Use of rituximab in SARS-CoV-2-positive renal transplant recipient with EBV reactivation and probable haemophagocytic lymphohistiocytosis.

We present a case of a rapid clinical recovery in a critically ill kidney transplant recipient with SARS-CoV-2 positivity, Epstein-Barr virus (EBV) reactivation and probable secondary hemophagocytic lymphohistiocytosis (HLH) treated with etoposide-free regimen, based on dexamethasone and a single dose of rituximab. Although rituximab is often a part of EBV-HLH treatment strategy, its use in simultaneous Coronavirus 2019 disease (COVID-19) and solid-organ transplantation has not been reported yet. We review the current evidence for the potential of SARS-CoV-2 to trigger EBV reactivation, leading to a severe clinical illness. Finally, we compare the clinical features of hyper-inflammatory response typical for severe COVID-19 and classical secondary HLH and discuss the benefits of therapeutic B-cell depletion in both conditions.

COVID-19 associated EBV reactivation and effects of ganciclovir treatment.

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.

Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU.

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.