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Researchers in the United States have conducted a study showing that the activity of the filling system is primarily linked to the pathogenesis of coronary virus disease 2019 (COVID-19), rather than a more widespread symptom of acute coronary heart disease. .
The filling system is a network of tightly regulated proteins that work together as the first line of immune defense against the invasion of pathogens.
Now, a team of scientists from Washington University School of Medicine, Marian University, University of Pittsburgh, Yale School of Medicine and Yale New Haven Health System have identified additive activity as a unique immunologic feature of COVID-19.
Hrishikesh Kulkarni of the University of Washington School of Medicine says filling activity differentiates those at higher risk of developing severe disease after infection with the causative agent – true respiratory coronavirus syndrome 2 (SARS-CoV-2).
In addition, the study showed that it has increased activity on the other filling pathway associated with this more severe disease.
The team also identified parts of the other route that are significantly elevated in hard COVID-19, thus providing specific targets that could be used for risk prediction and drug detection.
“Our findings could modernize the approach to therapeutic targeting of the filling system in severe SARS-CoV-2 disease,” the researchers wrote.
A pre-printed version of the research paper can be found on the bioRxiv* server, while the article is under peer review.
The immune components that contribute to true COVID-19 are not well understood
The morbidity and mortality associated with severe COVID-19 has been due to hyperinflammatory rate and the so-called “cytokine” storm.
However, although high levels of certain cytokines are associated with COVID-19 mortality, their circulation rates do not differ from those measured in patients with other viral diseases such as influenza.
On the other hand, clinical findings and autopsy reports have shown that at least some patients with COVID-19, have specific immunologic responses due to specific coagulopathic events.
“Understanding the underlying mechanisms of these relatively specific aspects of COVID19 is crucial for targeting therapies and may provide us with an insight into the pathogenesis of respiratory distress syndrome more closely. more, “the researchers wrote.
What about the filling system?
The filling system has been involved in the pathogenesis of COVID-19 malignancy since early in the pandemic.
Multiple studies have revealed high levels of filler activation results such as C5a and sC5b-9 in patients with COVID-19 and deposition of active filler proteins in cigarettes and injured organs.
“As a result, these studies have created a precedent for targeting the filling system in a number of follow-up phase II and phase III clinical trials using filler protectors in COVID-19, “said Kulkarni and colleagues.
However, many cytokines that have been implicated in COVID-19 are also elevated in other forms of severe disease, including those leading to respiratory failure.
The authors state that most studies to date examining the role of the filling system in COVID-19 have not included control groups of patients with infections. other breaths or severe respiratory failure.
Therefore, it is not yet known whether filling activity is a specific feature of COVID-19 malignancy or simply a broader symptom of acute illness.
Symptoms of filler activation are specific to COVID-19 compared with non-COVID-19 respiratory failure. Plasma for the detection of circulatory symptoms of filler activation was obtained in patients with COVID-19 and influenza at Barnes-Jewish Hospital (BJH) / Washington University School of Medicine (WUSM). (A) CONSORT flow diagram showing patient enrollment, satisfaction, and outcomes in the COVID-19 cohort. The CONSORT diagram for the numbers of respiratory flu and non-COVID is in Figure S1. Box and whiskey block differences in sC5b-9 between (B) influenza (EDFLU) and COVID-19, (C) non-COVID (Immune in Pneumonia and Sepsis, IPS) and respiratory failure COVID19 covariates, and (D) limiting the cohorts in Fig.1C to those who died. The center of the box represents the median value, and the length of the box represents the interquartile range. The whiskers represent the lowest and highest values in each group. Statistical significance is determined using the Mann-Whitney U. test.
What did the current study find?
The team examined augmentation activity in blood samples from 134 COVID-19 patients present at emergency departments, 54 hospitalized patients with influenza, and 22 intensive care unit (ICU) patients with non-acute respiratory failure. COVID-19.
The researchers found that circulatory markers of filling activity such as sC5b-9 were higher in patients with COVID-19 than in patients with influenza or non-COVID-19 respiratory failure.
These signs of fill activation helped differentiate COVID-19 patients who were at higher risk for worse outcomes, such as requiring ICU access or aggressive mechanical ventilation.
In addition, the results indicated that there was improved activity on the alternative filling pathway in patients with severe COVID-19 which was also responsible for the worse outcomes in this group.
In addition, components of the other pathway were associated with endothelial injury markers such as angiopoietin-2 and hypercoagulability markers such as thrombomodulin and von Willebrand factor.
The researchers say these symptoms are also clinico-physiologic signs of severe COVID-19 vasculopathy.
What should be the next step?
“The next step is to understand the mechanical basis of this interaction and assess whether the other pathway-mediated activity of this vicious circle that sustains a tension injury could be inhibited, at least in sub. -set of patients with severe COVID-19 who have this phenotype., “said Kulkarni and colleagues.
“There is still much work to be done to better understand how and when to focus on the filling deficit, with the aim of reducing the incidence of SARS-CoV-2 infection,” the team concludes. .
* Important message
bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.