Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 29;21(1):398.
doi: 10.1186/s12879-021-06094-8.

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients

Mei Meng #  1   2 , Limin Chen #  1 , Sheng Zhang #  1 , Xuan Dong #  3 , Wenzhe Li #  1   2 , Ranran Li  1 , Yunxin Deng  1   2 , Tao Wang  1   2 , Yan Xu  1   2 , Jiao Liu  1   2 , Yanxia Huang  1   2 , Yizhu Chen  1   2 , Sisi Huang  1 , Zhenliang Wen  1   2 , Lidi Zhang  1   2 , Hangxiang Du  1   2 , Yongan Liu  1   2 , Djillali Annane  4 , Jieming Qu  5   6 , Dechang Chen  7
Affiliations

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients

Mei Meng et al. BMC Infect Dis. .

Abstract

Background: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors.

Method: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data.

Results: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19.

Conclusions: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.

Keywords: COVID-19; Cytokine storm; Ferritin; HScore; Platelet; Secondary Hemophagocytic Lymphohistiocytosis; Triglycerides.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Receiver operating characteristic curve for peak TG (a), ferritin (b), PLT (c) respectively. Receiver operating characteristic curve for the multivariable logistic regression model, including TG, ferritin, PLT (d). Abbreviations: AUC, area under the curve; TG, triglyceride; PLT, platelet
Fig. 2
Fig. 2
Internal validation to validate a prediction model
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes A. Surviving Sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19) Intensive Care Med. 2020;46(5):854–887. doi: 10.1007/s00134-020-06022-5. - DOI - PMC - PubMed
    1. Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, et al. Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report. 2020.
    1. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034. doi: 10.1016/S0140-6736(20)30628-0. - DOI - PMC - PubMed
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed
    1. Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: a new character in the spectrum of the hyperferritinemic syndrome? Autoimmun Rev. 2020;19(7):102573. doi: 10.1016/j.autrev.2020.102573. - DOI - PMC - PubMed

MeSH terms