Table 12.

GRADE assessment for narrative synthesis outcomes in MERS studies.

Summary of findings:
Combination or non-combination IFN treatment compared to No IFN/A different treatment protocol including IFN for MERS
Patient or population: MERS Setting: 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	Meta-analysis conducted. Also, 2 additional studies for narrative synthesis detected the use of IFN therapy was possibly of no use (Alfaraj et al and Sherbini et al.).	(26 observational studies)	⨁◯◯◯ VERY LOWa
Discharge	Garout et al. showed a discharge rate of 20% in the RBV + IFN-α (n = 35) group vs. 35.2% in the no RBV + IFN-α group (n = 17).	(26 observational studies)	⨁◯◯◯ VERY LOWa
Chest x-ray	Comparative assessments are lacking.	(26 observational studies)	–
Inflammatory profile	A study compared IFN-α with IFN-β, and found the difference in CRP levels was not significant (p = 0.61) (Shalhoub et al.).	(26 observational studies)	⨁◯◯◯ VERY LOWb
Severity	Al Ghamdi et al. showed a negative relation with severity for IFN-α but not IFN-β. Precisely, Univariable analysis of the influence of severity of disease on medications administered showed a significant negative risk association of – 4.62, 95% CI: (−8.40,−0.84) (p = 0.018) for IFN-α, and a negative but non-significant risk association of – 1.24, 95% CI: (−6.71,4.24) (p = 0.652) for IFN-β. Moreover, a multivariable analysis, which included a biomarker of disease severity, showed a strong association between disease severity and decreased survival, and no association between treatment with IFN-β and mortality (OR = 0.68, 95% CI: (0.04,10.28)) (p = 0.778)	(26 observational studies)	⨁⨁◯◯ LOW
Hospital durations	The length of hospital stay in RBV/IFN vs no RBV/IFN was not significantly different (p = 0.48) (Arabi et al.).	(26 observational studies)	⨁⨁◯◯ LOW
ADEs	In 7 studies, ADEs were recorded while using regimen containing IFNs, including multi-organ damage, adverse change in blood profile, thrombocytopenia, kidney disease, fever, and pancreatitis (Al-Tawfiq et al., Rhee et al., Kim et al., Cha et al., Al-Qaseer et al., Omrani et al., Khalid et al.).	(26 observational studies)	⨁◯◯◯ VERY LOWa,c
*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, CI: Confidence interval, CRP: C-reactive protein, IFN: interferon, MERS: Middle-Eastern respiratory syndrome, RBV: ribavirin.
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.

^aDifferent IFN-based regimen were used, and were compared to varied treatment options. Results should be taken as speculative, rather than as for net efficacy of IFN.

^bAll important inflammatory elements, such as major inflammatory cytokines are required for proper assessment of inflammatory state.

^cCombination therapies of IFN as well as lack of a comparator group makes it difficult to determine whether such adverse events are a direct result of IFNs administration.