Sara van den Berg

63 3 CMV on influenza vaccination: a systematic review Figure 3. Summary of conclusions from studies on latent CMV infection on the influenza antibody response. Conclusion per study, are shown for the effect of CMV infection on the influenza antibody response, separated for young (<65 years of age) or old (>60 years of age) individuals. A flow diagram of records available per re- ported conclusion out of the 15 articles is presented in supplementary figure 1. Note that the article of Furman et al contained the outcome of three study populations and was thus assessed as three individual studies. The study group in Nielsen et al had an age range of 21-77 years, covering both young and old adults, therefore the reported conclusion (no effect) was included in both young and old bar graphs. Statistics per study were per- formed by parametric tests on log-transformed influenza antibody data, unless indicated otherwise in footnotes. 1 A Mann Whitney test was performed on raw influenza antibody data (post-titer). 2 Data was presented as a geo- metric mean of three different influenza strains titer. Also, we could not verify how the geometric mean of three influenza strains per individual was handled in the measurement of spread on group level. 3 A Mann Whitney test was performed on fold increase of influenza antibody data. 4 Antibody data was analysed with non-parametric test (Spearman correlation) on non-log-transformed antibody data (for both CMV and influenza antibodies). 5 We could not verify what statistics were used, since it is stated in the paper that the GMT and 95%CI of day 21 post-vaccination are presented in figure 1 of the article, but the 95% CI showed equally distributed error bars on a linear scale. Also, it is stated that Mann-Whitney was used to compare GMTs, which is statistically not possible. Impact of CMV on antibody titers after influenza vaccination No effect of CMV-serostatus on influenza antibody titer to influenza vaccination (GMR) (outcome a) We first examined the geometric mean titer pre-/post-vaccination ratio (GMR) to influenza vaccination for CMV-seropositive and CMV-seronegative individuals (outcome a). In 10/17 studies the GMR per CMV-serostatus could be estimated from figures [40] or could be recalculated with the reported data [26, 28, 47-51] ( Supplementary figure 2 ). For only 5 of these 10 studies, the 95% confidence interval (CI) could be extracted [40, 47, 50-52]. These 95% CI were either estimated directly from figures or calculated based on depicted SD/ SE. We refrained from calculating the ratios of the GMR of CMV-seropositive versus CMV- seronegative individuals since the measure of spread was estimated from figures, and thus