Abstract
BackgroundCytomegalovirus (CMV) infection causes significant morbidity after transplant. Patients can be stratified by donor and recipient CMV serostatus, but the infection phenotype remains variable. We hypothesized that some of this variability might be explained by circadian rhythms influenced by time of transplant.MethodsVirological, demographic and transplant data were reviewed for liver and kidney transplant patients (n = 1,111) managed between 2002 and 2015 using pre-emptive therapy. Donor circulatory arrest time and reperfusion time in the recipient were split into four categories, chosen a priori. Patients were categorised into three groups depending on donor and recipient CMV serostatus. Differences between groups were assessed using chi-squared and Kruskall–Wallis tests.ResultsFor the donor seropositive/recipient seronegative group (D+R−) all CMV parameters were highest when reperfusion occurred in the day or evening, and the lowest in the night or morning (see table).Day 10 a.m.–4 p.m. N = 101 Evening 4 p.m.–10 p.m. N = 53Night 10 p.m.–4 a.m. N = 30Morning 4 a.m.–10 a.m. N = 20 P ValueDeveloped CMV Viraemia Within 90 Days % (n)Yes76.2 (77)73.6 (39)66.7 (20)45.0 (9)0.039No23.8 (24)26.4 (14)33.3 (10)55.0 (11)Received anti-CMV Treatment % (n)Yes63.4 (64)64.2 (34)50.0 (15)45.0 (9)0.264No36.6 (37)35.9 (19)50.0 (15)55.0 (11)Among those that became viraemicPeak viral load, copies/mLMedian (IQR)14,870 (3,220–97,551)23,789 (3,509–58,314)5,685.5 (2,711–26,407)6,238 (2,839–8,131)0.074Duration viraemia, daysMedian (IQR)42 (24–63)42 (18–70)31 (21–57)34 (26–35)0.555Duration treatment, daysMedian (IQR)48 (33–64)47.5 (29–67)42 (29–66)28 (21–41)0.257No such pattern was seen for circulatory arrest time, or in the D-R+ or D+R+ groups.ConclusionTime of day of transplant surgery appears to be associated with development of CMV viraemia and the parameters of infection in one subgroup of transplant patients. These differences could be explained by circadian rhythms of CMV replication and/or immunological parameters varying throughout the day. These data therefore provide support for further study of circadian effects on CMV replication and host CMV immunity.Disclosures P. Griffiths, shire: Scientific Advisor, funds paid to my institution not to me; chimerix: Scientific Advisor, funds paid to my institution not to me; sanofi pasteur: Grant Investigator, funds paid to my institution not to me; genentech: Scientific Advisor, funds paid to my institution not to me.
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