Antibody blockade effective in treatment of severe COVID-19

August 31, 2020

Osaka, Japan - As countries around the world race to develop a vaccine for SARS-CoV-2, the virus responsible for COVID-19, researchers are working to understand exactly how it causes the myriad of symptoms that seem to linger long after active viral infection. In a study published in scientific journal PNAS, researchers led by Osaka University identified an effective treatment for the deadly over-activation of the inflammatory response seen in many severe COVID-19 patients.

Cytokines are a group of small proteins that can either enhance or inhibit our body's immune response to infection, trauma, and diseases such as cancer. One of their main roles is to stimulate inflammation, which initiates the healing process. The problem is, overstimulation of the inflammatory response has an array of harmful complications, ranging from asthma to severe autoimmune diseases. One such complication, called cytokine release syndrome (CRS), is seen in patients suffering a hyperimmune response to microbial infection or trauma and can lead to multiple organ failure and even death.

"Despite knowing which cytokines are involved, there is still no specific immunotherapy for CRS and treatment is limited to supportive care," says study lead author Sujin Kang. "To better understand the molecular mechanisms of CRS pathogenesis, we first studied the cytokine profiles of 91 patients diagnosed with CRS associated with bacterial sepsis, acute respiratory distress syndrome, or burns."

Strikingly, patients from all three groups had elevated levels of proinflammatory cytokines IL-6, IL-8, IL-10, and MCP-10, as well as a protein called PAI-1, which causes small blood clots in vessels throughout the body, including the lungs. Importantly, increased PAI-1 levels are associated with more severe cases of pneumonia, a common cause of death among COVID-19 patients.

Because IL-6 was positively associated with the levels of the other cytokines and PAI-1, the researchers concluded that IL-6 signaling is crucial for the development of CRS following infection or trauma, and may play a role in the pathogenesis of COVID-19.

"Examination of cytokine profiles in severe COVID-19 patients revealed an increase in IL-6 early in the disease process, causing release of PAI-1 from blood vessels," says study senior author Tadamitsu Kishimoto. "Interestingly, PAI-1 levels were significantly higher in COVID-19 patients with severe respiratory impediment."

Most significantly though, when severe COVID-19 patients were treated with a human monoclonal antibody-based drug called Actemra®, which blocks IL-6 signaling, PAI-1 levels rapidly declined and severe disease symptoms were alleviated. IL-6 signaling blockade could therefore prove useful for the treatment of both CRS and the severe respiratory complications of COVID-19.
-end-
The article, "IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome," was published in Proceedings of the National Academy of Sciences of the United States of America at DOI: https://doi.org/10.1073/pnas.2010229117.

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en/top

Osaka University

Related Infection Articles from Brightsurf:

Halving the risk of infection following surgery
New analysis by the University of Leeds and the University of Bern of more than 14,000 operations has found that using alcoholic chlorhexidine gluconate (CHG) halves the risk of infection in certain types of surgery when compared to the more commonly used povidone-iodine (PVI).

How plants shut the door on infection
A new study by an international team including University of Maryland scientists has discovered the key calcium channel responsible for closing plant pores as an immune response to pathogen exposure.

Sensing infection, suppressing regeneration
UIC researchers describe an enzyme that blocks the ability of blood vessel cells to self-heal.

Boost to lung immunity following infection
The strength of the immune system in response to respiratory infections is constantly changing, depending on the history of previous, unrelated infections, according to new research from the Crick.

Is infection after surgery associated with increased long-term risk of infection, death?
Whether experiencing an infection within the first 30 days after surgery is associated with an increased risk of another infection and death within one year was the focus of this observational study that included about 660,000 veterans who underwent major surgery.

Revealed: How E. coli knows how to cause the worst possible infection
The discovery could one day let doctors prevent the infection by allowing E. coli to pass harmlessly through the body.

UK study shows most patients with suspected urinary tract infection and treated with antibiotics actually lack evidence of this infection
New research presented at this week's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (April 13-16, 2019) shows that only one third of patients that enter the emergency department with suspected urinary tract infection (UTI) actually have evidence of this infection, yet almost all are treated with antibiotics, unnecessarily driving the emergence of antimicrobial resistance.

Bacteria in urine doesn't always indicate infection
Doctors should think carefully before testing patients for a urinary tract infection (UTI) to avoid over-diagnosis and unnecessary antibiotic treatment, according to updated asymptomatic bacteriuria (ASB) guidelines released by the Infectious Diseases Society of America (IDSA) and published in Clinical Infectious Diseases.

Subsidies for infection control to healthcare institutions help reduce infection levels
Researchers compared three types of infection control subsidies and found that under a limited budget, a dollar-for-dollar matching subsidy, in which policymakers match hospital spending for infection control measures, was the most effective at reducing the number of hospital-acquired infections.

Dengue virus infection may cause severe outcomes following Zika virus infection during pregnancy
This study is the first to report a possible mechanism for the enhancement of Zika virus progression during pregnancy in an animal model.

Read More: Infection News and Infection Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.