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1.
S Afr Med J ; 110(9): 837-841, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32880263

RESUMO

The potential role for serological tests in the current COVID-19 pandemic has generated very considerable recent interest across many sectors worldwide, inter alia pathologists seeking additional weapons for their armoury of diagnostic tests; epidemiologists seeking tools to gain seroprevalence data that will inform improved models of the spread of disease; research scientists seeking tools to study the natural history of COVID-19 disease; vaccine developers seeking tools to assess vaccine efficacy in clinical trials; and companies and governments seeking tools to aid return-to-work decision-making. However, much of the local debate to date has centred on questions surrounding whether regulatory approval processes are limiting access to serological tests, and has not paused to consider the intrinsically limiting impact of underlying fundamental biology and immunology on where and how different COVID-19 serological tests can usefully be deployed in the response to the current pandemic. We review, from an immunological perspective, recent experimental evidence on the time-dependency of adaptive immune responses following SARS-CoV-2 infection and the impact of this on the sensitivity and specificity of COVID-19 antibody tests made at different time points post infection. We interpret this scientific evidence in terms of mooted clinical applications for current COVID-19 antibody tests in identifying acute infections, in confirming recent or past infections at the individual and population level, and in detecting re-infection and protective immunity. We conclude with guidance on where current COVID-19 antibody tests can make a genuine impact in the pandemic.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Fatores de Tempo
3.
Monaldi Arch Chest Dis ; 90(4)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945643

RESUMO

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as "Whether there are differences based on gender in risk and severity of infection or mortality rate?" and "What are the biological explanation and mechanisms underlying these differences?" Emerging evidences have proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. At immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Estrogênios/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Testosterona/imunologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Mortalidade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Caracteres Sexuais , Fatores Sexuais
4.
Eur J Endocrinol ; 183(5): R133-R147, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32755992

RESUMO

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Imunidade Inata/imunologia , Imunocompetência/imunologia , Pulmão/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Vitamina D/imunologia , Peptídeos Catiônicos Antimicrobianos/imunologia , Autofagia/imunologia , Betacoronavirus , Defensinas/imunologia , Humanos , Pandemias , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Vitamina D/análogos & derivados
5.
JCI Insight ; 5(18)2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32796155

RESUMO

Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Betacoronavirus/fisiologia , Infecções por Coronavirus , Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral , Glicoproteína da Espícula de Coronavírus/imunologia , Imunidade Adaptativa/imunologia , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Ligação Proteica , Sensibilidade e Especificidade , Soroconversão , Testes Sorológicos/métodos
6.
Subst Use Misuse ; 55(11): 1900-1901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32657207

RESUMO

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.


Assuntos
Analgésicos Opioides/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Infecções por Coronavirus/complicações , Hospedeiro Imunocomprometido/imunologia , Transtornos Relacionados ao Uso de Opioides/complicações , Pneumonia Viral/complicações , Insuficiência Respiratória/induzido quimicamente , Imunidade Adaptativa/imunologia , Analgésicos Opioides/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Interações Medicamentosas , Humanos , Imunidade Inata/imunologia , Metadona/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/imunologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Insuficiência Respiratória/fisiopatologia
7.
Ther Adv Respir Dis ; 14: 1753466620942129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32684101

RESUMO

BACKGROUND: In December of 2019, coronavirus disease 2019 (Covid-19) was reported in Wuhan, China, and has now rapidly swept around the world. Much research has been carried out since the outbreak, but few studies have focused on the dysfunction of the adaptive immunity. METHODS: In this retrospective and multi-center study, 373 patients with laboratory-confirmed COVID-19 from Shanghai Public Health Clinical Center and Affiliated Hospital of Putian University were recruited. Demographic, clinical, radiological features, and laboratory data were recorded and analyzed at admission and at discharge. Results of immunological tests were followed up until the patients were discharged. RESULTS: Of the 373 patients with COVID-19 pneumonia, 322 were in the non-severe group and 51 were in the severe group. Number of T cells, CD4+ and CD8+ T cells, and total lymphocytes declined remarkably upon admission and elevated when the patients were discharged. At admission, counts of total lymphocytes, T cells, CD4+ and CD8+ T cells, and levels of C3 and C4 in the severe group were lower than those in the non-severe group, whereas the neutrophil to lymphocyte ratio (NLR) was higher in the severe group. Counts of T cells, CD4+ and CD8+ T cells, and total lymphocytes were negatively correlated with lactate dehydrogenase and C-reactive protein. CONCLUSION: COVID-19 might target adaptive immunity and cause a decrease in lymphocytes, especially T cells and subsets. Physicians should pay close attention to the adaptive immunity of patients upon admission. Monitoring NLR, T lymphocytes, and subsets would help physicians with the proper diagnosis and treatment of COVID-19.The reviews of this paper are available via the supplemental material section.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença
8.
Immunity ; 53(2): 248-263, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32717182

RESUMO

A key goal to controlling coronavirus disease 2019 (COVID-19) is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, common cold coronaviruses, and SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Imunidade Adaptativa/imunologia , Animais , Betacoronavirus/patogenicidade , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/imunologia
9.
Eur J Clin Invest ; 50(9): e13342, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645207

RESUMO

COVID-19 pandemia is a major concern for patients and healthcare systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analysing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, United States and Europe did not reveal an higher risk of infection, either for rheumatoid arthritis, juvenile idiopathic arthritis nor for lupus erythematosus. Antimalarials, anti-IL6-Anti-IL6 receptor, anti-IL1, anti-GM-CSF receptor and JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection suggests that the immunological consequences of the infection need to be strictly understood. Reporting of the study conforms to broad EQUATOR guidelines (Simera et al January 2010 issue of EJCI).


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Imunossupressores/administração & dosagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Doenças Reumáticas/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Idoso , Antirreumáticos/administração & dosagem , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Fatores Imunológicos/administração & dosagem , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Medição de Risco , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia
10.
JCI Insight ; 5(17)2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32687484

RESUMO

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-É£ and monocyte TFN-α production. Circulating T cell subsets were profoundly reduced in COVID-19 patients. Additionally, stimulated blood mononuclear cells produced less than 40%-50% of the IFN-É£ and TNF-α observed in septic and CINS patients, consistent with markedly impaired immune effector cell function. Approximately 25% of COVID-19 patients had increased IL-6 levels that were not associated with elevations in other canonical proinflammatory cytokines. Collectively, these findings support the hypothesis that COVID-19 suppresses host functional adaptive and innate immunity. Importantly, IL-7 administered ex vivo restored T cell IFN-É£ production in COVID-19 patients. Thus, ELISpot may functionally characterize host immunity in COVID-19 and inform prospective therapies.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Tolerância Imunológica/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Sepse/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Estudos de Casos e Controles , Estado Terminal , ELISPOT , Feminino , Voluntários Saudáveis , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Pandemias , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
11.
mBio ; 11(3)2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576678

RESUMO

It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 "don't eat me" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents.IMPORTANCE Immune responses to infectious agents are initiated when a pathogen or its components bind to pattern recognition receptors (PRRs). PRR binding sets off a cascade of events that activates immune responses. We now show that, in addition to activating immune responses, PRR signaling also initiates an immunosuppressive response, probably to limit inflammation. The importance of the current findings is that blockade of immunomodulatory signaling, which is mediated by the upregulation of the CD47 molecule, can lead to enhanced immune responses to any pathogen that triggers PRR signaling. Since most or all pathogens trigger PRRs, CD47 blockade could be used to speed up and strengthen both innate and adaptive immune responses when medically indicated. Such immunotherapy could be done without a requirement for knowing the HLA type of the individual, the specific antigens of the pathogen, or, in the case of bacterial infections, the antimicrobial resistance profile.


Assuntos
Betacoronavirus/imunologia , Antígeno CD47/metabolismo , Imunomodulação/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Células A549 , Imunidade Adaptativa/imunologia , Animais , Antígeno CD47/genética , Linhagem Celular Tumoral , Citocinas/imunologia , Feminino , Humanos , Imunidade Inata/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/imunologia , Regulação para Cima/imunologia
13.
J Exp Med ; 217(6)2020 06 01.
Artigo em Inglês | MEDLINE | ID: covidwho-156716

RESUMO

The novel 2019 strain of coronavirus is a source of profound morbidity and mortality worldwide. Compared with recent viral outbreaks, COVID-19 infection has a relatively high mortality rate, the reasons for which are not entirely clear. Furthermore, treatment options for COVID-19 infection are currently limited. In this Perspective, we explore the contributions of the innate and adaptive immune systems to both viral control as well as toxicity during COVID-19 infections and offer suggestions to both understand and therapeutically modulate anti-COVID immunity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/terapia , Humanos , Hipóxia/patologia , Hipóxia/terapia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Linfopenia/imunologia , Linfopenia/patologia , Linfopenia/terapia , Macrófagos/imunologia , Macrófagos/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade
17.
PLoS Med ; 17(5): e1003115, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32379748

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association. METHODS AND FINDINGS: Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity. CONCLUSIONS: In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.


Assuntos
Imunidade Adaptativa/imunologia , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Imunidade Inata/imunologia , Idoso , Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia
19.
J Exp Med ; 217(6)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32353870

RESUMO

The novel 2019 strain of coronavirus is a source of profound morbidity and mortality worldwide. Compared with recent viral outbreaks, COVID-19 infection has a relatively high mortality rate, the reasons for which are not entirely clear. Furthermore, treatment options for COVID-19 infection are currently limited. In this Perspective, we explore the contributions of the innate and adaptive immune systems to both viral control as well as toxicity during COVID-19 infections and offer suggestions to both understand and therapeutically modulate anti-COVID immunity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/terapia , Humanos , Hipóxia/patologia , Hipóxia/terapia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Linfopenia/imunologia , Linfopenia/patologia , Linfopenia/terapia , Macrófagos/imunologia , Macrófagos/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade
20.
PLoS One ; 15(4): e0231498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287290

RESUMO

The Polycomb group (PcG) proteins are chromatin factors underlying the process of transcriptional memory to preserve developmental decisions and keep cellular identities. However, not only developmental signals need to be memorized and thus maintained during the life of an organism. For host protection against pathogens, also a memory of previous exposures to an immunogenic stimulus is crucial to mount a more protective immune response upon re-exposure. The antigen-specific adaptive immunity in vertebrates is an example of such a memory to previous immunogenic stimulation. Recently, adaptive characteristics were also attributed to innate immunity, which was classically seen to lack memory. However, the mechanistic details of an adaptive innate immune response are yet to be fully understood and chromatin-based epigenetic mechanisms seem to play an important role in this phenomenon. Possibly, PcG proteins can contribute to such an epigenetic innate immune memory. In this study, we analyzed whether the PcG system can mediate a transcriptional memory of exposure to lipopolysaccharides (LPS). To this end, various forms of LPS pre-treatment were applied to reporter cells and expression kinetics of PcG target genes were analyzed after a second LPS exposure. Neither single nor multiple LPS pre-treatment affected the induction of endogenous LPS-responsive transcripts upon re-exposure. Altogether, our extensive analyses did not provide any evidence for a PcG system-mediated memory of LPS stimulation.


Assuntos
Memória Imunológica/genética , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/imunologia , Imunidade Adaptativa/genética , Imunidade Adaptativa/imunologia , Animais , Linhagem Celular , Cromatina/genética , Drosophila/imunologia , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Epigênese Genética/genética , Imunidade Inata/genética , Imunidade Inata/imunologia , Memória Imunológica/imunologia , Lipopolissacarídeos/genética , Lipopolissacarídeos/imunologia , Proteínas do Grupo Polycomb/metabolismo
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