Table 11.
GRADE assessment for narrative synthesis outcomes in COVID-19 studies.
| Summary of findings: | |||
|---|---|---|---|
| Combination or non-combination IFN treatment compared to No IFN/A different treatment protocol including IFN for COVID-19 | |||
| Patient or population: COVID-19 Setting: RCTs, non-randomized trials, and observational studies Intervention: Combination or non-combination IFN treatment Comparison: No IFN/A different treatment protocol including IFN | |||
| Outcomes | Impact | Studies | Certainty of the evidence (GRADE) |
| Mortality | Both studies did not report a remarkable difference in total mortality. Considerable variations were present among study designs. | (2 RCTs) | ⨁⨁⨁◯ MODERATEa |
| Comparative assessments are lacking. | (2 non-randomized trials) | – | |
| Comparative assessments are lacking. | (25 observational studies) | ⨁⨁◯◯ LOW |
|
| Discharge | Wang et al. showed higher discharge rate in IFN + REM group compared to IFN + Placebo. | (2 RCTs) | ⨁⨁⨁⨁ HIGH |
| Comparative assessments are lacking. | (2 non-randomized trials) | – | |
| Comparative assessments are lacking. | (25 observational studies) | – | |
| Chest X-ray | Comparative assessments are lacking. | (2 RCTs) | – |
| Cai et al. showed FPV + IFN-α was significantly linked to improvement in CXR compared with LPV/RTV + IFN-α treatment (p = 0.004). | (2 non-randomized trials) | ⨁⨁⨁⨁ HIGH |
|
| Comparative assessments are lacking. | (25 observational studies) | – | |
| Severity | Meta-analysis conducted. | (2 RCTs) | -b |
| Jiang et al. showed cases treated with IFN-β + LPV/RTV, 39 (80%) were non-severe and 3 (38%) were severe (p = 0.045). Also, among cases treated with IFN-β + LPV/RTV + ARB, 10 (19%) were non-severe and 5 (63%) were severe (p = 0.019) | (2 non-randomized trials) | ⨁⨁⨁◯ MODERATEc |
|
| A cohort by Yuan et al. showed IFN treatment durations varied significantly among severe, moderate, and mild cases (p = 0.01). | (25 observational studies) | ⨁◯◯◯ VERY LOWd |
|
| Inflammatory profile | Hung et al. did not find any significant difference in inflammatory profile. | (2 RCTs) | ⨁⨁⨁◯ MODERATEe |
| In a study with FPV + IFN-α and LPV/RTV + IFN-α arms, Cai et al. did not show a significant different in IL-6 and CRP. | (2 non-randomized trials) | ⨁⨁⨁◯ MODERATEe |
|
| Zhou et al. showed a higher efficacy for IFN and its combination therapies vs. therapy without IFN in reducing inflammatory elements. | (25 observational studies) | ⨁◯◯◯ VERY LOWe |
|
| Hospital durations | Comparative assessments are lacking. | (2 non-randomized trials) | – |
| Hung et al. showed LPV/RTV + RBV + IFN-β group had a reduced hospitalization time compared to LPV/RTV. Wang et al. included two arms both of which used IFN, and detected no difference in hospitalization duration. | (2 RCTs) | ⨁⨁⨁⨁ HIGH |
|
| No significant effects were detected in 3 studies. Xu et al. 15 (45.5%) cases with symptoms lasting longer than ten days and 19 (65.5%) cases with symptoms lasting shorter than or equal to 10 days received IFN alone or in combination with ARB, RBV, or LPV/RTV. In the study by Zhou et al. IFN, IFN + ARB, and ARB arms were not significantly different in regards to symptom onset to hospital admission (p = 0.87). Yuan et al. showed that the duration of hospitalization was significantly correlated with PCR negative conversion durations in the IFN-α + LPV/RTV + RBV group (p = 0.0215), as well as the IFN-α + LPV/RTV group (p = 0.012) | (25 observational studies) | ⨁◯◯◯ VERY LOWf,g |
|
| ADEs | Significant and clear association was not established. | (2 RCTs) | ⨁⨁⨁◯ MODERATEh |
| Cai et al. showed FPV + IFN-α was significantly linked to less total ADEs compared with LPV/RTV + IFN-α treatment (p = 0.001). | (2 non-randomized trials) | ⨁⨁⨁⨁ HIGH |
|
| Comparative assessments are lacking. | (25 observational studies) | – | |
| *The 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). ADEs: adverse drug events, ARB: arbidol, CI: Confidence interval, FPV: favipiravir, IL: interleukin, LPV: lopinavir, RCT: randomized controlled trial, REM: remdesivir, RTV: ritonavir. | |||
|
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 | |||
Explanations.
a
Different study designs with considerably different combination or non-combination IFN treatments may introduce inconsistency.
c
No explanation of randomization process both in trial document and the article.
d
IFN durations are indirectly related to our question. Our question is whether IFN use vs. a different treatment therapy is linked to COVID-19 severity. Duration of therapy is related but may not provide a direct answer.
e
All important inflammatory elements, such as major inflammatory cytokines are required for proper assessment of inflammatory state.
f
Different hospital durations have been comparatively described in different arms of 2 studies, which can not be assessed with consistency.
g
Hospital durations and IFN use is the main question. However, Xu et al. synthesized IFN use by duration of symptoms. Although related, this might be seriously indirect in answering the research question.
h
Assessment depending on specific ADEs, serious ADEs, or any ADEs could result in different interpretations of the same study.