Platelet Dysregulation in the Pathobiology of COVID-19

2021 ◽  
Author(s):  
Rebecca A. Mellema ◽  
Jacob Crandell ◽  
Aaron C. Petrey
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcomes ◽  
Adhesion Molecules ◽  
Broad Spectrum ◽  
Current Knowledge ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Multiple Organs ◽  
Disease Present

AbstractCoronavirus disease 2019 (COVID-19) encompasses a broad spectrum of clinical manifestations caused by infection with severe acute respiratory syndrome coronavirus 2.Patients with severe disease present with hyperinflammation which can affect multiple organs which often include observations of microvascular and macrovascular thrombi. COVID-19 is increasingly recognized as a thromboinflammatory disease where alterations of both coagulation and platelets are closely linked to mortality and clinical outcomes. Although platelets are most well known as central mediators of hemostasis, they possess chemotactic molecules, cytokines, and adhesion molecules that are now appreciated as playing an important role in the regulation of immune response. This review summarizes the current knowledge of platelet alterations observed in the context of COVID-19 and their impact upon disease pathobiology.

scholarly journals Deciphering SARS-CoV-2 Virologic and Immunologic Features

2020 ◽  
Vol 21 (16) ◽  
pp. 5932 ◽  
Author(s):  
Grégorie Lebeau ◽  
Damien Vagner ◽  
Étienne Frumence ◽  
Franck Ah-Pine ◽  
Xavier Guillot ◽  
...  
Keyword(s):  
Immune Response ◽  
Intensive Care ◽  
Life Cycle ◽  
Severe Acute Respiratory Syndrome ◽  
Critical Point ◽  
Clinical Outcomes ◽  
Current Knowledge ◽  
Physiological Functions ◽  
Multiple Organs ◽  
Virus Biology

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 and its associated pathology, COVID-19, have been of particular concerns these last months due to the worldwide burden they represent. The number of cases requiring intensive care being the critical point in this epidemic, a better understanding of the pathophysiology leading to these severe cases is urgently needed. Tissue lesions can be caused by the pathogen or can be driven by an overwhelmed immune response. Focusing on SARS-CoV-2, we and others have observed that this virus can trigger indeed an immune response that can be dysregulated in severe patients and leading to further injury to multiple organs. The purpose of the review is to bring to light the current knowledge about SARS-CoV-2 virologic and immunologic features. Thus, we address virus biology, life cycle, tropism for many organs and how ultimately it will affect several host biological and physiological functions, notably the immune response. Given that therapeutic avenues are now highly warranted, we also discuss the immunotherapies available to manage the infection and the clinical outcomes.

scholarly journals COVID-19: a review of current knowledge regarding exposure, quarantine, isolation and other preventive measures

2021 ◽  
Vol 8 ◽  
pp. 204993612110320
Author(s):  
Robert Rosolanka ◽  
Andres F. Henao-Martinez ◽  
Larissa Pisney ◽  
Carlos Franco-Paredes ◽  
Martin Krsak
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Response ◽  
Preventive Measures ◽  
Current Knowledge ◽  
Therapeutic Options ◽  
Exposure Control ◽  
Knowledge Gaps ◽  
Vaccination Strategies ◽  
Speed Up

Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.

scholarly journals Distorted TCR repertoires define multisystem inflammatory syndrome in children

2021 ◽  
Author(s):  
Amna Malik ◽  
Eszter N. Tóth ◽  
Michelle S. Teng ◽  
Jacob Hurst ◽  
Eleanor Watt ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
High Confidence ◽  
T Cell Clones ◽  
Severity Of Disease ◽  
Cell Clones ◽  
Inflammatory Syndrome ◽  
Independent Expansion

While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with severe (n=12) or mild (n=8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n=8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of severely ill children are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines severity of disease in children.

scholarly journals Immune Response to SARS-CoV-2 Infection

2020 ◽  
Vol 03 (10) ◽  
Author(s):  
Dr. Ahmed Al-Shukaili ◽  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Global Health ◽  
Immune Cells ◽  
Current Knowledge ◽  
Adaptive Immune ◽  
Proinflammatory Mediators ◽  
Adaptive Immune Cells ◽  
New Type

In December 2019 a new type of coronaviruses appeared in China and named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the disease associated with this virus is called Coronavirus Disease 2019 or COVID-19. Currently, COVID19 is the main global health threat. In this review, we focus in the current knowledge of immune response to SARS-CoV-2. Dysregulation of immune system, such as elevation levels of proinflammatory mediators and their roles in disease progression and pathogenesis as well as imbalance between innate and adaptive immune cells, are discussed in this review.

scholarly journals The epidemiology, clinical presentation, and predictors of severe Tick-borne encephalitis in Lithuania, a highly endemic country: A retrospective study of 1040 patients

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241587
Author(s):  
Daiva Radzišauskienė ◽  
Jurgita Urbonienė ◽  
Gintaras Kaubrys ◽  
Saulius Andruškevičius ◽  
Dalius Jatužis ◽  
...  
Keyword(s):  
Immune Response ◽  
Retrospective Study ◽  
Clinical Presentation ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
University Hospital ◽  
Disease Course ◽  
Tick Borne Encephalitis ◽  
Vilnius University ◽  
Severity Of The Disease

Introduction In recent decades, the incidence of Tick-borne encephalitis (TBE) has been increasing and posing a growing health problem because of the high costs to the healthcare system and society. The clinical manifestations are well studied but there is a lack of research analyzing the severity of the disease. Objective The aim of this study was to analyze the epidemiology and clinical presentation of severe TBE, to identify the predictors for a severe disease course, and also predictors for meningoencephalomyelitic and severe meningoencephalitic/encephalitic forms. Methods A retrospective study was conducted in the Center of Infectious Diseases and the Center of Neurology at Vilnius University Hospital Santaros Klinikos in the years 2005–2017 to describe the clinical and epidemiological features of TBE in adults. Results 1040 patients were included in the study. A total of 152/1040 (14.6%) patients had a severe course. The highest proportion of severe cases, reaching 41.2%, was reported in the 70–79 year-old age group. A total of 36/152 (23.7%) severe patients presented meningoencephalomyelitis. Myelitic patients were older, were frequently infected in their living areas, and usually reported a monophasic disease course compared with severe meningoencephalitic/encephalitic patients. Severe meningoencephalitic/encephalitic patients, compared with non-severe meningoencephalitic/encephalitic, were older, less often noticed the tick bite, and often had a monophasic course. The sequelae on discharge were observed in 810/1000 (81%) of patients. Conclusions The prognostic factors associated with a severe disease course and severe meningoencephalitic form are: older age, comorbidities, a monophasic course, a fever of 40˚C and above, CRP more than 30 mg/l, CSF protein more than 1 g/l, delayed immune response of TBEV IgG, pathological findings in CT. Age above 60 years, presence of CNS disease, bulbar syndrome, pleocytosis 500x106/l and above, and delayed immune response of TBEV IgG are predictors of the most severe myelitic form.

scholarly journals Inflammasomes and SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2513
Author(s):  
Juha Kaivola ◽  
Tuula Anneli Nyman ◽  
Sampsa Matikainen
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Influenza A ◽  
Protein Complexes ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Multiple Organs ◽  
New Type ◽  
Pro Inflammatory Cytokines

SARS-CoV-2 is a new type of coronavirus that has caused worldwide pandemic. The disease induced by SARS-CoV-2 is called COVID-19. A majority of people with COVID-19 have relatively mild respiratory symptoms. However, a small percentage of COVID-19 patients develop a severe disease where multiple organs are affected. These severe forms of SARS-CoV-2 infections are associated with excessive production of pro-inflammatory cytokines, so called “cytokine storm”. Inflammasomes, which are protein complexes of the innate immune system orchestrate development of local and systemic inflammation during virus infection. Recent data suggest involvement of inflammasomes in severe COVID-19. Activation of inflammasome exerts two major effects: it activates caspase-1-mediated processing and secretion of pro-inflammatory cytokines IL-1β and IL-18, and induces inflammatory cell death, pyroptosis, via protein called gasdermin D. Here, we provide comprehensive review of current understanding of the activation and possible functions of different inflammasome structures during SARS-CoV-2 infection and compare that to response caused by influenza A virus. We also discuss how novel SARS-CoV-2 mRNA vaccines activate innate immune response, which is a prerequisite for the activation of protective adaptive immune response.

scholarly journals SARS, MERS and COVID-19: clinical manifestations and organ-system complications: a mini review

2020 ◽  
Vol 78 (4) ◽  
Author(s):  
Jad Gerges Harb ◽  
Hussein A Noureldine ◽  
Georges Chedid ◽  
Mariam Nour Eldine ◽  
Dany Abou Abdallah ◽  
...  
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Disease Process ◽  
Organ System ◽  
Middle East Respiratory Syndrome ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Clinical Presentations

ABSTRACT Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) are caused by three distinct coronaviruses belonging to the same genus. COVID-19 and its two predecessors share many important features in their clinical presentations, and in their propensity for progression to severe disease which is marked by high rates of morbidity and mortality. However, comparison of the three viral illnesses also reveals a number of specific differences in clinical manifestations and complications, which suggest variability in the disease process. This narrative review delineates the pulmonary, cardiac, renal, gastrointestinal, hepatic, neurological and hematologic complications associated with these three respiratory coronaviruses. It further describes the mechanisms of immune hyperactivation—particularly cytokine release syndrome—implicated in the multi-organ system injury seen in severe cases of MERS, SARS and COVID-19.

scholarly journals SARS-CoV-2 and Autoimmune Cytopenia

Hemato ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 463-476
Author(s):  
Ryann Quinn ◽  
Irina Murakhovskaya
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Thrombocytopenic Purpura ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Autoimmune Cytopenias ◽  
Autoimmune Cytopenia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a variety of clinical manifestations related to viral tissue damage, as well as a virally induced immune response. Hyperstimulation of the immune system can serve as a trigger for autoimmunity. Several immune-mediated manifestations have been described in the course of SARS-CoV-2 infection. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are the most common hematologic autoimmune disorders seen in the course of SARS-CoV-2 infection. Vaccine-induced thrombocytopenia is a unique autoimmune hematologic cytopenia associated with SARS-CoV-2 vaccination. This paper will review the current literature on the association of SARS-CoV-2 infection and vaccination with autoimmune cytopenias and the clinical course of autoimmune cytopenias in patients with COVID-19.

scholarly journals Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission

2021 ◽  
Vol 12 ◽  
Author(s):  
Xianwu Pang ◽  
Pu Li ◽  
Lifeng Zhang ◽  
Lusheng Que ◽  
Min Dong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
High Coverage ◽  
Reading Frame ◽  
Treatment And Prevention ◽  
High Prevalence ◽  
Enzyme Mutation ◽  
Editing Enzyme

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.

scholarly journals Natural Mucosal Barriers and COVID-19 in Children

2021 ◽  
Author(s):  
Carl A. Pierce ◽  
Sharlene Sy ◽  
Benjamin Galen ◽  
Doctor Y Goldstein ◽  
Erika Orner ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
Mucosal Immune Response ◽  
Innate Immune ◽  
Interferon Signaling ◽  
Expression Of Genes ◽  
Gene And Protein Expression ◽  
Ifn Γ ◽  
Nasal Fluid

AbstractCOVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesized that a more robust early innate immune response to SARS-CoV-2 may protect against severe disease and compared clinical outcomes, viral copies and cellular gene and protein expression in nasopharyngeal swabs from 12 children and 27 adults upon presentation to the Emergency Department. SARS-CoV-2 copies were similar, but compared to adults, children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected in nasal fluid from both groups and correlated negatively with mucosal IL-18. These findings suggest that a vigorous mucosal immune response in children compared to adults contributes to favorable clinical outcomes.

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