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1.
Front Immunol ; 13: 837524, 2022.
Article in English | MEDLINE | ID: covidwho-1731784

ABSTRACT

Effectively treating infectious diseases often requires a multi-step approach to target different components involved in disease pathogenesis. Similarly, the COVID-19 pandemic has become a global health crisis that requires a comprehensive understanding of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection to develop effective therapeutics. One potential strategy to instill greater immune protection against COVID-19 is boosting the innate immune system. This boosting, termed trained immunity, employs immune system modulators to train innate immune cells to produce an enhanced, non-specific immune response upon reactivation following exposure to pathogens, a process that has been studied in the context of in vitro and in vivo clinical studies prior to the COVID-19 pandemic. Evaluation of the underlying pathways that are essential to inducing protective trained immunity will provide insight into identifying potential therapeutic targets that may alleviate the COVID-19 crisis. Here we review multiple immune training agents, including Bacillus Calmette-Guérin (BCG), ß-glucan, and lipopolysaccharide (LPS), and the two most popular cell types involved in trained immunity, monocytes and natural killer (NK) cells, and compare the signaling pathways involved in innate immunity. Additionally, we discuss COVID-19 trained immunity clinical trials, emphasizing the potential of trained immunity to fight SARS-CoV-2 infection. Understanding the mechanisms by which training agents activate innate immune cells to reprogram immune responses may prove beneficial in developing preventive and therapeutic targets against COVID-19.


Subject(s)
COVID-19/immunology , Immunity, Innate/immunology , Humans , Killer Cells, Natural/immunology , Monocytes/immunology , SARS-CoV-2/immunology
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313437

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has spread globally. However, the association between COVID-19 and disseminated intravascular coagulation (DIC) has been scarcely addressed. We aimed to systematically characterize the clinical features and examine risk factors for DIC development in COVID-19 patients. Methods: : In this single-centered, retrospective, and observational study, all patients with DIC (N=59) and 270 patients without DIC were matched by propensity score matching based on age, sex, and comorbidities. Demographic data, symptoms, radiological, laboratory examinations, and clinical outcomes were compared between patients with and without DIC. Furthermore, univariable and multivariable logistic regression were used to explore the risk factors associated with DIC development in COVID-19 patients. Results: : Higher proportion of patients with DIC and COVID-19 (54 of 59 [91·53%]) developed into death than non DIC patients (58 of 270 [21·48%]). Patients with DIC presented aggravated inflammation responses, liver damage, and especially coagulation dysfunction. Moreover, in addition to previously reported coagulation-related markers, such as FDP, D-dimer, and platelet, we also identified several novel risk factors associated with DIC development, including decreased fibrinogen (OR=0·476, 95%CI=0·380-0·596, P <0·0001) and ALB (0·901, 0·845- 0·961, P =0·0015), and elevated IL-6 (1·010, 1·005-1·015, P =0·00017) and TNF-α (1·053, 1·016-1·091, P =0·0045). Conclusions: : Patients with DIC and COVID-19 were predisposed to poor clinical outcomes. These risk factors identified may be helpful for early surveillance of disease progression and making standardized treatment strategies.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323601

ABSTRACT

Background: The COVID-19 pandemic has been considered a great threat to global public health. We aimed to clarify the risk factors associated with the development of acute respiratory distress syndrome (ARDS) and progression from ARDS to death and construct a risk prediction model. Methods: : In this single-centered, retrospective, and observational study, 796 COVID-19 patients developed ARDS and 735 COVID-19 patients without ARDS were matched by propensity score at an approximate ratio of 1:1 based on age, sex and comorbidities. Demographic data, symptoms, radiological findings, laboratory examinations, and clinical outcomes were compared between those with or without ARDS. Univariable and multivariable logistic regression models were applied to explore the risk factors for development of ARDS and progression from ARDS to death and establish a comprehensive risk model. Results: : Higher SOFA, qSOFA, APACHE II and SIRS scores, elevated inflammatory cytokines, dysregulated multi-organ damage biomarkers, decreased immune cell subsets were associated with higher proportion of death (34.17% vs 1.22%;P <0.001) and increased risk odds of death (OR=57.216, 95%CI=28.373-115.378;P <0.001) in COVID-19 patients with ARDS. In addition to previous reported risk factors related to ARDS development and death, such as neutrophils, IL-6, D-Dimer, leukocytes and platelet, we identified elevated TNF-α (OR=1.146, 95%CI=1.100-1.194;P <0.001), CK-MB (OR=1.350, 95%CI=1.180-1.545;P <0.001), declined ALB (OR=0.834, 95%CI=0.799-0.872;P <0.001), CD8 + T cells (OR=0.983, 95%CI=0.976-0.990;P <0.001) and CD3 - CD19 + B cells (OR=0.992, 95%CI=0.988-0.997;P =0.003) as novel risk factors. Most importantly, the predictive accuracy of the combined model integrating four score systems and these risk factors demonstrated highest among all models for the development of ARDS (AUC= 0.904) and the progression from ARDS to death (AUC= 0.959). Conclusion: COVID-19 patients with ARDS were more likely to develop into death. The potential risk factors and the comprehensive prediction model could be helpful to identify patients that are at risk of developing ARDS with poor prognosis at an early stage, which might help physicians to formulate a timely therapeutic strategy.

4.
Front Med ; 16(1): 111-125, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1356049

ABSTRACT

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.


Subject(s)
COVID-19 , Hepatitis B, Chronic , Cohort Studies , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Humans , Retrospective Studies , Risk Factors
5.
Virus Res ; 304: 198508, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1331289

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Pandemics , Spike Glycoprotein, Coronavirus/immunology , Adult , CD8-Positive T-Lymphocytes/cytology , COVID-19/epidemiology , Female , Humans , Immunodominant Epitopes/immunology , Male , Middle Aged , SARS-CoV-2/immunology , Young Adult
6.
Int J Dermatol Venereol ; 2020 Mar 13.
Article in English | MEDLINE | ID: covidwho-1292185

ABSTRACT

The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.

7.
Sci Rep ; 11(1): 5558, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1125779

ABSTRACT

The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell-cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell-cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Spike Glycoprotein, Coronavirus/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , Cell Fusion/methods , Female , Humans , Immunization, Passive/methods , Male , Membrane Fusion/drug effects , Middle Aged , Pandemics/prevention & control , Plasma/chemistry , Receptors, Virus/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
9.
Emerg Infect Dis ; 26(11): 2755-2758, 2020 11.
Article in English | MEDLINE | ID: covidwho-647120

ABSTRACT

During January-February 2020, coronavirus disease (COVID-19) and tuberculosis were diagnosed for 3 patients in Wuhan, China. All 3 patients had COVID-19 pneumonia. One severely ill patient died after acute respiratory distress syndrome developed. Clinicians and public health officials should be aware of underlying chronic infections such as tuberculosis in COVID-19 patients.


Subject(s)
Betacoronavirus , Coinfection/microbiology , Coronavirus Infections/microbiology , Mycobacterium , Pneumonia, Viral/microbiology , Tuberculosis, Pulmonary/microbiology , Adult , COVID-19 , China , Fatal Outcome , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2
10.
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 , COVID-19 , China/epidemiology , Cities/epidemiology , Coronavirus Infections/complications , Female , Hospitalization , Humans , Male , Middle Aged , Neoplasms/complications , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index
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