scholarly journals Early immune pathology and persistent dysregulation characterise severe COVID-19

2021 ◽  
Author(s):  
Laura Bergamaschi ◽  
Federica Mescia ◽  
Lorinda Turner ◽  
Aimee Hanson ◽  
Prasanti Kotagiri ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Symptom Onset ◽  
Immune Cell ◽  
Adaptive Responses ◽  
Robust Immune Response ◽  
Mild Disease ◽  
Preventative Intervention ◽  
Cellular Abnormalities ◽  
Immune Pathology ◽  
Inflammatory Changes

SummaryIn a study of 207 SARS-CoV2-infected individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation already evident at around symptom onset. Such early evidence of inflammation suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation replace those driven by TNF and IL-6. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to “long COVID”.

scholarly journals Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs

2020 ◽  
Author(s):  
Vikramjeet Singh ◽  
Alexander Beer ◽  
Andreas Kraus ◽  
Xiaoni Zhang ◽  
Jinhua Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Injury ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Risk Group ◽  
Tissue Injury ◽  
Lung Epithelial Cells ◽  
Experimental Stroke ◽  
Virus Surface ◽  
Protein Levels

AbstractBackgroundThe newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated.MethodsMice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1β were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry.ResultsStrikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1β in the lungs. Higher gene expression of cytokines IL-6 and IL-1β was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression.ConclusionsWe demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions.HighlightsBrain tissue injury increases ACE2 levels in the lungsBrain injury induces pro-inflammatory cytokine expression in the lungsBrain injury causes parenchymal inflammation and systemic lymphopenia

scholarly journals Effects of Colchicine on Measures of Lipolysis in Adults With Obesity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A9-A10
Author(s):  
Zahra Sarrafan-Chaharsoughi ◽  
Jordan A Levine ◽  
Tushar P Patel ◽  
Sheila M Brady ◽  
K Karthik Chivukula ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Immune Cell ◽  
Intravenous Glucose Tolerance Test ◽  
Cell Populations ◽  
Post Intervention ◽  
Double Blind ◽  
Immune Cell Population ◽  
Intravenous Glucose ◽  
Neutrophil Lymphocyte Ratio ◽  
Anti Inflammatory

Abstract Background: Obesity-associated inflammation promotes adipose tissue (AT) dysfunction and contributes to the progression of type 2 diabetes and cardiovascular disease. Recent clinical studies have demonstrated that colchicine may improve metabolic and cardiovascular outcomes; however, colchicine’s effects on metabolic and inflammatory measures within AT remain unclear. Methods: The aim of this study was to examine if colchicine’s anti-inflammatory effects would improve measures of lipolysis and immune cell populations in subcutaneous AT (SAT). This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 nondiabetic adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6mg or placebo twice daily for 3 months. Blood samples for insulin, glucose, and free fatty acids were collected in the fasted state and during a frequently-sampled intravenous glucose tolerance test. Noninsulin-suppressible (l0), insulin-suppressible (l2), and maximal (l0+l2) lipolysis rates were calculated by minimal model analysis. Body composition was determined by DXA. SAT immune cell populations were characterized by flow cytometry fluorescence-activated single cell sorting of the stromovascular fractions obtained after collagenase digestion of SAT samples obtained using a mini-liposuction technique pre- and post-intervention. Results: Data from 18 subjects in the colchicine group (Mean ± SD: age 48.4 ± 13.5 y; BMI 39.3 ± 6.3 kg/m2; sex: female 72.2%) and 18 subjects in the placebo group (age 44.7 ± 10.2 y; BMI 41.8 ± 8.2 kg/m2; sex: female 77.8%) were available for this study. Colchicine treatment significantly reduced l2 (p = 0.04) and l0+l2 (p = 0.04) versus placebo. These changes were significantly associated with reductions in systemic inflammation, including the changes in high-sensitivity C-reactive protein concentrations, white blood cell count, circulating monocyte and neutrophil populations, and the neutrophil-lymphocyte ratio (p’s < 0.015). Colchicine did not significantly alter SAT immune cell population distributions (p’s > 0.05). Conclusions: In adults with obesity and MetS, colchicine may improve insulin action at the level of AT. These improvements were positively associated with the suppression of systemic inflammation. However, no local AT inflammatory cell populations were significantly affected by colchicine use in our study, suggesting that colchicine’s systemic, rather than local, anti-inflammatory effects may be more consequential in ameliorating AT metabolic pathways in MetS. Further studies are warranted to elucidate the biological mechanisms underlying colchicine’s effects in AT, as these investigations could potentially shed light on treatments to improve metabolic outcomes in human obesity.

scholarly journals Iron Chelation in Murine Models of Systemic Inflammation Induced by Gram-Positive and Gram-Negative Toxins

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 283 ◽  
Author(s):  
Danielle Fokam ◽  
Kayle Dickson ◽  
Kiyana Kamali ◽  
Bruce Holbein ◽  
Patricia Colp ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Immune Cell ◽  
Essential Element ◽  
Host Cells ◽  
Cellular Damage ◽  
Microvascular Blood Flow ◽  
Morphologic Change ◽  
Murine Models ◽  
Gram Positive ◽  
Gram Negative

Iron is an essential element for various physiological processes, but its levels must remain tightly regulated to avoid cellular damage. Similarly, iron plays a dual role in systemic inflammation, such as with sepsis. Leukocytes utilize iron to produce reactive oxygen species (ROS) to kill bacteria, but pathologically increased iron-catalyzed ROS production in sepsis can lead to damage of host cells, multi-organ failure and death. Temporary reduction in bioavailable iron represents a potential therapeutic target in sepsis. This study investigates the effect of the novel iron chelator, DIBI, in murine models of systemic (hyper-)inflammation: C57BL/6 mice were challenged with toxins from Gram-positive (Staphylococcus aureus: lipoteichoic acid, peptidoglycan) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae: lipopolysaccharide). Intravital microscopy (IVM) was performed to assess immune cell activation and its impact on microvascular blood flow in vivo in the microcirculation of the gut. Plasma inflammatory mediators were measured via multiplex assay, and morphologic change in intestinal tissue was evaluated. DIBI treatment decreased leukocyte (hyper-)activation induced by Gram-positive and Gram-negative toxins. In some cases, it preserved capillary perfusion, reduced plasma inflammatory markers and attenuated tissue damage. These findings support the utility of DIBI as a novel treatment for systemic inflammation, e.g., sepsis.

scholarly journals The Ironman Triathlon shifts innate/adaptive immune cell populations and increases systemic inflammation (705.3)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Colleen Munoz ◽  
Jenna Apicella ◽  
Shlomit Radom‐Aizik ◽  
Carl Maresh ◽  
Faddia Haddad ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Immune Cell ◽  
Cell Populations ◽  
Adaptive Immune ◽  
Adaptive Immune Cell ◽  
Ironman Triathlon

scholarly journals Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France

2020 ◽  
Author(s):  
Samira Fafi-Kremer ◽  
Timothee Bruel ◽  
Yoann Madec ◽  
Rebecca Grant ◽  
Laura Tondeur ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Rapid Test ◽  
Humoral Response ◽  
Hospital Staff ◽  
Sample Collection ◽  
Future Studies ◽  
Neutralizing Activity ◽  
Neutralization Capacity ◽  
Mild Disease

Background: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. Methods: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity).The neutralizing activity of the sera was tested with a pseudovirus-based assay. Results: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV- 2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P=0.02). Conclusion: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.

scholarly journals Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

2020 ◽  
Author(s):  
Carlo Cervia ◽  
Jakob Nilsson ◽  
Yves Zurbuchen ◽  
Alan Valaperti ◽  
Jens Schreiner ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Healthcare Workers ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Patient Age ◽  
Mild Disease ◽  
Specific Serum ◽  
Patient Âgé ◽  
Serum Iga ◽  
Very High

AbstractBackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

scholarly journals Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience

2020 ◽  
Author(s):  
Sarfraz A Saleemi ◽  
Abdulrahman Alrajhi ◽  
Mohammed Alhajji ◽  
Areej Alfattani ◽  
Faisal Albaiz
Keyword(s):  
Disease Severity ◽  
Median Time ◽  
Symptom Onset ◽  
Viral Clearance ◽  
P Value ◽  
Nasopharyngeal Swab ◽  
Multivariate Regression Model ◽  
Mild Disease ◽  
Virus Clearance

Background: The role of hydroxychloroquine (HCQ) and azithromycin in the treatment of COVID-19 and its effect on SARS-CoV-2 viral clearance is not known. Methods: This is a retrospective observational study to assess the effect of HCQ and Azithromycin on duration from symptom onset to negative SARS-CoV-2 PCR using nasopharyngeal swab in hospitalized patient with COVID-19. Eighty-five patients were included in the study, 65 in HCQ (Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from symptom onset to negative PCR and effect of gender, age and disease severity on time to viral clearance was measured. Results: Median time to negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, 19 days (IQR: 8, Mean 18+6, N=20), (p <0.05). Forty-one (63%) patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate regression model (F=6.8, P<0.002, R2=0.20) shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) and with every year increase in the age, the time to negative PCR would be delayed by 0.12 days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on duration (p 0.142 and 0.156 respectively) but older patients >60 year had longer duration compared to patients <60 year of age although p value did not reach significance (p 0.073). Median time to negative PCR in mild-HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was longer when compared with non-HCQ group (p <0.05). On day 28, all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ group. Conclusion: Hydroxychloroquine (HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with COVID-19 and it is correlated with older age. Larger studies are needed to confirm this finding.

scholarly journals Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Benjamin Wilde ◽  
Antonios Katsounas
Keyword(s):  
Liver Cirrhosis ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Kidney Injury ◽  
Immune Dysfunction ◽  
Developed Countries ◽  
Bacterial Peritonitis ◽  
End Stage

Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.

Immunology of Bipolar Disorder

2018 ◽  
pp. 211-226
Author(s):  
Izabela G. Barbosa ◽  
Moises E. Bauer ◽  
Jair C. Soares ◽  
Antônio L. Teixeira
Keyword(s):  
Bipolar Disorder ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Course Of Illness ◽  
Wide Range ◽  
High Prevalence ◽  
The Central Nervous System ◽  
Immune Changes ◽  
Inflammatory Changes

Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with a high prevalence of medical and psychiatric comorbidities, cognitive impairment, and a progressive course of illness. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Here we review several data supporting the presence of immunological dysfunction in BD: (1) increased frequency of autoimmune diseases; (2) distinct immune cell profile; (3) altered release of cytokines by stimulated mononuclear cells; (4) elevated levels of circulating immune markers; (5) inflammatory changes in the central nervous system; (6) relationship with clinical comorbidities; and (7) the effect of current treatments on the immune system and the role of immunomodulatory agents.

Sign in / Sign up

Export Citation Format

Share Document