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2.
Science ; 377(6608): 803, 2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35981036

RESUMO

Study implicates lack of key hormone, battle-weary immune cells, and awakened viruses.


Assuntos
COVID-19 , COVID-19/sangue , COVID-19/imunologia , Humanos , Hidrocortisona/sangue , Linfócitos T/imunologia
3.
Nutrients ; 14(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36014781

RESUMO

BACKGROUND: Vitamin D deficiency has been associated with the severity of COVID-19. The role of vitamin D in pregnant women with COVID-19 has been poorly investigated to date. The aim of this study was to evaluate the influence of vitamin D in affecting some clinical features in pregnancy between SARS-CoV-2 positive and negative patients. METHODS: Vitamin D pathway related polymorphisms and 25-hydroxyvitamin D levels were quantified in pregnant women followed from the first to the third trimester of pregnancy. Vitamin D deficiency was considered with values ≤ 30 ng/mL. RESULTS: In total, 160 women were enrolled: 23 resulted positive for at least one SARS-CoV-2 related test (molecular swab or antibody tests). Vitamin D-associated polymorphisms were able to affect vitamin D levels in SARS-CoV-2 negative and positive subjects: remarkably, all the VDR TaqICC genotype patients were negative for SARS-CoV-2. In a sub-population (118 patients), vitamin D levels correlated with pregnancy-related factors, such as alpha-fetoprotein levels. Third-trimester vitamin D levels were lower in preterm births compared to full-term pregnancy: this trend was highlighted for SARS-CoV-2 positive patients. CONCLUSIONS: This is the first study demonstrating a role of vitamin D in affecting the clinical characteristics of pregnant women during the COVID-19 era. Further studies in larger and different cohorts of patients are required to confirm these findings.


Assuntos
COVID-19 , Gravidez , Nascimento Prematuro , Deficiência de Vitamina D , Vitamina D , COVID-19/sangue , COVID-19/complicações , Feminino , Humanos , Recém-Nascido , Gravidez/sangue , Nascimento Prematuro/sangue , SARS-CoV-2 , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações
4.
Proc Natl Acad Sci U S A ; 119(34): e2117089119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35943976

RESUMO

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Convalescença , Citocinas , Dipeptídeos , Inibidores da Dipeptidil Peptidase IV , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Formação de Anticorpos , COVID-19/sangue , COVID-19/tratamento farmacológico , COVID-19/imunologia , Citocinas/sangue , Dipeptídeos/sangue , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Aprendizado de Máquina , Metaboloma , Camundongos , SARS-CoV-2 , Vacinação
5.
Proc Natl Acad Sci U S A ; 119(30): e2203659119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858456

RESUMO

This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until ∼70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-γ remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (TH) cells followed by an equally synchronous and durable TH1-like reactivity reflecting long-lasting T cell memory.


Assuntos
COVID-19 , Citocinas , SARS-CoV-2 , Linfócitos T Auxiliares-Indutores , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , COVID-19/sangue , COVID-19/imunologia , Convalescença , Citocinas/sangue , Humanos , Interferon gama/sangue , Proteínas do Nucleocapsídeo/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
6.
Science ; 377(6608): 890-894, 2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35857529

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Imunização Secundária , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Biomolecules ; 12(7)2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35883435

RESUMO

The development of inexpensive, fast, and reliable screening tests for COVID-19 is, as yet, an unmet need. The present study was aimed at evaluating the usefulness of serum arylesterase activity of paraoxonase-1 (PON1) measurement as a screening test in patients with different severity levels of COVID-19 infection. We included 615 COVID-19-positive patients who were classified as asymptomatic, mildly symptomatic, severely symptomatic, or fatally symptomatic. Results were compared with 50 healthy volunteers, 330 patients with cancer, and 343 with morbid obesity. Results showed PON1 activity greatly decreased in COVID-19 compared to healthy volunteers; a receiver operating characteristics plot showed a high diagnostic accuracy. The degree of COVID-19 severity did not influence PON1 levels. Our results indicated that PON1 determination was efficient for disease diagnosis, but not for prognosis. Furthermore, patients with obesity or cancer presented alterations similar to those of COVID-19 patients. As such, elevated levels of PON1 indicate the absence of COVID-19, but low levels may be present in various other chronic diseases. The assay is fast and inexpensive. We suggest that PON1 measurement could be used as an initial, high cut-off point screening method, while lower values should be confirmed with the more expensive nucleic acid amplification test.


Assuntos
Arildialquilfosfatase , COVID-19 , Arildialquilfosfatase/sangue , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/enzimologia , Hidrolases de Éster Carboxílico , Humanos , Soro
8.
Front Immunol ; 13: 934264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844548

RESUMO

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-ß. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-ß were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.


Assuntos
COVID-19 , Proteínas de Ligação a DNA , Fibrose Pulmonar , COVID-19/sangue , COVID-19/imunologia , COVID-19/patologia , Proteínas de Transporte , Caspase 1/imunologia , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/imunologia , Humanos , Inflamassomos/sangue , Inflamassomos/imunologia , Interferon-alfa/metabolismo , Leucócitos Mononucleares/imunologia , Fibrose Pulmonar/sangue , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/virologia , SARS-CoV-2 , Fator de Crescimento Transformador beta/metabolismo
9.
Proc Natl Acad Sci U S A ; 119(33): e2203437119, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35895716

RESUMO

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.


Assuntos
COVID-19 , Pulmão , Cadeias Leves de Miosina , SARS-CoV-2 , Índice de Gravidade de Doença , Tromboinflamação , Vasculite , COVID-19/sangue , COVID-19/complicações , COVID-19/patologia , Humanos , Leucócitos Mononucleares , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Cadeias Leves de Miosina/sangue , RNA-Seq , SARS-CoV-2/isolamento & purificação , Análise de Célula Única , Espectrometria por Raios X , Tromboinflamação/patologia , Tromboinflamação/virologia , Vasculite/patologia , Vasculite/virologia
10.
J Biomed Sci ; 29(1): 52, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35820906

RESUMO

BACKGROUND: Coronavirus-induced disease 19 (COVID-19) infects more than three hundred and sixty million patients worldwide, and people with severe symptoms frequently die of acute respiratory distress syndrome (ARDS). Recent studies indicated that excessive neutrophil extracellular traps (NETs) contributed to immunothrombosis, thereby leading to extensive intravascular coagulopathy and multiple organ dysfunction. Thus, understanding the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation would be helpful to reduce thrombosis and prevent ARDS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We incubated SARS-CoV-2 with neutrophils in the presence or absence of platelets to observe NET formation. We further isolated extracellular vesicles from COVID-19 patients' sera (COVID-19-EVs) to examine their ability to induce NET formation. RESULTS: We demonstrated that antagonistic mAbs against anti-CLEC5A mAb and anti-TLR2 mAb can inhibit COVID-19-EVs-induced NET formation, and generated clec5a-/-/tlr2-/- mice to confirm the critical roles of CLEC5A and TLR2 in SARS-CoV-2-induced lung inflammation in vivo. We found that virus-free extracellular COVID-19 EVs induced robust NET formation via Syk-coupled C-type lectin member 5A (CLEC5A) and TLR2. Blockade of CLEC5A inhibited COVID-19 EVs-induced NETosis, and simultaneous blockade of CLEC5A and TLR2 further suppressed SARS-CoV-2-induced NETosis in vitro. Moreover, thromboinflammation was attenuated dramatically in clec5a-/-/tlr2-/- mice. CONCLUSIONS: This study demonstrates that SARS-CoV-2-activated platelets produce EVs to enhance thromboinflammation via CLEC5A and TLR2, and highlight the importance of CLEC5A and TLR2 as therapeutic targets to reduce the risk of ARDS in COVID-19 patients.


Assuntos
COVID-19 , Lectinas Tipo C , Neutrófilos , Pneumonia , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Trombose , Animais , Plaquetas/imunologia , Plaquetas/patologia , Plaquetas/virologia , COVID-19/sangue , COVID-19/imunologia , Humanos , Lectinas Tipo C/imunologia , Camundongos , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/virologia , Pneumonia/imunologia , Pneumonia/patologia , Pneumonia/virologia , Receptores de Superfície Celular , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2/imunologia , Trombose/sangue , Trombose/imunologia , Trombose/virologia , Receptor 2 Toll-Like/imunologia
11.
Iran J Allergy Asthma Immunol ; 21(3): 254-262, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35822676

RESUMO

The role of microRNA (miR)200c-3p in regulating ACE2 gene expression in viral and bacterial respiratory diseases has been established. Since ACE2 reduces the acute inflammatory effects in lung diseases and acts as a coronavirus receptor to invade the lung cells, this study investigates the relationship between miR-200c-3p and ACE2 expression in COVID -19 patients. In this study, COVID-19 patients were divided into two groups: mild phase (PCR-positive and mild symptoms) and severe phase (PCR-positive with acute pulmonary symptoms and inflammation). Then, the subjects' demographic, clinical, and paraclinical characteristics were recorded using a prepared checklist. Total RNA was isolated from all samples according to the Trizol kit protocol to evaluate gene expression. Subsequently, the extracted product was analysed for miR-200c expression and ACE2 target gene expression by real-time PCR. The results of the checklist data showed that smoking, cough, and the factors ESR and HCT were statistically significant between the two groups of patients in the mild and acute phases. Also, the mean expression of the miR-200c gene in the mild and acute patients was 1.87±0.70 and 1.87±0.62, respectively, which was not statistically significant. Still, the mean expression of the ACE2 gene, which was 3.96±0.76 and 3.28±0.52 in the mild and acute disease groups, respectively, showed a significant difference between the two groups. This study showed that the expression levels of ACE2 were significantly reduced in people with severe inflammation compared to people with mild inflammation.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , MicroRNAs , Enzima de Conversão de Angiotensina 2/biossíntese , Enzima de Conversão de Angiotensina 2/genética , COVID-19/sangue , COVID-19/enzimologia , COVID-19/genética , Expressão Gênica , Humanos , MicroRNAs/sangue , MicroRNAs/genética
12.
Saudi Med J ; 43(7): 723-729, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35830989

RESUMO

OBJECTIVES: To examine D-dimer, coagulation profile, and platelet count among patients hospitalized with coronavirus disease-19 (COVID-19) and compare them to findings from non-COVID-19 subjects. METHODS: The participants in this retrospective hospital-based observational study design included 112 confirmed diagnosed with COVID-19 who were admitted to King Khaled Hospital, Najran, Saudi Arabia, and another 112 non-COVID-19 subjects as a comparative group. Laboratory investigations, demographic and clinical records were obtained from participants' electronic indexed medical records. Coronavirus disease-19 diagnosis was confirmed according to positive real time polymerase chain reaction assay carried out at the hospital's central laboratory, where samples were extracted from a nasopharyngeal swab. Pneumonia related to COVID-19 is classified as critical, severe, moderate, mild, and asymptomatic whereas thrombocytopenia was marked when the platelet count was <150.00×109/L. Suitable statistical analysis was applied to determine possible differences between the findings from the 2 groups. RESULTS: The D-dimer and activated partial thromboplastin clotting time mean values were significantly elevated (p<0.001). The international normalized ratio and platelet count mean values confirmed a significant decrease (p<0.001). Thrombocytopenia was found 9 times in COVID-19 higher than in the non-COVID-19. D-dimer and prothrombin time mean values increased significantly among the COVID-19 patients with all patterns of symptoms on admission (p<0.001). CONCLUSION: D-dimer mean values increased significantly in deceased COVID-19 and in hospitalized intensive care unit (ICU) wards patients (p<0.001), indicating a potential predictive and prognostic severity marker, particularly among COVID-19 patients in the ICU.


Assuntos
COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio , Trombocitopenia , COVID-19/sangue , COVID-19/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Prognóstico , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/virologia
13.
J Mol Cell Cardiol ; 170: 121-123, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35764120

RESUMO

BACKGROUND: There is growing recognition that COVID-19 does cause cardiac sequelae. The underlying mechanisms involved are still poorly understood to date. Viral infections, including COVID-19, have been hypothesized to contribute to autoimmunity, by exposing previously hidden cryptic epitopes on damaged cells to an activated immune system. Given the high incidence of cardiac involvement seen in COVID-19, our aim was to determine the frequency of anti-DSG2 antibodies in a population of post COVID-19 patients. METHODS AND RESULTS: 300 convalescent serum samples were obtained from a group of post COVID-19 infected patients from October 2020 to February 2021. 154 samples were drawn 6 months post-COVID-19 infection and 146 samples were drawn 9 months post COVID infection. 17 samples were obtained from the same patient at the 6- and 9- month mark. An electrochemiluminescent-based immunoassay utilizing the extracellular domain of DSG2 for antibody capture was used. The mean signal intensity of anti-DSG2 antibodies in the post COVID-19 samples was significantly higher than that of a healthy control population (19 ± 83.2 in the post-COVID-19 sample vs. 2.1 ± 7.2 (p < 0. 0001) in the negative control healthy population). Of note, 29.3% of the post COVID-19 infection samples demonstrated a signal higher than the 90th percentile of the control population and 8.7% were higher than the median found in ARVC patients. The signal intensity between the 6-month and 9-month samples did not differ significantly. CONCLUSIONS: We report for the first time that recovered COVID-19 patients demonstrate significantly higher and sustained levels of anti-DSG2 autoantibodies as compared to a healthy control population, comparable to that of a diagnosed ARVC group.


Assuntos
COVID-19 , Autoanticorpos/imunologia , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , Desmogleína 2/imunologia , Humanos
14.
Saudi Med J ; 43(6): 572-578, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35675942

RESUMO

OBJECTIVES: To evaluate the role of different peripheral blood count parameters as a cheap and rapid test in determination of coronavirus disease -19 (COVID-19) severity and patients' outcome. METHODS: The data of 462 confirmed COVID-19 patients who attended at the Security Force Hospital, Makkah, Saudi Arabia, from October 2020 to March 2021 was retrospectively reviewed and C. Patients with viral infection and respiratory diseases other than COVID-19 were excluded from the study. Complete blood count parameters were compared in accordance with the severity of the clinical presentation, age, and disease outcome. RESULTS: A total of 277 (60%) were male and 185 (40%) female. Clinically, 32 (6.9%) had severe illness and 430 (93.1%) showed moderate clinical disease. Organ failure occurred in 2.8% of the patients. There was significant leucocytosis, neutrophilia, lymphopenia, high neutrophil-lymphocyte (N/L) ratio, and anemia in patients with severe COVID-19 diseases as well as in non-survivors' cases (p<0.001). Similarly, the inflammatory markers (C-reactive protein [CRP] and serum ferritin) were significantly elevated in the above-mentioned 2 groups (p<0.001). Significant decrease of the platelets count was detectable in clinically severe cases and non-survivors (p<0.01). Older age (>60 years) was associated with high leucocyte, neutrophil count, lymphopenia, anemia, organ failure, and poor outcome. CONCLUSION: Leucocytosis, neutrophilia, lymphopenia, and high N/L ratio together with elevated serum level of ferritin and CRP are eminent features of COVID-19 severity. The inclusion of these parameters in the regimens for patients' categorization on admission will enable early effective intervention and proper decision making during clinical case management.


Assuntos
Contagem de Células Sanguíneas , COVID-19 , Proteína C-Reativa , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Ferritinas , Humanos , Linfopenia , Masculino , Neutrófilos , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Arábia Saudita/epidemiologia
15.
EBioMedicine ; 80: 104077, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35644124

RESUMO

BACKGROUND: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. METHODS: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. FINDINGS: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. INTERPRETATION: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. FUNDING: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.


Assuntos
COVID-19 , Complexo Antígeno L1 Leucocitário , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Índice de Gravidade de Doença
16.
Biomolecules ; 12(6)2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35740907

RESUMO

For the first time, the influence of COVID-19 on blood microrheology was studied. For this, the method of filtering erythrocytes through filters with pores of 3.5 µm was used. Filterability was shown to significantly decrease with the increasing severity of the patient's condition, as well as with a decrease in the ratio of hemoglobin oxygen saturation to the oxygen fraction in the inhaled air (SpO2/FiO2). The filterability of ≤ 0.65, or its fast decrease during treatment, were indicators of a poor prognosis. Filterability increased significantly with an increase in erythrocyte count, hematocrit and blood concentrations of hemoglobin, albumin, and total protein. The effect of these parameters on the erythrocyte filterability is directly opposite to their effect on blood macrorheology, where they all increase blood viscosity, worsening the erythrocyte deformability. The erythrocyte filterability decreased with increasing oxygen supply rate, especially in patients on mechanical ventilation, apparently not due to the oxygen supplied, but to the deterioration of the patients' condition. Filterability significantly correlates with the C-reactive protein, which indicates that inflammation affects the blood microrheology in the capillaries. Thus, the filterability of erythrocytes is a good tool for studying the severity of the patient's condition and his prognosis in COVID-19.


Assuntos
COVID-19 , Deformação Eritrocítica , COVID-19/sangue , Eritrócitos , Hemoglobinas , Humanos , Oxigênio , Reologia
17.
Sci Rep ; 12(1): 9045, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35641545

RESUMO

Long-term antibody responses to SARS-CoV-2 have focused on responses to full-length spike protein, specific domains within spike, or nucleoprotein. In this study, we used high-density peptide microarrays representing the complete proteome of SARS-CoV-2 to identify binding sites (epitopes) targeted by antibodies present in the blood of COVID-19 resolved cases at 5 months post-diagnosis. Compared to previous studies that evaluated epitope-specific responses early post-diagnosis (< 60 days), we found that epitope-specific responses to nucleoprotein and spike protein have contracted, and that responses to membrane protein have expanded. Although antibody titers to full-length spike and nucleoprotein remain steady over months, taken together our data suggest that the population of epitope-specific antibodies that contribute to this reactivity is dynamic and evolves over time. Further, the spike epitopes bound by polyclonal antibodies in COVID-19 convalescent serum samples aligned with known target sites that can neutralize viral activity suggesting that the maintenance of these antibodies might provide rapid serological immunity. Finally, the most dominant epitopes for membrane protein and spike showed high diagnostic accuracy providing novel biomarkers to refine blood-based antibody tests. This study provides new insights into the specific regions of SARS-CoV-2 targeted by serum antibodies long after infection.


Assuntos
Anticorpos Antivirais , COVID-19 , Convalescença , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/terapia , Proteínas do Nucleocapsídeo de Coronavírus , Epitopos , Humanos , Imunização Passiva , Fosfoproteínas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
18.
N Engl J Med ; 386(21): 2011-2023, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35544369

RESUMO

BACKGROUND: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 µg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. RESULTS: In part 1 of the trial, 751 children received 50-µg or 100-µg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-µg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 µg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-µg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-µg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. CONCLUSIONS: Two 50-µg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Vacina de mRNA-1273 contra 2019-nCoV/efeitos adversos , Vacina de mRNA-1273 contra 2019-nCoV/imunologia , Vacina de mRNA-1273 contra 2019-nCoV/uso terapêutico , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Criança , Método Duplo-Cego , Humanos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Eficácia de Vacinas , Adulto Jovem
19.
Intern Emerg Med ; 17(6): 1777-1784, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35624344

RESUMO

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.


Assuntos
COVID-19 , Cirrose Hepática , Índice de Gravidade de Doença , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/complicações , COVID-19/mortalidade , Estudos de Coortes , Serviço Hospitalar de Emergência , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Oxigênio/sangue , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos
20.
Biomed Res Int ; 2022: 2755246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35540724

RESUMO

Background: To investigate the association between interleukins (IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10) and the disease severity of coronavirus disease 2019 (COVID-19). Materials and Methods: We systematically searched records investigating the role of interleukins (IL-1ß, IL-2, IL-4, IL-6, IL-8, and IL-10) in COVID-19 patients in Web of Science, Pubmed, and Embase through December 2020. Data were extracted and pooled, and the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. The funnel plot and the nonparametric trim and fill method were used to visualize and adjust the publication bias. Results: In total, 61 studies enrolled 14,136 subjects (14,041 patients and 95 healthy subjects) were enrolled in this meta-analysis. Our results showed that serum IL-2, IL-4, IL-6, and IL-10 levels were elevated in COVID-19 patients compared to healthy controls, and IL-6, IL-8, and IL-10 levels were increased in severe COVID-19 cases compared to nonsevere patients. Additionally, the levels of IL-1ß, IL-6, and IL-8 were elevated in nonsurvivor patients compared to survivors. For patients in the intensive care unit (ICU), IL-6 and IL-8 levels were increased than that in non-ICU patients. Conclusions: Elevated levels of IL-6, IL-8, and IL-10 were associated with the disease severity of COVID-19, and elevated levels of IL-1ß, IL-6, and IL-8 were related to the prognosis of COVID-19 patients, which could be used to evaluate COVID-19 patients' disease severity and prognosis.


Assuntos
COVID-19 , Interleucinas , COVID-19/sangue , Humanos , Interleucinas/sangue , Índice de Gravidade de Doença
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