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1.
Front Immunol ; 13: 821595, 2022.
Article in English | MEDLINE | ID: covidwho-1686485

ABSTRACT

Heterologous immunity, when the memory T cell response elicited by one pathogen recognizes another pathogen, has been offered as a contributing factor for the high variability in coronavirus disease 2019 (COVID-19) severity outcomes. Here we demonstrate that sensitization with bacterial peptides can induce heterologous immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) derived peptides and that vaccination with the SARS-CoV-2 spike protein can induce heterologous immunity to bacterial peptides. Using in silico prediction methods, we identified 6 bacterial peptides with sequence homology to either the spike protein or non-structural protein 3 (NSP3) of SARS-CoV-2. Notwithstanding the effects of bystander activation, in vitro co-cultures showed that all individuals tested (n=18) developed heterologous immunity to SARS-CoV-2 peptides when sensitized with the identified bacterial peptides. T cell recall responses measured included cytokine production (IFN-γ, TNF, IL-2), activation (CD69) and proliferation (CellTrace). As an extension of the principle of heterologous immunity between bacterial pathogens and COVID-19, we tracked donor responses before and after SARS-CoV-2 vaccination and measured the cross-reactive T cell responses to bacterial peptides with similar sequence homology to the spike protein. We found that SARS-CoV-2 vaccination could induce heterologous immunity to bacterial peptides. These findings provide a mechanism for heterologous T cell immunity between common bacterial pathogens and SARS-CoV-2, which may explain the high variance in COVID-19 outcomes from asymptomatic to severe. We also demonstrate proof-of-concept that SARS-CoV-2 vaccination can induce heterologous immunity to pathogenic bacteria derived peptides.


Subject(s)
Bacterial Infections/immunology , COVID-19/immunology , Immunity, Heterologous/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , COVID-19 Vaccines/immunology , Cells, Cultured , Coculture Techniques , Female , Humans , Immunity, Cellular/immunology , Male , Spike Glycoprotein, Coronavirus/immunology
2.
Am J Physiol Regul Integr Comp Physiol ; 322(2): R99-R111, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1630162

ABSTRACT

A prominent health issue nowadays is the COVID-19 pandemic, which poses acute risks to human health. However, the long-term health consequences are largely unknown and cannot be neglected. An especially vulnerable period for infection is pregnancy, when infections could have long-term health effect on the child. Evidence suggests that maternal immune activation (MIA) induced by either bacteria or viruses presents various effects on the offspring, leading to adverse phenotypes in many organ systems. This review compares the mechanisms of bacterial and viral MIA and the possible long-term outcomes for the offspring by summarizing the outcome in animal LPS and Poly I:C models. Both models are activated immune responses mediated by Toll-like receptors. The outcomes for MIA offspring include neurodevelopment, immune response, circulation, metabolism, and reproduction. Some of these changes continue to exist until later life. Besides different doses and batches of LPS and Poly I:C, the injection day, administration route, and also different animal species influence the outcomes. Here, we specifically aim to support colleagues when choosing their animal models for future studies.


Subject(s)
COVID-19/complications , COVID-19/immunology , Lipopolysaccharides/toxicity , Poly I-C/toxicity , Prenatal Exposure Delayed Effects/immunology , SARS-CoV-2 , Bacterial Infections/immunology , Female , Humans , Pregnancy
3.
Cells ; 11(2)2022 01 07.
Article in English | MEDLINE | ID: covidwho-1615837

ABSTRACT

Oxidized cholesterols, the so-called oxysterols, are widely known to regulate cholesterol homeostasis. However, more recently oxysterols have emerged as important lipid mediators in the response to both bacterial and viral infections. This review summarizes our current knowledge of selected oxysterols and their receptors in the control of intracellular bacterial growth as well as viral entry into the host cell and viral replication. Lastly, we briefly discuss the potential of oxysterols and their receptors as drug targets for infectious and inflammatory diseases.


Subject(s)
Bacterial Infections/immunology , Oxysterols/immunology , Virus Diseases/immunology , Animals , Humans
4.
Front Immunol ; 12: 792448, 2021.
Article in English | MEDLINE | ID: covidwho-1581318

ABSTRACT

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis via enzyme-linked immunospot assay. We found that circulating inflammatory markers were significantly higher early after bacterial sepsis compared with SARS-CoV-2. Both cohorts exhibited profound immune suppression through 21 days (suppressed HLA-DR expression, reduced mononuclear cell IFN-gamma production), and expanded numbers of myeloid-derived suppressor cells (MDSCs). In addition, MDSC expansion and ex vivo production of IFN-gamma and TNF-alpha were resolving over time in bacterial sepsis, whereas in SARS-CoV-2, immunosuppression and inflammation were accelerating. Despite less severe initial physiologic derangement, SARS-CoV-2 patients had similar incidence of secondary infections (23% vs 30%) as bacterial sepsis patients. Finally, COVID patients who developed secondary bacterial infections exhibited profound immunosuppression evident by elevated sPD-L1 and depressed HLA-DR. Although both bacterial sepsis and SARS-CoV-2 are associated with inflammation and immune suppression, their immune dyscrasia temporal patterns and clinical outcomes are different. SARS-CoV-2 patients had less severe early inflammation and organ dysfunction but had persistent inflammation and immunosuppression and suffered worse clinical outcomes, especially when SARS-CoV-2 infection was followed by secondary bacterial infection.


Subject(s)
Bacterial Infections/immunology , COVID-19/immunology , Immune Tolerance/immunology , Sepsis/immunology , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2
5.
Am J Physiol Regul Integr Comp Physiol ; 322(2): R99-R111, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1555140

ABSTRACT

A prominent health issue nowadays is the COVID-19 pandemic, which poses acute risks to human health. However, the long-term health consequences are largely unknown and cannot be neglected. An especially vulnerable period for infection is pregnancy, when infections could have long-term health effect on the child. Evidence suggests that maternal immune activation (MIA) induced by either bacteria or viruses presents various effects on the offspring, leading to adverse phenotypes in many organ systems. This review compares the mechanisms of bacterial and viral MIA and the possible long-term outcomes for the offspring by summarizing the outcome in animal LPS and Poly I:C models. Both models are activated immune responses mediated by Toll-like receptors. The outcomes for MIA offspring include neurodevelopment, immune response, circulation, metabolism, and reproduction. Some of these changes continue to exist until later life. Besides different doses and batches of LPS and Poly I:C, the injection day, administration route, and also different animal species influence the outcomes. Here, we specifically aim to support colleagues when choosing their animal models for future studies.


Subject(s)
COVID-19/complications , COVID-19/immunology , Lipopolysaccharides/toxicity , Poly I-C/toxicity , Prenatal Exposure Delayed Effects/immunology , SARS-CoV-2 , Bacterial Infections/immunology , Female , Humans , Pregnancy
6.
JCI Insight ; 7(1)2022 01 11.
Article in English | MEDLINE | ID: covidwho-1523122

ABSTRACT

Neutrophils are recognized as important circulating effector cells in the pathophysiology of severe coronavirus disease 2019 (COVID-19). However, their role within the inflamed lungs is incompletely understood. Here, we collected bronchoalveolar lavage (BAL) fluids and parallel blood samples of critically ill COVID-19 patients requiring invasive mechanical ventilation and compared BAL fluid parameters with those of mechanically ventilated patients with influenza, as a non-COVID-19 viral pneumonia cohort. Compared with those of patients with influenza, BAL fluids of patients with COVID-19 contained increased numbers of hyperactivated degranulating neutrophils and elevated concentrations of the cytokines IL-1ß, IL-1RA, IL-17A, TNF-α, and G-CSF; the chemokines CCL7, CXCL1, CXCL8, CXCL11, and CXCL12α; and the protease inhibitors elafin, secretory leukocyte protease inhibitor, and tissue inhibitor of metalloproteinases 1. In contrast, α-1 antitrypsin levels and net proteolytic activity were comparable in COVID-19 and influenza BAL fluids. During antibiotic treatment for bacterial coinfections, increased BAL fluid levels of several activating and chemotactic factors for monocytes, lymphocytes, and NK cells were detected in patients with COVID-19 whereas concentrations tended to decrease in patients with influenza, highlighting the persistent immunological response to coinfections in COVID-19. Finally, the high proteolytic activity in COVID-19 lungs suggests considering protease inhibitors as a treatment option.


Subject(s)
Bacterial Infections , Bronchoalveolar Lavage Fluid , COVID-19 , Coinfection , Influenza, Human , Adult , Aged , Bacterial Infections/complications , Bacterial Infections/immunology , Bacterial Infections/metabolism , Bacterial Infections/pathology , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , COVID-19/complications , COVID-19/diagnosis , COVID-19/immunology , COVID-19/pathology , Coinfection/immunology , Coinfection/metabolism , Coinfection/pathology , Cytokines/analysis , Female , Humans , Inflammation , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/immunology , Influenza, Human/pathology , Lung/immunology , Lung/metabolism , Lung/pathology , Male , Middle Aged
7.
Int Immunopharmacol ; 102: 108384, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1521088

ABSTRACT

Tocilizumab decreases inflammatory response in the cytokine storm which is one of the mechanisms behind the development of ARDS in COVID-19 patients. The objective of our study was to determine response of tocilizumab in patients suffering from COVID-19 by analyzing clinical parameters and inflammatory markers. A single-arm observational retrospective study was conducted from March 15, 2020 to March 15, 2021. Clinical outcomes in terms of mortality, weaning from mechanical ventilator, improvement in laboratory parameters including inflammatory cytokines, and length of hospital stay were documented. Reduction in values of inflammatory markers, and patients discharged home in stable condition were defined as an improvement after tocilizumab administration. A total of 514 patients received tocilizumab, majority of whom were critically sick 333 (64.8%). Out of the total sample 363 (70.6%) patients were discharged home in stable condition. Overall mean length of stay was 11.50 ± 8.4 days. There was significant difference in length of stay of patients who required invasive mechanical ventilation as compared to those who were kept only on supplemental oxygen (p < 0.05). Patients who were discharged home showed significant improvement in inflammatory markers and neutrophil to lymphocyte ratio as compared to those who expired (p < 0.05). A total of 21 (4.1%) patients had positive blood culture while 57 (11.1%) had positive culture of tracheal aspirate. Hence, tocilizumab is found to be a reasonable therapeutic option for worsening COVID-19 pneumonia by decreasing the need for mechanical ventilation. However, it is associated with adverse events including bacterial and fungal infections.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Bacterial Infections/epidemiology , COVID-19/drug therapy , COVID-19/therapy , Mycoses/epidemiology , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Bacterial Infections/chemically induced , Bacterial Infections/immunology , Critical Illness/therapy , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Mycoses/chemically induced , Mycoses/immunology , Pakistan/epidemiology , Patient Discharge/statistics & numerical data , Respiration, Artificial/instrumentation , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
8.
Toxins (Basel) ; 12(4)2020 04 02.
Article in English | MEDLINE | ID: covidwho-1453289

ABSTRACT

Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na+ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.


Subject(s)
Bacteria/pathogenicity , Bacterial Infections/microbiology , Bacterial Toxins/metabolism , Lung/microbiology , Respiratory Tract Infections/microbiology , Adaptive Immunity , Animals , Bacteria/immunology , Bacteria/metabolism , Bacterial Infections/immunology , Bacterial Infections/metabolism , Bacterial Infections/pathology , Disease Progression , Host-Pathogen Interactions , Humans , Immunity, Innate , Lung/immunology , Lung/metabolism , Lung/pathology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/pathology , Signal Transduction
9.
Int J Mol Sci ; 22(20)2021 Oct 16.
Article in English | MEDLINE | ID: covidwho-1480793

ABSTRACT

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.


Subject(s)
Antimicrobial Cationic Peptides/immunology , Antimicrobial Cationic Peptides/pharmacology , Bacteria/drug effects , Bacteria/immunology , Bacterial Infections/drug therapy , Bacterial Infections/immunology , Immunomodulation , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Bacterial Infections/microbiology , Drug Resistance, Bacterial , Host Microbial Interactions , Humans , /pharmacology
10.
Biochem Soc Trans ; 49(5): 2411-2429, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1397910

ABSTRACT

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.


Subject(s)
Anti-Bacterial Agents/immunology , Bacteria/immunology , Bacterial Infections/immunology , Carbohydrates/immunology , Glycoconjugates/immunology , Vaccines, Synthetic/immunology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carbohydrate Sequence , Carbohydrates/chemistry , Glycoconjugates/chemistry , Glycoconjugates/therapeutic use , Humans , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/therapeutic use
11.
Front Immunol ; 12: 696003, 2021.
Article in English | MEDLINE | ID: covidwho-1299397

ABSTRACT

Antiviral, antibacterial, and antiparasitic drugs and vaccines are essential to maintaining the health of humans and animals. Yet, their production can be slow and expensive, and efficacy lost once pathogens mount resistance. Chicken immunoglobulin Y (IgY) is a highly conserved homolog of human immunoglobulin G (IgG) that has shown benefits and a favorable safety profile, primarily in animal models of human infectious diseases. IgY is fast-acting, easy to produce, and low cost. IgY antibodies can readily be generated in large quantities with minimal environmental harm or infrastructure investment by using egg-laying hens. We summarize a variety of IgY uses, focusing on their potential for the detection, prevention, and treatment of human and animal infections.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Bacterial Infections/drug therapy , Chickens/immunology , Immunoassay , Immunoglobulins/therapeutic use , Parasitic Diseases/drug therapy , Virus Diseases/drug therapy , Animals , Antibodies, Bacterial/biosynthesis , Antibodies, Bacterial/immunology , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/immunology , Antibodies, Protozoan/biosynthesis , Antibodies, Protozoan/immunology , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , Antibody Formation , Antibody Specificity , Bacterial Infections/diagnosis , Bacterial Infections/immunology , Bacterial Infections/virology , Humans , Immunoglobulins/biosynthesis , Immunoglobulins/immunology , Parasitic Diseases/diagnosis , Parasitic Diseases/immunology , Parasitic Diseases/virology , Predictive Value of Tests , Virus Diseases/diagnosis , Virus Diseases/immunology , Virus Diseases/virology
12.
Cells ; 10(5)2021 05 04.
Article in English | MEDLINE | ID: covidwho-1223958

ABSTRACT

Sphingolipids are important structural membrane components and, together with cholesterol, are often organized in lipid rafts, where they act as signaling molecules in many cellular functions. They play crucial roles in regulating pathobiological processes, such as cancer, inflammation, and infectious diseases. The bioactive metabolites ceramide, sphingosine-1-phosphate, and sphingosine have been shown to be involved in the pathogenesis of several microbes. In contrast to ceramide, which often promotes bacterial and viral infections (for instance, by mediating adhesion and internalization), sphingosine, which is released from ceramide by the activity of ceramidases, kills many bacterial, viral, and fungal pathogens. In particular, sphingosine is an important natural component of the defense against bacterial pathogens in the respiratory tract. Pathologically reduced sphingosine levels in cystic fibrosis airway epithelial cells are normalized by inhalation of sphingosine, and coating plastic implants with sphingosine prevents bacterial infections. Pretreatment of cells with exogenous sphingosine also prevents the viral spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from interacting with host cell receptors and inhibits the propagation of herpes simplex virus type 1 (HSV-1) in macrophages. Recent examinations reveal that the bactericidal effect of sphingosine might be due to bacterial membrane permeabilization and the subsequent death of the bacteria.


Subject(s)
Bacterial Infections/immunology , Mycoses/immunology , Signal Transduction/immunology , Sphingosine/metabolism , Virus Diseases/immunology , Animals , Bacterial Infections/drug therapy , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Cell Wall/drug effects , Ceramides/metabolism , Disease Models, Animal , Herpesvirus 1, Human/immunology , Humans , Lysophospholipids/metabolism , Membrane Microdomains/immunology , Membrane Microdomains/metabolism , Mycoses/drug therapy , Mycoses/metabolism , Mycoses/microbiology , SARS-CoV-2/immunology , Sphingolipids/metabolism , Sphingosine/analogs & derivatives , Sphingosine/pharmacology , Sphingosine/therapeutic use , Virus Diseases/drug therapy , Virus Diseases/metabolism , Virus Diseases/virology
13.
Front Immunol ; 12: 634181, 2021.
Article in English | MEDLINE | ID: covidwho-1177976

ABSTRACT

Bacterial respiratory tract infections are the hallmark of primary antibody deficiencies (PADs). Because they are also among the most common infections in healthy individuals, PADs are usually overlooked in these patients. Careful evaluation of the history, including frequency, chronicity, and presence of other infections, would help suspect PADs. This review will focus on infections in relatively common PADs, discussing diagnostic challenges, and some management strategies to prevent infections.


Subject(s)
Bacterial Infections/immunology , Immunocompromised Host , Immunoglobulins/deficiency , Primary Immunodeficiency Diseases/immunology , Respiratory Tract Infections/immunology , Agammaglobulinemia/blood , Agammaglobulinemia/immunology , Agammaglobulinemia/therapy , Animals , Bacterial Infections/blood , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Class I Phosphatidylinositol 3-Kinases/blood , Class I Phosphatidylinositol 3-Kinases/immunology , Common Variable Immunodeficiency/blood , Common Variable Immunodeficiency/immunology , Common Variable Immunodeficiency/therapy , Humans , Immunoglobulins/blood , Primary Immunodeficiency Diseases/blood , Primary Immunodeficiency Diseases/therapy , Prognosis , Respiratory Tract Infections/blood , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/prevention & control , Risk Assessment , Risk Factors
14.
Mol Immunol ; 130: 154-158, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065484

ABSTRACT

Mucosal associated invariant T (MAIT) cells have a recognised innate-like capacity for antibacterial host defence, consequent on the specificity of their T cell receptor (TCR) for small molecule metabolites produced by a range of prokaryotic and fungal species, their effector memory phenotype, and their expression of cytotoxic molecules. However, recent studies have identified at least two other important functions of MAIT cells in antiviral immunity and in tissue homeostasis and repair. Each are related to distinct transcriptional programmes, which are activated differentially according to the specific immune context. Here we discuss these diverse functions, we review the evidence for the newly identified role of MAIT cells in promoting tissue repair, and we discuss emerging data pointing to the future directions of MAIT cell research including roles in cancer, in antiviral immunity and recent studies in the immune response to SARS-CoV-2 infection. Overall these studies have made us aware of the potential for pleiotropic roles of MAIT cells and related cell populations in micee and humans, and have created a simple and attractive new paradigm for regulation in barrier tissues, where antigen and tissue damage are sensed, integrated and interpreted.


Subject(s)
Mucosal-Associated Invariant T Cells/immunology , Animals , Bacterial Infections/immunology , Homeostasis , Humans , Mucosal-Associated Invariant T Cells/cytology , Mucosal-Associated Invariant T Cells/metabolism , Neoplasms/immunology , Receptors, Antigen, T-Cell , Virus Diseases/immunology
15.
Cytometry A ; 99(5): 435-445, 2021 05.
Article in English | MEDLINE | ID: covidwho-1046850

ABSTRACT

The identification of a bacterial, viral, or even noninfectious cause is essential in the management of febrile syndrome in the emergency department (ED), especially in epidemic contexts such as flu or CoVID-19. The aim was to assess discriminative performances of two biomarkers, CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), using a new flow cytometry procedure, in patients presenting with fever to the ED during epidemics. Eighty five adult patients presenting with potential infection were included during the 2019 flu season in the ED of La Timone Hospital. They were divided into four diagnostic outcomes according to their clinical records: no-infection, bacterial infection, viral infection and co-infection. Seventy six patients with confirmed SARS-CoV-2 infection were also compared to 48 healthy volunteers. For the first cohort, 38 (45%) patients were diagnosed with bacterial infections, 11 (13%) with viral infections and 29 (34%) with co-infections. mCD169 was elevated in patients with viral infections, with a majority of Flu A virus or Respiratory Syncytial Virus, while nCD64 was elevated in subjects with bacterial infections, with a majority of Streptococcus pneumoniae and Escherichia coli. nCD64 and mCD169 showed 90% and 80% sensitivity, and 78% and 91% specificity, respectively, for identifying patients with bacterial or viral infections. When studied in a second cohort, mCD169 was elevated in 95% of patients with SARS-CoV-2 infections and remained at normal level in 100% of healthy volunteers. nCD64 and mCD169 have potential for accurately distinguishing bacterial and acute viral infections. Combined in an easy and rapid flow cytometry procedure, they constitute a potential improvement for infection management in the ED, and could even help for triage of patients during emerging epidemics.


Subject(s)
Bacterial Infections/diagnosis , COVID-19/diagnosis , Emergency Service, Hospital , Flow Cytometry , Monocytes/immunology , Receptors, IgG/blood , Sialic Acid Binding Ig-like Lectin 1/blood , Adult , Aged , Bacterial Infections/blood , Bacterial Infections/immunology , Bacterial Infections/microbiology , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Diagnosis, Differential , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Monocytes/microbiology , Monocytes/virology , Predictive Value of Tests , Prospective Studies , Reproducibility of Results
16.
Front Immunol ; 11: 598404, 2020.
Article in English | MEDLINE | ID: covidwho-983710

ABSTRACT

Background: Bacterial sepsis has been used as a prototype to understand the pathogenesis of severe coronavirus disease 2019 (COVID-19). In addition, some management programs for critically ill COVID-19 patients are also based on experience with bacterial sepsis. However, some differences may exist between these two types of sepsis. Methods: This retrospective study investigated whether there are differences in the immune system status of these two types of sepsis. A total of 64 bacterial sepsis patients and 43 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sepsis were included in this study. Demographic data were obtained from medical records. Laboratory results within 24 h after the diagnosis of sepsis were provided by the clinical laboratory. Results: The results of blood routine (neutrophil, lymphocyte, and monocyte counts), infection biomarkers (C-reactive protein, ferritin, and procalcitonin levels), lymphocyte subset counts (total T lymphocyte, CD4+ T cell, CD8+ T cell, B cell, and NK cell counts), and lymphocyte subset functions (the proportions of PMA/ionomycin-stimulated IFN-γ positive cells in CD4+, CD8+ T cells, and NK cells) were similar in bacterial sepsis patients and SARS-CoV-2 sepsis patients. Cytokine storm was milder, and immunoglobulin and complement protein levels were higher in SARS-CoV-2 sepsis patients. Conclusions: There are both similarities and differences in the immune system status of bacterial sepsis and SARS-CoV-2 sepsis. Our findings do not support blocking the cytokine storm or supplementing immunoglobulins in SARS-CoV-2 sepsis, at least in the early stages of the disease. Treatments for overactivation of the complement system and lymphocyte depletion may be worth exploring further.


Subject(s)
Bacterial Infections , COVID-19 , Cytokine Release Syndrome , Lymphocyte Subsets , SARS-CoV-2 , Sepsis , Adult , Aged , Bacterial Infections/blood , Bacterial Infections/immunology , COVID-19/blood , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Female , Humans , Lymphocyte Count , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Sepsis/blood , Sepsis/immunology
17.
J Infect Public Health ; 13(10): 1397-1404, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-888663

ABSTRACT

Secondary bacterial infections are commonly associated with prior or concomitant respiratory viral infections. Viral infections damage respiratory airways and simultaneously defects both innate and acquired immune response that provides a favorable environment for bacterial growth, adherence, and facilitates invasion into healthy sites of the respiratory tract. Understanding the molecular mechanism of viral-induced secondary bacterial infections will provide us a chance to develop novel and effective therapeutic approaches for disease prevention. The present study describes details about the secondary bacterial infection during viral infections and their immunological changes.The outcome of discussion avails an opportunity to understand possible secondary bacterial infections associated with novel SARS-CoV-2, presently causing pandemic outbreak COVID-19.


Subject(s)
Bacterial Infections/immunology , Bacterial Infections/virology , Coronavirus Infections/immunology , Influenza, Human/immunology , Pneumonia, Viral/immunology , Adaptive Immunity , Bacteria/growth & development , Bacterial Adhesion , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Humans , Immune Tolerance , Immunity, Innate , Inflammation/complications , Influenza, Human/complications , Microbial Interactions , Pandemics , Patient Acuity , Pneumonia, Viral/complications , SARS-CoV-2
19.
Exp Cell Res ; 396(1): 112276, 2020 11 01.
Article in English | MEDLINE | ID: covidwho-752714

ABSTRACT

Autophagy is an evolutionary conserved catabolic process devoted to the removal of unnecessary and harmful cellular components. In its general form, autophagy governs cellular lifecycle through the formation of double membrane vesicles, termed autophagosomes, that enwrap and deliver unwanted intracellular components to lysosomes. In addition to this omniscient role, forms of selective autophagy, relying on specialized receptors for cargo recognition, exert fine-tuned control over cellular homeostasis. In this regard, xenophagy plays a pivotal role in restricting the replication of intracellular pathogens, thus acting as an ancient innate defense system against infections. Recently, selective autophagy of the endoplasmic reticulum (ER), more simply ER-phagy, has been uncovered as a critical mechanism governing ER network shape and function. Six ER-resident proteins have been characterized as ER-phagy receptors and their orchestrated function enables ER homeostasis and turnover overtime. Unfortunately, ER is also the preferred site for viral replication and several viruses hijack ER machinery for their needs. Thus, it is not surprising that some ER-phagy receptors can act to counteract viral replication and minimize the spread of infection throughout the organism. On the other hand, evolutionary pressure has armed pathogens with strategies to evade and subvert xenophagy and ER-phagy. Although ER-phagy biology is still in its infancy, the present review aims to summarize recent ER-phagy literature, with a special focus on its role in counteracting viral infections. Moreover, we aim to offer some hints for future targeted approaches to counteract host-pathogen interactions by modulating xenophagy and ER-phagy pathways.


Subject(s)
Autophagosomes/immunology , Bacterial Infections/immunology , Endoplasmic Reticulum/immunology , Host-Pathogen Interactions/immunology , Macroautophagy/immunology , Virus Diseases/immunology , Autophagosomes/metabolism , Bacteria/immunology , Bacterial Infections/genetics , Bacterial Infections/microbiology , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/microbiology , Endoplasmic Reticulum/virology , Endoplasmic Reticulum Stress/genetics , Endoplasmic Reticulum Stress/immunology , Homeostasis/genetics , Homeostasis/immunology , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate , Lysosomes/immunology , Lysosomes/metabolism , Macroautophagy/genetics , Virus Diseases/genetics , Virus Diseases/virology , Viruses/immunology
20.
Cell Rep Med ; 1(2): 100019, 2020 05 19.
Article in English | MEDLINE | ID: covidwho-741543

ABSTRACT

People with Down syndrome show signs of chronic immune dysregulation, including a higher prevalence of autoimmune disorders, increased rates of hospitalization during respiratory viral infections, and higher mortality rates from pneumonia and sepsis. At the molecular and cellular levels, they show markers of chronic autoinflammation, including interferon hyperactivity, elevated levels of many inflammatory cytokines and chemokines, and changes in diverse immune cell types reminiscent of inflammatory conditions observed in the general population. However, the impact of this immune dysregulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and CoV disease of 2019 (COVID-19) remains unknown. This Perspective outlines why individuals with Down syndrome should be considered an at-risk population for severe COVID-19. Specifically, the immune dysregulation caused by trisomy 21 may result in an exacerbated cytokine release syndrome relative to that observed in the euploid population, thus justifying additional monitoring and specialized care for this vulnerable population.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Down Syndrome/immunology , Bacterial Infections/immunology , Coinfection , Cytokines/immunology , Cytokines/metabolism , Humans , Inflammation , Interferons/immunology , Interferons/metabolism , SARS-CoV-2
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