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A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes
A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19.
In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses.
Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval.
The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients.
Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19.
Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.”
“This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said.
This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28.
-PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0)
-ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/
Graduate School of Medical Science and EngineeringKAIST
2021.08.04 View 10836 -
Study of T Cells from COVID-19 Convalescents Guides Vaccine Strategies
Researchers confirm that most COVID-19 patients in their convalescent stage carry stem cell-like memory T cells for months
A KAIST immunology research team found that most convalescent patients of COVID-19 develop and maintain T cell memory for over 10 months regardless of the severity of their symptoms. In addition, memory T cells proliferate rapidly after encountering their cognate antigen and accomplish their multifunctional roles. This study provides new insights for effective vaccine strategies against COVID-19, considering the self-renewal capacity and multipotency of memory T cells.
COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. When patients recover from COVID-19, SARS-CoV-2-specific adaptive immune memory is developed. The adaptive immune system consists of two principal components: B cells that produce antibodies and T cells that eliminate infected cells. The current results suggest that the protective immune function of memory T cells will be implemented upon re-exposure to SARS-CoV-2.
Recently, the role of memory T cells against SARS-CoV-2 has been gaining attention as neutralizing antibodies wane after recovery. Although memory T cells cannot prevent the infection itself, they play a central role in preventing the severe progression of COVID-19. However, the longevity and functional maintenance of SARS-CoV-2-specific memory T cells remain unknown.
Professor Eui-Cheol Shin and his collaborators investigated the characteristics and functions of stem cell-like memory T cells, which are expected to play a crucial role in long-term immunity. Researchers analyzed the generation of stem cell-like memory T cells and multi-cytokine producing polyfunctional memory T cells, using cutting-edge immunological techniques.
This research is significant in that revealing the long-term immunity of COVID-19 convalescent patients provides an indicator regarding the long-term persistence of T cell immunity, one of the main goals of future vaccine development, as well as evaluating the long-term efficacy of currently available COVID-19 vaccines.
The research team is presently conducting a follow-up study to identify the memory T cell formation and functional characteristics of those who received COVID-19 vaccines, and to understand the immunological effect of COVID-19 vaccines by comparing the characteristics of memory T cells from vaccinated individuals with those of COVID-19 convalescent patients.
PhD candidate Jae Hyung Jung and Dr. Min-Seok Rha, a clinical fellow at Yonsei Severance Hospital, who led the study together explained, “Our analysis will enhance the understanding of COVID-19 immunity and establish an index for COVID-19 vaccine-induced memory T cells.”
“This study is the world’s longest longitudinal study on differentiation and functions of memory T cells among COVID-19 convalescent patients. The research on the temporal dynamics of immune responses has laid the groundwork for building a strategy for next-generation vaccine development,” Professor Shin added. This work was supported by the Samsung Science and Technology Foundation and KAIST, and was published in Nature Communications on June 30.
-Publication:
Jung, J.H., Rha, MS., Sa, M. et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Communications 12, 4043 (2021). https://doi.org/10.1038/s41467-021-24377-1
-Profile:
Professor Eui-Cheol Shin
Laboratory of Immunology & Infectious Diseases (http://liid.kaist.ac.kr/)
Graduate School of Medical Science and Engineering
KAIST
2021.07.05 View 10383 -
ACS Nano Special Edition Highlights Innovations at KAIST
- The collective intelligence and technological innovation of KAIST was highlighted with case studies including the Post-COVID-19 New Deal R&D Initiative Project. -
KAIST’s innovative academic achievements and R&D efforts for addressing the world’s greatest challenges such as the COVID-19 pandemic were featured in ACS Nano as part of its special virtual issue commemorating the 50th anniversary of KAIST. The issue consisted of 14 review articles contributed by KAIST faculty from five departments, including two from Professor Il-Doo Kim from the Department of Materials Science and Engineering, who serves as an associate editor of the ACS Nano.
ACS Nano, the leading international journal in nanoscience and nanotechnology, published a special virtual issue last month, titled ‘Celebrating 50 Years of KAIST: Collective Intelligence and Innovation for Confronting Contemporary Issues.’
This special virtual issue introduced KAIST’s vision of becoming a ‘global value-creative leading university’ and its progress toward this vision over the last 50 years. The issue explained how KAIST has served as the main hub for advanced scientific research and technological innovation in South Korea since its establishment in 1971, and how its faculty and over 69,000 graduates played a key role in propelling the nation’s rapid industrialization and economic development.
The issue also emphasized the need for KAIST to enhance global cooperation and the exchange of ideas in the years to come, especially during the post-COVID era intertwined with the Fourth Industrial Revolution (4IR). In this regard, the issue cited the first ‘KAIST Emerging Materials e-Symposium (EMS)’, which was held online for five days in September of last year with a global audience of over 10,000 participating live via Zoom and YouTube, as a successful example of what academic collaboration could look like in the post-COVID and 4IR eras.
In addition, the “Science & Technology New Deal Project for COVID-19 Response,” a project conducted by KAIST with support from the Ministry of Science and ICT (MSIT) of South Korea, was also introduced as another excellent case of KAIST’s collective intelligence and technological innovation. The issue highlighted some key achievements from this project for overcoming the pandemic-driven crisis, such as: reusable anti-virus filters, negative-pressure ambulances for integrated patient transport and hospitalization, and movable and expandable negative-pressure ward modules.
“We hold our expectations high for the outstanding achievements and progress KAIST will have made by its centennial,” said Professor Kim on the background of curating the 14 review articles contributed by KAIST faculty from the fields of Materials Science and Engineering (MSE), Chemical and Biomolecular Engineering (CBE), Nuclear and Quantum Engineering (NQE), Electrical Engineering (EE), and Chemistry (Chem).
Review articles discussing emerging materials and their properties covered photonic carbon dots (Professor Chan Beum Park, MSE), single-atom and ensemble catalysts (Professor Hyunjoo Lee, CBE), and metal/metal oxide electrocatalysts (Professor Sung-Yoon Chung, MSE).
Review articles discussing materials processing covered 2D layered materials synthesis based on interlayer engineering (Professor Kibum Kang, MSE), eco-friendly methods for solar cell production (Professor Bumjoon J. Kim, CBE), an ex-solution process for the synthesis of highly stable catalysts (Professor WooChul Jung, MSE), and 3D light-patterning synthesis of ordered nanostructures (Professor Seokwoo Jeon, MSE, and Professor Dongchan Jang, NQE).
Review articles discussing advanced analysis techniques covered operando materials analyses (Professor Jeong Yeong Park, Chem), graphene liquid cell transmission electron microscopy (Professor Jong Min Yuk, MSE), and multiscale modeling and visualization of materials systems (Professor Seungbum Hong, MSE).
Review articles discussing practical state-of-the-art devices covered chemiresistive hydrogen sensors (Professor Il-Doo Kim, MSE), patient-friendly diagnostics and implantable treatment devices (Professor Steve Park, MSE), triboelectric nanogenerators (Professor Yang-Kyu Choi, EE), and next-generation lithium-air batteries (Professor Hye Ryung Byon, Chem, and Professor Il-Doo Kim, MSE).
In addition to Professor Il-Doo Kim, post-doctoral researcher Dr. Jaewan Ahn from the KAIST Applied Science Research Institute, Dean of the College of Engineering at KAIST Professor Choongsik Bae, and ACS Nano Editor-in-Chief Professor Paul S. Weiss from the University of California, Los Angeles also contributed to the publication of this ACS Nano special virtual issue.
The issue can be viewed and downloaded from the ACS Nano website at https://doi.org/10.1021/acsnano.1c01101.
Image credit: KAIST
Image usage restrictions: News organizations may use or redistribute this image,with proper attribution, as part of news coverage of this paper only.
Publication:
Ahn, J., et al. (2021) Celebrating 50 Years of KAIST: Collective Intelligence and Innovation for Confronting Contemporary Issues. ACS Nano 15(3): 1895-1907. Available online at https://doi.org/10.1021/acsnano.1c01101
Profile:
Il-Doo Kim, Ph.D
Chair Professor
idkim@kaist.ac.kr
http://advnano.kaist.ac.kr
Advanced Nanomaterials and Energy Lab.
Department of Materials Science and Engineering
Membrane Innovation Center for Anti-Virus and Air-Quality Control
https://kaist.ac.kr/
Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea
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2021.03.05 View 25220 -
Ushering in a New Era at the 50th Innoversary Ceremony
President Moon Jae-In declares KAIST the future of Korea
KAIST reaffirmed its goal of becoming an institute that can serve the world for the next century, marking its 50th anniversary on February 16. The KAIST community and distinguished guests gathered online during the official ceremony to commemorate KAIST’s anniversary and envisioned ways to serve the world, a major shift from its founding mission focusing on national growth.
The ceremony celebrated the legacy of KAIST, which has become a trailblazer by fostering the most competent scientists and engineers and making breakthroughs which led to the nation becoming a global high-tech leader.
President Moon Jae-In applauded KAIST as “the future of Korea” in his online congratulatory message, saying that “KAIST has made us feel proud when the nation stays ahead in science and technology. The dream of KAIST has been the dream of Korea. The passion of KAIST has been the passion of Korea. KAIST is the future of Korea.”
“KAIST has overcome challenges and created innovations for advancing the nation, from the first internet network to launching our first satellite in the early 80s to the Mobile Clinic Module (MCM), a negative pressure ward module in response to COVID-19. Whenever the nation faced a challenge, KAIST was there.”
President Moon also asked KAIST researchers to find sustainable ways to balance nature and humanity in this time of climate change and the Fourth Industrial Revolution.
Executive Chairman of the World Economic Forum Dr.Klaus Schwab also congratulated, saying "KAIST is a leader in ensuring social inclusion. Founded with the support of USAID, today it is paying it forward and sharing the same support through the Kenya-KAIST project."
The ceremony first brought Dr. KunMo Chung to the stage, the man who proposed the idea of founding the first advanced science and technology institute in Korea. His proposal to the then administrator of USAID John Hannah resulted in the Korean government meriting a 6 million USD loan for to start KAIST. He was the only Korean member of the USAID feasibility study team led by Dr. Frederick Terman, the former vice president of Stanford University. Dr. Chung wrote the Terman Report, which gave a green light to the establishment of KAIST in Korea in 1970.
Dr. Chung said the nation’s strong desire to escape from poverty through the advancement of science and technology was thoroughly realized by KAIST. “The Terman Report’s vision was perfectly realized. Now it’s time to envision the next dream of KAIST for another century.”
President Sung-Chul Shin said in his anniversary speech that KAIST has now transformed into a university that will serve the all of humanity by advancing science and technology while fostering new talents best fit for the new global environment. President Shin said that to fulfill KAIST’s second dream, the university will drive innovation in the five major areas of education, research, technology commercialization, globalization, and future strategy, under the C3 spirit of a Challenging spirit, Creativity, and Caring minds.
“In the next 50 years, KAIST hopes to fulfill the 10-10-10 Dream, that is, to have 10 Singularity Professors who have produced world-class achievements, 10 Decacorn startups valued at 10 trillion won, and global campuses in 10 countries.”
Then, four young KAIST professors who are conducting research in the flagship fields of mobility, new materials, post-AI, and bio-medicine presented their research vision and gave speeches. Professor Hae-Won Park from the Department of Mechanical Engineering and Professor Jihyeon Yeom from the Department of Materials Science and Engineering said the advent of new mobility combined with robotics and new nano-materials scaled down into spintronics, ‘KAISTronic materials’, will provide new momentum for the industry and the wellbeing of humanity. Professor Kijung Shin from the Graduate School of AI spoke on the new future transformed by quantum computers. Professor Young Seok Ju from the Graduate School of Medical Science and Engineering predicted a future in which cancer will no longer be a terminal disease and digital cells and the digitization of bio-medicine will significantly improve our quality of life. He said the combination of anti-aging and reverse aging studies will make a difference in our lives.
After the official ceremony, KAIST’s administrative leadership including President Shin and Dr. Kun-Mo Chung attended a ceremony to dedicate the sky lounge at the Academic Cultural Complex as the John Hannah Hall. Terman Hall, located in the Creative Learning Building, was dedicated in 2004 in honor of Dr. Frederick Terman.
2021.02.17 View 11109 -
Top University Leaders Urge Innovation for the Post-COVID Era at the KAIST Summit
- Presidents of KAIST, MIT, Tokyo Tech, and Northwestern to define new roles and responsibilities of universities for the post-COVID and 4IR eras during an online summit in celebration of KAIST’s 50th anniversary. -
Universities are facing ever-mounting pressure to address impacts brought on by COVID-19 and the emerging technologies of the Fourth Industrial Revolution (4IR).
Presidents from MIT, Tokyo Tech, and Northwestern University will join the KAIST Summit to explore new directions for higher education during the post-COVID era intertwined with the 4IR. They agree that addressing these dual challenges requires pushing for innovations to rebuild the competitive edges of universities.
This summit is one of KAIST’s series of events to envision the future of KAIST and higher education in celebration of its 50th anniversary. The online summit will be live streamed on KAIST’s official YouTube channel (https://www.youtube.com/c/KAISTofficial) on February 3, 2021, from 10 a.m. to 12:00 p.m. Korean time (February 2, 7:00-9:00 p.m. CST and 8:00-10:00 p.m. EST, respectively).
The KAIST Summit titled “The Roles and Responsibilities of Universities in a Global Crisis” will discuss a range of issues affecting many aspects of universities in the coming decades.
“This summit will allow us to measure the level of risk that universities face today and will face in the future. Although there will be varying views on what a post-COVID world might look like, one thing for sure is that universities cannot go back to the way they used to exist and operate. Moreover, the 4IR continues to infiltrate and shake up our daily lives. Changes are inevitable, and universities must pursue bold and innovative responses to remain sustainable and relevant to society,” said KAIST President Sung-Chul Shin on the background of hosting the event.
The keynote speakers include KAIST President Shin, MIT President L. Rafael Reif, Tokyo Tech President Kazuya Masu, and Northwestern University President Morton Schapiro. After the keynote speech session, the speakers will take part in a panel discussion on three topics: “The Digital Divide,” “Emerging Challenges in AI,” and “Social Entrepreneurship and University-Industry Collaboration.” A Q&A session with an online audience consisting of KAIST faculty, staff, and students as well as high school students across the nation will follow shortly afterwards.
President Reif of MIT will congratulate KAIST on its successful 50-year journey from meager beginnings to achieving its current status as one of the finest global universities in science and technology. Then he will give a talk titled “Universities as Engines of Change” to present how universities have played a critical role in advancing solutions to humanity’s most urgent problems.
President Masu of Tokyo Tech will stress the importance of universities’ continuous dialogue with society as drivers of innovation. In his speech titled “Designing Our Future—Tokyo Tech DLab’s Approach,” he will introduce the activities of Tokyo Tech’s Laboratory for Design of Social Innovation in Global Networks (DLab) and explain how DLab collaborates for the future with members of society.
President Schapiro of Northwestern University will speak about how universities might incorporate the lessons they learned in dealing with COVID-19 to improve their research, teaching, and public service in the post-pandemic era. He will also look into issues arising from changing labor market needs associated with the 4IR and the aftermath of COVID-19 in his talk titled “The University in the ‘New Normal.’”
Finally, President Shin of KAIST will deliver a presentation on the “Visions & Innovations for the Next Dream of KAIST.” He will reflect on the remarkable track record from KAIST’s first 50 years and how it has contributed significantly to the rapid growth of Korea as a hi-tech powerhouse. Furthermore, he will elaborate on a new vision for the development of KAIST over the next 50 years and roll out a set of strategic innovation plans in the five areas of education, research, technology commercialization, globalization, and future strategy.
In the panel discussion, the four presidents will dive into a more intense conversation on such topics as universities’ role in bridging the increasing digital divide through their research, education, and international cooperation; the socioeconomic implications and ethical challenges of the fast deployment of AI and robotics; 4IR disruptions that will transform higher education; ways to foster social innovation and youth entrepreneurship; and how to build university-industry cooperation.
More information on KAIST’s 50th anniversary celebrations can be found on its special celebratory website at https://50.kaist.ac.kr/eng/. The official anniversary ceremony is scheduled for February 16, 2021, from 10 a.m. Korean time, and live-streaming will also be made available on KAIST’s official YouTube channel at https://www.youtube.com/c/KAISTofficial.
(END)
2021.02.01 View 12544 -
Professor Kyu-Young Whang Donates Toward the 50th Anniversary Memorial Building
Distinguished Professor Kyu-Young Whang from the School of Computing made a gift of 100 million KRW toward the construction of the 50th Anniversary Memorial Building during a ceremony on November 3 at the Daejeon campus. "As a member of the first class of KAIST, I feel very delighted to play a part in the fundraising campaign for the 50th anniversary celebration. This is also a token of appreciation to my alma mater and I look forward to alumni and the KAIST community joining this campaign," said Professor Emeritus Whang. KAIST will name the Kyu-Young Whang and Jonghae Song Christian Seminar Room at the 50th Anniversary Memorial Building. The ground will be broken in 2022 for construction of the building.
2020.11.04 View 5341 -
'Mini-Lungs' Reveal Early Stages of SARS-CoV-2 Infection
Researchers in Korea and the UK have successfully grown miniature models of critical lung structures called alveoli, and used them to study how the coronavirus that causes COVID-19 infects the lungs.
To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, the virus that causes COVID-19, especially in patients that develop pneumonia, appear to be alveoli – tiny air sacs in the lungs that take up the oxygen we breathe and exchange it with carbon dioxide to exhale.
To better understand how SARS-CoV-2 infects the lungs and causes disease, a team of Professor Young Seok Ju from the Graduate School of Medical Science and Engineering at KAIST in collaboration with the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge turned to organoids – ‘mini-organs’ grown in three dimensions to mimic the behaviour of tissue and organs.
The team used tissue donated to tissue banks at the Royal Papworth Hospital NHS Foundation Trust and Addenbrooke’s Hospital, Cambridge University NHS Foundations Trust, UK, and Seoul National University Hospital to extract a type of lung cell known as human lung alveolar type 2 cells. By reprogramming these cells back to their earlier ‘stem cell’ stage, they were able to grow self-organizing alveolar-like 3D structures that mimic the behaviour of key lung tissue.
“The research community now has a powerful new platform to study precisely how the virus infects the lungs, as well as explore possible treatments,” said Professor Ju, co-senior author of the research.
Dr. Joo-Hyeon Lee, another co-senior author at the Wellcome-MRC Cambridge Stem Cell Institute, said: “We still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease. Our approach has allowed us to grow 3D models of key lung tissue – in a sense, ‘mini-lungs’ – in the lab and study what happens when they become infected.”
The team infected the organoids with a strain of SARS-CoV-2 taken from a patient in Korea who was diagnosed with COVID-19 on January 26 after traveling to Wuhan, China. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.
When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infection. Replication enables the virus to spread throughout the body, infecting other cells and tissue.
Around the same time, the cells began to produce interferons – proteins that act as warning signals to neighbouring cells, telling them to activate their antiviral defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infection.
Sixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.
Although the researchers observed changes to the lung cells within three days of infection, clinical symptoms of COVID-19 rarely occur so quickly and can sometimes take more than ten days after exposure to appear. The team say there are several possible reasons for this. It may take several days from the virus first infiltrating the upper respiratory tract to it reaching the alveoli. It may also require a substantial proportion of alveolar cells to be infected or for further interactions with immune cells resulting in inflammation before a patient displays symptoms.
“Based on our model we can tackle many unanswered key questions, such as understanding genetic susceptibility to SARS-CoV-2, assessing relative infectivity of viral mutants, and revealing the damage processes of the virus in human alveolar cells,” said Professor Ju. “Most importantly, it provides the opportunity to develop and screen potential therapeutic agents against SARS-CoV-2 infection.”
“We hope to use our technique to grow these 3D models from cells of patients who are particularly vulnerable to infection, such as the elderly or people with diseased lungs, and find out what happens to their tissue,” added Dr. Lee.
The research was a collaboration involving scientists from KAIST, the University of Cambridge, Korea National Institute of Health, Institute for Basic Science (IBS), Seoul National University Hospital and Genome Insight in Korea.
- ProfileProfessor Young Seok JuLaboratory of Cancer Genomics https://julab.kaist.ac.kr the Graduate School of Medical Science and EngineeringKAIST
2020.10.26 View 9863 -
Biomarker Predicts Who Will Have Severe COVID-19
- Airway cell analyses showing an activated immune axis could pinpoint the COVID-19 patients who will most benefit from targeted therapies.-
KAIST researchers have identified key markers that could help pinpoint patients who are bound to get a severe reaction to COVID-19 infection. This would help doctors provide the right treatments at the right time, potentially saving lives. The findings were published in the journal Frontiers in Immunology on August 28.
People’s immune systems react differently to infection with SARS-CoV-2, the virus that causes COVID-19, ranging from mild to severe, life-threatening responses.
To understand the differences in responses, Professor Heung Kyu Lee and PhD candidate Jang Hyun Park from the Graduate School of Medical Science and Engineering at KAIST analysed ribonucleic acid (RNA) sequencing data extracted from individual airway cells of healthy controls and of mildly and severely ill patients with COVID-19. The data was available in a public database previously published by a group of Chinese researchers.
“Our analyses identified an association between immune cells called neutrophils and special cell receptors that bind to the steroid hormone glucocorticoid,” Professor Lee explained. “This finding could be used as a biomarker for predicting disease severity in patients and thus selecting a targeted therapy that can help treat them at an appropriate time,” he added.
Severe illness in COVID-19 is associated with an exaggerated immune response that leads to excessive airway-damaging inflammation. This condition, known as acute respiratory distress syndrome (ARDS), accounts for 70% of deaths in fatal COVID-19 infections.
Scientists already know that this excessive inflammation involves heightened neutrophil recruitment to the airways, but the detailed mechanisms of this reaction are still unclear.
Lee and Park’s analyses found that a group of immune cells called myeloid cells produced excess amounts of neutrophil-recruiting chemicals in severely ill patients, including a cytokine called tumour necrosis factor (TNF) and a chemokine called CXCL8.
Further RNA analyses of neutrophils in severely ill patients showed they were less able to recruit very important T cells needed for attacking the virus. At the same time, the neutrophils produced too many extracellular molecules that normally trap pathogens, but damage airway cells when produced in excess.
The researchers additionally found that the airway cells in severely ill patients were not expressing enough glucocorticoid receptors. This was correlated with increased CXCL8 expression and neutrophil recruitment.
Glucocorticoids, like the well-known drug dexamethasone, are anti-inflammatory agents that could play a role in treating COVID-19. However, using them in early or mild forms of the infection could suppress the necessary immune reactions to combat the virus. But if airway damage has already happened in more severe cases, glucocorticoid treatment would be ineffective.
Knowing who to give this treatment to and when is really important. COVID-19 patients showing reduced glucocorticoid receptor expression, increased CXCL8 expression, and excess neutrophil recruitment to the airways could benefit from treatment with glucocorticoids to prevent airway damage. Further research is needed, however, to confirm the relationship between glucocorticoids and neutrophil inflammation at the protein level.
“Our study could serve as a springboard towards more accurate and reliable COVID-19 treatments,” Professor Lee said.
This work was supported by the National Research Foundation of Korea, and Mobile Clinic Module Project funded by KAIST.
Figure. Low glucocorticoid receptor (GR) expression led to excessive inflammation and lung damage by neutrophils through enhancing the expression of CXCL8 and other cytokines.
Image credit: Professor Heung Kyu Lee, KAIST. Created with Biorender.com.
Image usage restrictions: News organizations may use or redistribute these figures and image, with proper attribution, as part of news coverage of this paper only.
-Publication:
Jang Hyun Park, and Heung Kyu Lee. (2020). Re-analysis of Single Cell Transcriptome Reveals That the NR3C1-CXCL8-Neutrophil Axis Determines the Severity of COVID-19. Frontiers in Immunology, Available online at https://doi.org/10.3389/fimmu.2020.02145
-Profile: Heung Kyu Lee
Associate Professor
heungkyu.lee@kaist.ac.kr
https://www.heungkyulee.kaist.ac.kr/
Laboratory of Host Defenses
Graduate School of Medical Science and Engineering (GSMSE)
The Center for Epidemic Preparedness at KAIST Institute
http://kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
Profile: Jang Hyun Park
PhD Candidate
janghyun.park@kaist.ac.kr
GSMSE, KAIST
2020.09.17 View 13349 -
Professor Park at UPC-Barcelona Tech Receives Jeong Hun Cho Award
Professor Hyuk Park was honored to be the recipient of the Jeong Hun Cho Award which was presented at the Universitat Politècnica de Catalunya Barcelona Tech. The award recognizes young scientists in the field of aerospace engineering.
Professor Park, a graduate of KAIST’s Department of Mechanical Engineering in 2001, earned his MS and PhD at the Gwangju Institute of Science and Technology, and works at the Castelldefels School of Telecommunications and Aerospace Engineering at UPC-Barcelona Tech. He won this year’s award, which honors former PhD candidate Jeong Hun Cho at the Aerospace Engineering Department who died in a lab accident in 2003. Professor Park also received 25 million KRW prize money. Cho’s family endowed the award and scholarship in his memory. Since 2005, the scholarship has selected three young scholars every year who specialize in aerospace engineering from Cho’s alma maters of KAIST, Korea University, and Kongju National University High School.
Professor Park was selected as this year’s awardee in recognition of his studies of synthetic-aperture radar (SAR) satellite radiometer system, remote sensing radio frequency interference reduction system development, and 3CAT series research.
The Award Committee also chose three students for scholarships: PhD candidate Sang-Woo Chung from the Department of Aerospace Engineering at KAIST with 4 million KRW, PhD candidate Eun-Hee Kang from the School of Mechanical Engineering at Korea University with 4 million KRW, and Chan-Ho Song from Kongju National University High School with 3 million KRW.
2019.05.14 View 6144 -
KAIST-KU Joint Research Center for Smart Healthcare & Transportation
(President Shin shakes hands with KU acting Presidedent Arif Al Hammdi at the KAIST-KU Joint Research Center opening ceremony on April 8.)
KAIST opened the KAIST-Khalifa University Joint Research Center with Khalifa University on April 8. The opening ceremony was held at Khalifa University and was attended by President Sung-Chul Shin and Khalifa University Acting President Arif Al Hammadi.
The new research center reflects the evolution of the long-established partnership between the two institutions. The two universities have already made very close collaborations in research and education in the fields of nuclear and quantum engineering.
The launch of this center expanded their fields of collaboration to smart healthcare and smart transportation, key emerging sectors in the Fourth Industrial Revolution. President Shin signed an MOU with the UAE Minister of State for Advanced Science Sarah Amiri and Khalifa University to expand mutual collaboration in technology development and fostering human capital last year.
The center will conduct research and education on autonomous vehicles, infrastructure for autonomous vehicle operation, wireless charging for electric vehicles, and infrastructure for electric autonomous vehicles. As for smart healthcare, the center will focus on healthcare robotics as well as sensors and wearable devices for personal healthcare services.
President Shin, who accompanied a research team from the Graduate School of Green Transportation, said, “We are very delighted to enter into this expanded collaboration with KU. This partnership justifies our long-standing collaboration in the areas of emerging technologies in the Fourth Industrial Revolution while fostering human capital.”
KU Acting President Arif Al Hammadi added, “The outcome of these research projects will establish the status of both institutions as champions of the Fourth Industrial Revolution, bringing benefits to our communities. We believe the new research center will further consolidate our status as a globally active, research-intensive academic institution, developing international collaborations that benefit the community in general.”
2019.04.09 View 6799 -
The Center for Anthropocene Studies (CAS) Opens
KAIST will start Anthropocene research, a convergence field of study, to address issues related to the commencement of human activities that have had scientific, industrial, and economic impacts on the Earth’s ecosystem. The National Research Foundation (NRF) of Korea endorsed the KAIST Center for Anthropocene Studies as its Convergence Research Center project.
Anthropocene refers to a new geological age in which various polluting materials that humans have made during the post-industrial revolution era have made a significant impact on the Earth and the lives of humankind. The studies expand the diverse socio-economic and environmental sectors for responding to climate change, natural disasters, ecological destruction, the polarization of the inequality and wealth, and many others.
The KAIST research group at the center, in collaboration with the Graduate School of Science and Technology Policy, the Graduate School of Culture Technology, the School of Humanities & Social Sciences, the Department of Industrial Design, the School of Electrical Engineering, the Satellite Technology Research Center (SaRTec), and the KAIST Initiative for Disaster Studies will conduct multidisciplinary research to address intriguing challenges with complex but creative approaches incorporating the fields of engineering, socioeconomics, and art.
The group will investigate topics such as▲ surface and marine changes to the Earth by applying satellite data ▲disaster prediction and governance system building through AI modeling ▲sustainable housing, transportation, and lifestyles ▲ engineering and artistic approaches for envisioning a new future for humankind and the Earth.
Professor Buhm Soon Park, who is in charge of the center, said, “This pioneering research work will inspire the re-creation of a new paradigm of convergence studies in science, engineering, humanities, and social science. We will contribute to making the world better by designing new technologies and social policies.
2018.06.05 View 9749 -
Professor Il-Doo Kim Recevies the Song-gok Award
Professor Il-Doo Kim from the Department of Materials Science and Engineering at KAIST received the 20th Song-gok Science and Technology Award from Korea Institute of Science and Technology (KSIT).
The Song-gok Science and Technology Award was established to praise the accomplishments of the first president, Hyung-seop Choi, whose penname is Song-gok. The award selects a recipient in the field of materials and technology every other year.
Professor Kim, in recognition of his outstanding research and contributions to materials science in Korea, received the award during the 52nd anniversary ceremony of KIST on February 9.
Professor Kim focuses on developing nanofiber gas sensors for diagnosing disease in advance by analyzing exhaled biomarkers with electrospinning technology.
He has published more than 211 papers and has recorded more than 9,650 citations and 50 h-index.
Professor Kim has registered 107 patents and applied 38 patents in Korea while registering 29 patents and applying 16 patents overseas. Also, he transferred four technologies in 2017.
Professor Kim is recognized as one of the researchers who is leading nanofiber technology. On January 17, he made a keynote speech at the 5th International Conference on Electrospinning, which was his fourth keynote speech at that conference.
Moreover, he received the Technology Innovation Award at the College of Engineering, KAIST on December 19, 2017.
Professor Kim said, “It is my great honor to receive the Song-gok Science and Technology Award. I would like to bring distinction to KAIST by taking the lead in the commercializing a nanofiber-based highly sensitive nanosensors, diversifying and commercializing technology using nanofiber.”
2018.02.13 View 7292