Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. We compared polyfunctional CMV-specific T-cell responses in a prospective cohort of allogeneic HCT recipients who received letermovir to controls who received PCR-guided preemptive therapy prior to the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at three months post-HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen specific T-cell subsets (COMPASS). Letermovir use and reduction in viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjusting for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8+ responses to pp65; whereas CMV shedding rate was associated with greater CD4+ responses to IE-1. In conclusion, our study provides initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly due to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality may identify patients at risk for late CMV infection after HCT.

Running title: Burning and grassland management 60 word "summary of what is exciting about the MS": Within the context of evidence-based conservation, we provide clear evidence that spring burning is not a viable long-term alternative to grazing or mowing. We do this by using odds ratios for finding indicator species, rather than using more traditional methods of vegetation analyses, and by meta-analyses of the outcomes from 11 field trials. 1 Abstract Question:The management of species-rich semi-natural grasslands, a fragmented and threatened vegetation type in Europe, involves costs. Mowing is expensive and grazing can be difficult to achieve and maintain for logistical reasons. Is annual spring burning, potentially cheaper than mowing and grazing, a viable management tool for species-rich grasslands?Location: Long-term field trials in 11 grasslands in southern Sweden. Methods:We calculated the odds for a species being an indicator of good management, an indicator of poor management, and an indicator of nitrogen influence in spring-burnt plots, grazed plots, and annually mowed plots. Odds ratios contrasting spring-burnt plots with grazed plots and spring-burnt plots with mowed plots were subjected to meta-analyses in which we compared the odds ratios after 1, 8, and 14 spring burns. For a single trial, we also analysed data after 1, 8, 14, 28, and 39 spring burns. Results:Compared with mowed and grazed plots, the odds of the four different indicators of good management decreased in spring-burnt plots, while the odds for the two indicators of poor management increased. There was no trend in the two indicators of excess nitrogen. Therefore, the conservation value of vegetation in spring-burnt plots becomes impoverished over time relative to traditional management. Conclusions:Spring burning is not an appropriate long-term management method if the aim is to maintain the conservation value of the vegetation in traditionally managed semi-natural grasslands.

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