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SARS-CoV-2 infection in kidney transplant recipients

https://doi.org/10.28996/2618-9801-2021-2-174-184

Abstract

The study aimed to assess the clinical course and risk factors for adverse outcomes, as well as the treatment options for COVID-19 in renal transplant recipient (RTR). Patients and methods: a retrospective study included 279 RTRs (M 60.9%, age 49.9±10.9 years), infected with SARS-CoV-2 from 01.04.2020 to 30.11.2020. After confirmation of COVID-19 by PCR and chest СТ, MMF/Аza were canceled. In severe cases, the CNI dose was minimized while that of CS was increased. Observation endpoints: hospital discharge/recovery or death. Results: SARS-CoV-2 was identified in 84.2% of RTRs. In almost 90% of patients, the COVID-19 was confirmed by CT data. Duration after transplantation at the time of infection was 54.0 (14.0; 108.0) months, in 17.6% of cases it was 6 months or less. 223/79.9% RTRs were treated in the hospital. The period from the onset of the disease to the hospitalization was 6.8±4.5 days. Severe lung damage (>50%) occurred in 43.1% RTRs; 45.3% of patients required respiratory support. Hospital mortality was 13.9%, overall mortality was 11.1%. The most common cause of death (93.5%) was acute respiratory distress syndrome (ARDS). The risk factors associated with an unfavorable outcome were a high comorbidity index, the severity of the pulmonary lesion, the degree of graft dysfunction at the onset of the disease, decreased SpO2 and the use of mechanical ventilation, as well as anemia, leukocytosis, lymphocytopenia, and hypoalbuminemia, increased levels of creatinine, AST, CRP, LDH, and D-dimer, interleukin-6 and procalcitonin. Scr during the course of the disease increased from 171.6±78.0 μM to 221.5±121.3 μM (p<0.01) with no signs of acute rejection. In 2 recipients with severe graft failure at the time of infection with SARS-CoV-2, HD was resumed from the moment of hospitalization. We were unable to identify the effect of hydroxychloroquine on the outcome of COVID-19. At the same time, mortality in patients with hydroxychloroquine use was higher than in recipients treated with immunobiological drugs: 25.6% and 11.4%, respectively, p<0.02. When immunomodulators were combined with dexamethasone, mortality decreased to 4.8%. The independent factors of adverse outcome were high levels of procalcitonin (p<0.019) and mechanical ventilation (p<0.001). Conclusion: COVID-19 in RTRs is characterized by a severe course and high mortality, which necessitates hospitalization of the majority of infected patients. An increase in procalcitonin levels and the need for mechanical ventilation were independent predictors of an unfavorable outcome of COVID-19.

About the Authors

I. G. Kim
G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology; Moscow City Hospital No. 52
Russian Federation


L. Yu. Artyukhina
Moscow City Hospital No. 52
Russian Federation


N. F. Frolova
Moscow City Hospital No. 52
Russian Federation


E. S. Ivanova
Moscow City Hospital No. 52
Russian Federation


I. V. Ostrovskaya
Moscow City Hospital No. 52
Russian Federation


V. A. Berdinsky
Moscow City Hospital No. 52
Russian Federation


V. E. Vinogradov
Moscow City Hospital No. 52
Russian Federation


E. V. Volodina
G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology
Russian Federation


M. E. Maltseva
Moscow City Hospital No. 52
Russian Federation


A. A. Stolbova
Moscow City Hospital No. 52
Russian Federation


T. A. Buruleva
Moscow City Hospital No. 52
Russian Federation


A. V. Frolov
Moscow City Hospital No. 52
Russian Federation


E.A. Kalugin
Moscow City Hospital No. 52
Russian Federation


I. A. Skryabina
Moscow City Hospital No. 52
Russian Federation


D. A. Titov
Moscow City Hospital No. 52
Russian Federation


N. A. Tomilina
Moscow City Hospital No. 52; A.I. Evdokimov Moscow State University of Medicine and Dentistr
Russian Federation


M. L. Zubkin
G.N. Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology; N.N. Burdenko Main Military Clinical Hospital; S.M. Kirov Military Medical Academy
Russian Federation


References

1. СOVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU); https://coronavirus. jhu.edu/map.html.

2. Alfishawy M., Elbendary A., Mohame M., et al. COVID-19 Mortality in Transplant Recipients. International Journal of Organ Transplantation Medicine 2020;11(4):145-162.

3. Azzi Y, Parides M, Alani O, et al. COVID-19 infection in kidney transplant recipients at the epicenter of pandemics. Kidney International (2020), doi: https://doi.org/10.1016/j.kint.2020.10.004.

4. Alberici F., Delbarba E., Manenti Ch., et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia Kidney International (2020) 97, 1083-1088, https://doi.org/10.1016/J.KINT.2020.04.002.

5. Cravedi P., Mothi S.S., Azzi Y., et al. COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium. Am J Transplant 2020; 00:1-9; doi: 10.1111/ajt.16185.

6. THE ERA-EDTA COVID-19 DATABASE FOR PATIENTS ON DIALYSIS OR LIVING WITH A KIDNEY TRANSPLANT. https://www.era-edta.org.(на декабрь 2020).

7. Guan W.J., Ni Z.Y., Hu Y., et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032.

8. Grasselli G, Zangrillo A, Zanella A, et al. COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-81. doi: 10.1001/jama.2020.5394.

9. Yi Y, Lagniton PNP, Ye S, et al. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci. 2020;16(10):1753-66. doi: 10.7150/ijbs.45134.

10. Madjid M, Safavi-Naeini P, Solomon SD, et al. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol. 2020;5(7):831-40. doi: 10.1001/jamacardio.2020.1286.

11. Richardson S, Hirsch JS, Narasimhan M et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020; 323: 2052-2059. doi: 10.1001/jama.2020.6775.

12. Wang L, Li X, Chen H, et al. Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China. Am. J. Nephrol. 2020; 51(5):343-348. doi: 10.1159/000507471.

13. Lubetzky M., Aull M.J, Craig-Schapiro R., et al. Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center Nephrol Dial Transplant (2020) 35: 1250-1261 doi: 10.1093/ndt/gfaa154.

14. Alberici F., Delbarba E., Manenti Ch., et al. Management of Patients On Dialysis And With Kidney Transplant During SARS-COV-2 (COVID-19) Pandemic in Brescia, Italy. Kidney Int Rep. 2020 Apr 4;5(5):580-585. doi: 10.1016/j.ekir.2020.04.00.

15. ERA-EDTA WG Descartes expert opinion regarding the management of immunosuppressive medication for kidney transplant patients during the COVID-19 pandemic. https://www.era-edta.org/en/wp-content/uploads/2020/04/Expert-opinion-on-ISD-in-Covid-19.

16. Xia T., Wang Y. Coronavirus disease 2019 and transplantation: The combination of lopinavir/ritonavir and hydroxychloroquine is responsible for excessive tacrolimus trough level and unfavorable outcome. Am J Transplant. 2020 Sep;20(9):2630-2631. doi: 10.1111/ajt.15992.

17. Simpson T. F., Kovacs R.J., Stecker E.C. Ventricular arrhythmia risk due to hydroxychloroquine-azithromycin treatment for COVID-19. Cardiol Magaz, 29 March 2020;https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19/

18. Magagnoli J., Narendran S., Pereira F. et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv 2020; doi: 10.1101/2020.04.16.20065920.

19. Beigel J.H., Tomashek K.M., Dodd L.E, et al. Remdesivir for the treatment of COVID-19: preliminary report. N. Engl. J. Med. 2020; Nov5; 383(19):1813-1826. doi: 10.1056/NEJMoa2007764.

20. Horby P., Lim W.Sh., Emberson J.R, et al. The Recovery Collaborative Group. Dexamethasone in hospitalized patients with COVID-19 - preliminary report. N Engl J Med. 2021 Feb 25;384(8):693-704. doi:10.1056/NEJMoa2021436.

21. Xu X., Han M., Li T., et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020; 117(20): 10970- 10975. doi: 10.1073/pnas.2005615117.

22. Toniati P., Piva S., Cattalini M., et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia. Italy. Autoimmun Rev. 2020; 19(7): 102568. doi: 10.1016/j.autrev.2020.102568.

23. Fontana F., Alfano G., Mori G., et al. COVID-19 pneumonia in a kidney transplant recipient successfully treated with tocilizumab and hydroxychloroquine. Am J Transplant. 2020 Jul;20(7):1902-1906. doi: 10.1111/ajt.15935.

24. Pereira M. R., Mohan S., Cohen D.J., et al. COVID-19 in solid organ transplant recipients: Initial report from the US epicenter. Am J Transplant. 2020 Jul;20(7):1800-1808. doi: 10.1111/ajt.15941.

25. Pérez-Sáez M.J., Blasco M., Redondo-Pachón D., et al. Spanish Society of Nephrology COVID-19 Group. Use of tocilizumab in kidney transplant recipients with COVID-19. Am J Transplant 2020 Nov;20(11):3182-3190. doi: 10.1111/ajt.16192.

26. Временные методические рекомендации "Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)" Минздрава Российской Федерации (версии1-10).

27. Charlson M.E., Pompei P., Ales K.L. et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 1987; 40: 373-383. doi: 10.1016/0021-9681(87)90171-8.

28. Perico L., Benigni A., Remuzzi G. Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockad. Nephron. 2020;144(5):213-21. doi: 10.1159/000507305.

29. Bai Y., Yao L., Wei T., et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020;323(14):1406-7. doi: 10.1001/jama.2020.2565.

30. Li R, Pei S., Chen B., et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). Science. 2020;368(6490):489-493. doi: 10.1126/science.abb3221.

31. Akalin E., Azzi Y., Bartash R. et al. COVID-19 and kidney transplantation. N Engl J Med 2020; doi: 10.1056/NEJMc2011117.

32. Caillard S., Anglicheau D., Matignon M., et al. on behalf of the French SOT COVID Registry. An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants. Kidney International (2020), doi: https://doi.org/10.1016/j.kint.2020.08.005.

33. Fernández-Ruiz M., Andrés A., Loinaz C., et al. COVID-19 in solid organ transplant recipients: a single-center case series from Spain. Am J Transplant. 2020;20(7):1849-1858. doi: 10.1111/ajt.15929.

34. Hilbrands LB, Duivenvoorden R, Vart P, et al. COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration. Nephrol Dial Transplant. 2020 Nov 1;35(11):1973-1983. doi: 10.1093/ndt/gfaa261.

35. Jager K.J., Kramer A., Chesnaye N.C., et al. Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe., Kidney International (2020), doi: https://doi.org/10.1016/j.kint.2020.09.006.

36. Zhou F., Yu T., Du R., et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3.

37. Onder G., Rezza G., Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA - J Am Med Assoc. 2020. doi:10.1001/jama.2020.4683.

38. Kates O.S., Haydel B.M., Florman S.S. et al. COVID-19 in solid organ transplant: A multi-center cohort study. Clin Infect Dis;2020, Aug 7;ciaa1097. doi: 10.1093/cid/ciaa1097.

39. Lippi G., Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis Clin Chim Acta 2020 Jun;505:190-191. doi: 10.1016/j.cca.2020.03.004.

40. Johnson K. M., Belfer J.J., Peterson G.R., et al. Managing COVID-19 in Renal Transplant Recipients: A Review of Recent Literature and Case Supporting Corticosteroid-sparing Immunosuppression Pharmacotherapy.2020 Jun;40(6):517-524. doi: 10.1002/phar.2410.

41. Horby P, Mafham M, Linsell L, et al. Effect of hydroxychloroquine in hospitalized patients with COVID-19; preliminary results from a multi-centre, randomized, controlled trial. Medrxiv. [Epub ahead of print. July 15, 2020]. doi:10.1101/2020.07.15.20151852.

42. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China [e-pub ahead of print]. JAMA Intern Med. https://doi.org/10.1001/jamainternmed.2020.0994.

43. Morillas J.A., Canosa F.M., Srinivas P, et al. Tocilizumab therapy in 5 solid and composite tissue transplant recipients with early ARDS due to SARS-CoV-2 Am J Transplant. 2020 Nov;20(11):3191-3197. doi: 10.1111/ajt.16080.

44. Somers E.C., Eschenauer G.A., Troost J.P., et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Medrxiv. [Epub ahead of print. July 11, 2020]. doi:10.1101/2020/05/29.20117358.

45. Trujillo H., Caravaca-Fontán F., Sevillano Á., et al. Tocilizumab use in Kidney Transplant Patients with COVID-19 Clin Transplant. 2020 Nov;34(11):e14072. doi: 10.1111/ctr.14072.

46. Fernández-Ruiz M., López-Medrano F., Pérez-Jacoiste Asín M.A., et al. Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study. J Med Virol. 2021 Feb;93(2):831-842. doi: 10.1002/jmv.26308.

47. Albertini L., Soletchnik M., Razurel A., et al. Observational study on off-label use of tocilizumab in patients with severe COVID-19. Eur J Hosp Pharm. 2021 Jan;28(1):22-27. doi: 10.1136/ejhpharm-2020-002414.

48. Bossini N., Alberici F., Delbarba E., et al. Kidney transplant patients with SARS-CoV-2 infection: The Brescia Renal COVID task force experience. Am J of Transplant; November 2020, 20 (11): 3019-3029. doi /10.1111/ajt.16176.

49. Pereira M.R., Aversa M.M., Farr M.A, et al. Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study Am J Transplant 2020 Nov;20(11):3198-3205. doi: 10.1111/ajt.16314.


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For citations:


Kim I.G., Artyukhina L.Yu., Frolova N.F., Ivanova E.S., Ostrovskaya I.V., Berdinsky V.A., Vinogradov V.E., Volodina E.V., Maltseva M.E., Stolbova A.A., Buruleva T.A., Frolov A.V., Kalugin E., Skryabina I.A., Titov D.A., Tomilina N.A., Zubkin M.L. SARS-CoV-2 infection in kidney transplant recipients. Nephrology and Dialysis. 2021;23(2):174-184. (In Russ.) https://doi.org/10.28996/2618-9801-2021-2-174-184

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ISSN 1680-4422 (Print)
ISSN 2618-9801 (Online)