BACKGROUND:The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied.OBJECTIVE:To study the effect of COVID-19 on tacrolimus trough levels (primary outcome) in OTRs and the association of the later with acute kidney injury, bacterial infection, and oxygen requirements.METHODS:We studied adult (>18-year-old) hospitalized OTRs with COVID-19, who were receiving tacrolimus between 3/1 and 12/16/2020.RESULTS:Among 30 OTRs, 67% were men, 90% had a kidney transplant. Median age was 60.5 (interquartile range [IQR]: 45-68) years, median time from transplant 36 (IQR: 20-84) months. Tacrolimus troughs were higher on admission for COVID-19 than baseline (average over 6 months prior) (P = .001). Eighteen patients (60%) had admission tacrolimus trough >10, 5 (17%) >20 ng/mL. Patients with diarrhea had borderline higher tacrolimus troughs, compared to those without diarrhea (P = .09). Organ transplant recipients with a tacrolimus trough >10 ng/mL were more likely to have elevated aspartate aminotransferase on admission (P = .01) and require supplemental oxygen. (P = .026).CONCLUSION AND RELEVANCE:Tacrolimus trough levels were elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. Potential mechanisms are diarrhea and hepatic involvement in COVID-19. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed; management of immunosuppression should be individualized.

Clinical TransplantationAccepted Articles e14752 LETTER TO THE EDITOR Single-center experience with nirmatrelvir/ritonavir in kidney transplant recipients on tacrolimus maintenance immunosuppression Krista Mecadon PharmD, Krista Mecadon PharmD Department of Pharmacy, Rhode Island HospitalSearch for more papers by this authorPanos Arvanitis MS, Panos Arvanitis MS orcid.org/0000-0002-0098-6071 Warren Alpert Medical School of Brown UniversitySearch for more papers by this authorDimitrios Farmakiotis MD, Dimitrios Farmakiotis MD orcid.org/0000-0001-8489-108X Division of Infectious Diseases, Warren Alpert Medical School of Brown UniversitySearch for more papers by this authorRalph Rogers MD, Corresponding Author Ralph Rogers MD rrogers@lifespan.org Division of Infectious Diseases, Warren Alpert Medical School of Brown University Correspondence Ralph Rogers; Middle House, Suite 301, Rhode Island Hospital, 593 Eddy Street, Providence, RI, 02903. Email: rrogers@lifespan.orgSearch for more papers by this author Krista Mecadon PharmD, Krista Mecadon PharmD Department of Pharmacy, Rhode Island HospitalSearch for more papers by this authorPanos Arvanitis MS, Panos Arvanitis MS orcid.org/0000-0002-0098-6071 Warren Alpert Medical School of Brown UniversitySearch for more papers by this authorDimitrios Farmakiotis MD, Dimitrios Farmakiotis MD orcid.org/0000-0001-8489-108X Division of Infectious Diseases, Warren Alpert Medical School of Brown UniversitySearch for more papers by this authorRalph Rogers MD, Corresponding Author Ralph Rogers MD rrogers@lifespan.org Division of Infectious Diseases, Warren Alpert Medical School of Brown University Correspondence Ralph Rogers; Middle House, Suite 301, Rhode Island Hospital, 593 Eddy Street, Providence, RI, 02903. Email: rrogers@lifespan.orgSearch for more papers by this author First published: 17 June 2022 https://doi.org/10.1111/ctr.14752 ORCIDs: Krista Mecadon: 0000-0001-7015-2825 Panos Arvanitis: 0000-0002-0098-6071 Dimitrios Farmakiotis: 0000-0001-8489-108X Ralph Rogers: 0000-0003-0268-0188 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as https://doi.org/10.1111/ctr.14752 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future.e14752 RelatedInformation

Introduction: Observational studies suggest that low-dose valganciclovir prophylaxis (450 mg daily for normal renal function) is as effective as and perhaps safer than standard-dose valganciclovir (900 mg daily) in preventing CMV infection among kidney transplant recipients. However, this practice is not supported by current guidelines due to concerns for breakthrough infection from resistant CMV, mainly in high-risk CMV donor-seropositive/recipient-seronegative kidney transplant recipients. Standard-dose valganciclovir is costly and possibly associated with higher incidence of neutropenia and BKV DNAemia. Our institution adopted low-dose valganciclovir prophylaxis for intermediate-risk (seropositive) kidney transplant recipients in January 2018. Research Question: To analyze the efficacy (CMV DNAemia), safety (BK virus DNAemia, neutropenia, graft loss, and death), and cost savings associated with this change. Design: We retrospectively compared the above outcomes between CMV-seropositive kidney transplant recipients who received low-dose and standard-dose valganciclovir, transplanted within our institution, between 1/19/2014 and 7/15/2019, using propensity score-adjusted competing risk analyses. We also compared cost estimates between the two dosing regimens, for 3 months of prophylaxis, and for different percentage of patient-weeks with normal renal function, using the current average wholesale price of valganciclovir. Results: We studied 179 CMV-seropositive kidney transplant recipients, of whom 55 received low-dose and 124 standard-dose valganciclovir. The majority received nonlymphocyte depleting induction (basiliximab). Low-dose valganciclovir was at least as effective and safe as, and more cost-saving than standard-dose valganciclovir. Conclusion: This single-center study contributes to mounting evidence for future guidelines to be adjusted in favor of low-dose valganciclovir prophylaxis in CMV-seropositive kidney transplant recipients.