Biogen has announced it has entered into a definitive agreement to acquire Human Immunology Biosciences (HI-Bio) in a deal worth more than $1.8bn, gaining access to its lead asset to improve a range of immune-mediated and rare diseases. Anticipated to close in the third quarter of 2024, the acquisition will expand Biogens immunology portfolio while also addressing the serious unmet needs of three renal diseases. Immune-mediated diseases result from an abnormal immune system response, which causes the immune system to mistakenly target the body and create an inflammatory response that causes damage. Under the terms of the agreement, HI-Bio will receive an upfront payment of 1.15bn and will be eligible for additional payments of up to $650m contingent on certain development milestones. As part of the deal, Biogen will gain access to HI-Bios lead asset, felzartamab, an investigational fully human anti-CD38 monoclonal antibody that has been shown to selectively deplete CD38+ cells in a broad range of immune-mediated diseases, as well as its izastobart/HIB210, an anti-C5aR1 antibody in development to treat a range of complement-mediated diseases. Furthermore, Biogen aims to establish a San Francisco Bay Area team focused on expanding efforts in immune-mediated diseases. Felzartamab has already received Breakthrough Therapy Designation and Orphan Drug Designation (ODD) from the US Food and Drug Administration to treat primary membranous nephropathy and has received ODD to treat antibody-mediated rejection in kidney transplant recipients. In addition, phase 2 studies have been completed in both indications and remain ongoing in IgA nephropathy, a chronic kidney disease, with plans to advance each indication to phase 3. Priya Singhal, head of development, Biogen, commented: We believe this late-stage asset is a strategic addition to the Biogen portfolio as we continue to augment our pipeline and build on our expertise in immunology. We look forward to advancing potential therapies for patients with rare immune diseases with high unmet need. In July 2023, Biogen entered into a definitive agreement to acquire rare disease specialist Reata Pharmaceuticals in a deal worth approximately $7.3bn to gain access to the biotechs Skyclarys (omaveloxolone), the only US-approved treatment for Friedreichs ataxia, a rare and inherited neurologic disorder.
Read this article:
Biogen to expand immunology and rare disease portfolio with $1.8bn HI-Bio acquisition - PMLiVE
Biogen announced it will buy Human Immunology Biosciences (HI-Bio) in a deal worth up to $1.8 billion Wednesday morning.
Per terms of the transaction, Biogen will make an upfront payment of $1.15 billion to HI-Bio and the latters stockholders will be eligible for payments of up to an additional $650 million dependent on developmental milestones for the felzartamab programs.
The transaction is being financed by Biogens cash reserves and is expected to close in Q3, following customary closing conditions and regulatory approvals.
Felzartamab is HI-Bios lead investigational therapeutic human monoclonal antibody directed against CD38. The asset was originally developed by MorphoSys AG for treating multiple myeloma and has shown the ability to selectively deplete CD38+ plasma cells and natural killer cells in multiple Phase 2 studies.
This has prompted HI-Bio to plan on advancing these indications including primary membranous nephropathy (PMN), antibody-mediated rejection (AMR) and IgA nephropathy (IgAN) to Phase 3 trials.
Additionally, Biogen is picking up izastobart/HIB210, an anti-C5aR1 antibody currently in a Phase 1 trial, as well as HI-Bios discovery stage mast cell programs focused on treating a range of immune-mediated diseases.
Biogen stated in a company press release that it seeks to retain expertise and talent from HI-Bio and create a team based in the Bay Area to expand its efforts in immune-mediated diseases.
We believe this late-stage asset, which has demonstrated impact on key biomarkers and clinical endpoints in three renal diseases with serious unmet needs, is a strategic addition to the Biogen portfolio as we continue to augment our pipeline and build on our expertise in immunology, said Priya Singhal, MD, MPH, head of development at Biogen, in a statement. We look forward to welcoming HI-Bio employees into Biogen and, together, working to advance potential therapies for patients with rare immune diseases with high unmet need.
The HI-Bio deal was released about a month afterBiogen topped analyst expectationswith its latest quarterly earnings report.
While Biogens total revenue dropped 7% to $2.2 billion, its GAAP operating income grew 10% and its non-GAAP diluted earnings per share (EPS) rose 8% to $3.67 in Q1.
In light of the solid top line performance, Biogen reaffirmed its full-year financial guidance, which is not expected to be negatively impacted by the HI-Bio acquisition.
See the article here:
Biogen to buy Human Immunology Biosciences in deal worth up to $1.8B - MM+M Online
The COVID-19 pandemic is over, but the virus that caused it is still here, sending thousands of people to the hospital each week and spinning off new variants with depressing regularity. The viruss exceptional ability to change and evade immune defenses has led the World Health Organization (WHO) to recommend annual updates to COVID-19 vaccines.
But some scientists worry that the remarkable success of the first COVID-19 vaccines may work against updated versions, undermining the utility of an annual vaccination program. A similar problem plagues the annual flu vaccine campaign; immunity elicited by one years flu shots can interfere with immune responses in subsequent years, reducing the vaccines effectiveness.
A new study by researchers at Washington University School of Medicine in St. Louis helps to address this question. Unlike immunity to influenza virus, prior immunity to SARS-CoV-2, the virus that causes COVID-19, doesnt inhibit later vaccine responses. Rather, it promotes the development of broadly inhibitory antibodies, the researchers report.
The study, available online in Nature, shows that people who were repeatedly vaccinated for COVID-19 initially receiving shots aimed at the original variant, followed by boosters and updated vaccines targeting variants generated antibodies capable of neutralizing a wide range of SARS-CoV-2 variants and even some distantly related coronaviruses. The findings suggest that periodic re-vaccination for COVID-19, far from hindering the bodys ability to recognize and respond to new variants, may instead cause people to gradually build up a stock of broadly neutralizing antibodies that protect them from emerging SARS-CoV-2 variants and some other coronavirus species as well, even ones that have not yet emerged to infect humans.
The first vaccine an individual receives induces a strong primary immune response that shapes responses to subsequent infection and vaccination, an effect known as imprinting, said senior authorMichael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine. In principle, imprinting can be positive, negative or neutral. In this case, we see strong imprinting that is positive, because its coupled to the development of cross-reactive neutralizing antibodies with remarkable breadth of activity.
Imprinting is the natural result of how immunological memory works. A first vaccination triggers the development of memory immune cells. When people receive a second vaccination quite similar to the first, it reactivates memory cells elicited by the first vaccine. These memory cells dominate and shape the immune response to the subsequent vaccine.
Subscribe to Technology Networks daily newsletter, delivering breaking science news straight to your inbox every day.
To understand how imprinting influences the immune response to repeat COVID-19 vaccination, Diamond and colleagues including first author Chieh-Yu Liang, a graduate student, studied the antibodies from mice or people who had received a sequence of COVID-19 vaccines and boosters targeting first the original and then omicron variants. Some of the human participants also had been naturally infected with the virus that causes COVID-19.
The first question was the strength of the imprinting effect. The researchers measured how many of the participants neutralizing antibodies were specific for the original variant, the omicron variant or both. They found that very few people had developed any antibodies unique to omicron, a pattern indicative of strong imprinting by the initial vaccination. But they also found few antibodies unique to the original variant. The vast majority of neutralizing antibodies cross-reacted with both.
The next question was how far the cross-reactive effect extended. Cross-reactive antibodies, by definition, recognize a feature shared by two or more variants. Some features are shared only by similar variants, others by all SARS-CoV-2 variants or even all coronaviruses. To assess the breadth of the neutralizing antibodies, the researchers tested them against a panel of coronaviruses, including SARS-CoV-2 viruses from two omicron lineages; a coronavirus from pangolins; the SARS-1 virus that caused the 2002-03 SARS epidemic; and the Middle Eastern Respiratory Syndrome (MERS) virus. The antibodies neutralized all the viruses except MERS virus, which comes from a different branch of the coronavirus family tree than the others.
Further experiments revealed that this remarkable breadth was due to the combination of original and variant vaccines. People who received only the vaccines targeting the original SARS-CoV-2 variant developed some cross-reactive antibodies that neutralized the pangolin coronavirus and SARS-1 virus, but the levels were low. After boosting with an omicron vaccine, though, the cross-reactive neutralizing antibodies against the two coronavirus species increased.
Taken together, the findings suggest that regular re-vaccination with updated COVID-19 vaccines against variants might give people the tools to fight off not only the SARS-CoV-2 variants represented in the vaccines, but also other SARS-CoV-2 variants and related coronaviruses, possibly including ones that have not yet emerged.
At the start of the COVID-19 pandemic, the world population was immunologically nave, which is part of the reason the virus was able to spread so fast and do so much damage, said Diamond, also a professor of molecular microbiology and of pathology & immunology. We do not know for certain whether getting an updated COVID-19 vaccine every year would protect people against emerging coronaviruses, but its plausible. These data suggest that if these cross-reactive antibodies do not rapidly wane we would need to follow their levels over time to know for certain they may confer some or even substantial protection against a pandemic caused by a related coronavirus.
Reference:Liang CY, Raju S, Liu Z, et al. Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines. Nature. 2024. doi: 10.1038/s41586-024-07539-1
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.
Original post:
COVID-19 Re-Vaccinations Elicit Neutralizing Antibodies Against Future Variants - Technology Networks
Register for free to listen to this article
Thank you. Listen to this article using the player above.
Want to listen to this article for FREE?
Complete the form below to unlock access to ALL audio articles.
Infection with HIV is currently manageable with lifelong antiretroviral medications, but neither a vaccine nor a cure is available. A critical roadblock in preventative vaccine development has been the inability to induce B-cell lineages of broadly neutralizing antibodies (bnAbs) that can combat rapidly evolving strains of the virus.
Now, an HIV vaccine candidate has reportedly triggered low levels of HIV bnAbs among a small group of people enrolled in a 2019 clinical trial.
The findings, reported in the journal Cell, not only provide proof that a vaccine can elicit bnAbs to fight diverse strains of HIV but that it can also initiate the process within weeks.
The vaccine candidate developed at the Duke Human Vaccine Institute targets an area on the HIV-1 outer envelope called the membrane-proximal external region (MPER), which remains stable even as the virus mutates. bnAbs against this stable region in the HIV-1 outer coat can block infection by many different circulating strains of HIV-1.
Discussing the decision to target the MPER of the HIV-1 outer envelope, Dr. Barton Haynes, director of the Duke Human Vaccine Institute, told Technology Networks, The MPER is targeted by the broadest of the neutralizing antibodies. We have isolated a version of MPER bnAbs from a person living with HIV that neutralized 99% of HIV strains.
Interfering with the interaction of the HIV-1 outer envelope with its host cell receptors, bnAbs interrupt viral replication through a mechanism that differs from most antiretroviral drugs. bnAbs can augment host antiviral immune responses by engaging effector responses. Their long in vivo half-life and favorable safety profile make them attractive clinical application candidates.
Potent bnAbs develop in people living with HIV-1, but only rarely and after many months to years after transmission. One of the questions we have worried about for many years is if it will take years to induce bnAbs with a vaccine like it takes for bnAbs to develop in people living with HIV, explained Haynes. Here we found that bnAb lineages developed after the second immunization.
The research team analyzed data from the HVTN 133 Phase 1 clinical trial. Twenty healthy, HIV-negative individuals enrolled in the trial. Fifteen participants received two of four planned doses of the investigational vaccine, and five received three doses.
After two immunizations, the vaccine showed a 95% serum response rate and a 100% blood CD4+ T-cell response rate, indicating strong immune activation.
Crucial immune cells remained in a state of development that allowed them to continue acquiring mutations so that they could evolve alongside the constantly changing virus.
The trial was halted when one participant experienced a non-lifethreatening allergic reaction. We suspect that the allergic reaction was a reaction to polyethelene glycol (PEG) and have studied such responses in vitro, said Haynes. We have evidence that this is the case and have remade the vaccine as a PEG-less MPER peptide-liposome for retesting in humans at lower doses. The latter lower doses because the vaccine worked better in the trial at the low dose.
While scientists have been striving to produce an HIV vaccine since the 1980s, several features of the virus have made it difficult to develop an effective vaccine.
A signature of HIV infection is its vast genetic diversity and the virus's ability to evolve rapidly within and between infected individuals. Scientists have identified that an effective HIV vaccine will need to be able to produce an immune response that can prevent infection by the diverse HIV strains circulating in the world.
Subscribe to Technology Networks daily newsletter, delivering breaking science news straight to your inbox every day.
This work shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV and has provided important insights into the design and feasibility of HIV-1 vaccine development efforts.
Discussing the steps they are taking to improve the vaccine, Haynes said, We have added additional regions of the MPER to give the response more potency and breadth. We have deleted PEG from the vaccine, and we have designed mRNAs that boost the responses induced by the original vaccine.
The researchers stress there is still more work to be done to create a more robust response. They hope to replicate what was done in this research with immunogens that target the other vulnerable sites on the virus envelope.
Dr. Barton Haynes was speaking to Blake Forman, Senior Science Writer and Editor for Technology Networks.
About the interviewee:
Dr. Barton Haynes is the Frederic M. Hanes Professor of Medicine and Immunology, and director of the Duke Human Vaccine Institute. Haynes leads a team of investigators working on vaccines for emerging infections, including tuberculosis, pandemic influenza, emerging coronaviruses and HIV/AIDS.
Reference: Williams WB, Alam SM, Ofek G, et al. Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans. Cell. 2024. doi: 10.1016/j.cell.2024.04.033
Visit link:
HIV Vaccine Candidate Induces Broadly Neutralizing Antibodies in Humans - Technology Networks
Inaugurated this Friday (5/17), the Pasteur Fiocruz Center on Immunology and Immunotherapy, located at Fiocruz Cear, brings together scientists from the Institut Pasteur and Fiocruz, two members of the Pasteur Network, to develop an integrative approach towards immunotherapies applied to both infectious and non-communicable diseases. This scientific cooperation aims to accelerate research in immunology and immunotherapy at regional, national, and international levels. It counts on the support of the Cear state government and the French Ministry for Europe and Foreign Affairs, through its Embassy in Brasilia.
Participating in the inauguration ceremony were the president of Fiocruz, Mario Moreira; the senior executive vice-president of Scientific Affairs at the Institut Pasteur, Christophe dEnfert; the governor of the State of Cear, Elmano de Freitas; the French ambassador to Brazil, Emmanuel Lenain. The Secretary of Science, Technology, Innovation and Health Complex of the Ministry of Health (SECTICS/MS), Carlos Gadelha, was representing the minister of Health, Nisia Trindade. The ceremony also included the participation of the vice-president of Education, Information and Communication (VPEIC/Fiocruz), Cristiani Vieira Machado; the coordinator of the Fiocruz Agenda 2030 Strategy (EFA 2030/Fiocruz), Paulo Gadelha;the coordinator of Fiocruz Cear, Carla Celidnio; the consul general of France, Serge Gas; the special advisor to the Presidency of Fiocruz for Cooperation with French Institutions, Wilson Savino; and the mayor of Eusbio, Acilon Gonalves Pinto Filho, as well as members of the Pasteur Network in the Americas, such as the Institut Armand Frappier, Institut Pasteur de Guadeloupe, Institut Pasteur de Guyanne, Institut Pasteur de So Paulo and Institut Pasteur de Montevideo.
A new model of collaboration
The new Center is located in Fiocruz Cear Campus, in Eusbio, 30 minutes from Fortaleza (the state's capital in Northeastern Brazil), in a building with 2,350 sqm. The Center will also benefit from the structure of Fiocruzs regional unit, created in 2008 and that is today the technological anchor of the Industrial and Technological Health Hub in Cear (Polo Industrial e Tecnolgico da Sade - PITS).
The president of Fiocruz, Mario Moreira, highlighted the Center as a priority project for the Foundation. It is an exemplary project that inspires us not only because of its scientific competence, but also because it is a model of new institutional arrangements that Fiocruz can adopt to develop activities outside of Rio de Janeiro, he emphasized. In addition to the joy that surrounds this celebration, the Center also brings with it a responsibility to contribute to scientific and technological development that can enable new health products, he commented. We have many projects to develop in this region, in the very particular political institutional arrangement, which is the association of federal, state and municipal governments. This basis justifies Fiocruzs success in Cear, he stated.
Moreira, D'Enfert, Martins and Caroline at the Center's reception where a poster pays homage to Louis Pasteur and Oswaldo Cruz (photo: Iratu Freitas)
The vice president of the Institut Pasteur, Christophe DEnfert, highlighted the project as a new step in the long and solid partnership between Brazil and France. Oswaldo Cruz completed his studies in Paris and returned to Brazil founding Fiocruz. There is a little of France in the Foundation, he mentioned. This ambitious project is fully aligned with the strategies of both institutions involved and will certainly create synergies for innovative science and the benefit of both people, he added. Another point highlighted by DEnfert was the institutions commitment to training future generations of scientists in the field of immunology and immunotherapy.
The Secretary of Science, Technology, Innovation and Health Complex of the Ministry of Health (SECTICS/MS), Carlos Gadelha, highlighted the project as an important commitment to regional equity. We are celebrating a concrete possibility of national development. It is a country project that involves regional development, in the Northeast and Cear, he emphasized.
To the governor of Cear, Elmano de Freitas, the event was a moment that changes the history of his people. My pride in being here is being able to say that what we want to migrate from Cear is the scientific knowledge that will be produced here. Not only do we trust science, but we also understand that it is a path to the country's development. Science cannot be done without partnership and cooperation, he reinforced.
Public health strategy
The development of new immunotherapies is an important public health strategy. This kind of treatment is based of the modulation of the immune system and can directly target an infectious agent, damaged cells and tissues, or regulate the immune microenvironment promoting a proper immune response to fight a given disease. It has revolutionized cancer treatment in recent years, but is not restricted to the oncology field. Indeed, its use in treating other non-communicable diseases (NCDs), and infectious diseases is rapidly increasing.
The Center has three priority scientific areas: cancer; infectious and neglected diseases; autoimmune, neurodegenerative and inflammatory diseases. Among the projects hosted by the Center are: the development of Integrin Inhibitors for Treating Neurodegenerative Diseases; the development of Antibody-Drug Conjugates; the development of nanobody/antibody fragments for Neglected Tropical Diseases; CAR-T cells; and immunotherapies to enhance T cell functions to tackle infectious diseases.
Brazil and France have vast and diverse territories, their populations are frequently affected by infectious and tropical neglected diseases caused by viruses, bacteria, parasites and snakebites. Moreover, mosquito-borne diseases such as dengue, chikungunya, yellow fever, malaria and Zika are endemic in some regions of both countries. Additionally, both countries face a rise in non-communicable diseases. This scenario signs an upward demand for innovative therapeutics.
The first bilateral framework agreement envisioning the creation of the Center was defined in 2015, and renewed in 2021. The following year, it was decided that Fiocruz Cear would receive a researcher from Institut Pasteur to contribute in the efforts for integrated research. The chosen was the Brazilian immunologist Caroline Pereira Bittencourt Passaes, who has a Master's and Doctoral Degree from Oswaldo Cruz Institute (IOC/Fiocruz) and has then been working at the Institut Pasteur for eleven years. Amongst others, Caroline is aco-author in the study regarding the third case of AIDS cure.
One of the Centers privileges is having as patrons two of the greatest scientists in the world: Oswaldo Cruz and Louis Pasteur. Its creation represents a significant milestone in the advancement of knowledge in immunology and immunotherapy. Research on these topics is crucial for the development of new prevention, diagnosis and treatment strategies, said the Centers coordinator, Joo Hermnio. The other Center's coordinator, Caroline Passaes, emphasized that the partnership became a reality thanks to the work done in recent years. The space, previously dedicated to the diagnosis of COVID-19, has been given a new meaning and now begins a new phase, with a focus on developing advanced therapies for the benefit of the population, he pointed out.
Coordinator of Fiocruz Cear, Carla Celednio was moved when she cited the project as a reaffirmation of the century-old collaboration between the institutions. This reinforces the driving power of action for one of Fiocruz Cears vocations: the development of new therapies and technologies for the health of our population, she said. This reality would not have been possible if it were not for the actions to decentralize science and technology in the South-Southeast axis, he stated..
At the end of the ceremony, the agreement to create the Pasteur Fiocruz Center on Immunology and Immunotherapy was signed by Mario Moreira, Christophe DEnfert, Joo Hermnio and Caroline Passaes. The occasion also featured the signing of the decree that establishes and regulates the Cear Health Innovation District, lin the municipality of Eusbio, by the governor Elmano de Freitas. After the signing, the group visited the Center and its laboratories. At reception, a plaque pays homage to Oswaldo Cruz and Louis Pasteur.
The Pasteur Fiocruz Center on Immunology and Immunotherapy is directly linked to the General Directorate of the Institut Pasteur and the Fiocruz Presidency. It counts with a Coordinating Committee and a Scientific Advisory Board (SAB). The Coordination Committee is made up of three representatives from the Institut Pasteur, three representatives from Fiocruz; one from the French Embassy in Brazil; and one from the Cear State Government. The SAB has six members, independent experts who carry out their scientific activities in both Europe and South America, jointly appointed by the Institut Pasteur and Fiocruz.
The governor of Cear, Elmano Freitas, and Mario Moreira at the inauguration ceremony (photo: Iratu Freitas)
Operations began even before its inauguration. The day before (5/16), the Pasteur Fiocruz Symposium on Immunology and Immunotherapy was organized, bringing together researchers from different parts of the world and addressing topics on basic and translational immunology, immunotherapies and innovative applications in the area.
The Pasteur Fiocruz Center on Immunology and Immunotherapy will collaborate closely with the Immunobiological Technology Institute (Bio-Manguinhos/Fiocruz), through a research and development laboratory that is being structured. The Center will also work in partnership with universities, research institutes and public or private companies. It functions in a multi-user operating model, which means that the use of the equipments is open to any collaborator who requests it. In addition to the inputs from Fiocruz and the Institut Pasteur, the Center counts on further financial support of the French Ministry for Europe and Foreign Affairs (through its Embassy in Brasilia), the Cear government and the state governmental agency for the development of Science (Funcap, as Portuguese acronym).
A long partnership
The ties linking the Institut Pasteur to Brazil date back to the late nineteenth century when Don Pedro II, then Emperor of Brazil, a strong supporter of scientific research, developed a keen interest in the work of Louis Pasteur. In 1879, Don Pedro II invited Louis Pasteur to Brazil to study and combat the yellow fever epidemic. Although Louis Pasteur could not travel to Brazil, a successful collaboration led to significant financial support from the emperor, which contributed to the creation of the Institut Pasteur in Paris, in 1887. Later on, Brazilian scientist Oswaldo Cruz traveled to Paris in 1897 and worked with the first generation of Pasteurians, including mile Roux. In mid-1899, with his studies completed, Oswaldo Cruz returned to Brazil and founded on May 25, 1900, the Serum Therapeutic Institute, that originated the Oswaldo Cruz Foundation. The rise of the Pasteur Fiocruz Center on Immunology and Immunotherapy represents a new chapter in such story.
The Pasteur Network
The Institut Pasteur and the Oswaldo Cruz Foundation are both members of the Pasteur Network. The Pasteur Network is an alliance of over 30 institutes that plays a crucial role in tackling global health challenges through science, innovation and public health. Its distinctive strength lies in the diversity and extensive geographic reach, spanning 25 countries across five continents, fostering a dynamic community of knowledge and expertise. The Pasteur Network is recognized as a WHO non-state actor, and members of the network are frequently embedded into local Ministries of Health. The Pasteur Network sustains a global infrastructure encompassing 50+ national and regional reference laboratories, which includes multiple Biosafety Level 3 Laboratories, and 17 WHO Collaborating Centers.
The Pasteur Network's work is guided by four strategic pillars: 1) Epidemic Preparedness, Intelligence, with focus on Climate sensitive diseases, 2) Research, Development, and Innovation, 3) Knowledge Communities, and 4) Good Governance and Equity.
Read the rest here:
Pasteur Fiocruz Center on Immunology and Immunotherapy is inaugurated in Cear - Fiocruz
(Reuters) - Biogen said on Wednesday it had agreed to buy privately held Human Immunology Biosciences for $1.15 billion in upfront and up to $650 million in potential milestone payments.
(Reporting by Manas Mishra in Bengaluru; Editing by Sriraj Kalluvila)
See more here:
Biogen to buy Human Immunology Biosciences in up to $1.8 billion deal - Marketscreener.com
Why did you choose medicine?
I have liked both natural sciences and humanities since childhood. Choosing medicine was gradual, partly influenced by my mom, who enrolled me in premedical classes at age 15, when I hardly knew anything about medicine. I did not know any doctors, but I was influenced by reading the collective image of a doctor from Russian literature, an ironically or tragically described intellectual, strivingand often strugglingto help people in the face of the merciless nature of biology and societal problems. Once in medical school, my interest solidified as I became fascinated by the logic of pathophysiology and met real patients.
I liked the people I interviewed with; even through Zoom, I sensed a friendly and supportive atmosphere. The Section of Rheumatology, Allergy and Immunology at Yale offers outstanding research opportunities, incredible mentors who are experts in their fields, and a wide range of clinical cases. The Department of Immunobiology is among the worlds best, providing a unique chance to learn from people who have made discoveries in the field. For me, the decision was obvious.
I did my internal medicine residency at a Bridgeport Hospital program affiliated with Yale and stayed there as an academic hospitalist for a few years. Rheumatology has fascinated me since medical school, and when I decided to pursue a fellowship, the opportunity to train at Yale presented itself.
I have a cat named after Leo Tolstoy.
Yale School of Medicines Section of Rheumatology, Allergy and Immunology is dedicated to providing care for patients with rheumatic, allergic, and immunologic disorders; educating future generations of thought leaders in the field; and conducting research into fundamental questions of autoimmunity and immunology. To learn more, visit Rheumatology, Allergy & Immunology.
Submitted by Serena Crawford on April 10, 2024
See the original post:
Fellow Focus in Four: Marat Kribis, MD, Rheumatology, Allergy and Immunology - Yale School of Medicine
People with long COVID have distinct patterns of inflammation detectable in the blood, which could potentially be targeted with immune therapies.
Findings from the largest UK study of patients hospitalised with SARS-CoV-2 infection show that long COVID leads to ongoing inflammation which can be detected in the blood.
In an analysis of more than 650 people who had been hospitalised with severe COVID-19, patients with prolonged symptoms showed evidence of immune system activation.
The exact pattern of this activation varied depending on the sort of symptoms that they predominantly had for example, mainly fatigue or cognitive impairment.
The research, led by Imperial College London, suggests that existing drugs which modulate the bodys immune system could be helpful in treating long COVID and should be investigated in future clinical trials.
The study, published in the journalNature Immunology, is the latest research from two collaborative UK-wide consortia, PHOSP-COVID and ISARIC-4C.
These involve scientists and clinicians from Imperial alongside collaborators from the Universities of Leicester, Edinburgh and Liverpool among others and funded by UK Research and Innovation (UKRI) and the National Institute for Health and Care Research (NIHR).
Subscribe to Technology Networks daily newsletter, delivering breaking science news straight to your inbox every day.
Professor Peter Openshaw, from Imperials National Heart & Lung Institute and an ISARIC-4C lead investigator, said: With one in ten SARS-CoV-2 infections leading to long COVID and an estimated 65 million people around the world suffering from ongoing symptoms, we urgently need more research to understand this condition. At the moment, its very hard to diagnose and treat.
This study, which includes detailed clinical data on symptoms and a raft of inflammatory blood plasma markers, is an important step forward and provides crucial insights into what causes long COVID.
In the latest study, researchers included a total of 426 people who were experiencing symptoms consistent with long COVID having been admitted to hospital with COVID-19 infection at least six months prior to the study.
They were compared with 233 people who were also hospitalised for COVID-19 but who had fully recovered. The researchers took samples of blood plasma and measured a total of 368 proteins known to be involved in inflammation and immune system modulation.
They found that, relative to patients who had fully recovered, those with long COVID showed a pattern of immune system activation indicating inflammation of myeloid cells and activation of a family of immune system proteins called the complement system.
Myeloid cells are formed in the bone marrow and produce various types of white blood cells that circulate in the blood and migrate into organs and tissues where they respond to damage and infection.
The complement system consists of a cascade of linked proteins that are activated in response to infection or tissue damage. Notably, overactivation of the complement system is known to be associated with many autoimmune and inflammatory conditions.
Dr Felicity Liew, from Imperials National Heart & Lung Institute, said: Our findings indicate that complement activation and myeloid inflammation could be a common feature of long COVID after hospitalisation, regardless of symptom type.
It is unusual to find evidence of ongoing complement activation several months after acute infection has resolved, suggesting that long COVID symptoms are a result of active inflammation.
"However, we cant be sure that this is applicable to all types of long COVID, especially if symptoms occur after non-hospitalised infection.
The researchers were also able to obtain comprehensive information about the range of symptoms that patients were experiencing, and which ones were most common.
They found that certain groups of symptoms appeared to be associated with specific proteins. For example, people with gastrointestinal symptoms had increased levels of a marker called SCG3, which has previously been linked to impaired communication between the gut and the brain.
Overall, there were five overlapping subtypes of long COVID with different immune signatures, despite some commonalities, namely: fatigue; cognitive impairment; anxiety and depression; cardiorespiratory; and gastrointestinal.
The researchers stress, however, that these groups are not mutually exclusive, and people can fall between groups depending on their symptoms.
Nevertheless, these long COVID subtypes seem to represent clear biological mechanisms of disease and highlight that different symptoms may have different underlying causes. The researchers suggest this could be useful in designing clinical trials, especially for treatments that target immune responses and inflammation.
One such treatment could include drugs called IL-1 antagonists, such as anakinra, which is commonly used to treat rheumatoid arthritis, as well as another drug class called JAK inhibitors, used to treat some types of cancers and severe forms of rheumatoid arthritis. Both drug types work by targeting components of the immune system that might be activated in long COVID.
The researchers highlight that one limitation of their study was that it only included people who had severe SARS-CoV-2 infections and who were hospitalised as a result. Yet a sizeable proportion of people who develop long COVID in the wider population only report mild initial SARS-CoV-2 infection and its unclear if the same immune mechanisms are at work.
Professor Openshaw concludes: This work provides strong evidence that long COVID is caused by post-viral inflammation but shows layers of complexity.
"We hope that our work opens the way to the development of specific tests and treatments for the various types of long COVID and believe that a one size fits all approach to treatment may not work.
COVID-19 will continue to have far reaching effects long after the initial infection has passed, impacting many lives. Understanding whats happening in the body, and how the immune system responds, is key to helping those affected.
Reference:Liew F, Efstathiou C, Fontanella S, et al. Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease. Nat Immunol. 2024. doi: 10.1038/s41590-024-01778-0
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
See more here:
Long COVID Can Now Be Detected in the Blood - Technology Networks