Impact and outcomes of primary cytomegalovirus disease in seronegative abdominal solid organ transplant recipients of cytomegalovirus unexposed donors (D-/R-)

Background: Primary cytomegalovirus (CMV) disease in high-risk (D+/R-) abdominal solid organ transplant recipients (aSOTRs) is well described, however, little is known of primary CMV disease in low-risk (D-/R-) patients.

Methods: Observational study of adult aSOTRs between 1/1/2009 and 9/1/2019 screened based on serostatus at transplant; D-/R- and D+/R- patients were included.

Primary objective: Describe epidemiology of primary CMV in D-/R- aSOTRs.

Secondary objective: Compare infectious and transplant-related outcomes of primary CMV disease in the first 90 days (early CMV) between D-/R- and D+/R-.

Results: Of 782 D-/R- aSOTRs in the study period, 13 developed CMV at any time after transplant to last follow-up. Of 671 D+/R- patients, 186 developed CMV. Early CMV disease was significantly more common in the D-/R- group (54% vs 15.6%, P = .0005) despite populations being similar demographically, including allograft subtype. D-/R- patients with early CMV disease had median viral load >100 000 IU/mL and 42.9% had end-organ manifestations; 71.4% required hospital admission. Immunosuppressive therapy was adjusted in 100% of patients, there was an approximately 14.3% rate of antiviral resistance and 28.6% had concomitant opportunistic infection. These findings were similar to D+/R- patients. There was no difference in risk of rejection or all-cause mortality associated with early CMV disease, however, graft loss was significantly higher in D-/R-.

Conclusion: D-/R- aSOTRs infrequently develop CMV, however, when it occurs, they present with disease manifestations similar to and graft outcomes inferior to D+/R- with CMV. Additionally, the majority of CMV disease in D-/R- occurs in the first 90 days after transplant, suggesting possible donor subclinical infection or transfusion source. The complicated course in D-/R- is likely caused by low clinical suspicion. Awareness of disease severity and aggressive upfront management may promote positive outcomes.