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. 2022 Apr;10(4):e597.
doi: 10.1002/iid3.597.

COVID-19 associated EBV reactivation and effects of ganciclovir treatment

Mei Meng  1 , Sheng Zhang  1 , Xuan Dong  2 , Wenqing Sun  3 , Yunfeng Deng  4 , Wenzhe Li  1 , Ranran Li  1 , Djillali Annane  5 , Zhixiong Wu  6 , Dechang Chen  1
Affiliations

COVID-19 associated EBV reactivation and effects of ganciclovir treatment

Mei Meng et al. Immun Inflamm Dis. 2022 Apr.

Abstract

Background: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain.

Methods: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics.

Results: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients.

Conclusion: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.

Keywords: COVID-19; EBV reactivation; ganciclovir; mortality.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Violin plot of VCA‐IgM, EBNA‐IgG, VCA‐IgG, and EA‐IgG concentration among survivors and nonsurvivors. EA‐IgG, EBV early antigens‐IgG; EBNA‐IgG, EBV nuclear antigens‐IgG; EBV, Epstein–Barr virus; IgG, immunoglobulin G; VCA‐IgG, EBV viral capsid antigen‐IgG; VCA‐IgM, EBV viral capsid antigen‐IgM
FIGURE 2
FIGURE 2
Violin plot of CMV‐IgM and CMV‐IgG concentration among survivors and nonsurvivors. CMV‐IgG, cytomegalovirus immunoglobulin G; CMV‐IgM, cytomegalovirus immunoglobulin M
FIGURE 3
FIGURE 3
Kaplan–Meier survival curves for patients with ganciclovir therapy or who did not receive ganciclovir therapy. COVID‐19, coronavirus disease 2019
FIGURE 4
FIGURE 4
Comparison of hemoglobin and prealbumin between ganciclovir treated group and matched controls
FIGURE 5
FIGURE 5
Comparison of lymphocyte count, platelet count, IL‐6, ferritin, fibrinogen, and ESR between ganciclovir treated group and matched controls. ESR, erythrocyte sedimentation rate; IL‐6, interleukin 6
FIGURE 6
FIGURE 6
Comparison of leukocyte count and serum creatinine between ganciclovir treated group and matched controls
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