| کلیدواژههای انگلیسی مقاله |
COVID-19, Hemophagocytic lymphohistiocytosis, Systematic review, Meta-analysis, What&,rsquo s Known The association of laboratory findings in severe COVID-19 with hemophagocytic lymphohistiocytosis is not clear. What&,rsquo s New Fever, lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, and high aspartate transferase level are common in severe COVID-19 and hemophagocytic lymphohistiocytosis. The leukocytosis, neutrophilia, and hyperfibrinogenemia observed in severe COVID-19 had contradictory roles in hemophagocytic lymphohistiocytosis. IntroductionThe pandemic coronavirus disease 2019 (COVID-19) has involved 105,394,301 cases with a mortality of 2,302,302 by February 8th, 2021. 1, There is a wide range of clinical and laboratory findings in COVID-19 patients, such as fever, dry cough, myalgia, changes in white blood cells (WBC), lymphopenia, high levels of c-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin, ferritin, aspartate transaminase (AST), alanine transaminase (ALT), inflammatory cytokines, along with coagulative disorders manifested with high levels of fibrinogen, D-dimer, and international normalized ratio (INR), longer prothrombin time (PT), and shorter activated partial thrombospondin time (APTT). 2, The National Health Commission of China released guidelines that stratified COVID-19 patients into four categories, mild, moderate, severe, and critical. 3, The majority of patients are asymptomatic or show mild/moderate symptoms. However, a considerable portion of the cases develop severe/critical manifestations with a high mortality rate, emphasizing the importance of biomarkers for better management of this group. A subset of COVID-19 patients is observed to develop acute respiratory distress syndrome (ARDS), threatening their lives. These severe/critical patients experienced fever, hyperferritinemia, and a massive release of inflammatory cytokines, known as a cytokine storm. 4, A cytokine storm is a syndrome identified with a systemic release of inflammatory cytokines such as interleukin (IL)-6, tumor-necrosing factor (TNF)-&,alpha , IL-1&,beta , IL-18, interferon (IFN)-&,gamma , and IL-33. Inflammatory cytokines, especially IL-6 in COVID-19, increase the vascular permeability leading to fluid perfusion into the alveoli. It is presumed that cytokine storm and overreaction of the immune system are major causes of ARDS and mortality in COVID-19. 5, Therefore, the administration of immunosuppressive and anti-inflammatory agents such as dexamethasone, prednisolone, naproxen, and tocilizumab (anti-IL-6 receptor antibody) is the first line of treatment in severe COVID-19 (sCOVID-19). 5,, 6, Notably, such immunosuppressive modalities weaken the anti-viral immune responses as well. 7, Hence, they might aggravate the viral pathogenesis in mild and moderate patients and should be prescribed only for those with severe and hyper-inflammatory responses. 8, Thus, the identification of clinical and laboratory parameters associated with severe disease could help the clinicians manage the outcomes. It has been reported that the hyper-inflammatory condition witnessed in sCOVID-19 could trigger hemophagocytic lymphohistiocytosis (HLH). 9, HLH is a fatal disease in which immune cells such as macrophages and lymphocytes get hyper-activated and attack the healthy cells and organs. 10, It is characterized by hyper-inflammation and a systemic release of inflammatory cytokines leading to multi-organ failure. Secondary HLH (sHLH) is not inherited and commonly occurs following autoimmune disorders or inappropriate immune responses to viral infections. 10, HLH diagnosis is based on a series of clinical and laboratory criteria called the hemophagocytic syndrome diagnostic score (HScore). 10, The HScore comprises several clinical and laboratory factors, including fever, one- or multi-lineage cytopenias, organomegaly, triglyceridemia, hyperferritinemia, hypofibrinogenemia, hypohemoglobinemia, high AST level, hemophagocytosis on bone marrow (BM) aspirate, and prolonged use of immunesuppressants. 11, Recently, the utilization of HScore has been suggested for detecting the hyper-inflammatory syndrome in sCOVID-19 patients in order to identify the patients for whom immunosuppressive agents could decrease mortality. 9, The cytokine profile and clinical features of sCOVID-19 resemble sHLH. 9,, 12,, 13, A key laboratory finding in sHLH is hyperferritinemia, 14,, 15, which is found in many sCOVID-19 cases. 4,, 9,, 12, Moreover, the presence of abnormal liver function and coagulopathy in both COVID-19 and sHLH suggests that a subgroup of COVID-19 pneumonia cases also have sHLH. 16,, 17, However, there are still controversies regarding the association of sCOVID-19 and sHLH. Several studies reported the association of sCOVID-19 and sHLH, and thereby suggested the use of HScore in the clinical management of sCOVID-19 patients. 9,, 12,, 18,, 19, Though, others are skeptical about the benefits of using HScore in sCOVID-19. 6,, 20,- 22, This controversy highlights the necessity of investigating the possible association between HScore parameters and the severity of COVID-19 in a meta-analysis. In this systematic review and meta-analysis, we attempted to find the possible association between the parameters listed in the HScore with the severity of COVID-19 in patients.MethodsSearch StrategyThe conducted systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. 23, A systematic electronic search was carried out separately by two independent authors (MHK and BHKD) in Medline via PubMed, EMBASE, and Cochrane using the keywords listed in table 1,. Keywords for COVID-19 were searched in title/abstract, while the keywords related to HScore were searched in full-text/all fields. Regarding the date of COVID-19 occurrence, the records published from January 1st - June 22nd, 2020, were imported to the reference manager software EndNote X8.1 (Clarivate Analytics, Philadelphia, PA, USA) for further management, including the removal of duplicates and identification of potentially eligible records. Moreover, the references of the selected articles were reviewed to prevent the loss of data sources. Searched fieldKeywords1Laboratory and Clinical general findingsLaboratory*, Clinic*2TemperatureTemperature*, Fever*, Heat*3CytopeniaCytopenia*, Pan-cytopenia*, Pan cytopenia*, Leukopenia*, Anemia*, Neutropenia*, Thrombocyto*, Lymphopenia*, White blood cell*, &,ldquo WBC&,rdquo , leukocyt*, lymphocyt*, neurophil*, monocyt*, eosinophil*, basophil*, platelet*4HemoglobinHemoglobin,5FerritinFerritin*, Isoferritin*6Serum aspartate aminotransferaseGlutamate Aspartate Transaminase*, glutamic oxaloacetic transaminase*, glutamat oxaloacetate transaminase*, &,ldquo SGOT&,rdquo , Aspartate Aminotransferase*, Aspartate Transaminase*, Transaminase*, &,ldquo AST&,rdquo 7OrganomegalyOrganomegal*, Hepatomegal*, Splenomegal*, Hepatosplenomegal*8TriglyceridesTriglyceride*, Triglyceridemia*, Hypertriglyceridemia*, Triacylglycerol*, Triacylglyceride*9FibrinogenFibrinogen*, Factor I, Factor 1, Factor-I, Factor-110Known ImmunosuppressantImmune deficiency*, Immune-deficiency*, Immunodeficiency*, Immune-deficient*, Immunodeficient*, Immune-compromised*, Immune compromised*, mmunocompromised*, Immunosuppressive*, Immune suppressive*, Immune-suppressive*, Immunosuppressant*, Immunosuppression*, Immune suppression*, Immune-suppression*, HIV, AIDS*, Chemotherap*, Methotrexate*, Glucocorticoids*, Cortone* Cortisone*, Hydrocortisone*, Prednisone*, Deltasone*, Orasone*, Budesonide*, Entocort*, Prednisolone*, Millipred*, Methylprednisolone*, Dexamethasone*, Cyclosporine*, Neoral*, Sandimmune*, SangCya*, Azathioprine*, Azasan*, Imuran*, Mycophenolate*, Mycophenolate mofetil*, CellCept*, Myfortic*, Sphingosine 1, Sphingosine-1-Phosphate*, Sphingosine-1 Phosphate*, Phosphate inhibitor*, Fingolimod*, FTY720*, Tacrolimus*, Astagraf*, Envarsus*, Prograf*, Tofacitinib*, Xeljanz*, Sirolimus*, Rapamune*, Everolimus*, Afinitor*, Zortress*, Leflunomide*, Arava*, Abatacept*, Orencia*, Adalimumab*, Humira*, Anakinra*, Kineret*, Certolizumab*, Cimzia*, Etanercept*, Enbrel*, Golimumab*, Simponi*, Infliximab*, Remicade, Ixekizumab*, Taltz*, Natalizumab*, Tysabri*, Rituximab*, Rituxan*, Secukinumab*, Cosentyx*, Tocilizumab*, Actemra*, Ustekinumab*, Stelara, Vedolizumab*, Entyvio*, Basiliximab*, Simulect*, Daclizumab*, Zinbryta*, Antilymphocyte serum*, Antilymphocyte antibod*, Antilymphocyte Globulin*, Antithymphocyte Globulin*, Anti-thymphocyte Globulin*, Anti thymphocyte Globulin*, Antilymphocyte immunoglobulin*, Anti-rejection therap*, Anti rejection therap*, Antirejection therap*, Transplantation, Transplant*, Graft*11COVID-19Covid*, sars-cov-2*, corona virus*, coronavirus*, cv 19, cv-19 2019-ncov, ncov*, Wuhan coronavirus*, Wuhan pneumonia*,All words were searched with a star at the end to cover all possible variants of the words. The keywords in sections 1-10 were searched with an &,ldquo OR&,rdquo together, and the keywords for COVID-19 (section 11) were searched with an &,ldquo OR&,rdquo separately. The results of these two searches were then retrieved with an &,ldquo AND&,rdquo . |