Mei Meng1,2, Limin Chen1, Sheng Zhang1, Xuan Dong3, Wenzhe Li1,2, Ranran Li1, Yunxin Deng1,2, Tao Wang1,2, Yan Xu1,2, Jiao Liu1,2, Yanxia Huang1,2, Yizhu Chen1,2, Sisi Huang1, Zhenliang Wen1,2, Lidi Zhang1,2, Hangxiang Du1,2, Yongan Liu1,2, Djillali Annane4, Jieming Qu5,6, Dechang Chen7. 1. Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Rui Jin 2nd road, Shanghai, 200025, China. 2. Department of Critical Care Medicine, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 3. Tuberculosis and Respiratory Department, Wuhan Infectious Diseases Hospital, Wuhan, China. 4. General intensive care unit, Raymond Poincaré Hospital (APHP), Laboratory of Inflammation and Infection U1173, University of Versailles SQY/INSERM 104 bd Raymond Poincaré, 92380, Garches, France. djillali.annane@aphp.fr. 5. Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jmqu0906@163.com. 6. Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Rui Jin 2nd road, Shanghai, 200025, China. jmqu0906@163.com. 7. Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Rui Jin 2nd road, Shanghai, 200025, China. 15168887139@163.com.
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.
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-19patients 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 ureanitrogen, 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-19patients. Importantly, COVID-19patients 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-19patients. 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.
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