Novel coronavirus infection and hemodialysis: course and predictors of unfavorable outcome

In the context of the COVID-19 pandemic, patients with end-stage CKD receiving hemodialysis replacement therapy (HD) were at risk of SARS-CoV-2 infection due to the specifics of treatment and the immunodeficiency state caused by uremia. The aim of the study was to analyze the characteristics of the course, prognostically unfavorable factors, and outcome of COVID-19 in HD patients of the second wave of the pandemic. Materials and methods: a retrospective study was carried out on the material of observations of 325 HD patients infected with SARS-CoV-2 in the period from 09/01/2020 to 12/31/2020. The patients' age was 60.1±14.0 years. The duration of HD treatment was 30.0 (9.5; 66.0) months. The endpoint was taken as the discharge from the hospital or death. Results: in 264 out of 325 (81.2%) patients, the diagnosis of COVID-19 was confirmed by the identification of SARS-CoV-2 RNA. CT scan of the chest showed signs of viral pneumonia in all patients. Mortality was 15.1% (49 out of 325 pts). In 79.7% of patients, the cause of death was ARDS. Comparative analysis showed that patients with a fatal outcome (group 2) were older (69.2±10.6 years) than patients with a successful course (group 1) of the disease (58.5±13.9 years), and differed in higher comorbidity index (7.8±1.9 versus 5.9±2.2, respectively). SpO2 in groups 2 and 1 was 65.2±10.1% and 92.1±6.4%, respectively (p<0.001). In the deceased patients, anemia, leukocytosis, thrombocytopenia, and hypoalbuminemia were significantly more pronounced, as well as indicators of GGT, alkaline phosphatase, ferritin, CRP, LDH, and D-dimer. In the fatal group, the proportion of patients with a procalcitonin level of more than 2 ng/ml was also higher. In multivariate analysis, only high comorbidity index and the need for mechanical ventilation were the independent predictors of the unfavorable outcome. In the group of patients with the favorable outcome, the combined therapy with immunobiological drugs and dexamethasone were used significantly more often than in the deceased group, while the frequency of their “isolated” use in the compared groups was comparable. Conclusions: COVID-19 in HD patients is characterized by severe course and high mortality. Independent predictors of an unfavorable outcome of the disease were a high comorbidity index and the need for invasive lung ventilation. Early use of immunobiological drugs and dexamethasone in combination with anticoagulants increases the effectiveness of treatment of severe forms of SARS-CoV-2 infection in HD patients.

hemodialysis, COVID-19, course, unfavorable outcome, predictors

1. СOVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU); https://coronavirus. jhu.edu/map.html (date of access 17 July, 2021).

2. 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):1054-62. doi: 10.1016/S0140-6736(20)30566-3.

3. Yang J., Zheng Ya, Gou Xi, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020 May;94:91-95. doi: 10.1016/j.ijid.2020.03.017.

4. Carney E.F. The impact of chronic kidney disease on global health. Nat. Rev. Nephrol. 2020, 16, 251. doi: 10.1038/s41581-020-0268-7.

5. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (zhangyp@chinacdc.cn). Vital Surveillances: The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) - China, 2020. China CDC Weekly; 2020, 2(8): 113-122.

6. CDC COVID-19 Response Team: Severe outcomes among patients with Coronavirus disease 2019 (COVID-19) - United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69: 343-346.

7. Richardson S., Hirsch J.S., 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.

8. 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 Int. 2020 Dec; 98(6):1540-1548. doi:10.1016/j.kint.2020.09.006.

9. Goicoechea M., Ca´mara L.A.S., Macı´as N., et al. COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain. Kidney International 2020; 98: 27-34. doi: 0.1016/j.kint.2020.04.031.

10. Alberici F., Delbarba E., Manenti C., et al. A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. Kidney International. 2020; 98: 27-34 doi: 10.1016/j.kint.2020.04.030.

11. Li C., Yonglong M., Can T., et al. An Analysis on the Clinical Features of MHD Patients with Coronavirus Disease 2019: A Single Center Study. 2020, https://doi.org/10.21203/rs.3.rs-18043/v1.

12. Guan W.J., Ni Z.Y., Hu Y. et al. China Medical Treatment Expert Group for Covid-19: Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382:1708-1720. DOI: 10.1056/NEJMoa2002032.

13. Wu Z., McGoogan J.M. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. JAMA - J Am Med Assoc. 2020. doi:10.1001/jama.2020.2648.

14. Khan M.M.A., Khan M.N., Mustagir M.G., et al. Effects of underlying morbidities on the occurrence of deaths in COVID-19 patients: A systematic review and meta-analysis. J Glob Health. 2020 Dec;10(2):020503. doi: 10.7189/jogh.10.020503.

15. Figliozzi S., Masci P.G., Ahmadi N., et al. Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis. European journal of clinical investigation. 2020 Oct;50(10):e13362. doi: 10.1111/eci.13362.

16. Zheng Z., Peng F., Xu B., et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. The Journal of infection. 2020 Aug;81(2):e16-e25. doi: 10.1016/j.jinf.2020.04.021.

17. Зелтынь-Абрамов Е.М., Белавина Н.И., Фролова Н.Ф. и др. Факторы риска неблагоприятного прогноза у пациентов на программном гемодиализе с COVID-19. Акцент на сердечно-сосудистую коморбидность (Опыт одного центра) Нефрология и диализ (ВАК) 2020 т 22 (спецвыпуск) 9-20. DOI: 10.28996/2618-9801-2020-Special_Issue-9-20).

18. Фролова Н.Ф., Ким И.Г., Ушакова А.И. и др. COVID-19 у больных, получающих лечение программным гемодиализом // Инфекционные болезни: новости, мнения, обучение. 2021. Т. 10, № 1. С. 14-23. DOI: https://doi.org/10.33029/2305-3496-2021-10-1-14-23.

19. Xiong М.F., Tang H., Liu L., et al. Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan, China J Am Soc Nephrol. 2020; 31(7): 1387-1397. doi: 10.1681/ASN.2020030354

20. Chen C.Y., Shao S.C., Chen Y.T. et al. Incidence and Clinical Impacts of COVID-19 Infection in Patients with Hemodialysis: Systematic Review and Meta-Analysis of 396,062 Hemodialysis Patients // Healthcare (Basel). 2021. Vol. 9. N 1. P. 47. DOI:10.3390/healthcare9010047).

21. Ossareh S., Bagheri S. M., Abbasi M., et al. A. Role of Screening for COVID-19 in Hemodialysis Wards, Results of a Single Center Study. IJKD 2020;14:389-98.

22. Clarke C., Prendecki M., Dhutia A., et al. High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening. JASN. 2020; 31: 1969-1975. doi: 10.1681/ASN.2020060827.

23. Albalate M., Arribas P., Torres E., et al. High Prevalence of Asymptomatic COVID-19 in Haemodialysis: Learning Day by Day in the First Month of the COVID19 Pandemic. Nefrologia. 2020; 40 (3): 279-286 doi 1016/j. nefro.2020.04.005.

24. Khatri M., Islam S., Dutka P. et al. COVID-19 Antibodies and Outcomes Among Outpatient Maintenance Hemodialysis Patients // Kidney360. 2021. Vol. 2. N 2. P. 263-269. DOI: 10.34067/KID.0006292020.

25. H.Tang, J-B. Tian, J-Wu Dong, et al. Serologic Detection of SARS-CoV-2 Infections in Hemodialysis Centers: A Multicenter Retrospective Study in Wuhan, China Am J Kidney Dis. 2020 Oct;76(4):490-499. doi: 10.1053/j.ajkd.2020.06.008.

26. Hilbrands L.B., Duivenvoorden R., Vart P., et al., ERACODA Collaborators. COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration. Nephrology Dialysis Transplantation, Volume 35, Issue 11, November 2020, Pages 1973-1983, https://doi.org/10.1093/ndt/gfaa261.

27. Report of the COVID-19 - ERA-EDTA Registry. URL: https://www.era-edta.org/en/registry/covid-19 (date of access 17 July, 2021)

28. European Centre for Disease Prevention and Control COVID-19 situation update for the EU/EEA and the UK (Available at: 14.07.21, https://www.ecdc.europa.eu/en/cases-2019-ncov-eueea.

29. Scarpioni R., Manini A., Valsania T., et al. COVID-19 and its impact on nephropathic patients: the experience at Ospedale «Guglielmo da Saliceto» in Piacenza. G Ital Nefrol. 2020; 37 (2): 1-5.

30. Creput C., Fumeron C., Toledano D., et al. COVID-19 in Patients Undergoing Hemodialysis: Prevalence and Asymptomatic Screening During a Period of High Community Prevalence in a Large Paris Center. Kidney Med. 2020; 2(6): 716-723. doi: 10.1016/j.xkme.2020.09.001.

31. Sánchez-Álvarez J. E., Pérez Fontán M., Martínc C. J., et al. Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN). Nefrologia. 2020; 40(3):272-278. doi: 10.1016/j.nefro.2020.04.002.

32. Ng H., Hirsch J.S., Wanchoo R., et al. Outcomes of patients with end-stage kidney disease hospitalized with COVID-19. Kidney Int. 2020 Dec;98(6):1530-1539. doi: 10.1016/j.kint.2020.07.030.

33. 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. Vol. 323, N 16. P. 1574-1581. doi: 10.1001/jama.2020.5394.

34. Fisher M., Yunes M., Mokrzycki M.H., et al. Chronic Hemodialysis Patients Hospitalized with COVID-19: Short-term Outcomes in the Bronx, New York. Kidney360 August 020, 1 (8) 755-762; DOI: https://doi.org/10.34067/KID.0003672020.

35. Valeri A.M., Robbins-Juarez S. Y, Stevens J.S., et al. Presentation and Outcomes of Patients with ESKD and COVID-19. JASN. 2020; 31:1409-1415. doi: https://doi.org/10.1681/ASN.202004047.

36. Savino M., Casula A., Santhakumaran S., et al. Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis PLOS ONE 2020| https://doi.org/10.1371/journal.pone.0241263.

37. CDC: Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019- COVID-NET, 14 states, March 1-30, 2020, 2020. Available at: https://www.cdc.gov/mmwr/volumes/69/wr/mm6915e3. htm. Accessed April 14, 2020.

38. Corbett R.W., Blakey S., Nitsch D., et al. Epidemiology of COVID-19 in an Urban Dialysis Center. JASN 31: 1815-1823, 2020. doi: https://doi.org/10.1681/ASN.2020040534.

39. Manganaro M., Baldovino S. on behalf of The Working group of the Piedmont and Aosta Valley Section of the SIN. First considerations on the SARS CoV 2 epidemic in the Dialysis Units of Piedmont and Aosta Valley, Northern Italy. J. Nephrol. 2020; 33(3):393-395. doi: 10.1007/s40620-020-00732-1.

40. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18: 844-847. doi: 10.1111/jth.14768.

41. Ruan Q., Yang K., Wang W., et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 46: 846-848, 2020. doi: 10.1007/s00134-020-05991-x.

42. Demir N.A., Sumer S., Celik G., Afsar R.E., Demir L.S., Ural O. How should procalcitonin and C-reactive protein levels be interpreted in haemodialysis patients? Internal Medicine Journal, Volume48, Issue10, October 2018, Pages 1222-1228, https://doi.org/10.1111/imj.13952.

43. Kubo S., Iwasaki M., Horie M., et al. Biological variation of procalcitonin levels in hemodialysis patients. Clinical and Experimental Nephrology volume 23, pages 402-408 (2019).

44. Dahaba A.A., Rehak P.H., List W.F. Procalcitonin and c-reactive protein plasma concentrations in nonseptic uremic patients undergoing hemodialysis. Intensive Care Med. 2003;29:579-83.

45. Simonovich VA, Burgos Pratx LD, Scibona P, et al. A Randomized Trial of Convalescent Plasma in COVID-19 Severe Pneumonia. PlasmAr Study Group. N Engl J Med. 2021 Feb 18;384(7):619-629. doi: 10.1056/NEJMoa2031304.

46. O'Donnell M.R., Grinsztejn B., Cummings M.J., et al. A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19. J Clin Invest. 2021, Jul 1;131(13): e150646. doi: 10.1172/JCI150646.

47. Casadevall A., Dragotakes Q., Johnson P.W., et al. Convalescent plasma use in the USA was inversely correlated with COVID-19 mortality. Elife. 2021 Jun 4;10:e69866. doi: 10.7554/eLife.69866.

48. S.A. Klassen, J.W. Senefeld, P.W. Johnson, R.E. Carter, C.C. Wiggins, S. Shoham et al. The effect of convalescent plasma therapy on mortality among patients with COVID-19: systematic review and meta-analysis. Mayo Clin Proc, 96 (2021), pp. 1262-1275. doi: 10.1016/j.mayocp.2021.02.008.

49. Garraud O., Burnouf T. Convalescent COVID-19 plasma: Back-to-basics and ethics, and next steps. Transfus Clin Biol. 2021 Aug;28(3):225-227. doi: 10.1016/j.tracli.2021.07.005.

50. Perotti C., Baldanti F., Bruno R., et al. Mortality reduction in 46 severe COVID-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial. Haematologica (2020). Dec1;105(12):2834-2840; doi:105:2834-40. 10.3324/haematol.2020.261784.

51. Briggs N., Gormally M.V., Li F., et al. Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19. PLoS One. 2021 Jul 28;16(7):e0254453. doi: 10.1371/journal.pone.0254453

52. González S.E., Regairaz L., Salazar M., et al. Timing of convalescent plasma administration and 28-day mortality for COVID-19 pneumonia. medRxiv [Preprint]. (2021). doi: 0.1101/2021.02.02.21250758.

53. Joyner MJ, Carter RE, Senefeld JW, et al. Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19. N Engl J Med. 2021 Mar 18;384(11):1015-1027. doi: 10.1056/NEJMoa2031893.