Donor Graft Cytomegalovirus Serostatus and the Risk of Arterial and Venous Thrombotic Events in Seronegative Recipients After Non-Thoracic Solid Organ Transplantation

Belga, Sara; MacDonald, Clayton; Chiang, Diana; Kabbani, Dima; Shojai, Soroush; Abraldes, Juan G.; Cervera, Carlos

doi:10.1093/cid/ciaa125

Cited by 10 publications

(13 citation statements)

References 52 publications

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“…Instead, these results are compatible with the hypothesis that the association is mediated by a combination of direct CMV diseaseassociated short-term mortality and CMV-associated indirect biological effects, including increased risk of thrombotic events, more severe hepatitis C virus (HCV) recurrence, and graft rejection. (2,6,7,10,12,22,23) Unfortunately, the accuracy and level of detail in the OPTN database preclude such assessments. Future studies to define the mechanism(s) through which CMV D+R− serostatus increases the risk for graft loss and death are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…(1,4,5) In addition to these direct short-term effects of CMV disease, CMV has also been implicated in a broad range of indirect (ie, not directly related to overt CMV disease) biological effects that could contribute to worse clinical outcomes. These indirect effects include increased systemic inflammation that could increase the risk for cardiovascular and thrombotic complications, (6,7) allograft inflammation that could lead to allograft injury, (8) and systemic immunosuppression that could predispose to secondary infection. (6,9,10) These biological effects of CMV can be mediated even during CMV latency or subclinical CMV reactivation (ie, independent of clinically recognized CMV disease) and occur more frequently in D+R− patients.…”

mentioning

confidence: 99%

“…These indirect effects include increased systemic inflammation that could increase the risk for cardiovascular and thrombotic complications, (6,7) allograft inflammation that could lead to allograft injury, (8) and systemic immunosuppression that could predispose to secondary infection. (6,9,10) These biological effects of CMV can be mediated even during CMV latency or subclinical CMV reactivation (ie, independent of clinically recognized CMV disease) and occur more frequently in D+R− patients. (6,10) Thus, it has been hypothesized that both the direct and indirect effects of CMV would disproportionately impact D+R− patients and lead to worse overall outcomes in this specific group of transplant recipients, as previously demonstrated among kidney and lung transplant recipients.…”

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confidence: 99%

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Association of Donor and Recipient Cytomegalovirus Serostatus on Graft and Patient Survival in Liver Transplant Recipients

et al. 2021

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Among solid organ transplant recipients, donor cytomegalovirus (CMV) seropositive (D+) and recipient seronegative (R−) status are associated with an increased risk of graft loss and mortality after kidney or lung transplantation. Whether a similar relationship exists among liver transplant recipients (LTR) is unknown. We assessed graft loss and mortality among adult LTRs from January 1, 2010, to March 14, 2020, in the Organ Procurement and Transplantation Network database. We used multivariable mixed Cox proportional hazards regression to analyze the association of donor and recipient CMV serostatus group with graft loss and mortality, with donor seronegative (D−) and recipient seronegative (R−) as the reference group. Among 54,078 LTRs, the proportion of D−R−, D− and recipient seropositive (R+), D+R−, and D+R+ was 13.4%, 22.5%, 22%, and 42%, respectively. By unadjusted Kaplan-Meier survival curve estimates, survival by the end of follow-up was 73.3%, 73.5%, 70.1%, and 69.7%, among the D−R−, D−R+, D+R−, and D+R+ groups, respectively. By multivariable Cox regression, the CMV D+R− serogroup, but not other serogroups, was independently associated with increased risks of graft loss (adjusted hazard ratio [aHR], 1.13; 95% confidence interval [CI], 1.05-1.22) and mortality (aHR, 1.13; 95% CI, 1.05-1.22). The magnitude of the association of the CMV D+R− serostatus group with mortality was similar when the Cox regression analysis was restricted to the first year after transplant and beyond the first year after transplant: aHR, 1.13 (95% CI, 1.01-1.27) and aHR, 1.13 (95% CI, 1.02-1.25), respectively. Even in an era of CMV preventive strategies, CMV D+R− serogroup status remains independently associated with increased graft loss and mortality in adult LTRs. Factors in addition to direct CMV-associated short-term mortality are likely, and studies to define the underlying mechanism(s) are warranted.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Association of Donor and Recipient Cytomegalovirus Serostatus on Graft and Patient Survival in Liver Transplant Recipients

et al. 2021

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“…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.…”

Section: Risk Of CMV In Transplant Settingsmentioning

confidence: 99%

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

Kotton

Torre‐Cisneros

Aguado

et al. 2022

Transplant Infectious Dis

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The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or hematopoietic stem cell transplantation. This review provides an overview of the presentations given by the expert faculty, supplemented with educational clinical cases. Topics discussed include CMV epidemiology and diagnosis, the burden of CMV infection and disease, CMV‐specific immunity and management of CMV in transplant settings. Major advances in the prevention and treatment of CMV in the past decade and increased understanding of CMV immunity have led to improved patient outcomes. In the future, management algorithms may be individualized based on the transplant recipient's immune profile, which will mark the start of a new era for patients with CMV.

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“…It is interesting to note that CMV has been associated with several diseases that increase risk for severe COVID-19, as well as with thrombotic events [16][17][18], which are main complications of COVID-19 disease. CMV is described in several case reports of atypical Kawasaki disease in children [19], in some aspects resembling the rare observed COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) occurring 3-6 weeks after a SARS-CoV-2 infection [20].…”

Section: Who Becomes Severely Ill In Covid-19 Disease?mentioning

confidence: 99%

Does reactivation of cytomegalovirus contribute to severe COVID-19 disease?

Söderberg‐Nauclér

2021

Immun Ageing

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The majority of people infected with SARS-CoV-2 are asymptomatic or have mild to moderate symptoms. However, for unknown reasons, about 15 % have severe pneumonia requiring hospital care and oxygen support, and about 5 % develop acute respiratory distress syndrome, septic shock, and multiorgan failure that result in a high mortality rate. The risk of severe COVID-19 is highest among those who are over 70 years of age. Why severe COVID-19 develops in some people but not others is not understood. Could some cases involve reactivation of latent cytomegalovirus (CMV)?

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Donor Graft Cytomegalovirus Serostatus and the Risk of Arterial and Venous Thrombotic Events in Seronegative Recipients After Non-Thoracic Solid Organ Transplantation

Cited by 10 publications

References 52 publications

Association of Donor and Recipient Cytomegalovirus Serostatus on Graft and Patient Survival in Liver Transplant Recipients

Association of Donor and Recipient Cytomegalovirus Serostatus on Graft and Patient Survival in Liver Transplant Recipients

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

Does reactivation of cytomegalovirus contribute to severe COVID-19 disease?

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