100.0 |
| Yan et al., 2020 (27)‡ | Lopinavir/ritonavir (400/100 mg) po b.i.d. for 10 d or longer | No lopinavir/ritonavir | Cohort | China | COVID-19 with mixed severity | 120 | 52.0 (35.0–63.0)† | 45 | 25.8 |
| Lopinavir/ritonavir versus no lopinavir/ritonavir, umifenovir versus no umifenovir | |||||||||
| Li et al., 2020 (28)‡ | A: lopinavir/ritonavir (200 mg/50 mg) 500 mg po q.12h for 7–14 d B: umifenovir (200 mg) po t.i.d. for 7–14 d | No lopinavir/ritonavir or umifenovir | RCT | China | Nonsevere COVID-19 | 44 | 49.4 ± 14.9 | 47.7 | 0 |
| Ribavirin versus no ribavirin | |||||||||
| Lau et al., 2009 (29) | Ribavirin | No ribavirin | Cohort | China Canada | SARS with mixed severity | 953 152 | NR | 48.7, 36.8 | NR |
| Leong et al., 2004 (30) | Ribavirin (1.2 g) po t.i.d. or 400 mg by intravenous injection q.8h for sicker patients who are severely ill and those who could not take it by mouth; mean treatment duration was 5.6 d | No ribavirin | Cohort | Singapore | SARS with mixed severity | 229 | 39.1 ± 16.8 | 31.9 | 20.1 (as outcome) |
| Muller et al., 2007 (31) | Ribavirin (2 g loading dose) by intravenous injection, followed by 1 g q.8h for 4 d, followed by 500 mg q.6h for 3 d** | No ribavirin | Cohort | Canada | SARS with mixed severity | 306 | NR | 37.3 | 41.6†† |
| Umifenovir v. no umifenovir | |||||||||
| Liu et al., 2020 (32)‡ | Umifenovir (dose not mentioned) | No umifenovir | Cohort | China | COVID-19 with mixed severity | 504 | 59.5 ± 14.9 | 51.4 | NR |
Note: b.i.d. = twice a day, COVID-19 = coronavirus disease 2019, im = intramuscular, IQR = interquartile range, MERS = Middle East respiratory syndrome, NR = not reported, po = by mouth, q.6h = every 6 hours, q.8h = every 8 hours, q.12h = every 12 hours, RCT = randomized controlled trial, SARS = severe acute respiratory syndrome, sc = subcutaneous, SD = standard deviation, t.i.d. = 3 times per day.
↵* Unless stated otherwise.
↵† Median (IQR).
↵‡ Preprint.
↵§ The course of treatment in both groups was 7–10 days. If necessary, the treatment time could have been extended to 10 days according to the judgment of researchers.
↵¶ Mean (range).
↵** Only 155 of 183 participants received this treatment regimen; the other 28 patients received several lower-dose treatment regimens.
↵†† Calculated from the baseline characteristic, admission oxygen saturation < 95%.