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1.
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240

ABSTRACT

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
2.
Chem Biol Interact ; 352: 109777, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1559106

ABSTRACT

OBJECTIVE: To determine the differences in the immune response against SARS-CoV-2 infection of patients based on sex and disease severity. METHODS: We used an analytical framework of 382 transcriptional modules and multi-omics analyses to discriminate COVID-19 patients based on sex and disease severity. RESULTS: Male and female patients overexpressed modules related to the innate immune response. The expression of modules related to the adaptive immune response showed lower enrichment levels in males than females. Inflammation modules showed ascending overexpression in male and female patients, while a higher level was observed in severe female patients. Moderate female patients demonstrated significant overexpression to interferon, cytolytic lymphocyte, T & B cells, and erythrocytes modules. Moderate female patients showed a higher adaptive immune response than males matched group. Pathways involved in metabolism dysregulation and Hippo signaling were upregulated in females than in male patients. Females and moderate cases showed higher levels of metabolic dysregulation. CONCLUSIONS: The immune landscape in COVID-19 patients was noticeably different between the sexes, and these differences may highlight disease vulnerability in males. This study suggested that certain treatments that increase or decrease the immune responses to SARS-CoV-2 might be necessary for male and female patients at certain disease stages.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Adaptive Immunity/immunology , Adult , Aged , COVID-19/pathology , Female , Humans , Immunity, Innate/immunology , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/pathology , Male , Middle Aged , SARS-CoV-2/immunology , Severity of Illness Index , Sex Characteristics
5.
Biomed Pharmacother ; 144: 112230, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1517059

ABSTRACT

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease. Metabolic changes induced by diabetes, especially hyperglycemia, can directly affect the immunometabolism of lymphocytes in part by affecting the activity of the mTOR protein kinase signaling pathway. High mTOR activity can enhance the progression of diabetes due to the activation of effector proinflammatory subpopulations of lymphocytes and, conversely, low activity promotes the differentiation of T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm. These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.


Subject(s)
COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Immunity, Cellular/drug effects , Metformin/therapeutic use , Severity of Illness Index , COVID-19/epidemiology , COVID-19/immunology , COVID-19/metabolism , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Diabetes Mellitus/metabolism , Humans , Hypoglycemic Agents/pharmacology , Immunity, Cellular/physiology , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/metabolism , Metformin/pharmacology , Mortality/trends , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/immunology , TOR Serine-Threonine Kinases/metabolism
6.
Front Immunol ; 12: 741061, 2021.
Article in English | MEDLINE | ID: covidwho-1506190

ABSTRACT

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, challenging both the medical and scientific community for the development of novel vaccines and a greater understanding of the effects of the SARS-CoV-2 virus. COVID-19 has been associated with a pronounced and out-of-control inflammatory response. Studies have sought to understand the effects of inflammatory response markers to prognosticate the disease. Herein, we aimed to review the evidence of 11 groups of systemic inflammatory markers for risk-stratifying patients and prognosticating outcomes related to COVID-19. Numerous studies have demonstrated the effectiveness of neutrophil to lymphocyte ratio (NLR) in prognosticating patient outcomes, including but not limited to severe disease, hospitalization, intensive care unit (ICU) admission, intubation, and death. A few markers outperformed NLR in predicting outcomes, including 1) systemic immune-inflammation index (SII), 2) prognostic nutritional index (PNI), 3) C-reactive protein (CRP) to albumin ratio (CAR) and high-sensitivity CAR (hsCAR), and 4) CRP to prealbumin ratio (CPAR) and high-sensitivity CPAR (hsCPAR). However, there are a limited number of studies comparing NLR with these markers, and such conclusions require larger validation studies. Overall, the evidence suggests that most of the studied markers are able to predict COVID-19 prognosis, however NLR seems to be the most robust marker.


Subject(s)
COVID-19/diagnosis , Inflammation/diagnosis , Lymphocytes/immunology , Neutrophils/immunology , SARS-CoV-2/physiology , Biomarkers , C-Reactive Protein/metabolism , Disease Progression , Humans , Prognosis , Severity of Illness Index
7.
Mol Syst Biol ; 17(10): e10387, 2021 10.
Article in English | MEDLINE | ID: covidwho-1478718

ABSTRACT

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.


Subject(s)
COVID-19/immunology , Computational Biology/methods , Databases, Factual , SARS-CoV-2/immunology , Software , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Computer Graphics , Cytokines/genetics , Cytokines/immunology , Data Mining/statistics & numerical data , Gene Expression Regulation , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Immunity, Innate/drug effects , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/virology , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/immunology , Myeloid Cells/drug effects , Myeloid Cells/immunology , Myeloid Cells/virology , Protein Interaction Mapping , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Signal Transduction , Transcription Factors/genetics , Transcription Factors/immunology , Viral Proteins/genetics , Viral Proteins/immunology
8.
Mol Med ; 27(1): 129, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1477255

ABSTRACT

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.


Subject(s)
COVID-19/diagnosis , Chemokine CXCL10/blood , Coronary Artery Disease/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/immunology , COVID-19/mortality , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/immunology , Coronary Artery Disease/mortality , Creatine/blood , Diabetes Mellitus/blood , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Female , Hospitalization , Humans , Hypertension/blood , Hypertension/immunology , Hypertension/mortality , Immunity, Humoral , Immunity, Innate , Inflammation , Intensive Care Units , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lymphocytes/immunology , Lymphocytes/pathology , Male , Middle Aged , Neutrophils/immunology , Neutrophils/pathology , Prognosis , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
9.
J Clin Immunol ; 41(8): 1709-1722, 2021 11.
Article in English | MEDLINE | ID: covidwho-1474048

ABSTRACT

BACKGROUND: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. METHODS: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. RESULTS: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. CONCLUSION: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunologic Deficiency Syndromes/immunology , SARS-CoV-2/immunology , Humans , Immunoglobulin G/blood , Immunologic Memory , Lymphocytes/immunology , Spike Glycoprotein, Coronavirus/immunology
10.
Dis Markers ; 2021: 2571912, 2021.
Article in English | MEDLINE | ID: covidwho-1463050

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is highly contagious and continues to spread rapidly. However, there are no simple and timely laboratory techniques to determine the severity of COVID-19. In this meta-analysis, we assessed the potential of the neutrophil-lymphocyte ratio (NLR) as an indicator of severe versus nonsevere COVID-19 cases. Methods: A search for studies on the NLR in severe and nonsevere COVID-19 cases published from January 1, 2020, to July 1, 2021, was conducted on the PubMed, EMBASE, and Cochrane Library databases. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) analyses were done on Stata 14.0 and Meta-disc 1.4 to assess the performance of the NLR. Results: Thirty studies, including 5570 patients, were analyzed. Of these, 1603 and 3967 patients had severe and nonsevere COVID-19, respectively. The overall sensitivity and specificity were 0.82 (95% confidence interval (CI), 0.77-0.87) and 0.77 (95% CI, 0.70-0.83), respectively; positive and negative correlation ratios were 3.6 (95% CI, 2.7-4.7) and 0.23 (95% CI, 0.17-0.30), respectively; DOR was 16 (95% CI, 10-24), and the AUC was 0.87 (95% CI, 0.84-0.90). Conclusion: The NLR could accurately determine the severity of COVID-19 and can be used to identify patients with severe disease to guide clinical decision-making.


Subject(s)
COVID-19/immunology , Lymphocytes/immunology , Neutrophils/immunology , SARS-CoV-2 , Area Under Curve , Biomarkers/blood , COVID-19/blood , Confidence Intervals , Humans , Leukocyte Count , Likelihood Functions , Odds Ratio , Sensitivity and Specificity , Severity of Illness Index
12.
Curr Top Microbiol Immunol ; 426: 21-43, 2020.
Article in English | MEDLINE | ID: covidwho-1451909

ABSTRACT

Pulmonary respiration inevitably exposes the mucosal surface of the lung to potentially noxious stimuli, including pathogens, allergens, and particulates, each of which can trigger pulmonary damage and inflammation. As inflammation resolves, B and T lymphocytes often aggregate around large bronchi to form inducible Bronchus-Associated Lymphoid Tissue (iBALT). iBALT formation can be initiated by a diverse array of molecular pathways that converge on the activation and differentiation of chemokine-expressing stromal cells that serve as the scaffolding for iBALT and facilitate the recruitment, retention, and organization of leukocytes. Like conventional lymphoid organs, iBALT recruits naïve lymphocytes from the blood, exposes them to local antigens, in this case from the airways, and supports their activation and differentiation into effector cells. The activity of iBALT is demonstrably beneficial for the clearance of respiratory pathogens; however, it is less clear whether it dampens or exacerbates inflammatory responses to non-infectious agents. Here, we review the evidence regarding the role of iBALT in pulmonary immunity and propose that the final outcome depends on the context of the disease.


Subject(s)
Bronchi/immunology , Immunity, Mucosal/immunology , Respiration/immunology , Humans , Lymphocytes/immunology
13.
PLoS One ; 16(10): e0254985, 2021.
Article in English | MEDLINE | ID: covidwho-1448572

ABSTRACT

BACKGROUND: The goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS). SUMMARY BACKGROUND DATA: No therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22. STUDY DESIGN: ARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4. RESULTS: In the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham. CONCLUSIONS: IL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.


Subject(s)
Immunoglobulin Fc Fragments/pharmacology , Interleukins/pharmacology , Lung Injury/drug therapy , Pneumonia/drug therapy , Respiratory Distress Syndrome/drug therapy , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Female , Lipopolysaccharides/toxicity , Lung Injury/pathology , Lymphocyte Count , Lymphocytes/immunology , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Neutrophils/immunology , Pneumonia/pathology , Receptors, Interleukin/metabolism , Recombinant Proteins/pharmacology , Respiratory Distress Syndrome/pathology , Respiratory Mucosa/pathology
14.
Signal Transduct Target Ther ; 6(1): 342, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415923

ABSTRACT

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16- natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.


Subject(s)
COVID-19 , Carrier State/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Transcriptome/immunology , Adolescent , Adult , COVID-19/genetics , COVID-19/immunology , Female , Humans , Male , Middle Aged , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/genetics
15.
Shock ; 56(3): 345-351, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1410907

ABSTRACT

ABSTRACT: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spread around the world and is currently affecting global public health. Clinical evidence indicates that the elevated number of peripheral neutrophils and higher ratio of neutrophils-to-lymphocytes are correlated with severe outcomes in COVID-19 patients, suggesting the possible immunopathological role of neutrophils during SARS-CoV-2 infection. As an abundant innate immune cell type, neutrophils are well known for their contributions to antimicrobial defense. However, their dysfunction is also associated with different inflammatory signatures during the pathogenesis of infection. Herein, in this mini-review, we summarize the recent progress on the potential role of neutrophils during COVID-19-associated inflammatory responses. In particular, we highlight the interactions between neutrophils and viruses as well as the relationship of neutrophils with cytokine storm and thrombosis in COVID-19 patients. Lastly, we discuss the importance of neutrophils as potential therapeutic targets for COVID-19.


Subject(s)
COVID-19/immunology , COVID-19/virology , Neutrophils/virology , SARS-CoV-2 , Animals , Cytokine Release Syndrome , Cytokines/immunology , Humans , Immune System , Immunity, Innate , Inflammation , Intercellular Adhesion Molecule-1/immunology , Lymphocytes/immunology , Mice , Neutrophils/metabolism , Pathogen-Associated Molecular Pattern Molecules/immunology , Thrombosis
16.
Front Immunol ; 12: 672523, 2021.
Article in English | MEDLINE | ID: covidwho-1389182

ABSTRACT

Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.


Subject(s)
COVID-19/immunology , Immunity, Mucosal/immunology , Lymphocytes/immunology , Pneumonia, Bacterial/immunology , Respiratory Mucosa/immunology , SARS-CoV-2/immunology , Bacteria/immunology , COVID-19/mortality , COVID-19/pathology , Immunity, Innate/immunology , Inflammation/immunology , Interleukin-17/metabolism , Interleukins/metabolism , Lung/immunology , Lymphocyte Activation/immunology , Respiratory Mucosa/cytology
17.
Clin Rev Allergy Immunol ; 60(2): 259-270, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1384600

ABSTRACT

Ultraviolet blood irradiation (UBI) was used with success in the 1930s and 1940s for a variety of diseases. Despite the success, the lack of understanding of the detailed mechanisms of actions, and the achievements of antibiotics, phased off the use of UBI from the 1950s. The emergence of novel viral infections, from HIV/AIDS to Ebola, from SARS and MERS, and SARS-CoV-2, bring back the attention to this therapeutical opportunity. UBI has a complex virucidal activity, mostly acting on the immune system response. It has effects on lymphocytes (T-cells and B-cells), macrophages, monocytes, dendritic cells, low-density lipoprotein (LDL), and lipids. The Knott technique was applied for bacterial infections such as tuberculosis to viral infections such as hepatitis or influenza. The more complex extracorporeal photopheresis (ECP) is also being applied to hematological cancers such as T-cell lymphomas. Further studies of UBI may help to create a useful device that may find applications for novel viruses that are resistant to known antivirals or vaccines, or also bacteria that are resistant to known antibiotics.


Subject(s)
COVID-19/therapy , Photopheresis/methods , SARS-CoV-2/radiation effects , Ultraviolet Rays , Bacteria/radiation effects , Bacterial Infections/microbiology , Bacterial Infections/therapy , COVID-19/virology , Cytokines/metabolism , Dendritic Cells/immunology , Dendritic Cells/radiation effects , Humans , Lymphocytes/immunology , Lymphocytes/radiation effects , Macrophages/immunology , Macrophages/radiation effects , Monocytes/immunology , Monocytes/radiation effects , Signal Transduction/immunology , Signal Transduction/radiation effects , Treatment Outcome
19.
Biomed Res Int ; 2021: 9987931, 2021.
Article in English | MEDLINE | ID: covidwho-1367496

ABSTRACT

Objective: Respiratory failure is the leading cause of mortality in COVID-19 patients, characterized by a generalized disbalance of inflammation. The aim of this study was to investigate the relationship between immune-inflammatory index and mortality in PSI IV-V patients with COVID-19. Methods: We retrospectively reviewed the medical records of COVID-19 patients from Feb. to Apr. 2020 in the Zhongfa Xincheng Branch of Tongji Hospital, Wuhan, China. Patients who presented high severity of COVID-19-related pneumonia were enrolled for further analysis according to the Pneumonia Severity Index (PSI) tool. Results: A total of 101 patients diagnosed with COVID-19 were identified at initial research. The survival analysis revealed that mortality of the PSI IV-V cohort was significantly higher than the PSI I-III group (p = 0.0003). The overall mortality in PSI IV-V patients was 32.1% (9/28). The fatal cases of the PSI IV-V group had a higher level of procalcitonin (p = 0.022) and neutrophil-to-lymphocyte ratio (p = 0.033) compared with the survivors. Procalcitonin was the most sensitive predictor of mortality for the severe COVID-19 population with area under receiver operating characteristic curve of 0.78, higher than the neutrophil-to-lymphocyte ratio (0.75) and total lymphocyte (0.68) and neutrophil (0.67) counts. Conclusion: Procalcitonin and neutrophil-to-lymphocyte ratio may potentially be effective predictors for mortality in PSI IV-V patients with COVID-19. Increased procalcitonin and neutrophil-to-lymphocyte ratio were associated with greater risk of mortality.


Subject(s)
COVID-19/immunology , COVID-19/physiopathology , Pandemics , SARS-CoV-2 , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/mortality , China/epidemiology , Cohort Studies , Female , Humans , Inflammation/immunology , Inflammation/physiopathology , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Procalcitonin/blood , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis
20.
J Med Virol ; 93(9): 5438-5445, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363683

ABSTRACT

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.


Subject(s)
COVID-19/blood , COVID-19/immunology , Pregnancy Trimesters/blood , SARS-CoV-2/pathogenicity , Selenium/blood , Adult , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/virology , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hematocrit , Hemoglobins/metabolism , Humans , Interleukin-6/blood , Lymphocytes/immunology , Lymphocytes/virology , Monocytes/immunology , Monocytes/virology , Neutrophils/immunology , Neutrophils/virology , Pregnancy , Pregnancy Trimesters/immunology , Severity of Illness Index
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