Table 2. Summary of evidence for the effectiveness and safety of antiviral agents.
| Outcome | No. of studies/design | Sample size | Quality of the evidence | Relative effect (95% CI) |
|---|---|---|---|---|
| LPV/r vs. no antivirals (COVID-19) | ||||
| Mortality | 1 RCT | 199 | Low | RR 0.77 (0.45 to 1.30) |
| Negative PCR result (%) | 1 cohort study and 2 RCTs | 232 | Very low | RR 0.98 (0.82 to 1.18) |
| Duration of disease (d) | 1 cohort study | 100 | Very low | WMD −1.00 (−2.51 to 0.51) |
| Adverse reactions (%) | 1 cohort study and 2 RCTs | 322 | Very low | RR 1.24 (0.67 to 2.28) |
| Serious adverse reactions (%) | 1 RCT | 194 | Moderate | RR 0.62 (0.38 to 1.01) |
| Radiographic abnormalities remission (%) | 1 cohort study and 1 RCT | 125 | Very low | RR 1.02 (0.70 to 1.48) |
| Time until clinical symptoms improved (d) | 1 RCT | 199 | Low | WMD −1.00 (−1.71 to −0.29) |
| Duration of hospitalization (d) | 1 RCT | 199 | Low | WMD −1.40 (−2.44 to −0.36) |
| LPV/r vs. no antivirals (SARS) | ||||
| Mortality | 2 cohort studies | 830 | Low | RR 0.16 (0.03 to 0.77) |
| Corticosteroid dose (g) | 2 cohort studies | 830 | Very low | WMD −0.82 (−2.03 to 0.40) |
| Intubation (%) | 1 cohort study | 678 | Very low | RR 0.10 (0.01 to 1.59) |
| ARDS (%) | 1 cohort study | 152 | Very low | RR 0.11 (0.02 to 0.77) |
| Elevated serum transaminase level (%) | 1 cohort study | 678 | Very low | RR 1.31 (0.49 to 3.48) |
| Elevated serum amylase level (%) | 1 cohort study | 678 | Very low | RR 1.92 (0.45 to 8.14) |
| Risk of oxygen desaturation episodes (%) | 1 cohort study | 678 | Low | RR 0.81 (0.66 to 0.99) |
| Nosocomial infection (%) | 1 cohort study | 152 | Very low | RR 0.05 (0.00 to 0.75) |
| Diarrhea (%) | 1 cohort study | 152 | Very low | RR 0.39 (0.23 to 0.69) |
| Recurrent fever (%) | 1 cohort study | 152 | Very low | RR 0.65 (0.43 to 0.98) |
| Radiographic abnormalities worsened (%) | 1 cohort study | 152 | Very low | RR 0.63 (0.46 to 0.86) |
| Arbidol vs. no antivirals (COVID-19) | ||||
| Duration of disease (d) | 1 cohort study | 82 | Very low | WMD −1.70 (−3.28 to −0.12) |
| Negative PCR result (%) | 2 cohort studies and 1 RCT | 114 | Very low | RR 1.27 (0.93 to 1.73) |
| Adverse reactions (%) | 1 cohort study | 82 | Very low | RR 1.06 (0.25 to 4.43) |
| Radiographic abnormalities remission (%) | 2 cohort studies and 1 RCT | 136 | Very low | RR 1.23 (0.63 to 2.40) |
| Incidence of receiving oxygen therapy (%) | 1 RCT | 23 | Moderate | RR 0.80 (0.51 to 1.26) |
| Incidence of clinical symptoms improvement | 1 RCT | 23 | Moderate | RR 1.02 (0.72 to 1.46) |
| IFN vs. no antivirals (SARS) | ||||
| Death (%) | 3 cohort studies | 1,980 | Very low | RR 0.72 (0.28 to 1.88) |
| Duration of hospitalization (d) | 2 cohort studies | 272 | Very low | WMD −2.76 (−5.80 to 0.28) |
| Duration of fever (d) | 2 cohort studies | 272 | Very low | WMD −0.04 (−1.64 to 1.55) |
| Corticosteroid dose (g) | 1 cohort study | 87 | Very low | WMD -0.14 (−0.21 to −0.07) |
| Duration of disease (d) | 1 cohort study | 1,518 | Very low | WMD −0.80 (−4.28 to −2.68) |
| Mechanical ventilation (%) | 1 cohort study | 22 | Very low | RR 0.48 (0.06 to 3.92) |
| Intubation (%) | 1 cohort study | 185 | Very low | RR 0.92 (0.24 to 3.57) |
| Admitted to ICU (%) | 1 cohort study | 22 | Very low | RR 0.87 (0.27 to 2.74) |
| Time of needing supplemental oxygen resolved (d) | 1 cohort study | 22 | Very low | WBD −4.00 (−9.05 to 1.05) |
| Time until clinical symptoms improved (d) | 1 cohort study | 185 | Very low | WMD 0.60 (−0.22 to 1.42) |
| Time until 50% radiographic abnormalities resolved (d) | 1 cohort study | 22 | Very low | WMD −5.00 (−6.46 to −3.54) |
| Time of pulmonary shadow resolved significantly (d) | 1 cohort study | 185 | Very low | WMD 0.30 (−0.92 to 1.52) |
| Time until X-ray results improved (d) | 1 cohort study | 87 | Very low | WMD −4.67 (−5.93 to −3.41) |
| IFN-α vs. IFN-β (MERS) | ||||
| Death (%) | 1 cohort study | 24 | Very low | RR 1.33 (0.80 to 2.20) |
| Intubation (%) | 1 cohort study | 24 | Very low | RR 1.41 (0.76 to 2.61) |
| RBV vs. no antivirals (SARS) | ||||
| Death (%) | 4 cohort studies | 2,236 | Very low | RR 0.68 (0.43 to 1.06) |
| Duration of corticosteroid use (d) | 1 cohort study | 90 | Very low | WMD −5.60 (−7.94 to −3.26) |
| Duration of disease (d) | 1 cohort study | 1,518 | Very low | WMD 1.04 (−0.44 to 2.52) |
| Mechanical ventilation (%) | 1 cohort study | 306 | Very low | RR 0.96 (0.56 to 1.64) |
| Admitted to ICU (%) | 1 cohort study | 229 | Very low | RR 0.96 (0.57 to 1.62) |
| Anemia (%) | 1 cohort study | 586 | Low | RR 1.67 (1.07 to 2.61) |
| Bradycardia (%) | 1 cohort study | 306 | Low | RR 2.02 (1.30 to 3.12) |
| Hypoxemia (%) | 1 cohort study | 51 | Very low | RR 2.71 (0.42 to 17.24) |
| Hyperamylasemia (%) | 1 cohort study | 306 | Low | RR 2.69 (1.04 to 6.97) |
| Hypocalcemia (%) | 1 cohort study | 306 | Low | RR 1.29 (1.00 to 1.66) |
| Hypomagnesemia (%) | 1 cohort study | 306 | High | RR 10.19 (4.61 to 22.55) |
| Myocardial injury (%) | 1 cohort study | 229 | Very low | RR 1.02 (0.23 to 4.46) |
| Peak CRP level (mg/dL) | 1 cohort study | 51 | Very low | WMD 4.50 (−1.23 to 10.23) |
| Peak LDH level (IU/L) | 1 cohort study | 51 | Very low | WMD 230.30 (114.0 to 346.6) |
| Oseltamivir vs. no antivirals (SARS) | ||||
| Death (%) | 3 cohort studies | 1,887 | Very low | RR 0.87 (0.55 to 1.38) |
| Mechanical ventilation (%) | 1 cohort study | 103 | Low | RR 2.67 (1.73 to 4.12) |
| Intubation (%) | 1 cohort study | 83 | Very low | RR 0.50 (0.03 to 9.19) |
| ARDS (%) | 1 cohort study | 103 | Very low | RR 1.29 (0.55 to 3.03) |
| Duration of disease (d) | 1 cohort study | 1,518 | Very low | WMD 3.91 (2.28 to 5.54) |
| Duration of hospitalization (d) | 1 cohort study | 83 | Very low | WMD −7.60 (−10.49 to −4.71) |
| Time until clinical symptoms improved (d) | 1 cohort study | 83 | Very low | WMD 2.60 (−0.25 to 5.45) |
| Duration of fever (d) | 1 cohort study | 83 | Very low | WMD 2.60 (0.50 to 4.70) |
| Pulmonary artery wide (mm) | 1 cohort study | 103 | Very low | WMD 1.69 (1.08 to 2.30) |
| Time of pulmonary shadow resolved significantly (d) | 1 cohort study | 83 | Very low | WMD 0.70 (−2.16 to 3.56) |
| Oseltamivir (early use alone) vs. oseltamivir (use alone) (SARS) | ||||
| Death (%) | 1 cohort study | 127 | Low | RR 1.62 (0.33 to 8.05) |
| ARDS (%) | 1 cohort study | 127 | Low | RR 2.60 (0.30 to 22.57) |
| Duration of disease (d) | 1 cohort study | 127 | Low | WMD −2.50 (−7.45 to 2,45) |
| Duration of fever (d) | 1 cohort study | 127 | Low | WMD −0.90 (−1.91 to 0.11) |
| RBV plus IFN vs. no antivirals (MERS) | ||||
| Death (%) | 2 cohort studies | 393 | Very low | RR 1.04 (0.74 to 1.46) |
| Invasive ventilation (%) | 2 cohort studies | 393 | Very low | RR 1.05 (0.97 to 1.13) |
| Mechanical ventilation (%) | 1 cohort study | 349 | Very low | RR 0.92 (0.77 to 1.09) |
| Blood transfusion (%) | 1 cohort study | 349 | Low | RR 1.42 (1.06 to 1.91) |
| Mean drop in haemoglobin (g/L) | 1 cohort study | 44 | Very low | WMD 2.18 (0.86 to 3.50) |
| Mean minimum absolute neutrophil count (×109/L) | 1 cohort study | 44 | Very low | WMD −1.43 (−2.55 to −0.32) |
| Favipiravir vs. Arbidol (COVID-19) | ||||
| Rate of clinical recovery of day 7(%) | 1 RCT | 236 | Low | RR 1.18 (0.95 to 1.48) |
| Adverse reactions (%) | 1 RCT | 236 | Low | RR 1.37 (0.90 to 2.08) |
| Dyspnea after taking medicine (%) | 1 RCT | 236 | Low | RR 0.30 (0.10 to 0.87) |
| Respiratory failure (%) | 1 RCT | 236 | Low | RR 1.03 (0.26 to 4.04) |
| HCQ vs. none (COVID-19) | ||||
| Negative PCR result (%) | 1 RCT | 30 | Low | RR 0.93 (0.73 to 1.18) |
| Radiographic abnormalities remission (%) | 1 RCT | 62 | Low | RR 1.47 (1.02 to 2.11) |
| Duration of fever (d) | 2 RCTs | 69 | Low | WMD −0.90 (−1.48 to −0.31) |
| Time until negative PCR result (d) | 1 RCT | 30 | Low | WMD 2.34 (−1.19 to 5.87) |
| Adverse reactions (%) | 2 RCTs | 92 | Low | RR 1.65 (0.50 to 5.50) |
LPV/r, lopinavir/ritonavir; IFN, interferon; RBV, ribavirin; HCQ, hydroxychloroquine; CI, confidence interval; RR, risk ratio; WMD, weighted mean difference; RCT: randomized controlled trial; COVID-19, Corona Virus Disease hyphen one nine; SARS, severe acute respiratory syndrome; MERS, Middle East respiratory syndrome ARDS, Acute respiratory distress syndrome; PCR, polymerase chain reaction; ICU, intensive care unit; CRP, C-reactive protein; LDH, lactate dehydrogenase.