Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 621
Filter
1.
Front Immunol ; 13: 1032331, 2022.
Article in English | MEDLINE | ID: covidwho-2154734

ABSTRACT

The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.


Subject(s)
COVID-19 , Complement Factor H , Humans , SARS-CoV-2 , Complement Activation , Immunologic Factors
3.
Proc Natl Acad Sci U S A ; 119(47): e2213361119, 2022 11 22.
Article in English | MEDLINE | ID: covidwho-2096949

ABSTRACT

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.


Subject(s)
COVID-19 , Thrombocytopenia , Humans , Male , Female , Platelet Factor 4 , Heparin , Antibodies , Immunologic Factors , Severity of Illness Index
4.
Discov Med ; 34(172): 83-95, 2022.
Article in English | MEDLINE | ID: covidwho-2083709

ABSTRACT

Sepsis is a life-threatening organ dysfunction caused by the maladjustment of the body's response to infection. Abnormal immune response plays an important role in the progression of sepsis, and immunomodulatory therapy is a promising therapeutic strategy for sepsis. Great efforts have been made recently to elucidate the mechanism by which immune dysfunction contributes to sepsis, and identify potential biomarkers and targets for the diagnosis and therapy of sepsis induced by emerging pathogens, especially for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)that causes COVID-19. In this review, we summarize recent progress on the understanding of immune dysregulation involved in sepsis, and highlight potential biomarkers and targets to evaluate immune status of the patients with sepsis for individualized and precise immunotherapy.


Subject(s)
COVID-19 , Sepsis , Humans , SARS-CoV-2 , COVID-19/therapy , Sepsis/therapy , Sepsis/diagnosis , Immunologic Factors , Immunotherapy , Biomarkers
5.
Clin Lab ; 68(10)2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-2080866

ABSTRACT

BACKGROUND: In this retrospective study, we aimed to compare the laboratory and clinical results of cytokine hem-adsorption as an immunomodulation therapy in COVID-19 ICU patients with or without sepsis. METHODS: The levels of PCT, CRP, and ferritin were determined as indicators of infection/sepsis; the levels of in-terleukins (IL-6, IL-8 and IL-10, and TNF-α) were determined as indicators of cytokine storm were compared. APACHE score, SOFA score, and mortality rates were compared for the progression of the disease in 23 COVID-19 patients. RESULTS: The therapy was generally successful in reducing the levels of IL-6, IL-8, IL-10, and TNF-α but the levels measured after the procedure did not differ among the patients with or without sepsis, suggesting that the presence of sepsis did not affect the efficacy and function of the cytokine hemadsorption procedure in COVID-19 patients. All parameters were reduced after the procedure except the levels of PCT and ferritin and mortality rates of patients diagnosed with sepsis. The level of PCT was significantly higher in these patients compared with the patients without sepsis while the ferritin and mortality did not show any significant difference between the two groups, suggesting that the cytokine hemadsorption may be safe in the treatment of critical COVID-19 patients. CONCLUSIONS: As a result, the progression of sepsis in COVID-19 may be avoided with cytokine hemadsorption applied as an immunomodulator therapy. However, this therapy should be further explored and validated prior to its introduction to everyday clinical practice when the epidemic conditions end.


Subject(s)
COVID-19 , Sepsis , Cytokines , Ferritins , Hemadsorption , Humans , Immunologic Factors/therapeutic use , Interleukin-10 , Interleukin-6 , Interleukin-8 , Prognosis , ROC Curve , Retrospective Studies , Sepsis/diagnosis , Sepsis/drug therapy , Tumor Necrosis Factor-alpha
6.
Front Immunol ; 13: 967737, 2022.
Article in English | MEDLINE | ID: covidwho-2080146

ABSTRACT

Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e. CD14 and CD16. We deeply dissected the heterogeneity of human circulating monocytes in healthy donors by transcriptomic analysis at single-cell level and identified 9 distinct monocyte populations characterized each by a profile suggestive of specialized functions. The classical monocyte subset in fact included five distinct populations, each enriched for transcriptomic gene sets related to either inflammatory, neutrophil-like, interferon-related, and platelet-related pathways. Non-classical monocytes included two distinct populations, one of which marked specifically by elevated expression levels of complement components. Intermediate monocytes were not further divided in our analysis and were characterized by high levels of human leukocyte antigen (HLA) genes. Finally, we identified one cluster included in both classical and non-classical monocytes, characterized by a strong cytotoxic signature. These findings provided the rationale to exploit the relevance of newly identified monocyte populations in disease evolution. A machine learning approach was developed and applied to two single-cell transcriptome public datasets, from gastrointestinal cancer and Coronavirus disease 2019 (COVID-19) patients. The dissection of these datasets through our classification revealed that patients with advanced cancers showed a selective increase in monocytes enriched in platelet-related pathways. Of note, the signature associated with this population correlated with worse prognosis in gastric cancer patients. Conversely, after immunotherapy, the most activated population was composed of interferon-related monocytes, consistent with an upregulation in interferon-related genes in responder patients compared to non-responders. In COVID-19 patients we confirmed a global activated phenotype of the entire monocyte compartment, but our classification revealed that only cytotoxic monocytes are expanded during the disease progression. Collectively, this study unravels an unexpected complexity among human circulating monocytes and highlights the existence of specialized populations differently engaged depending on the pathological context.


Subject(s)
COVID-19 , Gastrointestinal Neoplasms , Humans , Monocytes , Immunologic Factors/metabolism , Interferons/metabolism , HLA Antigens/metabolism
7.
Rinsho Ketsueki ; 63(9): 1233-1241, 2022.
Article in Japanese | MEDLINE | ID: covidwho-2056364

ABSTRACT

The levels of anti-platelet factor 4 (PF4) antibodies, also known as anti-PF4 or heparin complex antibodies, are used to diagnose heparin-induced thrombocytopenia (HIT). In HIT, anti-PF4 antibodies induced by heparin exposure cause thrombocytopenia and thrombosis. However, anti-PF4 antibodies were recently reported to be associated with the development of fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination for coronavirus disease 2019. HIT and VITT are caused by anti-PF4 antibodies and have similar pathological conditions. However, the severity of these conditions differs and the detection sensitivity of their antibodies varies depending on the assays used. Herein, we review HIT and VITT associated with anti-PF4 antibodies.


Subject(s)
COVID-19 , Heparin , Platelet Factor 4 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Antibodies , Anticoagulants/adverse effects , COVID-19/prevention & control , Heparin/adverse effects , Humans , Immunologic Factors , Purpura, Thrombocytopenic, Idiopathic/complications , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/etiology , Thrombosis/pathology , Vaccines/adverse effects
8.
J Thromb Haemost ; 20(12): 2896-2908, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2052857

ABSTRACT

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology. OBJECTIVES: To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset. PATIENTS/METHODS: Asserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78-179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate; n = 476), and rapid immunological chemiluminescence anti-PF4 assay (n = 460), in a multicenter study. RESULTS: For first episode presentations, 190/1284 (14.8%) ELISA tests were positive. Conversely, most (445/460; 96.7%) chemiluminescence anti-PF4 test results were negative. All functional assays showed associations of higher median ELISA optical density with functional positivity and with high rates of ELISA positivity (64.0% to 85.2%). Data also identified functional positivity in 14.8%-36.0% of ELISA negative samples, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases. CONCLUSION: To our knowledge, this is the largest multicenter evaluation of anti-PF4 testing for investigation of VITT. Discrepancies in test results (ELISA vs. ELISA or ELISA vs. functional assay) in some patients highlighted limitations in relying on single methods (ELISA and functional) for PF4 antibody detection in VITT, and also highlights the variability in phenotypic test presentation and pathomechanism of VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Humans , Platelet Factor 4 , Heparin/adverse effects , Australia , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/diagnosis , Immunologic Factors/adverse effects , Immunoglobulin G
9.
Int Immunopharmacol ; 111: 109161, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2049345

ABSTRACT

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19.


Subject(s)
COVID-19 , Vaccines , Antiviral Agents/therapeutic use , COVID-19/therapy , Genetic Therapy , Humans , Immunologic Factors , Immunotherapy , SARS-CoV-2
10.
Cells ; 11(19)2022 Sep 21.
Article in English | MEDLINE | ID: covidwho-2043596

ABSTRACT

The coronavirus disease 2019 (COVID-19) is accompanied by a cytokine storm with the release of many proinflammatory factors and development of respiratory syndrome. Several SARS-CoV-2 lineages have been identified, and the Delta variant (B.1.617), linked with high mortality risk, has become dominant in many countries. Understanding the immune responses associated with COVID-19 lineages may therefore aid the development of therapeutic and diagnostic strategies. Multiple single-cell gene expression studies revealed innate and adaptive immunological factors and pathways correlated with COVID-19 severity. Additional investigations covering host-pathogen response characteristics for infection caused by different lineages are required. Here, we performed single-cell transcriptome profiling of blood mononuclear cells from the individuals with different severity of the COVID-19 and virus lineages to uncover variant specific molecular factors associated with immunity. We identified significant changes in lymphoid and myeloid cells. Our study highlights that an abundant population of monocytes with specific gene expression signatures accompanies Delta lineage of SARS-CoV-2 and contributes to COVID-19 pathogenesis inferring immune components for targeted therapy.


Subject(s)
COVID-19 , COVID-19/genetics , Gene Expression , Humans , Immunologic Factors , SARS-CoV-2
11.
Clin Lab ; 68(9)2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-2040370

ABSTRACT

BACKGROUND: Proper identification of patients at risk of developing serious disease in the context of SARS-CoV-2 infection, as well as the initiation of early treatment, is one of the fundamental elements for successful management of COVID-19. The main objective of this study was to evaluate the usefulness of serum biomarkers (neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6) to predict the early response to immunosuppressant therapy in COVID-19 patients. METHODS: This is a case-control study nested in a retrospective cohort, which included hospitalized patients with interstitial pneumonia and with elevation of some proinflammatory parameters. Each of the individuals who died during the 28-day follow-up was defined as a case. For each case, 4 controls were selected, matched by age, gender, and comorbidities. RESULTS: The initial cohort included 856 patients. The incidence of therapeutic failure in the cohort was 14%, thus we identified a total of 120 cases. After the application of a Cox regression model, high serum concentrations of LDH (> 451 IU/L), ferritin (> 1,014 ng/mL) and D-Dimer (> 1,300 ng/mL) were identified as predictors of poor response to treatment. Highly-specific cut-off points could not be established for any of these biomarkers. CONCLUSIONS: Some inflammatory biomarkers, such as LDH, ferritin, and D-dimer, may be helpful in identifying patients for whom an early immunomodulatory therapeutic intervention should be considered in the treatment of COVID-19 patients with pneumonia.


Subject(s)
COVID-19 , Biomarkers , C-Reactive Protein/analysis , COVID-19/drug therapy , Case-Control Studies , Ferritins , Humans , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Interleukin-6 , L-Lactate Dehydrogenase , Retrospective Studies , SARS-CoV-2
12.
Front Immunol ; 13: 903419, 2022.
Article in English | MEDLINE | ID: covidwho-2022702

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been a pandemic for the past two years. Predicting patient prognosis is critical. Although immune checkpoints (ICs) were shown to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, quantitative studies of ICs in clinical practice are limited. In this study, various soluble ICs (sICs) and cytokine levels in patients with SARS-CoV-2 infection at different time points were compared between survivors and deaths; we also examined whether sICs are useful for predicting prognosis. sICs and cytokines were measured in serum samples from 38 patients diagnosed with COVID-19 in the first and second week post-diagnosis. All assays were performed by bead-based multiplexed immunoassay system using Luminex Bio-Plex 200 system. The correlation of sICs and cytokines with laboratory markers was evaluated, and the levels of sICs in survivors were compared with those in deaths. Among the sICs, the second-week levels of soluble cluster of differentiation (sCD27, p = 0.012), sCD40 (p< 0.001), cytotoxic T-lymphocyte-associated protein 4 (sCTLA-4, p< 0.001), herpes virus entry mediator (sHVEM, p = 0.026), and T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3, p = 0.002) were significantly higher in deaths than in survivors. The levels of nine cytokines assessed in the second week of deaths were significantly higher than those in survivors. The sICs sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines chemokine CC motif ligand 2 (CCL2), GM-CSF, IL-10, and IL-8 showed significant positive correlations with the levels of C-reactive protein (CRP) and procalcitonin and were negatively correlated with the absolute lymphocyte count and platelet values. Increased levels of sICs including sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines were significant factors for poor prognosis. sICs, together with cytokines and inflammatory markers, may be useful as prognostic stratification markers in SARS-CoV-2-infected patients.


Subject(s)
COVID-19 , Biomarkers , Cytokines , Humans , Immunologic Factors , Pandemics , Prognosis , SARS-CoV-2
13.
BMJ Case Rep ; 15(8)2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2019952

ABSTRACT

A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293 units/L and bilirubin of 228 µmol/L, refractory to standard treatment with corticosteroids and rituximab. An emergency splenectomy was performed that slowed haemolysis but did not completely ameliorate it. Eculizumab, a terminal complement pathway inhibitor, was initiated to arrest intravascular haemolysis and showed a favourable response. AIHA is rare but described after the SARS-CoV-2 Pfizer-BioNTech vaccine. This case highlights the rare complication of AIHA, the use of emergency splenectomy for disease control, and the use of eculizumab.


Subject(s)
Anemia, Hemolytic, Autoimmune , BNT162 Vaccine , COVID-19 , Adolescent , Anemia, Hemolytic, Autoimmune/complications , Antibodies, Monoclonal, Humanized , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/adverse effects , Bilirubin , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Complement Inactivating Agents/therapeutic use , Hemoglobins , Hemolysis , Humans , Immunologic Factors/therapeutic use , Lactate Dehydrogenases , Male , RNA, Messenger/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2 , Splenectomy/adverse effects
14.
Neurotherapeutics ; 19(5): 1535-1545, 2022 09.
Article in English | MEDLINE | ID: covidwho-2014575

ABSTRACT

In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203-24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Sudden Infant Death , Humans , Immunologic Factors/adverse effects , Pandemics , Gadolinium/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Recurrence , Cytidine Diphosphate/therapeutic use , Multiple Sclerosis/drug therapy
15.
Immunotherapy ; 14(14): 1149-1164, 2022 10.
Article in English | MEDLINE | ID: covidwho-2009820

ABSTRACT

In the past decade, the emergence of biologics targeting human cytokine networks has advanced a new era in atopic dermatitis therapy. Dupilumab, in particular, the most widely studied and used IL-4/IL-13 inhibitor, has been considered a milestone in the treatment of patients with moderate-to-severe atopic dermatitis. In addition to the IL-4 and IL-13 pathways, many other cytokines and receptors have been newly targeted as therapeutic options. In this review, the authors provide an overview of the approved and tested biologics and JAK inhibitors for the treatment of atopic dermatitis, including their advantages and limitations.


Subject(s)
Biological Products , Dermatitis, Atopic , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Biological Products/therapeutic use , Dermatitis, Atopic/drug therapy , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Interleukin-13 , Interleukin-4
17.
J Nanobiotechnology ; 20(1): 380, 2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-2002186

ABSTRACT

Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.


Subject(s)
Immunity, Innate , Pathogen-Associated Molecular Pattern Molecules , Adjuvants, Immunologic , Immune System , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Receptors, Pattern Recognition
18.
Int Immunopharmacol ; 110: 109040, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1991087

ABSTRACT

Known as a pivotal immunohemostatic response, immunothrombosis is activated to restrict the diffusion of pathogens. This beneficial intravascular defensive mechanism represents the close interaction between the immune and coagulation systems. However, its uncontrolled form can be life-threatening to patients with the critical coronavirus disease 2019 (COVID-19). Hyperinflammation and ensuing cytokine storm underlie the activation of the coagulation system, something which results in the provocation of more immune-inflammatory responses by the thrombotic mediators. This vicious cycle causes grave clinical complications and higher risks of mortality. Classified as an evolutionarily conserved family of the small non-coding RNAs, microRNAs (miRNAs) serve as the fine-tuners of genes expression and play a key role in balancing the pro/anticoagulant and pro-/anti-inflammatory factors maintaining homeostasis. Therefore, any deviation from their optimal expression levels or efficient functions can lead to severe complications. Despite their extensive effects on the molecules and processes involved in uncontrolled immunothrombosis, some genetic agents and uncontrolled immunothrombosis-induced interfering factors (e.g., miRNA-single nucleotide polymorphysms (miR-SNPs), the complement system components, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and reactive oxygen species (ROS)) have apparently disrupted their expressions/functions. This review study aims to give an overview of the role of miRNAs in the context of uncontrolled immunothrombosis/thromboinflammation accompanied by some presumptive interfering factors affecting their expressions/functions in the critical COVID-19. Detecting, monitoring, and resolving these interfering agents mafy facilitate the design and development of the novel miRNAs-based therapeutic approaches to the reduction of complications incidence and mortality in patients with the critical COVID-19.


Subject(s)
COVID-19 , MicroRNAs , Thrombosis , Humans , Immunologic Factors , Inflammation/complications , Inflammation/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , SARS-CoV-2 , Thromboinflammation , Thrombosis/genetics
19.
J Investig Med ; 70(7): 1466-1471, 2022 10.
Article in English | MEDLINE | ID: covidwho-1986389

ABSTRACT

Coagulopathy, cytokine release, platelet hyperactivity and endothelial activation are regarded as potential major contributors to COVID-19 morbidity. Complement activation might provide a bridge linking these factors in severe COVID-19 illness. In this study, we investigated the prognostic significance of selected complement factors in hospitalized patients with severe COVID-19 infection. The study included 300 hospitalized adults with severe COVID-19 infection. Complement factors (C3, C3a, C4, sC5b-9) were assessed by commercial ELISA kits. Outcome parameters included mortality, intensive care unit admission and duration of hospital stay. It was found that survivors had significantly higher serum C3 (median (IQR): 128.5 (116.3-141.0) mg/dL vs 98.0 (70.0-112.8) mg/dL, p<0.001) and C4 (median (IQR): 36.0 (30.0-42.0) mg/dL vs 31.0 (26.0-35.0) mg/dL, p<0.001) levels when compared with non-survivors. On the other hand, it was shown that survivors had significantly lower C3a (median (IQR): 203.0 (170.3-244.0) ng/mL vs 385.0 (293.0-424.8) ng/mL, p<0.001) and sC5b-9 (median (IQR): 294.0 (242.0-318.8) ng/mL vs 393.0 (342.0-436.5) ng/mL, p<0.001) levels when compared with non-survivors. Multivariate logistic regression analysis identified C3a (OR: 0.97 (95% CI 0.96 to 0.99), p<0.001) and C4 (OR: 0.92 (95% CI 0.86 to 0.98), p=0.011) levels as significant predictors of mortality. In conclusion, serum levels of complement factors are related to mortality in severely ill patients with COVID-19.


Subject(s)
COVID-19 , Adult , Cytokines , Hospitalization , Humans , Immunologic Factors , Intensive Care Units , Prognosis
20.
Lancet Infect Dis ; 22(5): 565-567, 2022 05.
Article in English | MEDLINE | ID: covidwho-1967530
SELECTION OF CITATIONS
SEARCH DETAIL