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2.
Aging (Albany NY) ; 12(13): 12432-12440, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-634518

ABSTRACT

Severe/critical patients with coronavirus disease 2019 (COVID-19) have become the central issue in the current global pandemic due to their high mortality rate. However, the relationship between antibody response and clinical outcomes has not been well described in this group. We conducted a single-center, retrospective, cohort study to investigate the relationship between serum immunoglobulin G (IgG) and IgM and clinical outcomes in severe/critical patients with COVID-19. Seventy-nine severe/critical patients with COVID-19 admitted in Wuhan Asia General Hospital in Wuhan, China during January 22, 2020 to March 6, 2020 were included. Serum antibodies were measured at day 25 (SD, 7) post illness onset. The median IgG titer was 113 (IQR 81-167) AU/ml, and IgM titer was 50 (IQR, 23-105) AU/ml. Patients whose IgM titer ≥ 50 AU/ml had higher in-hospital mortality (p=0.026). IgM titer ≥ 50 AU/ml was also correlated with higher incidences of Acute Respiratory Distress Syndrome (ARDS) and sepsis shock. Antibody remeasurements were performed in 42 patients, where IgM titer declined significantly in survivors (p=0.031). Serum IgM titer changes according to the COVID-19 progression. The severe/critical patients with COVID-19 have a higher risk of clinical adverse events when IgM titer ≥ 50 AU/ml. Further decreasing of IgM could imply a better outcome in severe/critical cases.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/mortality , Immunoglobulin M/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Adult , Aged , Betacoronavirus/immunology , China/epidemiology , Cohort Studies , Coronavirus Infections/blood , Female , Hospital Mortality , Humans , Immunoglobulin G/blood , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Retrospective Studies
3.
Lancet Oncol ; 21(7): 893-903, 2020 07.
Article in English | MEDLINE | ID: covidwho-436717

ABSTRACT

BACKGROUND: COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk factors of COVID-19 disease severity for patients with cancer and COVID-19. METHODS: In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807. FINDINGS: Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22-38) in patients with cancer and 27 days (20-35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 [64%] of 232 vs 166 [32%] of 519; odds ratio [OR] 3·61 [95% CI 2·59-5·04]; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05-6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01-1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03-2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71-0·98; p=0·031), and reduced albumin-globulin ratio (0·12, 0·02-0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer. INTERPRETATION: Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19. FUNDING: China National Natural Science Foundation.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Neoplasms/epidemiology , Neoplasms/pathology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Aged , Betacoronavirus , China/epidemiology , Cities/epidemiology , Coronavirus Infections/complications , Female , Hospitalization , Humans , Male , Middle Aged , Neoplasms/complications , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Risk Factors , Severity of Illness Index
6.
Cell Host Microbe ; 27(6): 883-890.e2, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-165371

ABSTRACT

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Subject(s)
Bronchoalveolar Lavage Fluid/immunology , Coronavirus Infections/immunology , Immunity, Innate , Pneumonia, Viral/immunology , Respiratory System/immunology , Bronchoalveolar Lavage Fluid/cytology , Coronavirus Infections/pathology , Cytokine Release Syndrome , Cytokines/analysis , Host-Pathogen Interactions , Humans , Interferons/metabolism , Pandemics , Pneumonia, Viral/pathology , Respiratory System/pathology
8.
Chin. Trad. Herbal Drugs ; 5(51): 1113-1122, 20200312.
Article in Chinese | ELSEVIER | ID: covidwho-52367

ABSTRACT

Objective: To explore the active compounds of Huoxiang Zhengqi Oral Liquid for the treatment of coronavirus desease 2019 (COVID-19) by network pharmacology and molecular docking. Methods: The chemical constituents and action targets of Atractylodes chinensis, Citrus reticulata, Magnolia officinalis, Angelica dahurica, Poria cocos, Areca catechu, Pinellia ternata, Glycyrrhiza uralensis, Pogostemon cablin and Perilla frutescens were retrieved from TCMSP. Uniprot database was used to search the corresponding genes of targets, then Cyoscape 3.7.2 software was used to construct the network of medicinal materials-compound-target (gene) for visualization; GO function enrichment analysis and KEGG pathway enrichment analysis were performed through DAVID to predict its mechanism of action, and histograms and bubble maps were plotted by Prism software and Omicshare database for visualization. Results: The network of medicinal materials-compound-target contained 10 medicinal materials, 123 compounds and 257 corresponding target genes, and the key target genes involved PTGS2, HSP90AB1, AR, CAMSAP2, PPARG, NOS2, etc. GO functional enrichment analysis resulted in 278 GO entries (P < 0.05), including 178 biological processes (BP) entries and 36 cellular component (CC) entries, and 64 molecular function (MF) entries. KEGG pathway enrichment analysis revealed that there were 119 (P < 0.05) signaling pathways involving Hepatitis B, small cell lung cancer, non-small cell lung cancer, bladder cancer, prostate cancer and T cell receptor pathways. The results of molecular docking showed that the core compounds such as quercetin, isorhamnetin, irisolidone, kaempferol, wogonin, and baicalein were similar in affinity with the COVID-19 recommended medicine. Among them, quercetin, isorhamnetin and irisolidone had the strongest affinity. Conclusion: The compounds in Huoxiang Zhengqi Oral Liquid can combine with angiotensin converting enzyme II (ACE2) binding to PTGS2, HSP90AB1, AR, CAMSAP2 and other targets to regulate multiple signaling pathways, thus exerting a preventive or therapeutic effect on COVID-19.

11.
Chin Med J (Engl) ; 133(9): 1015-1024, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-122

ABSTRACT

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Subject(s)
Betacoronavirus , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , Aged , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , Tomography, X-Ray , Treatment Outcome
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