Patient with Jaundice, Dyspnea and Hyperferritinemia after COVID-19

The aim: to highlight the importance of considering hemophagocytic lymphohistiocytosis in patients with jaundice of unclear origin and systemic inflammatory manifestations after coronavirus infection. Key points. A 64-y.o. patient was admitted to the hospital with jaundice, pruritus, fatigue, weight loss. The complaints occurred 2 weeks after discharge from the hospital for treatment of patients with coronavirus infection. Laboratory tests revealed signs of hepatic insufficiency, markers of cholestasis and inflammation persisted in time. Upon instrumental examination no signs of hepatosplenomegaly, biliary tree changes, intra- and extrahepatic obstruction were found. S. aureus was identified in blood cultures, CT scan of the facial skull bones showcased the focus of infection in the area of the roots of teeth 2.4 and 2.5. Therefore, antibiotics were prescribed. Subsequently, the patient's condition was complicated by the development of two episodes of acute respiratory distress syndrome, which occurred during the withdrawal of glucocorticosteroid therapy. Liver biopsy was performed, morphological study revealed signs of "vanishing bile duct” syndrome, excessive activation of macrophages and hemosiderosis of sinusoidal cells. Identified lesions can be found in hemophagocytic lymphohistiocytosis (HLH), a life-threatening complication of coronavirus infection. Glucocorticosteroids therapy, transfusions of human immunoglobulin, albumin, and parenteral nutrition have led to patient's condition improvement. Conclusion. COVID-19 provokes the development of secondary HLH 10 times more often than other respiratory viral infections. The possibility of hemophagocytic syndrome development should be considered, including cases of overlap syndrome with sepsis, in patients with unresolved jaundice, hyperferritinemia after coronavirus infection. Routinely used scales and criteria for diagnosis of HLH (H-score, HLH 2004) in such cases lacks sensitivity, therefore, careful analysis of clinical picture and exclusion of other causes of jaundice are required. © 2022 Russian Journal of Gastroenterology, Hepatology, Coloproctology

Hemophagocytic Lymphohistiocytosis in a Patient With Post-acute COVID-19 Infection.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation with extensive inflammation and tissue destruction due to abnormal immune activation. Post-COVID-19 patients who have recovered with negative serologic tests may also present with secondary HLH, an unusual finding that our case demonstrates. A 73-year-old male with a notable past medical history of fall COVID-19 infection approximately 11 months prior presented initially to emergency services with a chief complaint of high fevers, lethargy, and progressive changes in mentation gradually progressive over the last 5 months' duration. This presentation was concerning for HLH in view of the patient's high H score and clinical suspicion for HLH, and he was initiated on dexamethasone 20 mg daily. intravenous immune globulin (IVIG) protocol was also trialed, despite which the patient continued to deteriorate before expiring during the course of the hospitalization. sHLH following COVID-19 infection remains a poorly understood phenomenon. The severity of the COVID-19 infection does not appear to be related to one's predisposition to develop sHLH. The mortality of HLH remains high even with appropriate therapy.

Evaluation of Outcome in Patients With Moderate and Severe COVID-19 Via H-Score

Background: Due to uncontrolled lymphocyte reaction, the overproduction of cytokines in COVID-19 patients can cause sepsis-like symptoms, suggesting sepsis, cytokine release syndrome (CRS), and secondary hemophagocytic lymphohistiocytosis (sHLH). Since different therapeutic approaches are used for each diagnosis, differentiation is essential. This study aims to use H-score as a possible prognostic tool in COVID-19 patients. Method(s): A sample of 64 moderate and severe COVID-19 patients was enrolled in this study. Clinical and laboratory findings were assessed. H-score was initially calculated and reevaluated among severe cases 72 hours later and among moderate cases showing severe features of COVID-19. Result(s): Mortality of 31.3% was reported. Laboratory findings, including triglycerides (TG), ferritin, and aspartate aminotransferase (AST) showed significantly higher initial and follow-up laboratory assessment levels in severe cases than in moderate cases. Moreover, fibrinogen was significantly higher among severe cases than moderate cases at the initial assessment, but no significant difference was reported in the second fibrinogen assessment. Conclusion(s): In this study, H-score was useful as a predictive tool for the initial evaluation of severe cases of COVID-19. H-score is much lower in these patients than in non-COVID-19 HLH patients may be due to the different underlying immunologic pathophysiology of COVID-19;thus, each H-score criterion must be evaluated for sensitivity and specificity in COVID-19 patients. The H-score cut-offs, H-score may be useful for diagnosing immune overreaction and determining the need for more exclusive immunomodulatory treatments. Copyright © 2022 Shahid Beheshti University of Medical Sciences. All rights reserved.

Rate of secondary HLH and performance of H-score in patients with severe COVID-19.

BACKGROUND: Severe COVID-19 is thought to be caused by immune overdrive and cytokine storm. One of the cytokine storm syndromes frequently induced by infections is secondary hemophagocytic lymphohistiocytosis (HLH) which can be assessed using H-score. In this study, we aimed to evaluate the rate of patients with COVID-19 who meet HLH criteria based on H-score and the association of H-score with poor outcomes. METHODS: In a prospective cohort study of 19 patients with COVID-19 requiring ICU stay from March to May, 2020, we collected demographic and clinical data that focused on H-score's variables and COVID-19 outcomes. H-score ≥ 169 was used to determine the percentage of patients who met the HLH criteria. Mann-Whitney, Kruskal-Wallis, and Spearman rho tests and multiple regression analyses were carried out to evaluate the associated factors. The optimal H-score cut-off to predict poor COVID-19 outcome (need for intubation ± ECMO) was determined using receiver operating characteristic (ROC) analysis. RESULTS: In 669 patients with severe COVID-19 with a mean ± SD age of 50.3 ± 12.8 years, which comprised 95% men; 66% required intubation, 4% ECMO, and 16% died. Only 2% had an H-score ≥ 169. Patients with poor outcomes had a higher mean (SD) H-score than those without; intubation (96.0 [50.0] vs 75.0 [35.0], p < 0.01), ECMO (113.0 [25.0] vs 93.0 [50.0], p < 0.01) and death (98.0 [62.0] vs 93.0 [48.0], p < 0.01). Factors associated with H-score were diabetes (ß coeff = - 10.4, p < 0.01), abdominal pain (ß coeff = 19.1, p < 0.01), duration of COVID-19 symptoms (ß coeff = - 0.7, p = 0.049), and days before ICU admission (ß coeff = - 1.2, p = 0.01). H-score showed a fair ability to discriminate COVID-19 outcomes (AUC 0.61, 95% CI 0.54-0.67). An H-score of 85 was the optimal cut-off with a sensitivity 69% and 1-specificity 53%. CONCLUSION: Despite its association with severity in COVID-19, H-score's ability to predict poor outcomes was only fair, indicating differences in the cytokine storm faced in COVID-19 compared with that during secondary HLH.