Table 4. Summary of evidence about treatment with nirmatrelvir-ritonavir versus standard treatment (without antivirals) for COVID-19.

Certainty assessment							№ of patients		Effect		Certainy	Importance
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Nirmatrelvir-ritonavir	Control	Relative (95% CI)	Absolute (95% CI)
Hospitalization in 35 days
11	observational study	very serious a	not serious	not seriousb	not serious	none	1559/234872 (0.7%)	10243/720674 (1.4%)	OR 0.47 (0.36 to 0.61)	7 fewer per 1.000 (from 9 fewer to 5 fewer)	⨁◯◯◯ Very low	IMPORTANT
Mortality in 35 days
13	observational study	seriousc	not serious	not seriousb	not serious	none	220/242409 (0.1%)	6848/889186 (0.8%)	OR 0.41 (0.35 to 0.52)	1 fewer per 1.000 (from 4 fewer to 3 fewer)	⨁⨁⨁◯ Moderate	CRITICAL
Mortality or hospitalization in 35 days
5	observational study	seriousd	not serious	not seriousb	not serious	none	309/22595 (1.4%)	6710/202857 (3.3%)	OR 0.44 (0.31 to 0.64)	18 fewer per 1.000 (from 23 fewer to 12 fewer)	⨁⨁⨁◯ Moderate	CRITICAL

CI: Confidence interval; OR: Odds ratio

Explications:

^a. Most studies were at serious risk of bias, with the study by Zhou et al., 2022 [27] showing critical risk of bias for the outcome of hospitalization within 30 days using the ROBINS-I tool.

^b. Do not go down because it is mortality / hospitalization for all causes, since COVID -19 is a new disease in which all the mechanisms that cause possible hospitalizations for other causes are not yet well understood.

^c. Most of the studies had a moderate risk of bias. However, two studies Aggarwal, et al., 2022 [24] and Patel et al., 2022 [26] showed a high risk of bias for the outcome of 30-day mortality using the ROBINS-I tool.

^d. All studies showed a moderate risk of bias for the ROBINS-I tool