Table 2. GRADE Evidence Profile Table.

Outcome	No. of studies	Certainty assessment						Effect			Certaintyb
		Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	No. of events	No. of individualsa	Rate, % (95% CI)
Incidence of anaphylaxis to a second dose of the SARS-CoV-2 mRNA vaccine in persons who had an allergic reaction to their first dose	22	Case studies and case reports	Not seriousc	Not serious	Not serious	Not serious	Large effect of tolerating and residual confounding would suggest an effect of reacting when none was detectedd	6	1366	0.16 (0.01-2.94)	+++ (Moderate)
Incidence of anaphylaxis to a second dose of the SARS-CoV-2 mRNA vaccine in persons who had anaphylaxis to their first dose	17	Case studies and case reports	Not seriousc	Not serious	Not serious	Not seriouse	Large effect of tolerating and residual confounding would suggest an effect of reacting when none was detectedd,e	4	78	4.94 (0.93-22.28)	++ (Low)
Incidence of mild allergic symptoms to a second dose of the SARS-CoV-2 mRNA vaccine in persons who had an allergic reaction to their first dose	22	Case studies and case reports	Not seriousc	Not serious	Not serious	Not serious	Large effect of tolerating and residual confounding would suggest an effect of reacting when none was detectedd	232	1366	13.65 (7.76-22.9)	+++ (Moderate)

Abbreviation: GRADE, Grading of Recommendation, Assessment, Development, and Evaluation.

^a Patient or population: patients receiving second mRNA COVID vaccination after a previous allergic reaction to a mRNA COVID vaccine dose.

^b GRADE Working Group grades of evidence: high certainty, we are very confident that the true effect lies close to that of the estimate of effect; moderate certainty, we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of 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 effect; and 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. The number of plus symbols indicates the degree of certainty, where more plus symbols indicate a higher degree of certainty.

^c Risk of bias addressed in subgroup and sensitivity analyses.

^d A history of allergic reaction to previous COVID vaccination was a priori thought to guarantee a reaction to repeated doses, but far fewer than all individuals who received the second dose had an allergic reaction or anaphylaxis. Furthermore, those receiving a second dose of the vaccine, after an initial allergic reaction, would be at higher likelihood to be intensely monitored for any possible allergic reaction, whereas those without any history of an allergic reaction would not be intensely monitored.

^e Imprecision in width of 95% CIs and total sample size sufficient to prevent rating up certainty for considerations of residual confounding, but not to rate down; the qualitative effect of the incidence of repeated anaphylaxis being not very high (eg, 100%) is more certain than the quantitative estimate of a mean of 4.9%.