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1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1795805

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
2.
Signal Transduct Target Ther ; 7(1): 114, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1778593

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/chemistry , Antibodies, Viral/chemistry , COVID-19 , Cryoelectron Microscopy , Humans , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
3.
Sci China Life Sci ; 2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1739404

ABSTRACT

Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.

4.
Front Immunol ; 12: 769442, 2021.
Article in English | MEDLINE | ID: covidwho-1686473

ABSTRACT

The prevention of the COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent, and re-detectable positive cases. We identified a set of V-J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V-J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.


Subject(s)
COVID-19/pathology , Immunoglobulin J-Chains/genetics , Immunoglobulin Variable Region/genetics , Receptors, Antigen, T-Cell/genetics , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adaptive Immunity/genetics , Adaptive Immunity/immunology , Adult , Aged , Asymptomatic Infections , COVID-19/immunology , Female , Gene Expression/genetics , Histocompatibility Antigens Class I/genetics , Humans , Male , Middle Aged , Receptors, Antigen, T-Cell/immunology , Severity of Illness Index , Young Adult
5.
Nat Commun ; 13(1): 460, 2022 01 24.
Article in English | MEDLINE | ID: covidwho-1651070

ABSTRACT

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.


Subject(s)
COVID-19/transmission , Contact Tracing/methods , Disease Outbreaks/prevention & control , SARS-CoV-2/isolation & purification , Animals , COVID-19/epidemiology , COVID-19/virology , Chlorocebus aethiops , Humans , RNA-Seq/methods , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Time Factors , Vero Cells , Viral Load/genetics , Viral Load/physiology , Virus Replication/genetics , Virus Replication/physiology , Virus Shedding/genetics , Virus Shedding/physiology
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293463

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo . Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

7.
EClinicalMedicine ; 40: 101129, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1401440

ABSTRACT

BACKGROUND: A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China. METHODS: We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital. FINDINGS: There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%, p = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86]; p = 0.01). INTERPRETATION: Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks. FUNDING: National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory.

8.
Front Cardiovasc Med ; 8: 604736, 2021.
Article in English | MEDLINE | ID: covidwho-1403460

ABSTRACT

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12-4.68; p = 0.023) and 2.02 (1.04-3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81-3.40 mmol/L (108.6-131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07-6.37; p = 0.035) and 2.36 (1.09-5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

9.
Front Immunol ; 12: 716075, 2021.
Article in English | MEDLINE | ID: covidwho-1359192

ABSTRACT

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.


Subject(s)
Asymptomatic Diseases , COVID-19/immunology , Carrier State/immunology , Leukocytes, Mononuclear/immunology , SARS-CoV-2/immunology , Transcriptome/genetics , Adult , Carrier State/virology , Complement Activation/immunology , Female , Gene Expression Profiling , Humans , Inflammation/immunology , Influenza, Human/complications , Interferons/blood , Interferons/immunology , Male , Middle Aged , NF-kappa B/metabolism , Transcriptome/immunology , Tumor Necrosis Factor-alpha/metabolism , Young Adult
10.
Front Immunol ; 12: 662465, 2021.
Article in English | MEDLINE | ID: covidwho-1337636

ABSTRACT

To systematically explore potential biomarkers which can predict disease severity in COVID-19 patients and prevent the occurrence or development of severe COVID-19, the levels of 440 factors were analyzed in patients categorized according to COVID-19 disease severity; including asymptomatic, mild, moderate, severe, convalescent and healthy control groups. Factor candidates were validated by ELISA and functional relevance was uncovered by bioinformatics analysis. To identify potential biomarkers of occurrence or development of COVID-19, patient sera from three different severity groups (moderate, severe, and critical) at three time points (admission, remission, and discharge) and the expression levels of candidate biomarkers were measured. Eleven differential factors associated with disease severity were pinpointed from 440 factors across 111 patients of differing disease severity. The dynamic changes of GDF15 reflect the progression of the disease, while the other differential factors include TRAIL R1, IGFBP-1, IGFBP-4, VCAM-1, sFRP-3, FABP2, Transferrin, GDF15, IL-1F7, IL-5Rα, and CD200. Elevation of white blood cell count, neutrophil count, neutrophil-lymphocyte ratio (NLR), Alanine aminotransferase and Aspartate aminotransferase, low lymphocyte and eosinophil counts in the severe group were associated with the severity of COVID-19. GDF15 levels were observed to be associated with the severity of COVID-19 and the dynamic change of GDF15 levels was closely associated with the COVID-19 disease progression. Therefore, GDF15 might serve as an indicator of disease severity in COVID-19 patients.


Subject(s)
Biomarkers/metabolism , COVID-19/immunology , Growth Differentiation Factor 15/metabolism , Inflammation Mediators/metabolism , SARS-CoV-2/physiology , Adult , Aged , Computational Biology , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
11.
J Appl Lab Med ; 6(5): 1133-1142, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1334229

ABSTRACT

BACKGROUND: We launched a retrospective analysis of SARS-CoV-2 antibodies in 192 patients with COVID-19, aiming to depict the kinetic profile of SARS-CoV-2 antibodies and explore the factors related to SARS-CoV-2 antibody expression. METHODS: Data on 192 confirmed patients with COVID-19 between January and February 2020 was collected from the designated hospital that received patients with COVID-19 in Guangzhou, China. Moreover, a cohort of 130 suspected patients with COVID-19 and 209 healthy people were also enrolled in this study. IgM and IgG antibodies to SARS-CoV-2 were detected by the chemiluminescence immunoassay kits in different groups. RESULTS: A total of 192 COVID-19 cases were analyzed, of which had 81.8% anti-SARS-CoV-2 IgM detected and 93.2% anti-SARS-CoV-2 IgG detected, respectively, at the time of sampling. The kinetics of anti-SARS-CoV-2 IgM and IgG showed that, the confirmed cases had anti-SARS-CoV-2 IgM seroconversion occurred 5-10 days after the onset of the symptoms, and then IgM rose rapidly to reach a peak within around 2-3 weeks, maintaining at its peak for 1 week before its decline. While they had anti-SARS-CoV-2 IgG seroconversion simultaneously or sequentially with IgM, reaching its peak within around 3 to 4 weeks and began to decline after the fifth week. Besides, correlation analysis showed that in patients with COVID-19 the level of IgM was related to gender and disease severity (P < 0.01), and the level of IgG was related to age and disease severity (P < 0.001). The univariate analysis of relevant factors indicated that the level of IgG had a weak correlation with age (r = 0.374, P < 0.01). The level of IgM in male patients was higher than that in female patients (P < 0.001). The expression level of anti-SARS-CoV-2 IgM and IgG were positively correlated with the severity of COVID-19 and the duration of the virus in the patients. CONCLUSION: The findings of this study show that anti-SARS-CoV-2 IgM and IgG can be important assisting COVID-19 diagnosis, especially in the early phase of infection. Furthermore, antibody expression in patients with COVID-19 is also correlated with disease severity, age, gender, and virus clearance or continuous replication.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Testing , Female , Hospitalization , Humans , Male , Retrospective Studies
12.
Case Rep Womens Health ; 31: e00321, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1213126

ABSTRACT

The effects of SARS-CoV-2 infection in the first trimester on the pregnant woman and the fetus remain unclear. We describe the complete follow-up of a pregnant woman with asymptomatic SARS-CoV-2 infection in the first trimester. The woman tested positive for SARS-CoV-2 viral RNA in nasopharyngeal swabs in her seventh week of gestation and was admitted to a local hospital for treatment. Although the woman had a BMI above 28 and a total gestational weight gain of 21 kg, no pregnancy complications or severe complications related to SARS-CoV-2 were reported. An ultrasound scan identified no fetal abnormalities at 22 weeks. The pregnancy ended at term (37 weeks), and the newborn's birth weight was 3100 g. Placental insufficiency was revealed by placental histology examination but this appeared not to be related to the SARS-CoV-2 infection. In-situ hybridisation and immunohistochemical tests for SARS-CoV-2 RNA, spike protein 1, and nucleocapsid proteins were negative. However, ACE-2 was positive in samples of the placenta, umbilical cord and fetal membrane. The baby was followed up through to 10 days after birth and grew normally. Our results suggest that asymptomatic SARS-CoV-2 infection in the first trimester of pregnancy might not have significant harmful effects on the mother and the developing fetus. This finding may be of interest to the general public, midwives and general practitioners. However, large population studies are needed to confirm our findings.

13.
Journal of Modern Laboratory Medicine ; 35(4):94-96, 2020.
Article in Chinese | GIM | ID: covidwho-1073551

ABSTRACT

Objective: To explore the application value of peripheral blood lymphocytes and their subgroups in patients with novel coronavirus pneumonia (COVID-19).

14.
Int J Med Sci ; 18(1): 29-41, 2021.
Article in English | MEDLINE | ID: covidwho-994132

ABSTRACT

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.


Subject(s)
COVID-19/immunology , Interleukin-6/blood , Lung Injury/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/diagnostic imaging , Female , Humans , Longitudinal Studies , Lung Injury/diagnostic imaging , Lung Injury/virology , Lymphocyte Count , Male , Middle Aged , Radiography, Thoracic , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
15.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-637

ABSTRACT

Background: Severe cases of coronavirus disease 2019 (COVID-19) rapidly develoacute respiratory distress leading to respiratory failure, with remarkably high

16.
Hum Immunol ; 81(12): 702-708, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-773666

ABSTRACT

To discover immune factors that can predict the progression of COVID-19, we evaluated circulating immune cells and plasma cytokines in COVID-19 patients. We found that T cells, including CD4+ T cells and CD8+ T cells, were significantly decreased in severe COVID-19 symptoms but not in mild symptoms, in comparison with healthy people. T cells remained at a low level after recovery from severe COVID-19. CD4+CD25+CD127low Treg-enriched cells were significantly increased in either mild or severe COVID-19 patients, regardless of recovery or not. Moreover, in either mild or severe COVID-19 patients, Treg-enriched cells up-regulated CD25 and down-regulated CD127. After recovery, CD25 was partially down-regulated but still higher than the normal level, while CD127 returned to the normal level in mild patients but not severe patients. B cells were decreased in mild patients and further decreased in severe patients, and remained low after recovery. NK cells were decreased only in severe COVID-19, with a tendency to return to the normal level after recovery. Plasma IL-6 and IL-10 were both elevated in severe patients but not in mild patients. After recovery, IL-6 remained higher than its normal level, while IL-10 returned to the normal level. Binary logistic regression analysis indicated that CD4+ T cells, B cells, IL-6, and IL-10 were significantly associated with COVID-19 severity. Therefore, these parameters are indicators of COVID-19 severity. Dynamic monitoring of these parameters would benefit therapy planning and prognosis evaluation.


Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Interleukin-10/blood , Interleukin-6/blood , Killer Cells, Natural/immunology , SARS-CoV-2/genetics , T-Lymphocytes, Regulatory/immunology , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Female , Humans , Inflammation/immunology , Lymphocyte Count , Male , Middle Aged , Prognosis , Severity of Illness Index , Up-Regulation/immunology
17.
Cell Mol Immunol ; 17(10): 1098-1100, 2020 10.
Article in English | MEDLINE | ID: covidwho-772968
18.
Clin Infect Dis ; 71(15): 833-840, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-612035

ABSTRACT

BACKGROUND: Because there is no reliable risk stratification tool for severe coronavirus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identification of cases at high risk of progression to severe COVID-19. METHODS: In this retrospective multicenter study, 372 hospitalized patients with nonsevere COVID-19 were followed for > 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and those who maintained a nonsevere state were assigned to the severe and nonsevere groups, respectively. Based on baseline data of the 2 groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluated its performance. RESULTS: The training cohort consisted of 189 patients, and the 2 independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.4%) patients developed severe COVID-19. Older age; higher serum lactate dehydrogenase, C-reactive protein, coefficient of variation of red blood cell distribution width, blood urea nitrogen, and direct bilirubin; and lower albumin were associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the training cohort (area under the curve [AUC], 0.912 [95% confidence interval {CI}, .846-.978]; sensitivity 85.7%, specificity 87.6%) and the validation cohort (AUC, 0.853 [95% CI, .790-.916]; sensitivity 77.5%, specificity 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analyses indicated that nomogram conferred high clinical net benefit. CONCLUSIONS: Our nomogram could help clinicians with early identification of patients who will progress to severe COVID-19, which will enable better centralized management and early treatment of severe disease.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Adult , Area Under Curve , Betacoronavirus/pathogenicity , COVID-19 , China , Coronavirus Infections/virology , Disease Progression , Female , Humans , Male , Middle Aged , Nomograms , Pandemics , Pneumonia, Viral/virology , Prognosis , Retrospective Studies , Risk Assessment/methods , Risk Factors , SARS-CoV-2
19.
Chin. J. Microbiol. Immunol. ; 4(40): 250-255, 20200430.
Article in Chinese | WHO COVID, ELSEVIER | ID: covidwho-478481

ABSTRACT

Objective: To evaluate the performance of three antibody kits for novel coronavirus (SARS-CoV-2) and to investigate the feasibility and advantages of them in clinical application. Methods: A total of 104 patients who were admitted to Guangzhou Eighth People's Hospital with COVID-19 from January to February 2020 were selected as research group. Fifty-one healthy subjects were selected during the same period as negative control group. Serum antibodies (IgM/IgG) against SARS-CoV-2 were detected using two kinds of colloidal gold kits (A and B kits) and one chemiluminescence kit (C kit). The positive rates of SARS-CoV-2 nucleic acid in different samples from patients with COVID-19 were retrospectively analyzed. Results: The clinical sensitivity of A kit to detect SARS-CoV-2-specific IgM and IgG was 77.88% (81/104) and 65.38% (68/104), respectively, and the clinical specificity was 70.59% (36/51) and 100.00% (51/51). However, the false positive rate in IgM detection was as high as 29.41% (15/51). The sensitivity of B kit to test total antibodies to SARS-CoV-2 was 63.46% (66/104), and the clinical specificity was 94.12% (48/51). The clinical sensitivity of C kit to detect SARS-CoV-2-specific IgM and IgG were respectively 31.73% (33/104) and 64.42% (67/104), and the clinical specificity were both 98.04% (50/51). There was a moderate correlation between the detection results of two colloidal gold kits and the chemiluminescence kit with the Kappa values of 0.462 and 0.587 (Z=6.157, P<0.01; Z=7.345, P<0.01). C kit had the highest positive detection rate for IgG, and would be more reliable to be used for IgG detection in COVID-19 patients 14 d after onset. The total positive detection rate of nucleic acid in all types of samples was 63.46% (66/104). The highest positive detection rate was in throat swabs or sputum samples, followed by those in blood samples and anal swabs. No viral nucleic acid was detected in urine samples for the time being. Conclusions: SARS-CoV-2-specific antibodies could be detected in the early or late stage of COVID-19. The method of antibody detection has the advantages of shorter detection time, simple operation and high biological safety, indicating that it could be used as a supplementary or auxiliary detection for the diagnosis of suspected COVID-19 cases with negative nucleic acid test results. The chemiluminescence kit has good sensitivity and specificity, and is well recommended for clinical laboratories.

20.
Immunology ; 160(3): 261-268, 2020 07.
Article in English | MEDLINE | ID: covidwho-381740

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with COVID-19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. Interleukin-6 (IL-6), IL-10 and C-reactive protein were remarkably up-regulated in patients with severe COVID-19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-6, IL-10 and C-reactive protein are reliable indicators of severe COVID-19.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Aged , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Betacoronavirus/physiology , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Lymphocytes/pathology , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/pathology , T-Lymphocytes, Regulatory/pathology
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