Abstract

Abstract Background and Aims Kidney transplant recipients (KTR) have adverse COVID-19 outcomes due to the immunosuppressed status and multiple comorbidities. Cytomegalovirus (CMV) is one of the most frequent opportunistic infections after kidney transplantation. However, data concerning its reactivation after COVID-19 is scarce. Herein, we present a single-center cohort of KRT presenting with CMV infection after COVID-19 and its clinical outcomes. Method Single-center cross-sectional study including 22 KTR with CMV viraemia detected by quantitative polymerase chain reaction up to 6 months after COVID-19, between 2020 and 2022. Demographic and clinical data were collected from the electronic records. Results A total of 22 KTR (13 male) were included with a mean age of 55.5±15.5 years and a median Charlson score of 4 (IQR 3-6). Median time after transplantation was 65 months (IQR 12.5-174.5; 3 KTR with <6 months) and only one patient had been submitted to living-donor transplantation. Eight patients received induction therapy with antithymocyte globulin (ATG). At transplantation time, CMV serologic status had been: 50% D+/R+, 13.6% D+/R- and 4.5% D-/R+. CMV infection prior to COVID-19 had been documented in 6 patients. Concerning COVID-19, severe or critical disease had been reported in 8 patients. Specific therapy had been used in 4 patients: 2 with remdesivir/baricitinib, one with remdesivir and one with molnupiravir. Moreover, immunosuppressive therapy had been adjusted in 11 patients, namely by withdrawing the antimetabolite and increasing steroids (7 patients). Median maximum steroid dose (expressed as equivalents of prednisone dose) had been 40 mg (IQR 20-40) and mean cumulative steroid dose had been 416±317 mg. CMV disease was documented in 8 patients (4 with gastrointestinal involvement) and the mean time of diagnosis after COVID-19 was 10±6 weeks. Maintenance immunosuppression included tacrolimus, antimetabolite and steroid in 12 patients; 6 patients had supratherapeutic levels of tacrolimus at CMV infection diagnosis. Median initial viraemia was 770 copies/mL (IQR 288-4106). Valganciclovir was used in 14 patients (one was already taking it as prophylaxis), ganciclovir in 4 patients and CMV enriched human intravenous immunoglobulin was used in one patient. Nine patients required hospitalization and 2 were transferred to an intensive care unit; one of these 2 patients died. Induction therapy with ATG, CMV serologic status at transplantation time, previous CMV infection, COVID-19 severity or supratherapeutic immunosuppressive drug levels were not associated with CMV infection severity or hospitalization. However, higher maximum steroid dose during COVID-19 was associated with CMV disease (p = 0.038), higher viraemia at diagnosis (p = 0.032) and hospitalization (p = 0.018). Conclusion CMV infection is a common and clinically relevant complication in KTR. Altered immunologic status after COVID-19 may predispose to this infection. In addition, immunosuppressive therapy adjustments, namely the increase in steroid dosing may be very relevant to favor reactivation of CMV. Larger studies are warranted, but careful monitoring could help identifying risk patients earlier and prophylaxis may be considered when increased corticosteroids are prescribed.

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