| Outcome |
Relative effect
(95% CI) |
Absolute effect
(95% CI)1 |
Certainty of the Evidence
(GRADE) |
Clinical improvement
D28 |
RR: 1.15
(0.97 - 1.38) |
71 more per 1000
(from 14 fewer to 180 more)
|
Very low certainty
Reasons to downgrade
Risk of bias: Serious
Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, deviation from intended intervention, outcome measurement and selection of the reported results Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious
due to very wide confidence interval consistent with the possibility for benefit and the possibility for no effect and low number of participants
|
| 3 trials
Shu L, 2020; Shi L, 2021; Lanzoni G, 2020
166 participants
|
|
Umbilical cord mesenchymal stem cell infusion
545 per 1,000
(459 - 654) |
Standard care/Placebo
474
per 1,000 |
|
Clinical improvement
D60 |
RR: 1.80
(0.85 - 3.79) |
333 more per 1000
(from 63 fewer to 1000 more)
|
Very low certainty
Reasons to downgrade
Risk of bias: Not serious Inconsistency: Not serious Indirectness: Serious
single study from a single institution therefore results in this population might not be generalizable to other settings Imprecision: Very serious
due to wide confidence interval consistent with the possibility for benefit and the possibility for no effect and low number of participants
|
| 1 trials
Lanzoni G, 2020
24 participants
|
|
Umbilical cord mesenchymal stem cell infusion
750 per 1,000
(354 - 1000) |
Standard care/Placebo
417
per 1,000 |
|
WHO progression score (level 7 or above)
D28 |
RR: 0.26
(0.01 - 4.43) |
46 fewer per 1000
(from 62 fewer to 214 more)
|
Very low certainty
Reasons to downgrade
Risk of bias: Serious
Risk of bias downgraded by 1 level: some concerns regarding adequate randomization, deviations from intended interventions, and selection of the reported results Inconsistency: Not serious Indirectness: Serious
Indirectness downgraded by 1 level: studies from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious
due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
|
| 2 trials
Shu L, 2020; Shi L, 2021
142 participants
|
|
Umbilical cord mesenchymal stem cell infusion
16 per 1,000
(1 - 277) |
Standard care/Placebo
63
per 1,000 |
|
WHO progression score (level 7 or above)
D60 |
Outcome not yet measured or reported
|
|
All-cause mortality
D28 |
RR: 0.60
(0.17 - 2.08) |
55 fewer per 1000
(from 115 fewer to 150 more)
|
Low certainty
Reasons to downgrade
Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious Imprecision: Very serious
due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
|
| 4 trials
Shi L, 2020; Shu L, 2020; Monsel A, 2022; Lanzoni G, 2020
213 participants
|
|
Umbilical cord mesenchymal stem cell infusion
83 per 1,000
(24 - 288) |
Standard care/Placebo
139
per 1,000 |
|
All-cause mortality
D60 |
RR: 0.18
(0.01 - 4.29) |
23 fewer per 1000
(from 28 fewer to 94 more)
|
Very low certainty
Reasons to downgrade
Risk of bias: Serious
Risk of bias downgraded by 1 level: some concerns regarding missing data, and selection of the reported results Inconsistency: Not serious Indirectness: Serious
despite a multicentre design this is a single study from a single country, therefore results in this population might not be generalizable to other settings. Imprecision: Very serious
due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm
|
| 1 trials
Shi L, 2022
101 participants
|
|
Umbilical cord mesenchymal stem cell infusion
5 per 1,000
(0 - 123) |
Standard care/Placebo
29
per 1,000 |
1 additional study was identified that assessed this outcome, but no results were reported. |
Viral negative conversion
D7 |
Outcome not yet measured or reported
|
|
Adverse events
|
RR: 1.04
(0.86 - 1.25) |
31 more per 1000
(from 107 fewer to 191 more)
|
Moderate certainty
Reasons to downgrade
Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious
We presume that the adverse event rates and the corresponding relative risks, are similar across diverse settings; therefore not downgraded for indirectness Imprecision: Serious
due to low number of participants/events
|
| 3 trials
Shi L, 2020; Monsel A, 2022; Lanzoni G, 2022
172 participants
|
|
Umbilical cord mesenchymal stem cell infusion
794 per 1,000
(657 - 955) |
Standard care/Placebo
764
per 1,000 |
|
Serious adverse events
|
RR: 0.66
(0.20 - 2.20) |
66 fewer per 1000
(from 156 fewer to 233 more)
|
Low certainty
Reasons to downgrade
Risk of bias: Not serious Inconsistency: Not serious Indirectness: Not serious
We presume that the adverse event rates and the corresponding relative risks, are similar across diverse settings; therefore not downgraded for indirectness Imprecision: Very serious
due to very wide confidence interval consistent with the possibility for benefit and the possibility for harm Other considerations: none
|
| 3 trials
Shi L, 2020; Monsel A, 2022; Lanzoni G, 2022
172 participants
|
|
Umbilical cord mesenchymal stem cell infusion
128 per 1,000
(39 - 428) |
Standard care/Placebo
194
per 1,000 |
|
1The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
