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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(7): 744-748, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32669172

RESUMO

OBJECTIVE: To study the clinical features of children with severe adenovirus pneumonia (SAP) and hemophagocytic syndrome (HPS). METHODS: A retrospective analysis was performed from the chart review data of 30 children with SAP and HPS who were admitted from January 2014 to June 2019. According to the prognosis, the children were divided into a good prognosis group (n=18) and a poor prognosis group (n=12). RESULTS: Among the 30 children with SAP and HPS, the ratio of male to female was 2:1. The median age of onset was 1 year and 3 months (range 3 months to 5 years), and the mean course of fever was 19±7 d. Of the 30 children, 28 (93%) experienced disease onset in January to June. High-throughput gene detection of serum pathogens showed that 16 (53%) children were positive for human adenovirus type 7 (HAdV-7), and the other 14 (47%) children were positive for HAdV antigen based on immunofluorescence assay for throat swab, with unknown type. Of all 30 children, 29 (97%) had respiratory complications, 24 (80%) had cardiovascular complications, 16 (53%) had gastrointestinal complications, and 9 (30%) had toxic encephalopathy. Eighteen children (60%) improved or recovered and 12 (40%) did not recover (3 died). Compared with the good prognosis group, the poor prognosis group had a significantly longer course from onset to diagnosis of HPS (P<0.05), significantly higher levels of fibrinogen and tumor necrosis factor-α (P<0.05), and a significantly lower level of interferon-γ (P<0.05). The mean follow-up time was 6±2 months; 11 (41%) children recovered, 1 (4%) experienced recurrence of HPS, and 15 (56%) had the sequela of post-infectious bronchiolitis obliterans (PIBO). CONCLUSIONS: HPS may be observed in children with SAP, and PIBO is the most common sequela of SAP.


Assuntos
Infecções por Adenoviridae , Linfo-Histiocitose Hemofagocítica , Pneumonia Viral , Adenoviridae , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(7): 749-754, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32669173

RESUMO

OBJECTIVE: To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH). METHODS: A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019. RESULTS: The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged <2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39°C to 41°C. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH. CONCLUSIONS: The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.


Assuntos
Linfo-Histiocitose Hemofagocítica , Adenoviridae , Pré-Escolar , Etoposídeo , Feminino , Humanos , Imunoglobulinas Intravenosas , Lactente , Masculino , Estudos Retrospectivos
3.
BMC Med ; 18(1): 214, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32664932

RESUMO

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.


Assuntos
Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/virologia , Linfo-Histiocitose Hemofagocítica/virologia , Pneumonia Viral/complicações , Betacoronavirus , Infecções por Coronavirus/terapia , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Pandemias , Pneumonia Viral/terapia
8.
Rev Soc Bras Med Trop ; 53: e20190491, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578702

RESUMO

INTRODUCTION: Visceral leishmaniasis (VL) is an ill-studied disease that is endemic to several regions of Brazil. It is often complicated by hemophagocytic lymphohistiocytosis (HLH), a potentially fatal disorder resulting from excessive non-malignant activation/proliferation of T lymphocytes and macrophages. Considering the overlapping clinical and laboratory characteristics of these diseases, diagnosing HLH is a challenge. Therefore, tracking the association between VL and HLH is necessary in endemic areas. Although HLH can be inapparent and resolve with antileishmanicides, this may not always occur. HLH causes high lethality; therefore, immunosuppressive therapy should be instituted immediately in order to avoid a fatal outcome. METHODS: We described the epidemiological, clinical, laboratory, and therapeutic profile of this association in a region of Brazil endemic for VL. RESULTS: We presented 39 patients with this association in a retrospective cohort of 258 children who were admitted from January 2012 to June 2017. Of the 39 patients, 31 were from urban areas (79.5%), and 21 (53%) were males. The mean age and weight were 2.86 (2.08) years and 14.03 (5.96) kg, respectively. The main symptoms were fever (100%), hepatosplenomegaly (100%), pallor of the skin and mucosa (82.5%), edema (38.5%), bleeding (25%), and jaundice (7.5%). Hemophagocytosis was identified in 16/37 (43.24%) patients, and direct examination revealed that 26/37 (70.27%) patients were positive for VL. The patients were treated as recommended by the Ministry of Health. CONCLUSIONS: It was observed that HLH is a common complication in endemic areas, and its diagnosis must consider the overlapping of clinical characteristics and pancytopenia.


Assuntos
Leishmaniose Visceral/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Estudos Retrospectivos
9.
Ann Hematol ; 99(7): 1575-1581, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500223

RESUMO

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/sangue , Doença de Hodgkin/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
10.
Ann Hematol ; 99(7): 1515-1523, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32506245

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory disorder. We found recently that repeated lipopolysaccharide (LPS) treatment induces HLH-like features in senescence-accelerated mice (SAMP1/TA-1) but not in senescence-resistant control mice (SAMR1). In this study, we analyzed the dynamics of hematopoiesis in this mouse model of HLH. When treated repeatedly with LPS, the numbers of myeloid progenitor cells (CFU-GM) and B-lymphoid progenitor cells (CFU-preB) in the bone marrow (BM) rapidly decreased after each treatment in both strains. The number of CFU-GM in SAMP1/TA-1 and SAMR1, and of CFU-preB in SAMR1, returned to pretreatment levels by 7 days after each treatment. However, the recovery in the number of CFU-preB in SAMP1/TA-1 was limited. In both strains, the BM expression of genes encoding positive regulators of myelopoiesis (granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-6), and negative regulators of B lymphopoiesis (tumor necrosis factor (TNF)-α) was increased. The expression of genes encoding positive regulators of B lymphopoiesis (stromal-cell derived factor (SDF)-1, IL-7, and stem cell factor (SCF)) was persistently decreased in SAMP1/TA-1 but not in SAMR1. Expression of the gene encoding p16INK4a and the proportion of ß-galactosidase-positive cells were increased in cultured stromal cells obtained from LPS-treated SAMP1/TA-1 but not in those from LPS-treated SAMR1. LPS treatment induced qualitative changes in stromal cells, which comprise the microenvironment supporting appropriate hematopoiesis, in SAMP1/TA-1; these stromal cell changes are inferred to disrupt the dynamics of hematopoiesis. Thus, hematopoietic tissue is one of the organs that suffer life-threatening damage in HLH.


Assuntos
Medula Óssea/patologia , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Nicho de Células-Tronco/fisiologia , Animais , Células da Medula Óssea/patologia , Células da Medula Óssea/fisiologia , Contagem de Células , Células Cultivadas , Microambiente Celular/fisiologia , Modelos Animais de Doenças , Células-Tronco Hematopoéticas/fisiologia , Lipopolissacarídeos , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Masculino , Camundongos , Células Estromais/patologia
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(6): 620-625, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32571462

RESUMO

OBJECTIVE: To study the effect of genetic variation on the prognosis of children with Epstein-Barr virus (EBV)-positive hemophagocytic lymphohistiocytosis (HLH) and its association with cytokines. METHODS: A total of 81 EBV-positive HLH children who received the sequencing of related genes were enrolled. According to the results of gene detection, they were divided into a non-mutation group and a mutation group. According to the pattern of gene mutation, the mutation group was further divided into three subgroups: single heterozygous mutation (SHM), double heterozygous mutation (DHM), and homozygous or compound heterozygous mutation (H-CHM). The serum levels of cytokines were measured and their association with HLH gene mutations was analyzed. RESULTS: UNC13D gene mutation had the highest frequency (13/46, 28%). The STXBP2 c.575G>A(p.R192H) and UNC13D c.604C>A(p.L202M) mutations (likely pathogenic) were reported for the first time. The mutation group had a significantly higher level of tumor necrosis factor alpha (TNF-α) than the non-mutation group, while it had a significantly lower level of interferon gamma (IFN-γ) than the non-mutation group (P<0.05). The IL-4 level of the DHM subgroup was higher than that of the non-mutation group, while the IL-4 level of the H-CHM subgroup was lower than that of the DHM group (P<0.0083). The H-CHM subgroup had a significantly lower 1-year overall survival rate than the non-mutation group, the SHM subgroup, and the DHM subgroup (39%±15% vs 85%±6%/86%±7%/91%±9%, P=0.001). CONCLUSIONS: There is a significant reduction in IFN-γ level in the mutation group. Children with homozygous or compound heterozygous mutation tend to have poorer prognosis, while other mutations do not have a significant impact on prognosis.


Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Criança , Citocinas , Infecções por Vírus Epstein-Barr/complicações , Testes Genéticos , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/genética , Proteínas de Membrana , Células Th1 , Células Th2
13.
Clin Rheumatol ; 39(7): 2085-2094, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32474885

RESUMO

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.


Assuntos
Antirreumáticos , Infecções por Coronavirus , Síndrome da Liberação de Citocina , Linfo-Histiocitose Hemofagocítica , Síndrome de Ativação Macrofágica , Pandemias , Pneumonia Viral , Antirreumáticos/classificação , Antirreumáticos/imunologia , Antirreumáticos/farmacologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/terapia , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/imunologia , Síndrome de Ativação Macrofágica/terapia , Seleção de Pacientes , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Tempo para o Tratamento
14.
Ugeskr Laeger ; 182(25)2020 06 15.
Artigo em Dinamarquês | MEDLINE | ID: mdl-32584762

RESUMO

Severely afflicted patients with the COVID-19 may become in need of mechanical ventilation. The cause of acute respiratory failure is a massive hyperinflammation in the lungs, and treatment with glucocorticoids is not recommended by the WHO. A rare haematological disease, the virus-associated haemophagocytic lymphohistiocytosis syndrome (HLS), is associated with high mortality and a similar hyperinflammation syndrome. Janus kinase (JAK) 1/2 inhibitor treatment is highly efficacious in HLS. In this review, we discuss the rationales and perspectives for using JAK1/2 inhibitors in severely afflicted patients with COVID-19 pneumonia.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/virologia , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Humanos , Pandemias
15.
BMC Infect Dis ; 20(1): 321, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370734

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.


Assuntos
Antituberculosos/uso terapêutico , Etoposídeo/uso terapêutico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Mycobacterium tuberculosis/isolamento & purificação , Inibidores da Topoisomerase II/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Biópsia , Diagnóstico Precoce , Ferritinas/sangue , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/microbiologia , Masculino , Pancitopenia , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/microbiologia
16.
N Engl J Med ; 382(19): 1811-1822, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32374962

RESUMO

BACKGROUND: Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS: We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS: At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Interferon gama/antagonistas & inibidores , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Adolescente , Idade de Início , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Neutralizantes/efeitos adversos , Quimiocina CXCL9/sangue , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Quimioterapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Infecções/etiologia , Estimativa de Kaplan-Meier , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Resultado do Tratamento
19.
Exp Biol Med (Maywood) ; 245(11): 970-976, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32460624

RESUMO

The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: "mild",symbolized as a "drizzle" of cytokines, severe as a "storm", and critical as a "hurricane". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a "cytokine-release syndrome", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.


Assuntos
Lesão Pulmonar Aguda/patologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Pneumonia Viral/patologia , Lesão Pulmonar Aguda/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Humanos , Linfo-Histiocitose Hemofagocítica/patologia , Linfopenia/patologia , Pandemias , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/patologia
20.
RMD Open ; 6(1)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32423970

RESUMO

Some of the articles being published during the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined 'hyperferritinemic syndrome', which already includes adult-onset Still's disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.


Assuntos
Infecções por Coronavirus/imunologia , Coronavirus/imunologia , Citocinas/imunologia , Síndrome de Ativação Macrofágica/imunologia , Pneumonia Viral/imunologia , Adulto , Síndrome Antifosfolipídica , Betacoronavirus , Criança , Coronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Humanos , Linfo-Histiocitose Hemofagocítica , Síndrome de Ativação Macrofágica/complicações , Síndrome de Ativação Macrofágica/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Doença de Still de Início Tardio , Carga Viral
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