Viral Infections in Critically Ill Cancer Patients

  • Gabriela Corsi-Vasquez
  • Luis Ostrosky-ZeichnerEmail author
Reference work entry


A variety of viral infections have been described as a significant cause of morbidity and mortality among all patient populations, but particularly in critically ill patients that require intensive medical care. Many of these viruses have serious outcomes in the setting of immunosuppression and chronic underlying medical disease. The herpesviruses, herpes simplex and varicella-zoster, are highly prevalent, lifelong infectious agents and commonly manifest with skin lesions in the immunocompetent host but can reactivate and involve the central nervous system in immunocompromised patients. Another widely spread member of the Herpesviridae family, Cytomegalovirus, has been studied in immunocompromised populations including stem cell and solid organ transplant recipients, in which it can cause tissue-invasive disease, particularly targeting the gastrointestinal tract and transplanted organs. Influenza virus is relevant for its public health implications and seasonality, leading to intensive vaccination efforts on a yearly basis aimed to protect susceptible populations such as the elderly and immunocompromised. In a similar fashion, respiratory syncytial virus can cause significant morbidity in patients with leukemia and recipients of bone marrow and solid organ transplants. Unlike influenza, there is no vaccine against RSV, and antiviral therapy is limited, highlighting the importance of implementing infection control measures to prevent spread of the virus. Other less frequently encountered agents such as Zika and Ebola will also be discussed given their high morbidity and mortality.


Viral infections Herpes simplex Varicella-zoster Cytomegalovirus Influenza RSV Zika Ebola Adenovirus Enterovirus 


  1. 1.
    Abbink P, Stephenson K, Barouch D. Zika virus vaccines. Nat Rev Microbiol. 2018;16:594–600.. s41579-018-0039-7CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Adhikary A, Banik U. Human adenovirus type 8: the major agent of epidemic keratoconjunctivitis (EKC). J Clin Virol. 2014;61(4):477–86.CrossRefPubMedGoogle Scholar
  3. 3.
    Aswathyraj S, Sane F, Raghu C, Sabeena S, Alidjinou EK, Arunkumar G, Hober D. Serum-derived IgG from coxsackievirus A6-infected patients can enhance the infection of peripheral blood mononuclear cells with coxsackievirus A6. Microb Pathog. 2018;125:7–11.CrossRefPubMedGoogle Scholar
  4. 4.
    Bitnun A, Yeh E. Acute flaccid paralysis and enteroviral infections. Curr Infect Dis Rep. 2018;20(9):34.CrossRefPubMedGoogle Scholar
  5. 5.
    Bociaga-Jasik M, Piatek A, Garlicki A. Ebola virus disease – pathogenesis, clinical presentation and management. Folia Med Cracov. 2014;54(3):49–55.PubMedGoogle Scholar
  6. 6.
    Casey J, Morris K, Narayana M, Nakagaki M, Kennedy G. Oral ribavirin for treatment of respiratory syncytial virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant. 2013;48(12):1558.CrossRefPubMedGoogle Scholar
  7. 7.
    Centers for Disease Control and Prevention. Years of Ebola viruses outbreaks: 40 years of Ebola virus disease around the world. 2018. Available on: Accessed 2 July 2018.
  8. 8.
    Coleman J, Shukla D. Recent advances in vaccine development for herpes simplex virus types I and II. Hum Vaccin Immunother. 2013;9(4):729–35.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    De la Hoz R, Stephens G, Sherlock C. Diagnosis and treatment approaches of CMV infections in adult patients. J Clin Virol. 2002;25(Suppl 2):S1–12.CrossRefGoogle Scholar
  10. 10.
    Dioverti M, Razonable R. Cytomegalovirus. Microbiol Spectr. 2016;4(4):97–125.Google Scholar
  11. 11.
    El-Haddad D, El Chaer F, Vanichanan J, Shah DP, Ariza-Heredia E, Mulanovich V, Gulbis A, Shpall E, Chemaly R. Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients: a single-center experience. Antivir Res. 2016;134:58–62.CrossRefPubMedGoogle Scholar
  12. 12.
    Falsey A, Hennessey P, Formica M, Cox C, Walsh E. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352(17):1749–59.CrossRefPubMedGoogle Scholar
  13. 13.
    Fisman D. Seasonality of viral infections: mechanisms and unknowns. Clin Microbiol Infect. 2012;18(10):946–54.CrossRefPubMedGoogle Scholar
  14. 14.
    Frange P, Leruez-Ville M. Maribavir, brincidofovir and letermovir: efficacy and safety of new antiviral drugs for treating cytomegalovirus infections. Med Mal Infect. 2018;48:495–502. S0399-077X(17)30787-4CrossRefPubMedGoogle Scholar
  15. 15.
    Gnann J. Chapter 65 Antiviral therapy of varicella-zoster virus infections. In Arvin A, Campadelli-Fiume G, Mocarski E, et al., (eds) Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge: Cambridge University Press; 2007.Google Scholar
  16. 16.
    Gorcea C, Tholouli E, Turner A, Saif M, Davies E, Battersby E, Dignan F. Effective use of oral ribavirin for respiratory syncytial viral infections in allogeneic haematopoietic stem cell transplant recipients. J Hosp Infect. 2017;95(2):214–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Guzman M, Harris E. Dengue. Lancet. 2015;385(9966):453–65.CrossRefPubMedGoogle Scholar
  18. 18.
    Haber N. Respiratory syncytial virus infection in elderly adults. Med Mal Infect. 2018;48:377–82. 13. pii: S0399-077X(16)30734-XCrossRefPubMedGoogle Scholar
  19. 19.
    Hall C, Simőes E, Anderson L. Clinical and epidemiologic features of respiratory syncytial virus. Curr Top Microbiol Immunol. 2013;372:39–57.PubMedGoogle Scholar
  20. 20.
    Heilman J, De Wolff J, Beards G, Basden B. Dengue fever: a Wikipedia clinical review. Open Med. 2014;8(4):e105–15.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Heslop R, Roberts H, Flower D, Jordan V. Interventions for men and women with their first episode of genital herpes. Cochrane Database Syst Rev. 2016;8:CD010684.Google Scholar
  22. 22.
    Ioos S, Mallet H, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika virus epidemiology and recent epidemics. Med Mal Infect. 2014;44(7):302–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Ison M, Hayden F. Viral infections in immunocompromised patients: what’s new with respiratory viruses? Curr Opin Infect Dis. 2002;15(4):355–67.CrossRefPubMedGoogle Scholar
  24. 24.
    Jadav S, Kumar A, Ahsan M, Jayaprakash V. Ebola virus: current and future perspectives. Infect Disord Drug Targets. 2015;15(1):20–31.CrossRefPubMedGoogle Scholar
  25. 25.
    Jubelt B, Lipton H. Enterovirus/picornavirus infections. Handb Clin Neurol. 2014;123:379–416.CrossRefPubMedGoogle Scholar
  26. 26.
    Kelesidis T, Mastoris I, Metsini A, Tsiodras S. How to approach and treat viral infections in ICU patients. BMC Infect Dis. 2014;14:321.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Kennedy P, Steiner I. Recent issues in herpes simplex encephalitis. J Neurovirol. 2013;19(4):346–50.CrossRefPubMedGoogle Scholar
  28. 28.
    Kilgore P, Grabenstein J, Salim A, Rybak M. Treatment of Ebola virus disease. Pharmacotherapy. 2015;35(1):43–53.CrossRefPubMedGoogle Scholar
  29. 29.
    Koshy E, Mengting L, Kumar H, Jianbo W. Epidemiology, treatment and prevention of herpes zoster: a comprehensive review. Indian J Dermatol Venereol Leprol. 2018;84(3):251–62.PubMedGoogle Scholar
  30. 30.
    Krammer F. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov. 2015;14(3):167–82.CrossRefPubMedGoogle Scholar
  31. 31.
    Krammer F, Smith G, Fouchier R, Peiris M, Kedzierska K, Doherty P, Palese P, Shaw M, Treanor J, Webster R, García-Sastre A. Influenza. Nat Rev Dis Primers. 2018;4(1):3.CrossRefPubMedGoogle Scholar
  32. 32.
    Labella A, Merel S. Influenza. Med Clin N Am. 2013;97(4):621–45.CrossRefPubMedGoogle Scholar
  33. 33.
    Lachance P, Chen J, Featherstone R, Sligl W. Association between cytomegalovirus reactivation and clinical outcomes in immunocompetent critically ill patients: a systematic review and meta-analysis. Open Forum Infect Dis. 2017;4(2):029.CrossRefGoogle Scholar
  34. 34.
    Leone P. Reducing the risk of transmitting genital herpes: advances in understanding and therapy. Curr Med Res Opin. 2005;21(10):1577–82.CrossRefPubMedGoogle Scholar
  35. 35.
    Lecrenier N, Beukelaers P, Colindres R, Curran D, De Kesel C, De Saegher J, Didierlaurent A, Ledent E, Mols J, Mrkvan T, Normand-Bayle M, Oostvogels L, Da Silva F, Vassilev V, Vinals C, Brecx A. Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention. Expert Rev Vaccines. 2018;17(7):619–34.CrossRefPubMedGoogle Scholar
  36. 36.
    Levin M, Weinberg A, Schmid D. Herpes simplex virus and varicella-zoster virus. Microbiol Spectr. 2016;4(3).Google Scholar
  37. 37.
    Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev. 2014;27(3):441–62.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Ljungman P, Marty F, Chemaly R, Maertens J, Duarte R, Teal V, et al. Letermovir for prevention of cytomegalovirus infections: results from a phase III randomized, double-blinded, placebo-controlled trial in adult allogeneic hematopoietic cell transplant recipients. 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation, Marseille, France. 2017.Google Scholar
  39. 39.
    Marcinkiewicz J, Bryniarski K, Nazimek K. Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention. Folia Med Cracov. 2014;54(3):39–48.PubMedGoogle Scholar
  40. 40.
    Mertz G. Asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. J Infect Dis. 2018;198(8):1098–100.CrossRefGoogle Scholar
  41. 41.
    Morens D, Taubenberger J, Harvey H, Memoli M. The 1918 influenza pandemic: lessons for 2009 and the future. Crit Care Med. 2010;38(4 Suppl):e10–20.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Nguyen C, Kaku S, Tutera D, Kuschner WG, Barr J. Viral respiratory infections of adults in the intensive care unit. J Intensive Care Med. 2016;31(7):427–41.CrossRefPubMedGoogle Scholar
  43. 43.
    Pangesti K, Abd El Ghany M, Walsh M, Kesson A, Hill-Cawthorne G. Molecular epidemiology of respiratory syncytial virus. Rev Med Virol. 2018;28(2).Google Scholar
  44. 44.
    Parody R, Rabella N, Martino R, Otegui M, del Cuerpo M, Coll P, Sierra J. Upper and lower respiratory tract infections by human enterovirus and rhinovirus in adult patients with hematological malignancies. Am J Hematol. 2007;82(9):807–11.CrossRefPubMedGoogle Scholar
  45. 45.
    Paules C, Subbarao K. Influenza. Lancet. 2017;390(10095):697–708.CrossRefPubMedGoogle Scholar
  46. 46.
    Peaper D, Landry M. Rapid diagnosis of influenza: state of the art. Clin Lab Med. 2014;34:365–85.CrossRefPubMedGoogle Scholar
  47. 47.
    Scheltema N, Kavelaars X, Thorburn K, Hennus M, van Woensel J, van der Ent C, Borghans J, Bont L, Drylewicz J. Potential impact of maternal vaccination on life-threatening respiratory syncytial virus infection during infancy. Vaccine. 2018;36(31):4693–700.CrossRefPubMedGoogle Scholar
  48. 48.
    Silva J, Ludwig-Begall L, Oliveira-Filho E, Oliveira R, Durães-Carvalho R, Lopes T, Silva D, Gil L. A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control. Acta Trop. 2018;188:213–24.CrossRefPubMedGoogle Scholar
  49. 49.
    Simmons S. Clinical manifestations and treatment considerations of herpes simplex virus infection. J Infect Dis. 2002;186(Suppl 1):S71–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Sissons P, Wills M. How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future. Med Microbiol Immunol. 2015;204:307–16.CrossRefPubMedGoogle Scholar
  51. 51.
    Singer M. The spread of Zika and the potential for global arbovirus syndemics. Glob Public Health. 2017;12(1):1–18.CrossRefPubMedGoogle Scholar
  52. 52.
    Sly J, Harris A. Recombinant zoster vaccine (Shingrix) to prevent herpes zoster. Nurs Womens Health. 2018;22(5):417–22.CrossRefPubMedGoogle Scholar
  53. 53.
    Sukhralia S, Verma M, Gopirajan S, Dhanaraj P, Lal R, Mehla N, Kant CR. From dengue to Zika: the wide spread of mosquito-borne arboviruses. Eur J Clin Microbiol Infect Dis. 2018;38:3–14.Google Scholar
  54. 54.
    Taleb S, Al Thani A, Al Ansari K, Yassine H. Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches. Eur J Clin Microbiol Infect Dis. 2018;37:1817–1827. s10096-018-3289-4.Google Scholar
  55. 55.
    Vairo F, Di Pietrantonj C, Pasqualini C, Mammone A, Lanini S, Nicastri E, Castilletti C, Ferraro F, Di Bari V, Puro V, Scognamiglio P, Di Caro A, Capobianchi M, Ippolito G. The surveillance of chikungunya virus in a temperate climate: challenges and possible solutions from the experience of Lazio Region, Italy. Viruses. 2018;10(9):501.CrossRefPubMedCentralGoogle Scholar
  56. 56.
    Walsh E. Respiratory syncytial virus infection in adults. Semin Respir Crit Care Med. 2011;32(4):423–32.CrossRefPubMedGoogle Scholar
  57. 57.
    Walsh E, Falsey A. Respiratory syncytial virus infection in adult populations. Infect Disord Drug Targets. 2012;12(2):98–102.CrossRefPubMedGoogle Scholar
  58. 58.
    Wang L, Zhu L, Zhu H. Efficacy of varicella (VZV) vaccination: an update for the clinician. Ther Adv Vaccines. 2016;4(1–2):20–31.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Whitley R, Kimberlin D, Roizman B. Herpes simplex viruses. Clin Infect Dis. 1998;26:541–55.CrossRefPubMedGoogle Scholar
  60. 60.
    Whitley R, Roizman B. Herpes simplex virus infections. Lancet. 2001;357:1513–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Widener R, Whitley R. Chapter 11: Herpes simplex virus. In Alex C. Tselis, John Booss (ed) Handbook of clinical neurology, Vol. 123 (3rd series). Neurovirology. Amsterdam: Elsevier B.V.; 2014.Google Scholar
  62. 62.
    Yong M, Lewin S, Manuel O. Immune monitoring for CMV in transplantation. Curr Infect Dis Rep. 2018;20:4.CrossRefPubMedGoogle Scholar
  63. 63.
    Zerboni L, Sen N, Oliver S, Arvin A. Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol. 2014;12(3):197–210.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Gabriela Corsi-Vasquez
    • 1
  • Luis Ostrosky-Zeichner
    • 2
    Email author
  1. 1.McGovern Medical SchoolUniversity of Texas at HoustonHoustonUSA
  2. 2.Infectious DiseasesThe University of Texas Health Science Center at HoustonHoustonUSA

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