COVID Abstracts August 2020

Strong link found between abnormal liver tests and poor COVID-19 outcomes


Date: August 7, 2020

Source: Yale University


Summary: Researchers found that patients with COVID-19 presented with abnormal liver tests at much higher rates than suggested by earlier studies. They also discovered that higher levels of liver enzymes -- proteins released when the liver is damaged -- were associated with poorer outcomes for these patients, including ICU admission, mechanical ventilation, and death.Share:

FULL STORY Researchers at the Yale Liver Center found that patients with COVID-19 presented with abnormal liver tests at much higher rates than suggested by earlier studies. They also discovered that higher levels of liver enzymes -- proteins released when the liver is damaged -- were associated with poorer outcomes for these patients, including ICU admission, mechanical ventilation, and death.

The study appeared online on July 29 in Hepatology.

Previous studies in China found that approximately 15% of patients with COVID-19 had abnormal liver tests. The Yale study, which looked retrospectively at 1,827 COVID-19 patients who were hospitalized in the Yale New Haven Health system between March and April, found that the incidence of abnormal liver tests was much higher -- between 41.6% and 83.4% of patients, depending on the specific test.

In all, the Yale researchers examined five liver tests, looking at factors such as elevations in aspartate aminotransferase (AST) and alanine transaminase (ALT), which indicate liver cell inflammation; an increase in bilirubin, which indicates liver dysfunction; and increased levels of alkaline phosphatase (ALP), which may indicate inflammation of bile ducts.

Although the researchers do not know why the incidence of abnormal liver tests was so much higher than in previous studies from China, senior author Dr. Joseph Lim, professor of medicine and director of the Yale Viral Hepatitis Program, said other health differences between the Chinese and U.S. populations could account for it.

"We can speculate that U.S. patients may have an increased rate of other risk factors such as alcoholic or non-alcoholic fatty liver disease," he said.

Liver disease is widespread in the U.S. population. Dr. Michael Nathanson, the Gladys Phillips Crofoot Professor of Medicine (digestive diseases), professor of cell biology, director of the Yale Liver Center, and a co-author of the study, said: "In the U.S., close to one-third of people have fatty liver disease, and several million people have chronic hepatitis B or C."

Because the Yale researchers had access to patients' health records, they were also able to look at their liver tests prior to being diagnosed with COVID-19. Approximately one-quarter of patients in the study had abnormal liver tests prior to being admitted for the virus. But regardless of whether patients came to the hospital with existing liver problems or developed them during their COVID-19-related hospitalization, a strong association was observed between abnormal liver tests and the severity of the COVID-19 cases, the researchers said.

Rather than the liver itself driving poorer outcomes in COVID-19 patients, the organ is more likely "a bystander" affected by the hyperinflammation associated with COVID-19 and by the side effects of related treatments, Nathanson said. advertisement The study noted a relationship between drugs used to treat severe COVID-19 and liver damage, most significantly the drug tocilizumab.

"We observed a strong association between the use of COVID-19 medications and abnormal liver tests," said Lim, but added that they could not confidently tease out that the abnormal tests were due to "drug-induced liver injury" as opposed to the disease. The researchers have additional clinical and lab-based studies underway to further understand COVID-19's impact on liver pathology. Nathanson noted that as one of only four National Institutes of Health-sponsored liver centers in the country, the Yale Liver Center is uniquely positioned to advance this research.

Additional Yale researchers involved in the study include lead author and internal medicine resident Dr. Melanie Hundt; biostatistician Yanhong Deng, co-director of analytics at the Yale Center for Analytical Sciences; and Maria Ciarleglio, associate professor at the Yale School of Public Health.


COVID-19: The virus and the vasculature



Date:August 7, 2020

Source: Ludwig-Maximilians-Universität München


Summary:In severe cases of COVID-19, the infection can lead to obstruction of the blood vessels in the lung, heart and kidneys. Researchers have now shown that activated immune cells and blood platelets play a major role in these pathologies.Share:

FULL STORY

In severe cases of COVID-19, the infection can lead to obstruction of the blood vessels in the lung, heart and kidneys. Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have now shown that activated immune cells and blood platelets play a major role in these pathologies.

The novel coronavirus SARS-CoV-2 infects the respiratory tract and in severe cases, the infection can result in lung failure, which necessitates the use of mechanical ventilation. In addition, these patients develop further complications, such as pulmonary embolisms or thromboses (clots) in their veins. Whether or not virus-associated respiratory failure is functionally related to the systemic increase in the incidence of intravascular clot formation has remained unclear. However, a new study led by LMU clinicians Leo Nicolai and Konstantin Stark, which appears in the journal Circulation, has identified a link between virus-induced changes in the blood vessels of the lung and the increased thrombotic risk. Upon post-mortem examination of the lungs of COVID-19 patients who had died of the disease, Nicolai and colleagues found many microclots within the finest branches of the pulmonary vasculature. Similar observations were made in the heart and the kidney.

These clots were primarily made up of platelets and activated immune cells, in particular neutrophils. Detailed analysis of the thrombi suggested that an activating interaction between platelets and neutrophils is responsible for promoting intravascular coagulation. Neutrophils belong to the innate immune system and their principal task is to fight invading pathogens. Their involvement in abnormal clotting has led to the designation of this process as immunothrombosis. In COVID-19 patients, the stimulation of clot formation eventually compromises the supply of blood to nearby tissues. This in turn ultimately leads to respiratory failure, while the tendency to trigger clotting becomes systemic.

Using multidimensional flow cytometry assays, the LMU researchers showed that in COVID-19 patients who had suffered lung failure and required mechanical ventilation, the numbers of activated neutrophils and platelets in the circulation were greatly enhanced. Since the two cell types reciprocally activate each other, these interactions lead to the formation of obstructive blood clots in the lung. In addition, activated neutrophils extrude mesh-like complexes made up of DNA and cytoplasmatic proteins, which are known as neutrophil extracellular traps (NETs). These normally serve to trap and destroy bacterial and viral pathogens, but they also play a significant role in immunothrombosis by stabilizing thrombi. While this process is initially localized in the lung exacerbating respiratory failure and result in a systemic thrombogenic state.

"These findings contribute to a better understanding of the pathophysiology that underlie disease progression in COVID-19," says Konstantin Stark. "The study also identifies immunothrombosis as a promising target for the prevention and treatment of lung failure and thrombotic complications that arise in cases of COVID-19." make a difference: sponsored opportunity Story Source: Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length. Journal Reference:

  1. Leo Nicolai, Alexander Leunig, Sophia Brambs, Rainer Kaiser, Tobias Weinberger, Michael Weigand, Maximilian Muenchhoff, Johannes C. Hellmuth, Stephan Ledderose, Heiko Schulz, Clemens Scherer, Martina Rudelius, Michael Zoller, Dominik Höchter, Oliver Keppler, Daniel Teupser, Bernhard Zwißler, Michael Bergwelt-Baildon, Stefan Kääb, Steffen Massberg, Kami Pekayvaz, Konstantin Stark. Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy. Circulation, 2020; DOI: 10.1161/CIRCULATIONAHA.120.048488


Ludwig-Maximilians-Universität München. "COVID-19: The virus and the vasculature." ScienceDaily. ScienceDaily, 7 August 2020. <www.sciencedaily.com/releases/2020/08/200807093804.htm>.


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