Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study - The Lancet

10/1/2020

Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study - The Lancet

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Fever (>38·0°C)	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁸ Fardet L Galicier L Lambotte O et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. ^, ¹⁰ Henter JI Horne A Aricó M et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. ^, ¹¹ Davì S Consolaro A Guseinova D et al. An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis. ^, ¹⁴ Parodi A Davì S Pringe AB et al. Macrophage activation syndrome in juvenile systemic lupus erythematosus: a multinational multicenter study of thirty-eight patients. ^, ¹⁵ Ravelli A Minoia F Davì S et al. 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. ^, ³³ Shimazaki C Inaba T Nakagawa M B-cell lymphoma-associated hemophagocytic syndrome. ^, ⁴⁴ Chen N Zhou M Dong X et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁴⁶ Wang D Hu B Hu C Zhu F Liu X Zhang J Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. ^, ⁴⁷ Xu XW Wu XX Jiang XG et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series.	>90% have fever
Hepatosplenomegaly	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	ND	Unknown
Encephalopathy	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ⁴⁸ Espinosa PS Rizvi Z Sharma P Hindi F Filatov A Neurological complications of coronavirus disease (COVID-19): encephalopathy, MRI brain and cerebrospinal fluid findings: case 2. ^, ⁴⁹ Kishfy L Casasola M Banankhah P et al. Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe Covid-19. ^, ⁵⁰ Hayashi M Sahashi Y Baba Y Okura H Shimohata T COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion. ^, ⁵¹ Zayet S Ben Abdallah Y Royer PY Toko-Tchiundzie L Gendrin V Klopfenstein T Encephalopathy in patients with COVID-19: ‘causality or coincidence?’. ^, ⁵² Filatov A Sharma P Hindi F Espinosa PS Neurological complications of coronavirus disease (COVID-19): encephalopathy.	Observed but incidence unknown
Haemoglobin, g/dL	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Moderate to low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Mildly low to normal ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.	12·2 vs 13·4
Platelets, 10⁹ cells per L	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Mildly low to normal	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Mildly low to normal ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁶ Deng Y Liu W Liu K et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. ^, ⁵⁷ Dysregulation of immune response in patients with COVID-19 in Wuhan, China. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.	143–187 vs 173–222
White blood count, 10⁹ cells per L	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Mildly low to normal	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Mildly low to normal ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁹ Richardson S Hirsch JS Narasimhan M et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area.	3·3–11·0 vs 4·7–5·3
Absolute lymphocyte count, 10⁹ cells per L	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Mildly low to normal	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal. ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁶ Deng Y Liu W Liu K et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. ^, ⁵⁷ Dysregulation of immune response in patients with COVID-19 in Wuhan, China. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. ^, ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death.	0·5–0·8 vs 1·0–1·4
Neutrophil to lymphocyte ratio	Mildly low to normal	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	ND	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁷ Dysregulation of immune response in patients with COVID-19 in Wuhan, China. ^, ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death. ^, ⁶¹ Wang Y Ju M Chen C et al. Neutrophil-to-lymphocyte ratio as a prognostic marker in acute respiratory distress syndrome patients: a retrospective study.	5·5–22·0 vs 2·8–4·4
Ferritin, ng/mL	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁷ Dysregulation of immune response in patients with COVID-19 in Wuhan, China. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. ^, ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death. ^, ⁶² Clinical and immunological features of severe and moderate coronavirus disease 2019.	800–1598 vs 337–523
Lactate dehydrogenase, U/L	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. ^, ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death. ^, ⁶² Clinical and immunological features of severe and moderate coronavirus disease 2019. ^, ⁶³ Mo P Xing Y Xiao Y et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China.	400–905 vs 221–297
D-dimer, μg/mL	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal. ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁶ Deng Y Liu W Liu K et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. ^, ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death. ^, ⁶² Clinical and immunological features of severe and moderate coronavirus disease 2019. ^, ⁶⁴ Zhang L Yan X Fan Q Liu H Liu X Liu Z D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. ^, ⁶⁵ Thachil J Tang N Gando S et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. ^, ⁶⁶ Goshua G Pine AB Meizlish ML et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.	0·6–4·0 vs 0·3–0·5
Triglycerides, mg/dL	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Mildly low to normal	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death.	180 vs 120
Fibrinogen, mg/dL	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Moderate to low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Extremely low ^‡ ‡ Indicates magnitude of decrease below the lower limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal. ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁶⁶ Goshua G Pine AB Meizlish ML et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.	630 vs 450
Aspartate aminotransferase, U/L	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ¹ Guan WJ Ni ZY Hu Y et al. Clinical characteristics of coronavirus disease 2019 in China. ^, ⁴⁵ Huang C Wang Y Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. ^, ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁶ Deng Y Liu W Liu K et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. ^, ⁶² Clinical and immunological features of severe and moderate coronavirus disease 2019. ^, ⁶³ Mo P Xing Y Xiao Y et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China.	38–288 vs 24–40
Interleukin-6, pg/mL	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal. ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁵ Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. ^, ⁵⁷ Dysregulation of immune response in patients with COVID-19 in Wuhan, China. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. ^, ⁶⁰ Jordan RE Adab P Cheng KK Covid-19: risk factors for severe disease and death. ^, ⁶³ Mo P Xing Y Xiao Y et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. ^, ⁶⁷ Chen X Zhao B Qu Y et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients.	6–72 vs 6–13
Soluble interleukin-2 receptor-α (also known as sCD25), pg/mL	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Mildly low to normal ⁵⁷ Dysregulation of immune response in patients with COVID-19 in Wuhan, China. ^, ⁶⁸ Hou H Zhang B Huang H et al. Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19.	757 vs 663
C-reactive protein ^§ § Not high-sensitivity C-reactive protein. , mg/L	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Moderate to high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal.	Extremely high ^† † Indicates magnitude of increase above the upper limit of normal. ⁵³ Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. ^, ⁵⁴ Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. ^, ⁵⁶ Deng Y Liu W Liu K et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. ^, ⁵⁸ Ruan Q Yang K Wang W Jiang L Song J Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. ^, ⁶⁹ Liu K Fang YY Deng Y et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province.	34–126 vs 8–23

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