TABLE 1

Summary of hospitalisation outcomes in trials included in the qualitative synthesis

StudyInterventionsHospitalisation outcomesICU outcomes
Time from randomisation to discharge daysPatients dischargedIncidence of ICU admittanceLength of ICU stay days
Antivirals
 Davoudi-Monfared [64]IFN-β-1a# (n=42)NRPatients discharged
Day 7: 19.04
Day 14: 66.66
Day 28: 73.80
45.237.7±8.8
Standard care (n=39)NRPatients discharged
Day 7: 28.20
Day 14: 43.58
Day 28: 58.97
58.978.5±7.5
Between-group difference/comparisonNRDay 7: OR 0.60 (95% CI 0.21–1.69)
Day 14: OR 2.5 (95% CI 1.05–6.37)*
Day 28: OR 1.96 (95% CI 0.76–5.01)
NRp=0.42
 Rahmani [67]IFN-β-1b# (n=33)NRPatients discharged
Day 7:15.2
Day 14: 78.8
Day 28: 93.9
42.49 (6–13)
Standard care (n=33)NRPatients discharged
Day 7: 6.1
Day 14: 54.6
Day 28: 81.8
66.78 (4–12)
Between-group difference/comparisonNRDay 7: OR 2.76 (95% CI 0.49–15.42); p=0.21
Day 14: OR 3.09 (95% CI 1.05–9.11); p=0.03*
Day 28: OR 3.44 (95% CI 0.64–18.50); p=0.12
p=0.04*p=0.55
 Abbaspour Kasgari[60]Sofosbuvir+daclatasvir+RBV (n=24)NRNR0NA
Hydroxychloroquine+lopinavir/ritonavir±RBV (n=24)NRNR172.5 (1.5–7.0)
Between-group difference/comparisonNRNRp=0.109NR
 Sadeghi [68]Sofosbuvir+daclatasvir# (n=33)6 (4–10)NRNRNR
Standard care (n=33)11 (6–17)NRNRNR
Between-group difference/comparisonProbability of hospital discharge: p=0.041*NRNRNR
 Wu [59]Trizavirin# (n=26)NRNR11.5NR
Placebo (n=26)NRNR11.5NR
Between-group difference/comparisonNRNRp=1.0NR
 Cao [31]Lopinavir/ritonavir# (n=99)12.0 (10.0–16.0)Patients not hospitalised
Day 7: 4
Day 14: 43.4
NR6.0 (2.0–11.0)
Standard care (n=100)14.0 (11.0–16.0)Patients not hospitalised
Day 7: 0
Day 14: 28
NR11.0 (7.0–17.0)
Between-group difference/comparisonDifference 1.0 (95% CI 0–3.0)NRNRDifference −5 (95% CI −9–0)
 Hung [37]Lopinavir/ritonavir+RBV+IFN-β-1b (n=86)NRNROverall: 5NR
Lopinavir/ritonavir (n=41)NRNRNR
Between-group difference/comparisonNRNRNR
 Goldman [61]Remdesivir, 5-day treatment# (n=200)NRWithin 14 days: 60NRNR
Remdesivir, 10-day treatment# (n=197)NRWithin 14 days: 52NRNR
Overall, symptoms <10 days#NRWithin 14 days: 62NRNR
Overall, symptoms >10 days#NRWithin 14 days: 49NRNR
Between-group difference/comparisonNRNRNRNR
 Wang [44]Remdesivir (n=158)21.0 (12.0–31.0)Patients discharged (alive)
Day 14: 25
Day 28: 61
NRNR
Placebo (n=78)21.0 (13.5–28.5)Patients discharged (alive) Day 14: 23
Day 28: 58
NRNR
Between-group difference/comparisonDifference 0.0 (95% CI −3.0–3.0)Day 14: OR 1.25 (95% CI 0.76–1.17)
Day 28: OR 1.15 (95% CI 0.67–1.96)
NRNR
 Shih+ [69]Remdesivir (n=158)NRDay 14 (n=151): 29.8
Day 28 (n=149): 66.4
NRNR
Placebo (n=78)NRDay 14 (n=78): 23.1
Day 28 (n=78): 60.5
NRNR
Between-group difference/comparisonNRNRNRNR
 Spinner [70]Remdesivir, 5-day treatment (n=191)NRPatients not hospitalised
Day 11: 70
Day 14: 76
Day 28: 89
NRNR
Remdesivir, 10-day treatment (n=193)NRPatients not hospitalised
Day 11: 65
Day 14: 76
Day 28: 90
NRNR
Standard care (n=200)NRPatients not hospitalised
Day 11: 60
Day 14: 67
Day 28: 83
NRNR
Between-group difference/comparisonNRNRNRNR
Antimalarial drugs
 Abd-Elsalam [45]Hydroxychloroquine# (n=97)NRNR11.3NR
Standard care (n=97)NRNR13.4NR
Between-group difference/comparisonNRNRp=0.83NR
Mucolytic drugs
 Ansarin [47]Bromhexine# (n=39)7.6±3.5NR5.1NR
Standard care (n=39)8.1±5.5NR28.2NR
Between-group difference/comparisonp=0.587NRp=0.006*NR
 Li [55]Bromhexine# (n=12)NRWithin 20 days: 83.3NRNR
Standard care (n=6)NRWithin 20 days: 33.3NRNR
Between-group difference/comparisonNRp=0.12NRNR
Anti-inflammatory drugs
 Angus [46]Hydrocortisone, fixed dose§ (n=137)NRNRNRAdjusted HR:
0.93±0.14
Median 0.92 (95% CI 0.68–1.24)
Hydrocortisone, shock-dependent dosing§ (n=141)NRNRNRAdjusted HR:
0.86±0.13
Median 0.85 (95% CI 0.62–1.15)
Standard care§ (n=101)NRNRNRMean: 1 (Reference)
Median: 1 (Reference)
Between-group difference/comparisonNRNRNRProbability of superiority to standard care, 29% (fixed dose) and 14% (shock-dependent dosing)
 Horby [43]Dexamethasone# (n=2104)NRWithin 28 days: 67.2NRNR
Standard care (n=4321)NRWithin 28 days: 63.5NRNR
Between-group difference/comparisonNRRR 1.10 (95% CI 1.03–1.17)*NRNR
 Dequin [50]Hydrocortisone (n=76)NRDischarge from ICU§: 57.3NRNR
Placebo (n=73)NRDischarge from ICU§: 43.8NRNR
Between-group difference/comparisonNRNRNRNR
 Edalatifard [52]Methylprednisolone# (n=34)Time to discharge/death: 11.62±4.81NRNRNR
Standard care (n=28)Time to discharge/death: 17.61±9.84NRNRNR
Between-group difference/comparisonp=0.006*NRNRNR
 Davoodi [35]Febuxostat (n=29)NR100 (of three patients hospitalised)0NR
Hydroxychloroquine (n=25)NR100 (of three patients hospitalised)0NR
Between-group difference/comparisonNRNRNRNR
Kinase inhibitors
 Cao [32]Ruxolitinib# (n=20)17.0 (11.0–21.0)NRNRNR
Placebo (n=21)16.0 (11.0–20.0)NRNRNR
Between-group difference/comparisonp=0.941NRNRNR
Immunomodulatory therapies
 Perotti [41]Hyperimmune plasma (n=46)NRWithin 7 days: 0NRNR
 Li [38]Standard care (n=51)Indeterminate (19.0–indeterminate)
Time from hospitalisation to discharge: 53.0 (35.0–indeterminate)
Within 28 days: 36.0NRNR
Convalescent plasma (n=52)28.0 (13.0–indeterminate)
Time from hospitalisation to discharge: 41.0 (31.0–indeterminate)
Within 28 days: 51.0NRNR
Between-group difference/comparisonHR 1.61 (95% CI 0.88–2.95); p=0.12
Hospitalisation to discharge: HR 1.68 (95% CI 0.92–3.08); p=0.09
OR 1.85 (95% CI 0.83–4.10); p=0.13NRNR
Standard care, severe disease (n=51)19.0 (11.0– indeterminate)
Time from hospitalisation to discharge: 41.0 (30.0–53.0)
Within 28 days: 68.2NRNR
Convalescent plasma, severe disease (n=23)13.0 (10.0–16.0)
Time from hospitalisation to discharge: 32.0 (26.0–40.0)
Within 28 days: 91.3NRNR
Between-group difference/comparisonHR 1.97 (95% CI 1.00–3.88); p=0.05
Hospitalisation to discharge: HR 1.74 (95% CI 0.89–3.41); p=0.11
OR 4.90 (95% CI 0.89–26.97); p=0.07NRNR
Standard care, life-threatening disease (n=22)Indeterminate
Time from hospitalisation to discharge: indeterminate
Within 28 days: 10.7NRNR
Convalescent plasma, life-threatening disease (n=28)Indeterminate
Time from hospitalisation to discharge: indeterminate (46.0–indeterminate)
Within 28 days: 17.9NRNR
Between-group difference/comparisonHR 1.77 (95% CI 0.42–7.40); p=0.44
Hospitalisation to discharge: HR 1.90 (95% CI 0.45–8.04); p=0.38
OR 1.81 (0.39–8.44); p=0.71NRNR
de Alencar [49]N-acetylcysteine# (n=67)NRNR439 (5–14)
Placebo# (n=68)NRNR478 (4–15)
Between-group difference/comparisonNRNROR 0.85 (95% CI 0.43–1.69); p=0.652p=0.557

Data are presented as median (interquartile range), % or mean±sd, unless otherwise stated. ICU: intensive care unit; IFN: interferon; NR: not reported; NA: not applicable; RBV: ribavirin. #: treatment administered in addition to standard care, as defined by the investigators in each trial; : outcome was reported as part of a modified 6- or 7-category ordinal scale of clinical status; +: re-analysis of data from Wang et al. [44], using different criteria; §: participants could be randomly assigned to other interventions within other therapeutic domains. *: statistically significant p-value or between-group comparison.