Secondary hemophagocytic lymphohistiocytosis and cytokine release syndrome in COVID-19, the same or different entities?

Abstract

Background: Excessive release of cytokines in severe COVID-19 resembles secondary hemophagocytic lymphohistiocytosis (sHLH). Aim: To compare the clinical and laboratory characteristics between sHLH and cytokine release syndrome (CRS) in COVID-19. Methods: A review of articles in the PubMed database was performed, using the following keywords "HLH and COVID", "HScore in COVID". Articles available until July 16, 2020 were included. Results: A comparative table was prepared based on the diagnostic criteria of the HLH 2004 protocol, HScore and characteristics of the CRS-COVID-19. Eighteen variables are used for comparison. Discussion: The CRS in COVID-19 presented similarity with the CRS of sHLH; however, it cannot be stated that they are the same entity. Case reports of sHLH in COVID-19 are small. HScore is a tool that could guide the diagnosis of sHLH in the context of CRS-COVID-19, in a more practical way than the classic criteria described in HLH-2004; however, its application in COVID-19 is limited due to the absence of key features of the hyperinflammatory state of COVID-19 that are included in HLH. Conclusions: CRS-COVID-19 is not synonymous with sHLH. Although this last entity may or may not be present in the severe COVID-19.