27182University of Cologne, Cologne, Germany.
J Intensive Care Med. 2022 Sep;37(9):1152-1158. doi: 10.1177/08850666211053990. Epub 2021 Nov 18.
Reactivation of viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common in critically ill patients and have been described in patients with severe COVID-19. However, it is unclear whether these reactivations are associated with increased mortality and whether targeted treatments are beneficial.
In a retrospective single-center cohort study, patients with severe COVID-19 treated on our intensive care unit (ICU) were screened for EBV and CMV reactivation as detected by polymerase chain reaction. If present, patient characteristics, temporal connections to severe acute respiratory syndrome coronavirus 2 diagnosis and corticosteroid use, the use of targeted treatments as well as the course of disease and outcome were analyzed. As control group, non-COVID-19 patients with sepsis, treated within the same time period on our ICU, served as control group to compare incidences of viral reactivation.
In 19 (16%) of 117 patients with severe COVID-19 treated on our ICU EBV reactivations were identified, comparable 18 (14%) of 126 in the non-COVID-19 control group ( = .672). Similarly, in 11 (9%) of 117 patients CMV reactivations were identified, comparable to the 16 (13%) of 126 in the non-COVID-19 sepsis patients ( = .296). The majority of EBV (58%) and CMV reactivations (55%) were detected in patients under systemic corticosteroid treatment. 7 (37%) of 19 patients with EBV reactivation survived the ICU stay, 2 (29%) of 7 patients with rituximab treatment and 5 (42%) of 12 patients without treatment ( = .568). Five (50%) of 10 patients with CMV reactivation survived the ICU stay, 5 (83%) of 6 patients with ganciclovir treatment and 0 of 4 patients without treatment ( = .048). Follow-up analysis in these patients showed that the initiation of treatment lead to decrease in viral load.
Critically ill patients with COVID-19 are at a high risk for EBV and CMV reactivations. Whether these reactivations are a cause of hyperinflammation and require targeted treatment remains uncertain. However, in patients with clinical deterioration or signs of hyperinflammation targeted treatment might be beneficial and warrants further studying.
病毒（如 Epstein-Barr 病毒 [EBV] 和巨细胞病毒 [CMV]）的再激活在重症患者中很常见，并且在重症 COVID-19 患者中已有描述。然而，目前尚不清楚这些再激活是否与死亡率增加有关，以及靶向治疗是否有益。
在一项回顾性单中心队列研究中，对在我们的重症监护病房（ICU）接受治疗的重症 COVID-19 患者进行 EBV 和 CMV 再激活的筛查，通过聚合酶链反应进行检测。如果存在，分析患者特征、与严重急性呼吸综合征冠状病毒 2 诊断和皮质类固醇使用的时间关系、靶向治疗的使用以及疾病过程和结果。非 COVID-19 败血症患者在同一时期在我们的 ICU 接受治疗，作为对照组，以比较病毒再激活的发生率。
在我们 ICU 接受治疗的 117 例重症 COVID-19 患者中，有 19 例（16%）发现 EBV 再激活，在非 COVID-19 对照组 126 例（18%）中也有 18 例（ = .672）。同样，在 117 例患者中有 11 例（9%）发现 CMV 再激活，在非 COVID-19 败血症患者中也有 16 例（13%）（ = .296）。大多数 EBV（58%）和 CMV 再激活（55%）在接受全身皮质类固醇治疗的患者中检测到。19 例 EBV 再激活患者中，有 7 例（37%）存活 ICU 治疗，7 例接受利妥昔单抗治疗的患者中有 2 例（29%）存活，12 例未接受治疗的患者中有 5 例（42%）存活（ = .568）。10 例 CMV 再激活患者中有 5 例（50%）存活 ICU 治疗，6 例接受更昔洛韦治疗的患者中有 5 例（83%）存活，4 例未接受治疗的患者中无 1 例存活（ = .048）。对这些患者的随访分析表明，治疗的开始导致病毒载量下降。
COVID-19 重症患者 EBV 和 CMV 再激活的风险很高。这些再激活是否是过度炎症的原因并需要靶向治疗尚不确定。然而，在临床恶化或出现过度炎症迹象的患者中，靶向治疗可能有益，并需要进一步研究。
