RESUMO
Numerous cases of pneumonia from a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China during December 2019.We determined the correlations of patient parameters with disease severity in patients with COVID-19.A total of 132 patients from Wuhan Fourth Hospital who had COVID-19 from February 1 to February 29 in 2020 were retrospectively analyzed.Ninety patients had mild disease, 32 had severe disease, and 10 had critical disease. The severe/critical group was older (Pâ<â.05), had a higher proportion of males (Pâ<â.05), and had a greater mortality rate (0% vs 61.9%, Pâ<â.05). The main symptoms were fever (nâ=â112, 84.8%) and cough (nâ=â96, 72.7%). Patients were treated with antiviral agents (nâ=â94, 71.2%), antibiotics (nâ=â92, 69.7%), glucocorticoids (nâ=â46, 34.8%), intravenous immunoglobulin (nâ=â38, 27.3%), and/or traditional Chinese medicine (nâ=â40, 30.3%). Patients in the severe/critical group received mechanical ventilation (nâ=â22, 16.7%) or high-flow nasal can-nula oxygen therapy (nâ=â6, 4.5%). Chest computed tomography (CT) indicated bilateral pneumonia in all patients. Relative to the mild group, the severe/critical group had higher levels of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, B-type natriuretic peptide (BNP), liver enzymes, and myocardial enzymes (Pâ<â.05), and decreased levels of lymphocytes and blood oxygen partial pressure (Pâ<â.05).The main clinical symptoms of patients from Wuhan who had COVID-19 were fever and cough. Patients with severe/critical disease were more likely to be male and elderly. Disease severity correlated with increased leukocytes, CRP, PCT, BNP, D-dimer, liver enzymes, and myocardial enzymes, and with decreased lymphocytes and blood oxygen partial pressure.
Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2RESUMO
INTRODUCTION: Although coronavirus disease (COVID-19) has been associated with gastrointestinal manifestations, its effect on the pancreas remains unclear. We aimed to assess the frequency and characteristics of hyperlipasemia in patients with COVID-19. METHODS: A retrospective cohort study of hospitalized patients across 6 US centers with COVID-19. RESULTS: Of 71 patients, 9 (12.1%) developed hyperlipasemia, with 2 (2.8%) greater than 3 times upper limit of normal. No patient developed acute pancreatitis. Hyperlipasemia was not associated with poor outcomes or symptoms. DISCUSSION: Although a mild elevation in serum lipase was observed in some patients with COVID-19, clinical acute pancreatitis was not seen.
Assuntos
Infecções por Coronavirus/epidemiologia , Lipase/sangue , Pancreatite/epidemiologia , Pneumonia Viral/epidemiologia , Dor Abdominal/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anorexia/epidemiologia , Betacoronavirus , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/sangue , Diarreia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/epidemiologia , Pancreatite/sangue , Pancreatite/diagnóstico por imagem , Pandemias , Pneumonia Viral/sangue , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologia , Vômito/epidemiologiaAssuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Publicações Periódicas como Assunto , Pneumonia Viral/tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/mortalidade , Transtornos da Coagulação Sanguínea/virologia , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , SARS-CoV-2 , Resultado do TratamentoRESUMO
Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.
Assuntos
Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Coagulação Sanguínea , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/virologia , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Fibrinogênio/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Contagem de Leucócitos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , SARS-CoV-2 , Fatores de TempoAssuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Pessoal de Saúde/estatística & dados numéricos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Infecções Assintomáticas/epidemiologia , Medicina do Comportamento/estatística & dados numéricos , COVID-19 , Infecções por Coronavirus/diagnóstico , Cuidados Críticos/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase , Prevalência , Psiquiatria/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2 , Centros de Traumatologia , Adulto JovemAssuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia por Raios X , Adulto , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , COVID-19 , Infecções Comunitárias Adquiridas/diagnóstico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Reações Falso-Positivas , Humanos , Masculino , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Radiografia Torácica , SARS-CoV-2Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Reações Falso-Negativas , Pneumonia Viral/diagnóstico , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/instrumentação , Técnicas de Laboratório Clínico/métodos , Controle de Doenças Transmissíveis , Infecções por Coronavirus/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Programas de Rastreamento , Pandemias , Pneumonia Viral/sangue , Testes Imediatos , Vigilância da População , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.
Assuntos
Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Vitamina D/análogos & derivados , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/diagnóstico , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase , Estudos Retrospectivos , SARS-CoV-2 , Suíça , Vitamina D/administração & dosagem , Vitamina D/sangueAssuntos
Glicemia , Infecções por Coronavirus/complicações , Diabetes Mellitus/terapia , Gerenciamento Clínico , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , China , Infecções por Coronavirus/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/virologia , Humanos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , SARS-CoV-2RESUMO
The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.
Assuntos
Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Adulto , Idoso , Variação Biológica Individual , COVID-19 , Análise por Conglomerados , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Citocinas/sangue , Regulação da Expressão Gênica , Humanos , Masculino , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Transcriptoma , Regulação para CimaRESUMO
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Formação de Anticorpos/imunologia , Antivirais/uso terapêutico , Betacoronavirus/genética , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported so far have been limited to alphacoronaviruses and betacoronaviruses3-5. Here we identify porcine deltacoronavirus strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the genes encoding Nsp15 and the spike glycoprotein. In particular, structural analysis predicts that one of the changes in the spike S1 subunit, which contains the receptor-binding domain, may affect the flexibility of the protein and its binding to the host cell receptor. Our findings highlight the potential for evolutionary change and adaptation leading to human infections by coronaviruses outside of the previously recognized human-associated coronavirus groups, particularly in settings where there may be close human-animal contact.
Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Deltacoronavirus/isolamento & purificação , Suínos/virologia , Zoonoses Virais/epidemiologia , Zoonoses Virais/virologia , Sequência de Aminoácidos , Animais , Teorema de Bayes , Criança , Chlorocebus aethiops , Sequência Conservada , Infecções por Coronavirus/sangue , Deltacoronavirus/classificação , Deltacoronavirus/genética , Deltacoronavirus/patogenicidade , Feminino , Haiti/epidemiologia , Humanos , Masculino , Modelos Moleculares , Mutação , Filogenia , Células Vero , Zoonoses Virais/sangueAssuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Estado Nutricional , Pneumonia Viral/sangue , Deficiência de Vitamina D/virologia , Vitamina D/análogos & derivados , Idoso , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Receptores de Calcitriol/sangue , SARS-CoV-2 , Vitamina D/administração & dosagem , Vitamina D/sangueRESUMO
BACKGROUND: "Cytokine storm" has been used to implicate increased cytokine levels in the pathogenesis of serious clinical conditions. Similarities with Severe Acute Respiratory Syndrome Coronoavirus-2 (SARS CoV-2) and the 2012 Middle Eastern Respiratory Syndrome led early investigators to suspect a "cytokine storm" resulting in an unregulated inflammatory response associated with the significant morbidity and mortality induced by SARS CoV-2. The threshold of blood cytokines necessary to qualify as a "cytokine storm" has yet to be defined. METHODS: A literature review was conducted to identify cytokine levels released during 11 assorted clinical conditions or diseases. Weighted averages for various cytokines were calculated by multiplying the number of patients in the paper by the average concentration of each cytokine. Correlation between cytokine levels for individual conditions or diseases were assessed using Pearson correlation coefficient. RESULTS: The literature was reviewed to determine blood levels of cytokines in a wide variety of clinical conditions. These conditions ranged from exercise and autoimmune disease to septic shock and therapy with chimeric antigen receptor T cells. The most frequently measured cytokine was IL-6 which ranged from 24,123âpg/mL in septic shock to 11âpg/mL after exercise. In patients with severe SARS CoV-2 infections, blood levels of IL-6 were only 43âpg/mL, nearly three magnitudes lower than IL-6 levels in patients with septic shock. The clinical presentations of these different diseases do not correlate with blood levels of cytokines. Additionally, there is poor correlation between the concentrations of different cytokines among the different diseases. Specifically, blood levels of IL-6 did not correlate with levels of IL-8, IL-10, or TNF. Septic shock had the highest concentrations of cytokines, yet multiple cytokine inhibitors have failed to demonstrate improved outcomes in multiple clinical trials. Patients with autoimmune diseases have very low blood levels of cytokines (rheumatoid arthritis, IL-6â=â34âpg/mL; Crohn's disease, IL-6â=â5âpg/mL), yet respond dramatically to cytokine inhibitors. CONCLUSION: The misleading term "cytokine storm" implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term "cytokine storm". "Cytokine storm" should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors.
Assuntos
COVID-19/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina , Citocinas/sangue , COVID-19/sangue , Infecções por Coronavirus/sangue , Humanos , Inflamação , Interleucina-6/sangue , Receptores de Antígenos Quiméricos/imunologia , SARS-CoV-2 , Choque Séptico/sangue , Choque Séptico/imunologia , Linfócitos T/imunologiaAssuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Fibrose Pulmonar , Tomografia Computadorizada por Raios X/métodos , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/etiologia , SARS-CoV-2 , Resultado do TratamentoAssuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Pulmão/diagnóstico por imagem , Pandemias , Administração dos Cuidados ao Paciente/métodos , Pneumonia Viral , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , SARS-CoV-2 , Avaliação de Sintomas/métodos , Resultado do TratamentoAssuntos
Betacoronavirus , Infecções por Coronavirus , Estado Terminal , Pandemias , Pneumonia Viral , Síndrome do Desconforto Respiratório/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Respiração Artificial , SARS-CoV-2 , Resultado do Tratamento , WashingtonAssuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , RNA Viral/isolamento & purificação , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/virologia , Broncoscopia/estatística & dados numéricos , COVID-19 , Criança , Pré-Escolar , China , Infecções por Coronavirus/sangue , Infecções por Coronavirus/urina , Fezes/virologia , Feminino , Dosagem de Genes , Genes Virais , Humanos , Masculino , Pessoa de Meia-Idade , Nariz/virologia , Fases de Leitura Aberta , Pandemias , Faringe/virologia , Pneumonia Viral/sangue , Pneumonia Viral/urina , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Escarro/virologia , Carga Viral , Adulto JovemRESUMO
OBJECTIVES: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed. RESULTS: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 µg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups. DISCUSSION: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients.
Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19 , China/epidemiologia , Comorbidade , Busca de Comunicante , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Diabetes Mellitus/sangue , Diabetes Mellitus/fisiopatologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Interleucina-6/sangue , Intubação Intratraqueal , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Viagem/estatística & dados numéricos , Eliminação de Partículas ViraisRESUMO
Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.