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. 2022 Feb 25;78(3):711-718.
doi: 10.1093/cid/ciac159. Online ahead of print.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19

Affiliations

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19

Madeleine R Heldman et al. Clin Infect Dis. .

Abstract

Introduction: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined.

Methods: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90.

Results: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61].

Conclusions: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

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Conflict of interest statement

Potential conflicts of interest. M. R. H. reports speaking honoraria from Cigna LifeSource and Thermo Fisher Scientific. O. S. K. reports an AST PSECOP PILOT grant outside of the submitted work, speaking honoraria from the Canadian Society of Transplantation and the American Foundation of Donation and Transplantation, a consulting fee from Bennett Jones, LLP, outside of the submitted work and AST ID COP Executive Committee. C. N. K. reports grants or contracts from Regeneron, Beigene, and the Mendez Foundation; consulting fees from Exevir; and is a participant in the data safety monitory board (DSBA) or advisory bord of Beigene. B. D. A. reports consulting fees from Scynexis; served as a site investigator for clinical trials for Scynexis, Cidara, Shire, F2G, Amplyx, and Astellas; royalties or licenses from UpToDate; and is on the Infectious Diseases Society of America (IDSA) Board of Directors. E. A. B. reports research funding from Regeneron for mAb for coronavirus disease 2019 (COVID), Merck letermovir for CMV prophylaxis, Takeda maribavir for CMV treatment, and Hologix for CMV testing unrelated the current work; honoraria from the American Society of Nephrology and UpToDate Section Editor (transplant); served on the DSMB for Ampylx (BK virus treatment); payment or honoraria from WebMD/Medscape for a CMV presentation and ASN for a COVID presentation; and served as American Society of Transplantation Public Policy Chair and American Journal of Transplantation Deputy Editor. M. H.-M. is an NIH T32 Transplant Infectious Diseases Training Grant recipient, funding ended before initiation of this work; served on the scientific review committee for BioNTech for BNT162-17; played an unpaid leadership or fiduciary role for LifeGift (local organ procurement organization) Houston, Texas; and served as a member of the Medical Advisory Committee. M. G. I. reports research support, paid to Northwestern University, from GlaxoSmithKline, Pulmocide, and Regeneron; payments made to self for RIV chapters from UpToDate; is a paid consultant for Adagio, ADMA Biologics, AlloVir, Cidara, Genentech, Roche, Janssen, Shionogi, Takeda, and Viracor Eurofins; and is a paid member of DSMBs for Allovir, CSL Behring, Janssen, Merck, Sequiris, Takeda, and Talaris. D. v. D. reports grants from NIH; personal fees from Achaogen, Allergan, Astellas, Neumedicine, T2biosystems, Roche, Karius, Entasis, Wellspring, Qpex, Pfizer, Utility, Union, and the British Society for Antimicrobial Chemotherapy; and grants and personal fees from Shionogi and Merck outside the submitted work. J. D. G. reports research support from Gilead Sciences, Eli Lilly and Company, Regeneron Pharmaceuticals, NIAID, NIH, BARDA (administered by Merck), and Viracor Eurofins; served as a consultant, speaker, or advisory board member for Gilead Sciences and Eli Lilly and Company; and collaborative services agreements from Labcorp, Monogram Biosciences, and Adaptive Biotechnologies. A. W. reports grants or contracts to their institution from NIH, Sanofi, and GlaxoSmithKline outside of the submitted work; royalties or licenses from UpToDate; travel reimbursement from Innovative Molecules; provision of vaccine for a clinical trial from Merck; consulting fees from Aicuris, Crozet, Auritec, Dxnow, and Gilead; and is a paid member of DSMBs for Merck, X-Vax, and Vir. A. P. L reports grants or contracts from Merck Moderna, Takeda, Allovir, GlaxoSmithKline, Johnson & Johnson, and Novartis outside of the submitted work; royalties or licenses from UpToDate; receipt of consulting fees from Merck, GlaxoSmithKline, Allovir, and Novartis; and served on a DSMB for Novartis. V. H. reports grants or contracts with their institution from Merck outside of the submitted work. E. D. L. reports grants or contracts from the Cystic Fibrosis Foundation outside of the submitted work and served as chair for the OPTN Lung Transplantation Committee and chair for the ISHLT Standards and Guidelines Committee. M. M. reports serving as chair of Digital Strategy Advisory Group for IDSA, Councilor, Transplant Infectious Disease, the Transplantation Society, and Member-at-Large, AST IDCOP Executive Committee. J. M. S. reports receipt of an American Society of Transplantation/CareDx Fellowship grant–research funding for hepatitis C in transplant patients and an NIH NIAID grant outside of the submitted work and has pending patents for gene expression-based classifiers of fungal infection. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Unadjusted Kaplan-Meier survival curves in SOT recipients hospitalized for coronavirus disease 2019 (COVID-19). Unadjusted Kaplan-Meier survival curves for hospitalized SOT recipients (A) and stratified by organ (B) and time period of diagnosis: early 2020 (before 20 June 2020) and late 2020 (on or after 20 June 2020) (C). Gray shading represents 95% confidence intervals. Vertical marks represent patients censored at time of last live encounter. Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SOT, solid organ transplant.
Figure 2.
Figure 2.
Proportion of deaths before and after day 28 in solid organ transplant (SOT) recipients hospitalized for coronavirus disease 2019 (COVID-19). Covariates of interest (total number of deaths between days 0 and 90) and proportion of deaths that occurred between days 0 and 28 (gray) and days 29 and 90 (black) in SOT recipients hospitalized for COVID-19. Abbreviations: BMI, body mass index; mTOR, mammalian target of rapamycin.

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