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Incorporating Translational Data into Immunosuppression Decisions During COVID-19

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Abstract

Purpose of Review

COVID-19 outcomes are worse in solid organ transplant recipients. How to manage immunosuppressants in transplant recipients is not well studied. Incorporating translational data can aid in making immunosuppression decisions.

Recent Findings

Both the adaptive and innate immune system play a role in SARS CoV2 clearance and mortality, while a dysregulated innate immune system can lead to cytokine storm and poor outcomes.

Summary

This review focuses on the immunology of COVID-19, including early mild disease to severe COVID-19, including cytokine storm and death. It summarizes the mechanisms of transplant immunosuppression and presents a logical approach to managing immunosuppression during COVID-19 in solid organ transplant recipients including a case study.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA. 2020;323(20):2052–9. This was the largest study at the epicenter of COVID-19 pandemic in the United States.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.

    Article  CAS  PubMed  Google Scholar 

  3. Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai FS, et al. Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(24):759–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014;383(9927):1503–16.

    Article  PubMed  Google Scholar 

  6. Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, et al. COVID-19 in kidney transplant recipients. Am J Transplant. 2020;20(7):1819–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Akalin E, Azzi Y, Bartash R, Seethamraju H, Parides M, Hemmige V, et al. Covid-19 and kidney transplantation. N Engl J Med. 2020;382(25):2475–7.

    Article  PubMed  Google Scholar 

  8. Zhu L, Gong N, Liu B, Lu X, Chen D, Chen S, et al. Coronavirus disease 2019 pneumonia in immunosuppressed renal transplant recipients: a summary of 10 confirmed cases in Wuhan. China Eur Urol. 2020;77(6):748–54.

    Article  CAS  PubMed  Google Scholar 

  9. Fernandez-Ruiz M, Andres A, Loinaz C, Delgado JF, Lopez-Medrano F, San Juan R, et al. COVID-19 in solid organ transplant recipients: a single-center case series from Spain. Am J Transplant. 2020;20(7):1849–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alberici F, Delbarba E, Manenti C, Econimo L, Valerio F, Pola A, 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 Int. 2020;97(6):1083–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pereira MR, Mohan S, Cohen DJ, Husain SA, Dube GK, Ratner LE, et al. COVID-19 in solid organ transplant recipients: Initial report from the US epicenter. Am J Transplant. 2020;20(7):1800–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. COVID-19 infection in kidney transplant recipients. Kidney Int. 2020;97(6):1076–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Haberman R, Axelrad J, Chen A, Castillo R, Yan D, Izmirly P, et al. Covid-19 in immune-mediated inflammatory diseases - case series from New York. N Engl J Med. 2020;383(1):85–8.

    Article  PubMed  Google Scholar 

  14. Gianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, Gossec L, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020;79(7):859–66.

    Article  CAS  PubMed  Google Scholar 

  15. Kuderer NM, Choueiri TK, Shah DP, Shyr Y, Rubinstein SM, Rivera DR, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lee LYW, Cazier JB, Starkey T, Turnbull CD, Team UKCCMP, Kerr R, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet. 2020;395(10241):1919–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nair V, Jandovitz N, Hirsch JS, Abate M, Satapathy SK, Roth N, et al. An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients. Am J Transplant. 2021;21(7):2522–31.

    Article  CAS  PubMed  Google Scholar 

  18. Fisher AM, Schlauch D, Mulloy M, Dao A, Reyad AI, Correll M, et al. Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States. Clin Transplant. 2021;35(4):e14216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Swan JT, Rizk E, Jones SL, Nwana N, Nicolas JC, Tran AT, et al. Hospitalization and survival of solid organ transplant recipients with coronavirus disease 2019: a propensity matched cohort study. PLoS ONE. 2022;17(12):e0278781.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sahota A, Tien A, Yao J, Dong E, Herald J, Javaherifar S, et al. Incidence, risk factors, and outcomes of COVID-19 infection in a large cohort of solid organ transplant recipients. Transplantation. 2022;106(12):2426–34. This was a large study of solid organ transplant recipients detailing the incidence and risk factors causing increased mortality and hospitalizations in the transplant population vs non transplant population.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hadi YB, Naqvi SFZ, Kupec JT, Sofka S, Sarwari A. Outcomes of COVID-19 in solid organ transplant recipients: a propensity-matched analysis of a large research network. Transplantation. 2021;105(6):1365–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Klompas M, Baker MA, Rhee C. Airborne transmission of SARS-CoV-2: theoretical considerations and available evidence. JAMA. 2020;324(5):441–2.

    Article  CAS  PubMed  Google Scholar 

  23. Wu Y, Kang L, Guo Z, Liu J, Liu M, Liang W. Incubation period of COVID-19 caused by unique SARS-CoV-2 strains: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(8): e2228008.

    Article  PubMed  PubMed Central  Google Scholar 

  24. World Health Organization. Symptoms. In: Coronavirus disease (COVID-19) Symptoms. World Health Organization. 2023. https://www.who.int/health-topics/coronavirus#tab=tab_3. Accessed 27 Mar 2023.

  25. Centers for Disease Control and Prevention. Variants & Genomic Surveillance. In: COVID data tracker. Centers for Disease Control and Prevention. 2023. https://covid.cdc.gov/covid-data-tracker/#variants-genomic-surveillance. Accessed 27 Mar 2023.

  26. Mohsin M, Mahmud S. Omicron SARS-CoV-2 variant of concern: a review on its transmissibility, immune evasion, reinfection, and severity. Medicine (Baltimore). 2022;101(19):e29165.

    Article  CAS  PubMed  Google Scholar 

  27. Araf Y, Akter F, Tang YD, Fatemi R, Parvez MSA, Zheng C, et al. Omicron variant of SARS-CoV-2: genomics, transmissibility, and responses to current COVID-19 vaccines. J Med Virol. 2022;94(5):1825–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kumar A, Narayan RK, Prasoon P, Kumari C, Kaur G, Kumar S, et al. COVID-19 mechanisms in the human body-what we know so far. Front Immunol. 2021;12:693938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D’Amico F, Baumgart DC, Danese S, Peyrin-Biroulet L. Diarrhea during COVID-19 infection: pathogenesis, epidemiology, prevention, and management. Clin Gastroenterol Hepatol. 2020;18(8):1663–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mayi BS, Leibowitz JA, Woods AT, Ammon KA, Liu AE, Raja A. The role of neuropilin-1 in COVID-19. PLoS Pathog. 2021;17(1):e1009153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Akhmerov A, Marban E. COVID-19 and the Heart. Circ Res. 2020;126(10):1443–55.

    Article  CAS  PubMed  Google Scholar 

  33. Huang W, Berube J, McNamara M, Saksena S, Hartman M, Arshad T, et al. Lymphocyte subset counts in COVID-19 patients: a meta-analysis. Cytometry A. 2020;97(8):772–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250–6.

    Article  CAS  PubMed  Google Scholar 

  35. Yao XH, He ZC, Li TY, Zhang HR, Wang Y, Mou H, et al. Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient. Cell Res. 2020;30(6):541–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. J Infect Dis. 2022;226(9):1593–607.

    Article  CAS  PubMed  Google Scholar 

  37. Callaway E. Scientists deliberately gave people COVID - here’s what they learnt. Nature. 2022;602(7896):191–2.

    Article  CAS  PubMed  Google Scholar 

  38. Lee JS, Shin EC. The type I interferon response in COVID-19: implications for treatment. Nat Rev Immunol. 2020;20(10):585–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of COVID-19 - preliminary report. N Engl J Med. 2020;383(19):1813–36.

    Article  CAS  PubMed  Google Scholar 

  40. Li Q, Wang Y, Sun Q, Knopf J, Herrmann M, Lin L, et al. Immune response in COVID-19: what is next? Cell Death Differ. 2022;29(6):1107–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7(6):998–1002.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):e138999.

  43. Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383(23):2255–73. This paper reviewed the pathophysiology and clinical signs and symptoms of cytokine storm.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rosas IO, Brau N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N Engl J Med. 2021;384(16):1503–16.

    Article  CAS  PubMed  Google Scholar 

  45. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;57(6):389–99.

    Article  CAS  PubMed  Google Scholar 

  46. Wendisch D, Dietrich O, Mari T, von Stillfried S, Ibarra IL, Mittermaier M, et al. SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis. Cell. 2021;184(26):6243–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Witkowski M, Tizian C, Ferreira-Gomes M, Niemeyer D, Jones TC, Heinrich F, et al. Untimely TGFbeta responses in COVID-19 limit antiviral functions of NK cells. Nature. 2021;600(7888):295–301.

    Article  CAS  PubMed  Google Scholar 

  48. Georg P, Astaburuaga-Garcia R, Bonaguro L, Brumhard S, Michalick L, Lippert LJ, et al. Complement activation induces excessive T cell cytotoxicity in severe COVID-19. Cell. 2022;185(3):493–512.

    Article  CAS  PubMed  Google Scholar 

  49. Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H, Mahajan VS, et al. Loss of Bcl-6-expressing T follicular helper cells and germinal centers in COVID-19. Cell. 2020;183(1):143–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 2020;11:827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mazzoni A, Salvati L, Maggi L, Capone M, Vanni A, Spinicci M, et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J Clin Invest. 2020;130(9):4694–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351(26):2715–29.

    Article  CAS  PubMed  Google Scholar 

  53. Brennan DC, Flavin K, Lowell JA, Howard TK, Shenoy S, Burgess S, et al. A randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation. 1999;67(7):1011–8.

    Article  CAS  PubMed  Google Scholar 

  54. Ward D, Gortz S, Thomson Ernst M, Andersen NN, Kjaer SK, Hallas J, et al. The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection. Eur Respir J. 2022;59(4):2100769.

  55. Group RC, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693–704.

    Article  Google Scholar 

  56. Zeraatkar D, Cusano E, Martinez JPD, Qasim A, Mangala S, Kum E, et al. Use of tocilizumab and sarilumab alone or in combination with corticosteroids for covid-19: systematic review and network meta-analysis. BMJ Med. 2022;1(1):e000036.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA

    Vinay Nair, Gayatri Nair, Frances Wallach, Ernesto Molmenti & Ilan Berlinrut

  2. Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA

    Vinay Nair, Nicholas Jandovitz & Ernesto Molmenti

  3. Department of Pharmacy, North Shore University Hospital, Manhasset, NY, USA

    Nicholas Jandovitz & Jeffery Lo

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  1. Vinay Nair
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Correspondence to Vinay Nair.

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Nair, V., Jandovitz, N., Nair, G. et al. Incorporating Translational Data into Immunosuppression Decisions During COVID-19. Curr Transpl Rep 10, 210–216 (2023). https://doi.org/10.1007/s40472-023-00415-3

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