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1.
Arch Pathol Lab Med ; 146(4): 507-519, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1791951

ABSTRACT

CONTEXT.­: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder of immune regulation that can eventually result in end-organ damage and death. HLH is characterized by uncontrolled activation of cytotoxic T lymphocytes, natural killer cells, and macrophages that can lead to a cytokine storm. The diagnosis of HLH is often challenging due to the diverse clinical manifestations and the presence of several diagnostic mimics. The prognosis is generally poor, warranting rapid diagnosis and aggressive management. OBJECTIVE.­: To provide a comprehensive review of the pathogenesis, clinical features, diagnosis, and management of HLH. DATA SOURCES.­: Peer-reviewed literature. CONCLUSIONS.­: HLH is a condition where a complete understanding of the pathogenesis, early diagnosis, and proper management has an important role in determining patient outcome. Genetic mutations causing impairment in the function of cytotoxic T lymphocytes and natural killer cells have been identified as the root cause of familial HLH; however, the specific pathogenesis of acquired HLH is unclear. The HLH-2004 protocol used in the diagnosis of HLH was originally developed for the pediatric population. The HLH-2004 protocol still forms the basis of the diagnosis of HLH in adults, although its use in adults has not been formally validated yet. Treatment of HLH is primarily based on the HLH-94 protocol, which involves suppressing the inflammatory response, but the treatment needs to be modified in adults depending on the underlying cause and comorbidities.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Child , Humans , Killer Cells, Natural , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/genetics , Lymphohistiocytosis, Hemophagocytic/therapy , Macrophages
2.
Exp Biol Med (Maywood) ; 247(4): 330-337, 2022 02.
Article in English | MEDLINE | ID: covidwho-1649719

ABSTRACT

Cytokine storm is an umbrella term that describes an inflammatory syndrome characterized by elevated levels of circulating cytokines and hyperactivation of innate and/or adaptive immune cells. One type of cytokine storm is hemophagocytic lymphohistiocytosis (HLH), which can be either primary or secondary. Severe COVID-19-associated pneumonia and acute respiratory distress syndrome (ARDS) can also lead to cytokine storm/cytokine release syndrome (CS/CRS) and, more rarely, meet criteria for the diagnosis of secondary HLH. Here, we review the immunobiology of primary and secondary HLH and examine whether COVID-19-associated CS/CRS can be discriminated from non-COVID-19 secondary HLH. Finally, we review differences in immunobiology between these different entities, which may inform both clinical diagnosis and treatment of patients.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Cytokine Release Syndrome/virology , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/therapy
3.
J Infect Dev Ctries ; 15(11): 1607-1614, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1572707

ABSTRACT

Novel coronavirus infections 2019 (COVID-19) associated hyperinflammatory syndromes are well-defined clinical conditions and have a potential risk for severe infection. Hemophagocytic lymphohistiocytosis (HLH), a rare type of acute progressive hyperinflammatory syndrome, has been reported in a limited number of COVID-19 cases. In this article, we aimed to present a patient with HLH secondary to COVID-19 diagnosed by bone marrow biopsy, and to summarize and review HLH cases associated with COVID-19 in the literature. A 47-year-old male patient presented with complaints of fever, cough, abdominal discomfort, and nausea-vomiting. He had recovered from COVID-19 a month ago and was readmitted to the hospital due to the re-appearance of clinical symptoms after a two-week interval. The patient was diagnosed with HLH secondary to COVID-19 on sixth day of admission and fully recovered with systemic pulse steroid, intravenous immunoglobulin, and plasma exchange therapy. Analysis of literature searches revealed that 22 cases were definitely diagnosed with COVID-19-associated HLH, 16 of them were male. They had been treated with different anti-cytokine drugs, of which nine had died. The increasing number of HLH cases, which have high mortality rates, shows the importance of hyperinflammatory syndromes in COVID-19 patients. Some patients may experience hemophagocytosis in the late period of COVID-19, even while in recovery. Increased awareness and early treatment for HLH triggered by COVID-19 can be a life-saving effort for reducing mortality in severe COVID-19 cases.


Subject(s)
COVID-19/complications , Lymphohistiocytosis, Hemophagocytic/diagnosis , SARS-CoV-2 , Diagnosis, Differential , Humans , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/therapy , Male , Middle Aged , Plasma Exchange
4.
Acta Paediatr ; 110(10): 2729-2736, 2021 10.
Article in English | MEDLINE | ID: covidwho-1258900

ABSTRACT

Primary (familial/hereditary) and secondary (non-familial/hereditary) hemophagocytic lymphohistiocytosis (HLH) are hyperinflammatory and hypercytokinemic syndromes. Secondary HLH includes infection- (eg viral/bacterial/fungal/parasitic) and non-infection- (eg collagen disease or malignancy) related diseases. Viral HLH is the major type among all age groups. Secondary viral HLH and primary HLH must be differentiated carefully because primary HLH can be associated with viral infection(s), and the outcome is dismal without a timely diagnosis and hematopoietic stem cell transplantation (HSCT). Epstein-Barr virus (EBV)-related HLH (EBV-HLH) is the most common type of viral HLH in childhood. For non-EBV-HLH, appropriate treatment of viral infection, followed by immunomodulatory agent(s) such as corticosteroids, intravenous immunoglobulin or cyclosporine A, is usually successful; however, recent SARS-CoV-2-related HLH may become life-threatening. EBV-HLH may occur heterogeneously associated with the primary infection, with chronic active EBV infection or with underlying primary HLH. Although immunomodulatory agent(s) are effective in the majority of EBV-HLH cases, management differs from that of non-EBV-HLH because severe and refractory cases may require etoposide-containing HLH-1994/2004 regimens or other experimental agents. The novel agent, emapalumab (an anti-IFN-γ monoclonal antibody) can be used to treat EBV-HLH cases to avoid the risk of secondary malignancy due to etoposide. Finally, HSCT is required for refractory EBV-HLH cases and can also be curative in some other cases.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Lymphohistiocytosis, Hemophagocytic , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/therapy , SARS-CoV-2
5.
BMC Pediatr ; 20(1): 288, 2020 06 09.
Article in English | MEDLINE | ID: covidwho-1228992

ABSTRACT

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that requires prompt diagnosis and appropriate treatment. A risk-stratification model that could be used to identify high-risk pediatric patients with HLH who should be considered for second-line therapies, including salvage regimens and allogeneic hematopoietic cell transplantation (HCT), was developed. METHODS: The medical records of 88 pediatric patients (median age 1.4 years, range 0.2-15 years) with non-malignancy associated secondary HLH were retrospectively reviewed. Treatment strategies included dexamethasone, etoposide, and cyclosporine. RESULTS: Survival analysis showed HLH patients with infections other than Epstein-Barr virus (EBV) and unknown causes experienced better 5-year overall survival (OS) than patients with HLH due to autoimmune disease, EBV or immunodeficiency (76% vs. 65, 33.3, 11%, p < 0.001). On multivariate analysis, among all patients, non-response at 8 weeks was the most powerful predictor of poor OS. When treatment response was excluded, hemoglobin < 60 g/L and albumin < 25 g/L at diagnosis were associated with poor OS. In patients with EBV-HLH, hemoglobin < 60 g/L at diagnosis was associated with poor OS. A prognostic risk score was established and weighted based on hazard ratios calculated for three parameters measured at diagnosis: hemoglobin < 60 g/L (2 points), platelets < 30 × 109/L (1 point), albumin < 25 g/L (2 points). Five-year OS of low-risk (score 0-1), intermediate-risk (score 2), and poor-risk (score ≥ 3) patients were 88, 38, and 22%, respectively (p < 0.001). CONCLUSIONS: These findings indicate that clinicians should be aware of predictive factors at diagnosis and consider 8-week treatment response to identify patients with high-risk of disease progression and the need for second-line therapy and allogeneic HCT.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Lymphohistiocytosis, Hemophagocytic , Neoplasms , Adolescent , Child , Child, Preschool , Herpesvirus 4, Human , Humans , Infant , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/therapy , Prognosis , Retrospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Treatment Outcome
6.
Blood Adv ; 4(15): 3754-3766, 2020 08 11.
Article in English | MEDLINE | ID: covidwho-1228984

ABSTRACT

We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P = .035). For children with verified FHL (family history/genetically verified, n = 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n = 53) was significantly lower (52%; 95% CI, 38-65) (P = .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival. This trial was registered at www.clinicaltrials.gov as #NCT00426101.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Lymphohistiocytosis, Hemophagocytic , Adolescent , Child , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/genetics , Lymphohistiocytosis, Hemophagocytic/therapy , Prospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
7.
Front Immunol ; 11: 2055, 2020.
Article in English | MEDLINE | ID: covidwho-807548

ABSTRACT

The clinical and laboratory features of COVID-19 are reviewed with attention to the immunologic manifestations of the disease. Recent COVID-19 publications describe a variety of clinical presentations including an asymptomatic state, pneumonia, a hemophagocytic lymphohistiocytosis like syndrome, Multisystem Inflammatory Syndrome in Children (MIS-C) but, also called Pediatric Inflammatory Multisystem Syndrome-Toxic Shock (PIMS-TS), Kawasaki Disease, and myocarditis. A common theme amongst multiple reports suggests an overexuberant autoimmune component of the disease but a common pathophysiology to explain the variations in clinical presentation has been elusive. Review of the basic science of other viral induced autoimmune disorders may give clues as to why immunosuppressive and immunomodulating regimens now appear to have some efficacy in COVID-19. Review of the immunopathology also reveals other therapies that have yet to be explored. There is potential use of T cell depleting therapies and possibly anti-CD20 therapy for COVID-19 and clinical research using these medications is warranted.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections , Immunosuppressive Agents/therapeutic use , Lymphocyte Depletion , Pandemics , Pneumonia, Viral , Systemic Inflammatory Response Syndrome , T-Lymphocytes , COVID-19 , Child , Child, Preschool , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Humans , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphohistiocytosis, Hemophagocytic/therapy , Lymphohistiocytosis, Hemophagocytic/virology , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/therapy , Mucocutaneous Lymph Node Syndrome/virology , Myocarditis/immunology , Myocarditis/therapy , Myocarditis/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy , Systemic Inflammatory Response Syndrome/virology , T-Lymphocytes/immunology , T-Lymphocytes/pathology
8.
Transfus Apher Sci ; 59(6): 102881, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-665570

ABSTRACT

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life-threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.


Subject(s)
COVID-19 , Cytokines/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Lymphohistiocytosis, Hemophagocytic , SARS-CoV-2/metabolism , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/therapy , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnostic imaging , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/diagnostic imaging , Lymphohistiocytosis, Hemophagocytic/therapy , Male , Middle Aged
9.
BMC Med ; 18(1): 214, 2020 07 15.
Article in English | MEDLINE | ID: covidwho-646772

ABSTRACT

BACKGROUND: COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly presents as fever, cough, dyspnea, and myalgia or fatigue. Although the majority of patients with COVID-19 have mild symptoms, some are more prone to serious outcomes, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening inflammatory syndrome associated with intense cytokine release (also known as a "cytokine storm"). Similar to COVID-19, HLH is characterized by aggressive course leading to multi-organ failure. MAIN TEXT: The purpose of this review article is to draw attention to the possibility of the complication of HLH in patients with the severe course of COVID-19. Indeed, some of the clinical characteristics observed in the more severe cases of COVID-19 are reminiscent of secondary HLH (which can be triggered by infections, malignancies, rheumatological diseases, or autoimmune/immunodeficiency conditions). The pathogenesis of SARS-CoV-2 infection also suggests that HLH or a similar hyperinflammatory syndrome is the cause of the severe course of the infection. CONCLUSION: The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring. Therefore, patients with severe COVID-19 should be screened for hyperinflammation using standard laboratory tests to identify those for whom immunosuppressive therapy may improve outcomes.


Subject(s)
Coronavirus Infections/complications , Cytokine Release Syndrome/virology , Lymphohistiocytosis, Hemophagocytic/virology , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Coronavirus Infections/therapy , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/therapy , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2
11.
Clin Rheumatol ; 39(7): 2085-2094, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-436778

ABSTRACT

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.


Subject(s)
Antirheumatic Agents , Coronavirus Infections , Cytokine Release Syndrome , Lymphohistiocytosis, Hemophagocytic , Macrophage Activation Syndrome , Pandemics , Pneumonia, Viral , Antirheumatic Agents/classification , Antirheumatic Agents/immunology , Antirheumatic Agents/pharmacology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Humans , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/therapy , Macrophage Activation Syndrome/etiology , Macrophage Activation Syndrome/immunology , Macrophage Activation Syndrome/therapy , Patient Selection , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , SARS-CoV-2 , Time-to-Treatment
13.
Chest ; 158(1): e15-e19, 2020 07.
Article in English | MEDLINE | ID: covidwho-213323

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Coronavirus Infections , Cytokine Release Syndrome , Lymphohistiocytosis, Hemophagocytic , Pandemics , Pneumonia, Viral , Adult , Aged , Anti-Infective Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Azithromycin/administration & dosage , Betacoronavirus/isolation & purification , C-Reactive Protein/analysis , COVID-19 , Clinical Deterioration , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Fatal Outcome , Female , Humans , Hydroxychloroquine/administration & dosage , Hypoxia/etiology , Hypoxia/therapy , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/therapy , Lymphohistiocytosis, Hemophagocytic/virology , Male , Myocarditis/therapy , Myocarditis/virology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiration, Artificial/methods , SARS-CoV-2 , Shock, Septic/etiology , Shock, Septic/therapy
14.
Cytotherapy ; 22(9): 474-481, 2020 09.
Article in English | MEDLINE | ID: covidwho-197744

ABSTRACT

Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.


Subject(s)
Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Adrenal Cortex Hormones/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Humans , Immune Reconstitution Inflammatory Syndrome/etiology , Immune Reconstitution Inflammatory Syndrome/therapy , Immunization, Passive , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Killer Cells, Natural/immunology , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/therapy , Pandemics , Plasmapheresis , Pneumonia, Viral/physiopathology , STAT Transcription Factors/antagonists & inhibitors
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