CMV reactivation in COVID-19 patients: pouring fuel on the fire


  • Racha Ibrahim Hotel-Dieu de France hospital
  • Marie-Ange Ghaleb Hotel-Dieu de France hospital, Beirut
  • Eddy Lilly Hotel-Dieu de France hospital, Beirut
  • Rebecca Kassab Saint-Joseph University, Beirut
  • Marie Chedid
  • Zeina Bou Chebl Hotel-Dieu de France hospital, Beirut
  • Christian Haddad
  • Nabil Chehata
  • Gebrael Saliba Hotel-Dieu de France hospital, Beirut
  • Jacques Choucair Hotel-Dieu de France hospital, Beirut
  • Elie Haddad



cytomegalovirus (CMV), reactivation, COVID-19, lymphopenia, hyperinflammatory response.


Severe SARS-CoV-2 infection could promote CMV reactivation, that further worsens disease prognosis.

This study included admitted patients with recent COVID-19 for one year period in a tertiary hospital, having clinical criteria of CMV reactivation and positive CMV DNAemia.

Fifteen of 559 COVID-19 patients were diagnosed with CMV reactivation (2.7%). 86.6% were male, with a mean age of 63.6 years. Immunodepression was significantly higher in the CMV positive group (p=0.008). Lymphopenia was significantly more important in patients who reactivated CMV (p=<0.001), whereas ferritin level (p=0.019) and IL-6 level (p=0.035) on admission appeared to be significantly lower in this group. There was no significant difference for COVID-19 treatments. ICU admission (p<0 .001) and bacterial infections (p<0.001) appeared to be significant for CMV reactivation. Also, the mortality was significantly higher in the CMV positive group (p=0.042).

This study raises the possible incrimination of lymphopenia, immunosuppression, critical illness, and bacterial infections in CMV reactivation.


WHO Coronavirus (COVID-19) Dashboard. Available from: accessed December 10, 2021.

Batah SS, Fabro AT. Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians. Respir Med. 2021 Jan ;176 :106239. doi: 10.1016/j.rmed.2020.106239

Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020 Jun; 11: 01446 doi:10.3389/fimmu.2020.01446

P, Horby, Lim Ws, Emberson Jr, et al. et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Nov 27;384(8); doi:10.1056/NEJMoa2021436

C, Zhang, Wu Z, Li Jw, Zhao H, and Wang Gq. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2021 Nov 27;55(5); doi: 10.1016/j.ijantimicag.2020.105954.

Cantini F, Niccoli L, Nannini C, et al. Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study. J Infect. 2020;81(4):647-679. doi:10.1016/j.jinf.2020.06.052

Le Balc’h P, Pinceaux K, Pronier C, Seguin P, Tadié J-M, Reizine F. Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients. Crit Care. 2020 Aug 28;24(1):530.

Jh, Naendrup, Borrega Jorge G, Dennis Alexander E, et al. Reactivation of EBV and CMV in Severe COVID-19-Epiphenomena or Trigger of Hyperinflammation in Need of Treatment? A Large Case Series of Critically ill Patients. J Intensive Care Med. 2021 Nov 18; doi:10.1177/08850666211053990

E, Forte, Zhang Z, Thorp Eb, and Hummel M. Cytomegalovirus Latency and Reactivation: An Intricate Interplay With the Host Immune Response. Front Cell Infect Microbiol [Internet]. 2020 Mar 31;10; doi:10.3389/fcimb.2020.00130

Wc, Carll, Rady My, Salomao Ma, et al.. Cytomegalovirus haemorrhagic enterocolitis associated with severe infection with COVID-19. BMJ Open Gastroenterol. 2021 Jan;8(1); doi:10.1136/bmjgast-2020-000556

My, Khatib, Shaik Ks, Ahmed Aa, et al, et al. Tocilizumab-induced cytomegalovirus colitis in a patient with COVID-19. Clin Case Rep 2020;9(1); doi:10.1002/ccr3.3487

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19 [Internet]. [cited 2021 Nov 27]. Available from:

Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients—Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9); doi:10.1111/ctr.13512

Foresta C, Rocca MS, Di Nisio A. Gender susceptibility to COVID-19: a review of the putative role of sex hormones and X chromosome. J Endocrinol Invest. 2021 May 1;44(5):951–6.

Iwatani Y, Amemiya N, Nokiba H, Yamazaki M, Sugiura H, Nitta K. Risk factors for cytomegalovirus reactivation in patients with kidney disease under immunosuppressive therapy. Clin Exp Nephrol 2021 Aug 3; doi:10.1007/s10157-021-02117-5

COVID-19 Guideline, Part 1: Treatment and Management. Available from: accessed November 27, 2021

O, Gundogdu, Demir B, Coskun Co, and Ersan I. Efficacy of pulse steroid therapy in patients critically ill with COVID-19. Bratisl Lek Listy 2021;122(11); doi:10.4149/BLL_2021_126

Má, López Zúñiga, Moreno-Moral A, Ocaña-Granados A, et al. High-dose corticosteroid pulse therapy increases the survival rate in COVID-19 patients at risk of hyper-inflammatory response. PloS One 2021;16(1). doi:10.1371/journal.pone.0243964

Vy, Mareev, Orlova Ya, Pavlikova Ep, et al. Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study). Kardiologiia 2020 Jul 7;60(6). doi:10.18087/cardio.2020.6.n1226

Scherlinger M, Alain S, and Richez C Monitoring of Epstein-Barr virus (EBV)/cytomegalovirus (CMV)/varicella-zoster virus (VZV) load in patients receiving tocilizumab for rheumatoid arthritis Joint Bone Spine 2018 Mar;85(2):259-260; doi: 10.1016/j.jbspin.2017.02.010. Epub 2017 Mar 28.

Fg, Frantzeskaki, Karampi Es, Kottaridi C, et al. Cytomegalovirus reactivation in a general, non-immunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers. J Crit Care. 2015 Apr;30(2). doi:10.1016/j.jcrc.2014.10.002

Mansfield S, Grießl M, Gutknecht M, Cook CH. Sepsis and cytomegalovirus: foes or conspirators? Med Microbiol Immunol (Berl). 2015 Jun;204(3):431–7.