The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis

Abstract Background Cytomegalovirus (CMV) infection continues to cause morbidity in kidney transplant recipients, despite prophylaxis and pre-emptive therapy. Predictors of poor outcomes remain incompletely characterized. We questioned whether markers of CMV replication (CMV peak viral load, recurrent episodes, or duration of CMV DNAemia) are associated with adverse outcomes in the current era. Methods We studied 605 people who underwent kidney transplant at Johns Hopkins University (2010 – 2018). Mean follow-up was 45.5 months. The average age was 51.85 years and 39.7% were female. Donor-seropositive, recipient seronegative (D+/R-) patients received valganciclovir 900 mg/day for 6 months, while R+ patients received valganciclovir 450 mg/day for 3 months. CMV recurrence was defined as CMV DNAemia after two undetectable CMV PCR’s. Outcomes of acute rejection, graft failure, and death were evaluated in univariate analysis; p values were calculated by Fisher’s exact test. Results Peak CMV viral load was not associated with any outcomes (Table 1). There was a trend of increased graft failure in people who had long duration ( >6 month) DNAemia (Table 2). More than two episodes of CMV reactivation was associated with graft failure and rejection (Table 3). Conclusion CMV reactivation is associated with kidney rejection and failure in univariate models. Multivariate analyses and longitudinal modeling will provide increased data upon which to better instruct preventative strategies. Acknowledgments Funding for the research study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Disclosures Robin K. Avery, MD, Aicuris (Grant/Research Support)Astellas (Grant/Research Support)Chimerix (Research Grant or Support)Merck (Grant/Research Support)Oxford Immunotec (Grant/Research Support)Qiagen (Grant/Research Support)Takeda/Shire (Grant/Research Support) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder) Kieren Marr, MD, Merck (Grant/Research Support, Advisor or Review Panel member)

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In-depth virological assessment of kidney transplant recipients with COVID-19

10.1101/2020.06.17.20132076 ◽

2020 ◽

Author(s):

Ilies Benotmane ◽

Gabriela Gautier Vargas ◽

Marie-Josée Wendling ◽

Peggy Perrin ◽

Aurélie Velay ◽

...

Keyword(s):

Viral Load ◽

Kidney Transplant ◽

Symptom Onset ◽

Plasma Viral Load ◽

Humoral Response ◽

Serological Response ◽

Upper Respiratory Tract ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Viral Loads

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies the second week after symptom onset that persisted for two months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.

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