scholarly journals Fundamentals in Covid-19-Associated Thrombosis: Molecular and Cellular Aspects

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniella M. Mizurini ◽  
Eugenio D. Hottz ◽  
Patrícia T. Bozza ◽  
Robson Q. Monteiro
Keyword(s):  
Laboratory Finding ◽  
Coagulation Cascade ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Complex Process ◽  
High Incidence ◽  
Novel Coronavirus ◽  
Plasma Factors ◽  
Common Laboratory ◽  
Pro Inflammatory Cytokines

The novel coronavirus disease (COVID-19) is associated with a high incidence of coagulopathy and venous thromboembolism that may contribute to the worsening of the clinical outcome in affected patients. Marked increased D-dimer levels are the most common laboratory finding and have been repeatedly reported in critically ill COVID-19 patients. The infection caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is followed by a massive release of pro-inflammatory cytokines, which mediate the activation of endothelial cells, platelets, monocytes, and neutrophils in the vasculature. In this context, COVID-19-associated thrombosis is a complex process that seems to engage vascular cells along with soluble plasma factors, including the coagulation cascade, and complement system that contribute to the establishment of the prothrombotic state. In this review, we summarize the main findings concerning the cellular mechanisms proposed for the establishment of COVID-19-associated thrombosis.

scholarly journals COVID-19 and Hypercoagulability: A Review

2020 ◽  
Vol 26 ◽  
pp. 107602962096285
Author(s):  
Asim Kichloo ◽  
Kirk Dettloff ◽  
Michael Aljadah ◽  
Michael Albosta ◽  
Shakeel Jamal ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Treatment Strategies ◽  
Coagulation Cascade ◽  
Vascular Endothelial ◽  
The Novel ◽  
High Incidence ◽  
Thrombotic Complications ◽  
Novel Coronavirus

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.

scholarly journals Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guillaume Carissimo ◽  
Weili Xu ◽  
Immanuel Kwok ◽  
Mohammad Yazid Abdad ◽  
Yi-Hao Chan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Whole Blood ◽  
Roc Analysis ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Cell Counts ◽  
Novel Coronavirus

Abstract SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

scholarly journals Autophagy Modulation in Lymphocytes From COVID-19 Patients: New Therapeutic Target in SARS-COV-2 Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Marta Vomero ◽  
Cristiana Barbati ◽  
Tania Colasanti ◽  
Alessandra Ida Celia ◽  
Mariangela Speziali ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Degradation Pathway ◽  
The Novel ◽  
Lysosomal Degradation ◽  
Tnf Α ◽  
Evolutionarily Conserved ◽  
Novel Coronavirus ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the “cytokine storm.” Among these, interleukin (IL)-6, tumor necrosis factor‐α (TNF‐α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF‐α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection.

scholarly journals Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1962
Author(s):  
Muhammad Aslam ◽  
Yury Ladilov
Keyword(s):  
Endocytic Pathway ◽  
Host Cells ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Late Endosomes ◽  
Proven Efficacy ◽  
Potential Impact ◽  
Potential Strategy ◽  
Novel Coronavirus ◽  
High Level

An outbreak of the novel coronavirus (CoV) SARS-CoV-2, the causative agent of COVID-19 respiratory disease, infected millions of people since the end of 2019, led to high-level morbidity and mortality and caused worldwide social and economic disruption. There are currently no antiviral drugs available with proven efficacy or vaccines for its prevention. An understanding of the underlying cellular mechanisms involved in virus replication is essential for repurposing the existing drugs and/or the discovery of new ones. Endocytosis is the important mechanism of entry of CoVs into host cells. Endosomal maturation followed by the fusion with lysosomes are crucial events in endocytosis. Late endosomes and lysosomes are characterized by their acidic pH, which is generated by a proton transporter V-ATPase and required for virus entry via endocytic pathway. The cytoplasmic cAMP pool produced by soluble adenylyl cyclase (sAC) promotes V-ATPase recruitment to endosomes/lysosomes and thus their acidification. In this review, we discuss targeting the sAC-specific cAMP pool as a potential strategy to impair the endocytic entry of the SARS-CoV-2 into the host cell. Furthermore, we consider the potential impact of sAC inhibition on CoV-induced disease via modulation of autophagy and apoptosis.

scholarly journals Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

2020 ◽  
Author(s):  
Guillaume Carissimo ◽  
Weili Xu ◽  
Immanuel Kwok ◽  
Mohammad Yazid Abdad ◽  
Yi-Hao Chan ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Marker ◽  
Whole Blood ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
Strongly Correlated ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Cell Counts ◽  
Novel Coronavirus

AbstractSARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 γδ T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

Neurological symptoms in patients after the novel coronavirus infection COVID-19, determining further rehabilitation strategy

2021 ◽  
pp. 5-12
Author(s):  
Albina Ayratovna Zvegintseva ◽  
Maksim Leonidovich Maksimov
Keyword(s):  
Large Scale ◽  
Neuronal Damage ◽  
Severe Form ◽  
Neurological Symptoms ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Spanish Flu ◽  
Cerebral Reorganization ◽  
Coronavirus Infection ◽  
Novel Coronavirus

Since the Spanish flu in 1918, there has not been such a large-scale pandemic, causing significant damage to the economy of Russia and other countries, as the novel coronavirus infection COVID-19, which began in December 2019. The SARS-CoV-2 virus is highly infectious and can proceed both asymptomatic and in an extremely severe form, especially in the presence of comorbidity. Despite the fact that the clinical picture is associated with respiratory syndrome, long-term neurological symptoms are increasingly observed. In this study, we tried to find out the most pronounced and long-lasting neurological symptoms in the first 6 months after the novel coronavirus infection COVID-19. An important role in the rehabilitation process of this group of patients is played by the strategy of neurocytoprotection, which is aimed at preventing and reducing neuronal damage by affecting the cellular mechanisms of neuroregeneration and cerebral reorganization, which leads not only to structural and metabolic, but also to functional recovery.

scholarly journals Pneumomediastinum and subcutaneous emphysema in COVID-19: barotrauma or lung frailty?

2020 ◽  
Vol 6 (4) ◽  
pp. 00385-2020
Author(s):  
Daniel H.L. Lemmers ◽  
Mohammed Abu Hilal ◽  
Claudio Bnà ◽  
Chiara Prezioso ◽  
Erika Cavallo ◽  
...  
Keyword(s):  
Subcutaneous Emphysema ◽  
Ideal Body Weight ◽  
Transpulmonary Pressure ◽  
Fold Increase ◽  
Plateau Pressure ◽  
The Novel ◽  
Mechanically Ventilated ◽  
High Incidence ◽  
Novel Coronavirus ◽  
Protective Mechanical Ventilation

BackgroundIn mechanically ventilated acute respiratory distress syndrome (ARDS) patients infected with the novel coronavirus disease (COVID-19), we frequently recognised the development of pneumomediastinum and/or subcutaneous emphysema despite employing a protective mechanical ventilation strategy. The purpose of this study was to determine if the incidence of pneumomediastinum/subcutaneous emphysema in COVID-19 patients was higher than in ARDS patients without COVID-19 and if this difference could be attributed to barotrauma or to lung frailty.MethodsWe identified both a cohort of patients with ARDS and COVID-19 (CoV-ARDS), and a cohort of patients with ARDS from other causes (noCoV-ARDS).Patients with CoV-ARDS were admitted to an intensive care unit (ICU) during the COVID-19 pandemic and had microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. NoCoV-ARDS was identified by an ARDS diagnosis in the 5 years before the COVID-19 pandemic period.ResultsPneumomediastinum/subcutaneous emphysema occurred in 23 out of 169 (13.6%) patients with CoV-ARDS and in three out of 163 (1.9%) patients with noCoV-ARDS (p<0.001). Mortality was 56.5% in CoV-ARDS patients with pneumomediastinum/subcutaneous emphysema and 50% in patients without pneumomediastinum (p=0.46).CoV-ARDS patients had a high incidence of pneumomediastinum/subcutaneous emphysema despite the use of low tidal volume (5.9±0.8 mL·kg−1 ideal body weight) and low airway pressure (plateau pressure 23±4 cmH2O).ConclusionsWe observed a seven-fold increase in pneumomediastinum/subcutaneous emphysema in CoV-ARDS. An increased lung frailty in CoV-ARDS could explain this finding more than barotrauma, which, according to its etymology, refers to high transpulmonary pressure.

scholarly journals Does the Bacillus Calmette–Guérin vaccine provide protection from COVID-19?

2020 ◽  
Vol 72 ◽  
pp. 17-20 ◽  
Author(s):  
Soumya Roy
Keyword(s):  
Interleukin 1 ◽  
The Novel ◽  
Bacillus Calmette Guerin ◽  
Bcg Vaccination ◽  
The Difference ◽  
Novel Coronavirus ◽  
Prevention And Cure ◽  
Heterologous Protection ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Objective: The novel coronavirus pandemic is ravaging throughout the world. It has infected more than 1.2 million people and killed more than 64,000. Frantic research is underway to find prevention and cure. Of late, Bacillus Calmette–Guérin (BCG) has been speculated as a possible protection from COVID-19. We sought to investigate the evidence behind the claim. Material and Methods: Data were collected regarding the total number of COVID-19 cases per million and total number of COVID-19 deaths per million in various countries. The BCG vaccination policies of these countries were also obtained. Results: It was seen that the countries with no universal BCG policy had a mean 1272.9 (median 795) cases per million and 80.7 deaths (median 18) per million population. On the contrary, the countries with a universal BCG vaccination policy had a mean 131.2 (median 40) cases per million and 4 deaths (median 1) per population. The difference is highly significant (P < 0.001). Conclusion: The data strongly support the hypothesis that BCG may offer protection from COVID-19. Heterologous protection offered by BCG through production of trained immunity, epigenetic reprogramming of monocytes, non-specific activation of NK cells, and increase of pro-inflammatory cytokines (particularly, tumor necrosis factor [TNF]-alpha and interleukin 1 beta) production may be the mechanism behind its cross- protection against the novel coronavirus.

scholarly journals Why lockdown? Simplified arithmetic tools for decision-makers, health professionals, journalists and the general public to explore containment options for the novel coronavirus

2020 ◽  
Author(s):  
Gerry F. Killeen ◽  
Samson S Kiware
Keyword(s):  
National Level ◽  
Epidemiological Surveillance ◽  
Contact Tracing ◽  
The Novel ◽  
Minimal Impact ◽  
High Incidence ◽  
United Republic Of Tanzania ◽  
Novel Coronavirus ◽  
User Friendly ◽  
Parameter Values

SummaryHalf the world’s population is already under lock-down and the remainder will have to follow if the ongoing novel coronavirus 2019 (COVID-19) virus pandemic is to be contained. Faced with such brutally difficult decisions, it is essential that as many people as possible understand (1) why lock-down interventions represent the only realistic way for individual countries to contain their national-level epidemics before they turn into public health catastrophes, (2) why these need to be implemented so early, so aggressively and for such extended periods, and (3) why international co-operation to conditionally re-open trade and travel between countries that have successfully eliminated local transmission represents the only way to contain the pandemic at global level. Here we present simplified arithmetic models of COVID-19 transmission, control and elimination in user-friendly Shiny and Excel formats that allow non-specialists to explore, query, critique and understand the containment decisions facing their country and the world at large. Based on parameter values representative of the United Republic of Tanzania, which is still early enough in its epidemic cycle and response to avert a national catastrophe, national containment and elimination with less than 10 deaths is predicted for highly rigorous lock down within 5 weeks of the first confirmed cases and maintained for 15 weeks. However, elimination may only be sustained if case importation from outside the country is comprehensively contained by isolating for three weeks all incoming travellers, except those from countries certified as COVID-free in the future. Any substantive relaxation of these assumptions, specifically shortening the lock-down period, less rigorous lock-down or imperfect importation containment, may facilitate epidemic re-initiation, resulting in over half a million deaths unless rigorously contained a second time. Removing contact tracing and isolation has minimal impact on successful containment trajectories because high incidence of similar mild symptoms caused by other common pathogens attenuates detection success of COVID-19 testing. Nevertheless, contact tracing is recommended as an invaluable epidemiological surveillance platform for monitoring and characterizing the epidemic, and for understanding the influence of interventions on transmission dynamics.

scholarly journals Analysis of cytokines in SARS-CoV-2 or COVID-19 patients in Erbil city, Kurdistan Region of Iraq

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250330
Author(s):  
Mohammed Yousif Merza ◽  
Rundk Ahmed Hwaiz ◽  
Badraldin Kareem Hamad ◽  
Karzan Abdulmuhsin Mohammad ◽  
Harmand Ali Hama ◽  
...  
Keyword(s):  
Severe Case ◽  
Control Group ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Recovery Group ◽  
Novel Coronavirus ◽  
Necrosis Factor

The emergence of the novel coronavirus and then pandemic outbreak was coined 2019- nCoV or COVID-19 (or SARS-CoV-2 disease 2019). This disease has a mortality rate of about 3·7 percent, and successful therapy is desperately needed to combat it. The exact cellular mechanisms of COVID-19 need to be illustrated in detail. This study aimed to evaluate serum cytokines in COVID-19 patients. In this study, serum was collected from volunteer individuals, moderate COVID-19 patients, severe cases of COVID-19 patients, and patients who recovered from COVID-19 (n = 122). The serum concentrations of interleukins such as IL-1, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α), were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-α were did not differ significantly among groups. However, the concentration of IL-6 was significantly higher in moderate COVID-19 and severe cases of COVID-19 groups compared to control and recovered groups indicating it to be an independent predictor in the coronavirus disease. The levels of IFN-γ and IL-4 were significantly lower in the recovery group than the severe case of the COVID-19 group. In contrast, the level of IL-10 in recovered COVID-19 patients was significantly higher in compare to severe cases, COVID-19 patients. Varying levels of cytokines were detected in COVID-19 group than control group suggesting distinct immunoregulatory mechanisms involved in COVID-19 pathogenesis. However, additional investigations are needed to be to be performed to understand the exact cellular mechanism of this disease.

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