RESUMO
Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.
Assuntos
Infecções por Coronavirus/sangue , Metabolômica , Pneumonia Viral/sangue , Proteômica , Adulto , Aminoácidos/metabolismo , Biomarcadores/sangue , COVID-19 , Análise por Conglomerados , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Metabolismo dos Lipídeos , Aprendizado de Máquina , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.
Assuntos
COVID-19 , Humanos , Proteômica , Anticorpos Antivirais , Imunoglobulina M , Imunoglobulina GRESUMO
BACKGROUND: Hyperuricaemia is common among obese children and adolescents, and is closely related to insulin resistance. The aim of this study was to explore the relationships between youth insulin resistance and hyperuricaemia, as well as their relationships with lifestyle factors in youths, to provide early guidance on the risk factors for hyperuricaemia in adolescents. METHODS: This study included 233 adolescents aged 10 to 20 years. Insulin resistance was evaluated via the homeostasis model assessment-insulin resistance (HOMA-IR) method. Binary logistic regression analysis was used to assess the associations of HOMA-IR with hyperuricaemia status and serum uric acid (UA) levels. The participants were subsequently divided into two groups, the noninsulin resistant group (HOMA-IR ≤ 3.2) and the insulin resistant group (HOMA-IR > 3.2), to further explore the factors that may affect the serum UA level. Finally, the predictive ability of different indicators of hyperuricaemia was evaluated via the ROC curve. RESULTS: Binary logistic regression analysis revealed a significant increase in the risk of developing hyperuricaemia for individuals with elevated HOMA-IR (p < 0.001) and insulin resistance (p < 0.01). Spearman's correlation analysis revealed a significant positive linear correlation between HOMA-IR and serum UA levels (r = 0.4652, p < 0.001). Among insulin-resistant adolescents, UA levels were positively correlated with weight ratings, frequency of staying up late, and sugary beverages intake. Notably, individuals who engaged in 1-3 h of weekly exercise had the lowest UA levels. The area under the ROC curve for HOMA-IR was 0.847 (cut-off value = 2.165, p < 0.001), and the optimal prediction model included HOMA-IR, BMI z-score, and other lifestyle factors (AUC: 0.870, p < 0.001)). CONCLUSION: HOMA-IR was identified as an independent risk factor for the development of hyperuricaemia and could be used as a sensitive indicator for the prediction its development in adolescents. In insulin-resistant adolescents with hyperuricaemia, maintaining normal weight, engaging in physical exercise for 1-3 h per week, avoiding staying up late and limiting sugary beverages intake are recommended to reduce the prevalence of hyperuricaemia among adolescents.
Assuntos
Hiperuricemia , Resistência à Insulina , Estilo de Vida , Humanos , Adolescente , Hiperuricemia/epidemiologia , Hiperuricemia/etiologia , Hiperuricemia/sangue , Masculino , Feminino , Criança , Fatores de Risco , Adulto Jovem , Obesidade/sangue , Biomarcadores/sangue , Prognóstico , Estudos Transversais , Ácido Úrico/sangue , Obesidade Infantil/sangueRESUMO
Unexpectedly facile dearomative intramolecular (4+3) cycloadditions of thiophenes with epoxy enolsilanes, providing sulfur-bridged cycloadducts, are reported. A total of fifteen thiophene substrates have been found to undergo (4+3) cycloaddition smoothly to produce endo and exo (4+3) adducts in yields of up to 83 % with moderate to good diastereoselectivity. Complete conservation of enantiomeric purity was observed when the optically enriched epoxide was used. The desulfurizing transformations of the sulfur-bridged skeleton of the cycloadducts provide functionalized 6,7-fused bicyclic frameworks consisting of 1,3-cycloheptadiene subunits. Density functional theory calculations reveal the origins of the facile dearomatization of thiophenes in these (4+3) cycloadditions.
RESUMO
RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.
Assuntos
COVID-19 , Humanos , Proteômica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Manejo de EspécimesRESUMO
OBJECTIVE: Reactive oxygen species are believed to be involved in the onset of RA, and the association between nuclear-encoded mitochondrial respiratory chain-related variants and RA has recently been revealed. However, little is known about the landscape of mitochondrial DNA (mtDNA) variants in RA. METHODS: Next-generation sequencing was conducted to profile mtDNA germline and somatic variants in 124 RA patients and 123 age- and sex-matched healthy controls in the Taizhou area, China. Fisher's exact test, SKAT and SKAT-O were used for gene-burden tests to investigate RA-related variants of mitochondrial genes. Predictive tools were applied to evaluate the pathogenicity of mtDNA variants, and mtDNA haplogroups were assigned according to mtDNA mutations recorded in PhyloTree database. The frequency distribution of mtDNA haplogroups between the groups was compared using χ2 analysis. RESULTS: We identified 467 RA-unique and 341 healthy control-unique mtDNA variants, with 443 common variants. Only MT-ATP6 with a significant burden of variants was identified by Fisher's exact test, SKAT and SKAT-O, even after Bonferroni adjustment, and the enrichment variants in MT-ATP6 was mainly driven by m.8830C>A, m.8833G>C and m.8843T>A variants. Besides, four frequently low-heteroplasmic variants including the three variants above and m.14135T>G of MT-ND5 were detected in RA only; except for m.8830C>A, they are considered potential pathogenicity based on functional predictions. χ2 analysis before Bonferroni adjustment revealed haplogroup F1/F1a to be negatively associated with RA (P < 0.05). CONCLUSION: These results profiled the landscape of germline and somatic mtDNA variants in RA and supported the effects of mitochondrial genes on RA.
Assuntos
Artrite Reumatoide/genética , DNA Mitocondrial/genética , Mutação , Estudos de Casos e Controles , China , Feminino , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , ATPases Mitocondriais Próton-Translocadoras/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.
Assuntos
Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Hemócitos/citologia , Pneumonia Viral/diagnóstico , Adulto , Betacoronavirus/patogenicidade , COVID-19 , China , Coronavirus/patogenicidade , Infecções por Coronavirus/sangue , Progressão da Doença , Feminino , Humanos , Contagem de Leucócitos/métodos , Leucopenia , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Contagem de Plaquetas/métodos , Pneumonia Viral/sangue , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
Objective: This study aimed to investigate the correlation between COVID-19 and the direct antiglobulin test (DAT) and establish an in-hospital mortality risk predictive model based on the DAT type, which can be used for the early prediction of inpatients with COVID-19. Methods: In this study, 502 patients admitted to our hospital who underwent DAT testing from January 29 to February 8, 2023, were included (252 DAT-positive and 250 DAT-negative). Among them, 241 cases of COVID-19 were screened(171 DAT-positive and 70 DAT-negative), clinical and laboratory indicators were compared between DAT-positive and DAT-negative groups. Univariate and multivariate logistic regression analysis, the Kaplan-Meier survival curve and receiver operating curves were used to explore the relation between the DAT type and in-hospital mortality of patients with COVID-19. Results: The proportion of confirmed COVID-19 cases was higher in the DAT-positive group than in the DAT-negative group (67.9 % vs. 28.0 %, P < 0.05). Patients with COVID-19 in the DAT-positive group had higher age-adjusted Charlson comorbidity index scores, red blood cell distribution width (RDW), lactate dehydrogenase, prothrombin time, D-dimer, creatinine, and high-sensitive cardiac troponin T levels than the negative group (P < 0.05), In contrast, hemoglobin and estimated glomerular filtration rate (eGFR) levels were lower in the DAT-positive group. The DAT-positive group also had a higher red blood cell usage volume and in-hospital mortality rate than the DAT-negative group. The mortality rate of patients with COVID-19 with both IgG and C3d positive was higher than that of the other groups. Multivariate logistic regression analysis showed that RDW and eGFR were associated with mortality in patients with COVID-19. The combined predictive model of DAT type, RDW, and eGFR showed an area under the curve of 0.782, sensitivity of 0.769, and specificity of 0.712 in predicting in-hospital mortality risk in patients with COVID-19. Conclusion: The established predictive model for in-hospital mortality risk of patients with COVID-19 based on DAT type, RDW, and eGFR can provide a basis for timely intervention to reduce the mortality rates of patients with COVID-19. This model is accessible at https://jijijiduola.shinyapps.io/0531// for research purposes.
RESUMO
Background: Self-care is crucial for maintaining the health and quality of life of individuals undergoing physical examinations, especially those with abnormal test results because they are at a higher risk of experiencing worse outcomes. However, there is currently a lack of comprehensive literature on the impact of sociodemographic and clinical factors on self-care practices related to serum potassium concentration among individuals undergoing physical examinations. Therefore, this study aimed to explore the sociodemographic and clinical factors influencing serum potassium concentration. Methods: Data from 43,151 individuals who underwent physical examinations were retrospectively collected in January, April, July, and October of 2019-2021. The serum potassium concentrations of these individuals were compared based on sex, age, and residential area. Additionally, the whole cohort and a subset of 6698 individuals with available occupational information were included to analyze the sociodemographic factors associated with serum potassium concentration using logistic regression analysis. Furthermore, a propensity score matching approach was employed to match 642 individuals with abnormal serum potassium concentrations to 642 with normal serum potassium concentrations. Pearson's correlation analysis was subsequently used to investigate the clinical factors contributing to abnormalities in serum potassium concentration. Results: High temperatures; older age; male sex; living in the southern part of the city; and chemical, communication system, and transportation occupations were associated with a higher likelihood of experiencing abnormal serum potassium concentrations. Individuals with abnormal serum potassium concentrations had a higher prevalence of underlying diseases. Compared with the hypokalemia group, the hyperkalemia group exhibited a higher incidence of diabetes and cardiovascular disease. In the hyperkalemia group, serum potassium concentration positively correlated with serum creatinine concentration and negatively correlated with the estimated glomerular filtration rate (eGFR). In contrast, in the hypokalemia group, serum potassium concentration negatively correlated with creatinine concentrations, blood glucose concentration, and systolic and diastolic blood pressure, and positively correlated with eGFR. Conclusions: Sociodemographic and clinical factors can affect blood potassium concentration. During daily self-care, it is essential for individuals with abnormal potassium concentrations to avoid exposure to relevant sociodemographic risk factors and seek medical attention as soon as possible to screen for diseases, such as hypertension, cardiovascular disease, and diabetes.
RESUMO
Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/ß receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Camundongos Endogâmicos C57BL , RNA Circular , Infecção por Zika virus , Zika virus , Animais , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/imunologia , Zika virus/imunologia , Zika virus/genética , Camundongos , Anticorpos Neutralizantes/imunologia , RNA Circular/genética , RNA Circular/imunologia , Anticorpos Antivirais/imunologia , Vírus da Dengue/imunologia , Vírus da Dengue/genética , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Humanos , Camundongos Knockout , Proteínas não Estruturais Virais/imunologia , Proteínas não Estruturais Virais/genética , Dengue/prevenção & controle , Dengue/imunologia , Feminino , Anticorpos Facilitadores , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/imunologia , Receptor de Interferon alfa e beta/genética , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genéticaRESUMO
This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.
RESUMO
BACKGROUND: White matter injury (WMI) is an important type of preterm brain injury, which may result in severe neurological sequelae and lack of effective treatments. It is ascertained that selective vulnerability of oligodendrocytes is closely related to the WMI in preterm infants. But the alteration of the endogenous oligodendrogenesis over long time after hypoxic-ischemic WMI is still not clearly elucidated. METHODS: We adopted an animal model of hypoxic-ischemic WMI in 3-day-old neonatal Sprague-Dawley rats. Immunofluorescence staining and western blotting were used to detect dynamic changes of oligodendrogenesis in the white matter region on postoperative day (POD) 1, 3, 7, 14, 28, 56 and 84. RESULTS: In the sham group, the oligodendrocyte lineage in the white matter reached a developmental peak from POD 3 to 14. The proliferation and development of oligodendrocyte precursor cells (OPCs) occurred primarily within POD 14. The number of mature oligodendrocytes showed an upward trend and a dynamic change in proliferation over time. While in the WMI group, the oligodendrocyte lineage was upregulated on POD1 and 3 but downregulated on POD 7 and 14. The proliferation of OPCs increased on POD 1 and decreased on POD 3 and 7, with the total number of OPCs significantly reduced from POD 3 to 14. The number of mature oligodendrocytes decreased from POD 3 to 28, and return to the level of the sham group on POD 56 and 84, whereas the MBP expression was still significantly downregulated on POD 56 and 84. CONCLUSIONS: Hypoxia-ischemia can have a long-term dynamic effect on the endogenous oligodendrogenesis of neonatal rat brain white matter. The proliferation of OPCs was promoted on POD 1 but inhibited from POD 3 to 14, which may be an early intervention target to improve oligodendrogenesis. The number of mature oligodendrocytes recover to the normal on POD 56 and 84 but the myelination is still blocked, which suggests it is essential to promote the maturation of oligodendrocyte and its function recovery at the same time within POD 28. Such efforts will provide the opportunity to test new interventions in pre-clinical studies for their promising clinical application.
Assuntos
Lesões Encefálicas , Substância Branca , Recém-Nascido , Humanos , Animais , Ratos , Animais Recém-Nascidos , Ratos Sprague-Dawley , Substância Branca/metabolismo , Recém-Nascido Prematuro , Hipóxia/metabolismo , Oligodendroglia/metabolismo , Lesões Encefálicas/metabolismo , Isquemia/metabolismoRESUMO
OBJECTIVES: Waning vaccine-induced immunity and emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants which may lead to immune escape, pose a major threat to the COVID-19 pandemic. Currently, enhanced efficacy of the neutralization antibodies (NAb) produced after the booster dose of vaccinations against the Omicron variant is the main focus of vaccine strategy research. In this study we have analyzed the potency of the NAbs and IgGs produced after the third vaccine dose in patients infected with Omicron variant and wild-type (WT) SARS-CoV-2. METHODS: We enrolled 75 patients with Omicron variant breakthrough infections, and 87 patients with WT infections. We recorded the clinical characteristics and vaccination information of all patients and measured the NAb and anti-S1 (spike protein) + N (nucleocapsid protein) IgG-binding antibodies against SARS-CoV-2 in serum samples of Omicron variant-infected patients at admission, and patients with WT COVID-19 infection from the time of admission and discharge, and one-year to two-years follow-ups. RESULTS: Our results demonstrated higher NAb levels, fewer clinical symptoms, and faster viral shedding in Omicron variant infected patients vaccinated with the booster dose. Hybrid immunity (natural infection plus vaccination) induces higher NAb levels than vaccine-only immunity. NAb and IgG levels decreased significantly at one-year follow-up in WT convalescents with natural infection. The NAb and IgG levels in booster-vaccinated COVID-19 patients were higher than those in two-dose-vaccinated patients. CONCLUSION: Our results suggest that booster vaccinations are required to improve the level of protective NAbs. Moreover, our data provide important evidence for vaccination strategies based on existing vaccines.
Assuntos
Anticorpos Neutralizantes , COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Imunoglobulina G , Anticorpos Antivirais , VacinaçãoRESUMO
Objective: Facing the challenge to manage the SARS-CoV-2 RNA re-positive in discharged COVID-19 patients, it is necessary to explore the limited early risk factors for identifying SARS-CoV-2 RNA re-positive. The triglyceride and glucose index (TyG) has been developed as a surrogate marker of insulin resistance. This study aims to evaluate the correlation of the TyG index with the re-positive of COVID-19. Methods: A total of 144 COVID-19 patients from Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (China) were enrolled in this study. All of them were discharged after recovery according to the guidelines. We compared the clinical characteristics and laboratory indexes of re-positive and non-re-positive COVID-19 patients, and analyzed the early risk factors for identifying SARS-CoV-2 RNA re-positive. Results: During the follow-up, a total of 18 patients were tested re-positive for SARS-CoV-2 RNA. Re-positive COVID-19 patients had higher proportion of abidol (P=0.018), antibiotic use (P=0.024) and hepatitis-based diseases (P=0.042), and higher heart rate (P=0.011) at admission (P=0.026), while lower TyG index (P=0.036), eGFR (P=0.034), TG (P=0.015) and C1q (P=0.023). Multivariate logistic regression analysis showed that TyG index was an independent risk factor for the re-positive of SARS-CoV-2 RNA (P=0.005). TyG index was significantly correlated with Glu (P<0.001), TG (P<0.001) and HDL-C (P<0.001). In addition, it was found that TyG index decreased at SARS-CoV-2 RNA positive stage and increased at negative stage (P<0.05). Conclusion: TyG index may be a valuable marker for identifying the re-positive of COVID-19 patients and may play a role in determining the stage of the patient's disease. We hope to provide a reliable theoretical basis for clinical prediction and effective control of re-positive episodes, and to provide a breakthrough for further research on the causes of re-positive episodes and the immune mechanism of the virus.
RESUMO
Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive and fatal gastrointestinal malignancies with high morbidity and mortality worldwide. Accumulating evidence has revealed the clinical significance of the interaction between the hypoxic microenvironment and cancer stemness in pancreatic cancer progression and therapies. This study aims to identify a hypoxia-stemness index-related gene signature for risk stratification and prognosis prediction in PAAD. Methods: The mRNA expression-based stemness index (mRNAsi) data of PAAD samples from The Cancer Genome Atlas (TCGA) database were calculated based on the one-class logistic regression (OCLR) machine learning algorithm. Univariate Cox regression and LASSO regression analyses were then performed to establish a hypoxia-mRNAsi-related gene signature, and its prognostic performance was verified in both the TCGA-PAAD and GSE62452 corhorts by Kaplan-Meier and receiver operating characteristic (ROC) analyses. Additionally, we further validated the expression levels of signature genes using the TCGA, GTEx and HPA databases as well as qPCR experiments. Moreover, we constructed a prognostic nomogram incorporating the eight-gene signature and traditional clinical factors and analyzed the correlations of the risk score with immune infiltrates and immune checkpoint genes. Results: The mRNAsi values of PAAD samples were significantly higher than those of normal samples (p < 0.001), and PAAD patients with high mRNAsi values exhibited worse overall survival (OS). A novel prognostic risk model was successfully constructed based on the eight-gene signature comprising JMJD6, NDST1, ENO3, LDHA, TES, ANKZF1, CITED, and SIAH2, which could accurately predict the 1-, 3-, and 5-year OS of PAAD patients in both the training and external validation datasets. Additionally, the eight-gene signature could distinguish PAAD samples from normal samples and stratify PAAD patients into low- and high-risk groups with distinct OS. The risk score was closely correlated with immune cell infiltration patterns and immune checkpoint molecules. Moreover, calibration analysis showed the excellent predictive ability of the nomogram incorporating the eight-gene signature and traditional clinical factors. Conclusion: We developed a hypoxia-stemness-related prognostic signature that reliably predicts the OS of PAAD. Our findings may aid in the risk stratification and individual treatment of PAAD patients.
RESUMO
Purpose: We evaluated the differences between patients with SARS-CoV-2 Omicron variant infections and Fever outpatients, so that prevention and control measures can be taken in time. Patients and Methods: This study retrospectively analyzed 65 patients with SARS-CoV-2 Omicron variant. Sixty-nine age- and sex-matched Fever outpatients were enrolled during the same period of time. We also reanalyzed data from 81 SARS-CoV-2 Wild-Type-infected patients. We compared the clinical characteristics and initial indexes of routine tests among the 3 groups. Results: A total of 93.8% of the patients with Omicron infections had clinical symptoms, and the major symptoms were cough, fever and pharyngalgia. Pharyngalgia was a specific manifestation in Omicron group compared to Wild-Type group. The white blood cell of the Omicron group was lower than that of the Fever group [5.0 (3.6-6.1) vs 10.1 (7.6-12.9) ×109/L, P < 0.001]. The neutrophil count in Omicron group was lower than that in Fever and Wild-Type group [2.6 (1.8-3.9) vs 8.1 (5.9-10.9), P < 0.001; 2.6 (1.8-3.9) vs 3.4 (2.5-4.7) ×109/L, P < 0.001]. The white blood cell and neutrophil counts were lower in Omicron group than in the Fever group. The top 5 major symptoms were fever, cough, pharyngalgia, headache and expectoration. Conclusion: There are differences between the patients with Omicron infections and Fever outpatients, both in clinical manifestations and initial routine hematology indicators. We hope to provide some clues for early identification combined with a history of living in the epidemic area.
RESUMO
According to previous studies, mental status in 1-year COVID-19 survivors might range from 6-43%. Longer-term psychological consequences in recovered COVID-19 subjects are unknown, so we analyzed longer-term quality of life and mental status in recovered COVID-19 subjects at 2 years after infection. Among 144 recovered COVID-19 subjects in the Taizhou region, 73 and 45 completed face-to-face follow-ups at the first year and second year after infection, respectively, with a 61.7% follow-up rate. The questionnaire, which was administered at both follow-ups, included questions about quality of life, psychological health, and post-traumatic stress disorder (PTSD). The Mann-Whitney U test was used to the differences of each scale between the first and second year. Among the 45 people who completed both follow-up visits, the incidence of psychological problems was 4.4% (2/45) in the first year, and no new psychological abnormalities were observed in the second year. Quality of life improved, while the General Health Questionnaire (GHQ-12) and Impact of Event Scale-Revised (IES-R) scores did not improve over time. The incidence of mental disorders was lower than those in previous studies. Multidisciplinary management for COVID-19 in this study hospital may have reduced the frequency to a certain extent. However, among those with mental health problems, such problems may exist for a long time, and long-term attention should be given to the psychological status of recovered COVID-19 subjects.
RESUMO
Objective: In 2022, a new coronavirus variant (Omicron) infection epidemic broke out in Shanghai, China. However, it is unclear whether the duration of this omicron variant is different from that of the prototype strain. Methods: We retrospectively analyzed 157 cases of Omicron variant infection in Taizhou Public Health Center from March 29, 2022, to April 18, 2022, and observed the dynamics of nucleic acid Ct values during the admission and discharge of patients. Clinical and laboratory indicators of these patients were also obtained. Results: Compared to the prototype strain, the Omicron variant showed a broad population susceptibility in infected individuals (regardless of age and presence of underlying disease) and had slight damage to the immune system and renal function; the viral loads peaked was 2-3 days from disease onset; the median duration of omicron variant was 15-18 days; the nucleic acid Ct value of nasopharyngeal swabs of infected patients is lower than that of throat swabs, and the Ct value of oropharyngeal swabs is unstable during the recovery period. Conclusion: Therefore, we found that the time to peak viral load of this Omicron variant was 2-3 days after the onset of the disease, and the duration was 15-18 days; symptomatic patients had higher viral load and longer hospitalization time. This finding will provide a basis for understanding omicron variants and formulating the national prevention and control strategy.
RESUMO
Responding to the fast-spreading SARS-CoV-2 Omicron variant, to improve screening efficiency, rapid antigen tests (RATs) were first added as a supplementary detection method in China in mid-March, 2022. What and how big a role RATs should play need to be supported by clinical data. Here, RAT performance and relevant factors in comparison with nucleic acid amplification tests (NAATs) were assessed in Omicron-infected inpatients. From the NAAT results, nasopharyngeal swabs (NPs) performed better than oropharyngeal swabs (OPs). RATs tested on NAAT positive NPs performed better than those with OP-positive samples. The RAT positivity rate was strongly associated with high levels of N and OFR1ab genes, especially in NPs where patients also had significantly longer hospital stays and shorter days from symptom onset to RAT testing. Self-performed RATs had a detection accuracy that was comparable to professionally performed RATs when the subjects were well guided. The antigen negative rate of the studied patients was 100% at discharge. These findings suggest that, in addition to a supplementary detection role, RATs can be an important strategy for evaluating the disease progression of Omicron-infected inpatients. This study provides important clinical data to support better rules regarding RATs under China's COVID-19 prevention and control policy.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , China , Progressão da DoençaRESUMO
The physical condition of individuals who contracted COVID-19 had a profound influence on mitigating the physical and psychological impact of the disease and the symptoms of posttraumatic stress disorder (PTSD). Little attention has been focused on the influence of physical condition on PTSD among recovered COVID-19 subjects. This study explored the relationship between physical and psychological status and PTSD and the potential mechanisms. Questionnaires were completed by 73 (50.7%, 73/144) COVID-19 recovered subjects who were diagnosed in Taizhou, Zhejiang, China. We conducted a face-to-face survey from January 17 to March 10, 2020. The mediation analysis approach was applied in this research. Our data show that recovered COVID-19 subjects who were in better physical condition exhibited fewer psychological problems [B (95%CI), (-1.65 -3.04, -0.26)] and lower PTSD [B (95%CI), -6.13 (-9.43, -2.83)]. In addition, the worse the psychological status of recovered COVID-19 subjects was, the stronger the PTSD (B [95%CI], 0.58 [0.02, 1.14]). Moreover, psychological status could significantly mediate the impact of physical condition on PTSD (ß1θ2 = -0.87). Together, COVID-19 recovered subjects who have better physical condition could decrease their PTSD, and the worse the physical condition of COVID-19 recovered subjects would increase their psychological problems. Our finding about psychological status could significantly mediate the impact of the physical condition on PTSD might be useful for medical institutions and the government seeking to help with the follow-up rehabilitation training of recovered COVID-19 subjects.