Table 4.

Summary of findings on influenza (including H1N1 and H7N9 (n = 7 studies))

Study ID	Country(s)	Design	Population	N	Intervention	Outcome	Key findings	RoB
Antivirals
Chen, 2020 [72]	China	Retrospective cohort	>14 y hospitalized with influenza B	386	Any NAI administered within 2 d after symptom onset	Invasive and non-invasive mechanical ventilation, admittance to the ICU, and 30-d mortality	Early NAI treatment was associated with the decreased risks of invasive ventilation (OR = 0.325,95% CI = 0.123 to 0.858; P = 0.023), admittance to ICU (OR = 0.425, 95% CI = 0.204 to 0.882; P = 0.022), and 30-d mortality (OR = 0.416, 95% CI = 0.184 to 0.944, P = 0.036).	Moderate
Chen, 2020 [73]	China	Retrospective cohort	>14 y hospitalized with Influenza A	693	Any NAI administered within 2 d after symptom onset.	Invasive ventilation,14-d and 30-d mortality	Early NAI therapy associated with decreased risk for invasive ventilation (OR = 0.511, 95% CI = 0.312 to 0.835) and 30-d mortality (OR = 0.533, 95% CI = 0.210 to 0.807).	Serious
Lenzi, 2012 [74]	Brazil	Retrospective cohort	Any age hospitalized with H1N1 influenza	1917	Treatment with Oseltamivir	Clinical cure; time to death	Decreased mortality with oseltamivir in regression (OR = 0.031, 95% CI = 0.015 to 0.065). Average time-to-death in untreated patients was 8.6 d vs 13.8 d in those who received oseltamivir; 32.3% increased risk of death for each additional day to oseltamivir initiation after symptom onset.	Moderate
Li, 2003 [75]	China	RCT	18-65 y with symptoms of influenza	451	PO Oseltamivir 75 mg BID vs placebo	Duration of symptoms; symptom severity score	Shorter time to symptom resolution in oseltamivir group vs placebo (P = 0.0466) with duration of illness 91.6 h (95% CI = 80.2 to 101.3) vs 95 h (95% CI = 84.5 to 105.3) and lower symptom severity (P = 0.0196).	Some Concerns
Lin, 2006 [76]	China	RCT	Adults with chronic respiratory or cardiac disease with influenza six within 48 h of symptom onset	56	PO Oseltamivir 75 mg BID vs placebo	Duration of symptoms; symptom severity score	Oseltamivir reduced duration of symptoms by 64 h or 36.8% (110 vs 174 h; P = 0.0479) and severity by 43.1%. Reduced time to baseline health status by 5 d (P = 0.0011), incidence of complications (11% vs 45%, P = 0.0053) and antibiotic use (37% vs 69% P = 0.0167).	High
Zhang, 2016 [77]	China	Retrospective cohort	≥18 y with H7N9 Influenza A (H7N9) virus	82	PO Oseltamivir + IV Peramivir vs PO Oseltamivir alone	Time to viral clearance; mortality; development of ARDS	No difference time to viral clearance (7.00 vs 6.50 d, P = 0.67), development of ARDS (77.78% vs 63.89%, P = 0.30) or mortality (43.6% vs 25.6%, P = 0.11) oseltamivir-peramivir vs oseltamivir monotherapy.	Moderate
Corticosteroids
Cao, 2016 [78]	China	Case-control	>14 y hospitalized with severe H7N9	288	At least one dose of corticosteroids equivalent to 25mg methyprednisolone	30-d and 60-d mortality	Increased 30-d (aHR = 3.05; 95%CI = 1.28 to 7.25; P = 0.012) and 60-d mortality in high-dose steroid (aHR = 4.05; 95% CI = 1.82 to 9.02); P = 0.001) but no effect with low or moderate dose. Corticosteroid cases had higher 60-d mortality vs no steroids (aHR = 1.98; 95% CI = 1.03 to 3.79; P = 0.04)	Serious

aHR – adjusted hazard ratio, ARDS – acute respiratory distress syndrome, BID – twice daily, CI – confidence interval, HR – heart rate, ICU – intensive care unit, IV – intravenous, LOS – length of stay, NAI – neuraminidase inhibitor, N – number of participants, OR – odds ratio, PO – per oral, RoB – risk of bias, RR – respiratory rate, ICU – intensive care unit