Transfusion-transmitted and community-acquired cytomegalovirus infection in seronegative solid organ transplant recipients receiving seronegative donor organs

Abstract

Solid organ transplant (SOT) recipients who are cytomegalovirus (CMV) seronegative (R−) and receive seronegative donor (D−) organs have a small but currently unquantified risk of both transfusion-transmitted CMV (TT-CMV) and community-acquired CMV (CA-CMV). We retrospectively studied the incidence and clinical symptoms of TT-CMV (infection <1 year posttransplant) and CA-CMV (infection >1 year posttransplant) in a cohort of D−/R− adult and pediatric SOT recipients receiving leukoreduced blood products not screened for CMV seronegativity transplanted at our center between 2000 and 2011. CMV infection was defined as IgG seroconversion or detectable CMV antigenemia/DNAemia. Among 536 consecutive D−/R− recipients, 398 (81.8%) had adequate follow-up, and 231 (58%) received cellular blood products (total: 1626 red blood cell units, 470 platelet units) 30 days pretransplant to 90 days posttransplant. We observed no confirmed TT-CMV cases, but 14 CA-CMV cases (64% symptomatic) were seen. The estimated incidence rate of CA-CMV was higher in children (3.0/100 patient years) than adults (0.46/100 patient years, incident rate ratio of 6.52). The absence of TT-CMV over 11 years suggests neither seronegative blood products nor CMV DNA blood donor screening would provide significant incremental safety when blood is already leukoreduced. D−/R− SOT recipients, particularly children, have a significantly higher and ongoing risk of CA-CMV.

Cytomegalovirus transmission in mismatched solid organ transplant recipients: Are factors other than anti-viral prophylaxis at play?

“…The D+/R‐ retrospective cohort included all adult (≥17‐year‐old) patients who had received a SOT (lung, heart, liver, kidney, pancreas, small bowel, or multivisceral) at the University of Alberta Hospital between January 2000 and December 2013. A contemporaneous cohort of D‐/R‐ patients transplanted between January 2000 and December 2011 previously described 15 provided a control group for transfusion and community‐acquired infection. Patients who died within 1 month of transplant were excluded.…”

“…Kidney and pancreas transplant recipients had prophylaxis extended from 14 weeks to 6 months in January 2013. CMV D‐/R‐ patients received only short‐term HSV prophylaxis unless Epstein‐Barr virus mismatched as previously described 15 …”

“…CMV D-/R-patients received only short-term HSV prophylaxis unless Epstein-Barr virus mismatched as previously described. 15…”

“…Patients received universally leukoreduced blood products. 15 CMV IgG results were considered false positive in recipients without positive antigenemia or CMV DNAemia and recent transfusion if they occurred within 8 weeks of plasma, red blood cell, platelet transfusion or within 16 weeks of IVIG administration; later posttransplant samples were tested to confirm seroconversion. The transfusion records of deceased donors whose organs did not transmit CMV infection were reviewed.…”

Cytomegalovirus in the transplant setting: Where are we now and what happens next? A report from the International CMV Symposium 2021

“…5,6 This impact on survival can either be a direct consequence of CMV disease (i.e., end-organ disease or systemic viral infection) or an indirect outcome resulting from an increased risk of opportunistic bacte-rial, viral or fungal infection, graft rejection, thrombotic events, or cardiovascular disease. [7][8][9][10] Poor survival is not only associated with CMV status in the recipient, as using stem cells from a CMV-positive donor in a CMV-negative recipient also increases the risk of mortality. 11 Per Ljungman set the tone of the symposium early by engaging the delegates in discussion during the first presentation of the meeting.…”