Summary
Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.
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Mahase E. Coronavirus covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate. BMJ, 2020,368:m641
Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med, 2020,46(5):846–848
Wu C, Chen X, Cai Y, et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med, 2020,180(7):934–943
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020,395(10229):1054–1062
Favara BE. Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. Semin Diagn Pathol, 1992, 9(1):63–74
LaRosee P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood, 2019,133(23):2465–2477
Janka GE. Familial hemophagocytic lymphohistiocytosis. Eur J Pediatr, 1983,140(3):221–230
Janka G, Imashuku S, Elinder G, et al. Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am, 1998,12(2):435–444
Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, et al. Adult haemophagocytic syndrome. Lancet, 2014,383(9927):1503–1516
Marsh RA. Epstein-Barr Virus and Hemophagocytic Lymphohistiocytosis. Front Immunol, 2017,8:1902
Schulert GS, Zhang M, Fall N, et al. Whole-Exome Sequencing Reveals Mutations in Genes Linked to Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome in Fatal Cases of H1N1 Influenza. J Infect Dis, 2016,213(7):1180–1188
Tseng YT, Sheng WH, Lin BH, et al. Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults. J Microbiol Immunol Infect, 2011, 44(3):191–197
Bhatia S, Bauer F, Bilgrami SA. Candidiasis-associated hemophagocytic lymphohistiocytosis in a patient infected with human immunodeficiency virus. Clin Infect Dis, 2003,37(11):e161–e166
Mehta P, McAuley DF, Brown M, et al. HLH Across Speciality Collaboration. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020,395(10229):1033
WHO. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020: World Health Organization; 2020.
Gando S, Iba T, Eguchi Y, et al. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med, 2006,34(3):625–631
Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016,315(8):801–810
Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA, 2012,307(23):2526–2533
Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol, 2014,66(9):2613–2620
Knaak C, Nyvlt P, Schuster FS, et al. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Crit Care, 2020,24(1):244
Karakike E, Giamarellos-Bourboulis EJ. Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis. Front Immunol, 2019,10:55
Beutel G, Wiesner O, Eder M, et al. Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection. Crit Care, 2011,15(2):R80
Veerakul G, Sanpakit K, Tanphaichitr VS, et al. Secondary hemophagocytic lymphohistiocytosis in children: an analysis of etiology and outcome. J Med Assoc Thai, 2002,85(2):S530–541
Jordan MB, Allen CE, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood, 2011,118(15):4041–4052
Chaib F. WHO welcomes preliminary results about dexamethasone use in treating critically ill COVID-19 patients. 2020, https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-resuts-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients.
Chinese Clinical Trial Registry A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19) Feb 13, 2020. http://www.chictr.org.cn/showprojen.aspx?proj=49409
Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet, 2020,395(10223):e30–e31
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Yang, K., Xing, My., Jiang, Ly. et al. Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19. CURR MED SCI 41, 39–45 (2021). https://doi.org/10.1007/s11596-021-2315-4
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DOI: https://doi.org/10.1007/s11596-021-2315-4