Introducing Leiden University Medical Center  – a CARE academic organisation

The LUMC has a long history and has its origins in the 16th century when in 1575, following a year-long siege, William of Orange granted Leiden the right to have a university. The university started with 3 faculties: Law, Theology and Medicine.

In 1996, the Leiden University Medical Center (LUMC) emerged from the collaboration between the Leiden University Hospital and the Faculty of Medicine of Leiden University.

Today, it is a centre of medical innovation that aims to improve patient care through scientific research. It trains doctors and biomedical researchers to contribute to this. In addition to general patient care, the LUMC offers specialist treatments that may only be performed in a limited number of medical centres. The LUMC distinguishes itself in particular as a referral center for complex medical questions for which there are no ready-made answers. As of 2024, all fundamental, translational and clinical research related to pathogens and infectious diseases will be integrated in the new Leiden University Center of Infectious Diseases (LUCID). This month, LUMC is opening a new Biosafety Level 3 (BSL-3) research facility, including two units to be used for studies on SARS-CoV-2 and other pathogenic coronaviruses.

The LUMC has 3 social spearheads: oncology, regenerative medicine and population health. These spearheads relate to important issues in society and medicine. Approximately 7000 people work at LUMC today.

Why did the LUMC choose to get involved in CARE?

The LUMC molecular virology team has a >30-year track record in studying the biology of coronaviruses, including a number of previous projects in antiviral drug research. LUMC decided to get involved with CARE because of the need to establish an international response to the rapidly developing SARS-CoV-2 pandemic, thus facilitating scientific collaboration and the sharing of expertise and toolboxes. Moreover, since February 2020, LUMC was coordinating the EU-funded SCORE project to target SARS-CoV-2, and its eight partners thus became a sub-network within CARE. This enabled the rapid exchange of knowledge, technologies, reagents, and candidate antiviral drugs between the two projects.

What has the LUMC delivered for CARE?

The LUMC’s achievements in CARE include many aspects in Work Packages (WP) 1, 2, 5, 6, 7 and 8 (For more information information about the different work packages, please click here.). LUMC developed assays and reagents in WP1 and 2 to better define coronavirus drug targets, and characterize and select antiviral compounds developed by other partners. Such studies into the mechanism-of-action of CARE’s drug candidates continue to constitute the bulk of LUMC’s contribution. Furthermore, LUMC performed “omics” studies in WP5, established animal models and performed preclinical studies on candidate antivirals in WP6; performed dual-transcriptomics studies in WP7; and organized a European Medicines Agency (EMA) meeting to obtain advice on combinational treatments for immune-compromised patients in WP8.

The LUMC CARE team currently includes: 

Montse Bárcena, Nina de Beijer, Jonna Bloeme, Brenda Bontes, Jutte de Vries, Mirjam Groenewold, Sytze Jorritsma, Marjolein Kikkert, Marissa Linger, Kees Mourik, Sebe Myeni, Ana Roque, Anna Roukens, Ed Schmidt, Eric Snijder, Thijs Steijaert, Ali Tas, Emmely Treffers, Martijn van Hemert, Peter van Veelen, Patrick Wanningen, and Jessika Zevenhoven.

Inserm VRI-led research reveals predictors of severe disease and long COVID symptoms

The CARE partner Inserm-VRI has recently published two articles pertaining to severe SARS-CoV-2 infected patients from the French COVID cohort. The first article delves into the severity of SARS-CoV2 infection, to identify markers associated with the extent of severity of SARS-CoV2 infection. The second article characterized gene expression and cellular markers related to the persistence of symptoms post a severe infection.

Identifying COVID-19 patients who are at high risk of worse prognosis after severe disease is challenging. Inserm-VRI studied the blood of 61 patients who were hospitalized with severe COVID-19 and compared it to healthy people. They found that certain immune cells were abnormal, and there were many markers of inflammation. They identified a specific neutrophil activation marker, called CD177, which is present in high levels in the sera of severe COVID-19 patients and could predict which patients might develop severe disease. More importantly, measuring CD177 over time allowed them to identify patients with poor prognosis from those who will recover. These findings suggest that neutrophil activation is a hallmark of severe COVID-19 disease, and CD177 assessment could help identify patients at high risk for severe disease. Click here for the publication.

After recovering from severe COVID-19, some people may still experience prolonged symptoms. The CARE partner Inserm-VRI investigated the immune system dysfunction that causes these long-lasting symptoms. They analyzed the blood of severe COVID-19 patients at 1, 3 and 6 months after leaving the hospital and found abnormalities that persisted up to 6 months after discharge. These included high levels of markers of inflammation, changes in certain types of immune cells, a decrease in antibodies against the virus, and changes in gene expression related to blood clotting. They also identified a set of genes associated with thrombotic events in the acute phase of infection. The fact that these abnormalities persisted for up to six months, even in patients who were no longer experiencing symptoms, suggests that continued monitoring and preventive measures may be necessary. Click here for the publication.

One new CARE deliverable is  now publicly available on CARE webpage “Resources“

How far has CARE progressed with its anti-coronavirus small molecule development?  Read about screening cascades for hit discovery and the hit development programmes currently ongoing in CARE in the latest Portfolio report (D3.12).

CARE latest annual project summary is  now publicly available on CARE webpage “Resources“

Do you wish to know more about the progress made by the CARE project? Read the summary for the third year of the project, presenting CARE’s main results achieved after three year of research (March 2023).

About CARE’S Scientific and Ethics Advisory Board

What is the SEAB?

SEAB stands for Scientific and Ethics Advisory Board. It is an independent group, appointed by the CARE Steering Committee (SCOM) that can provide objective feedback on the activities and plans of the consortium in order to ensure its obligations are fulfilled.

Who is in the SEAB?

It is a group comprising two ethics and three scientific experts. Of the scientific experts below, Professor Manabe is also a clinician.

What role does the SEAB play?

 The SEAB’s role is to advise the project as a whole on scientific and technical development as well as ethics aspects, to support with decision making. They are expected to meet annually, which takes place during the CARE Annual Meeting. The group are also invited by the CARE SCOM to provide non-binding feedback and advice to the CARE General Assembly and CARE SCOM at this time.

We asked some of the SEAB members for their views about CARE’s progress, plans and relevance to society today

How relevant is CARE today?

 Prof. Janet Mifsud (JM): The subject may not be as urgent as it was when it was originally funded, however the unique collaborations, insights and technologies developed over these last few years in the CARE project have a much wider and important impact in the scientific arena. CARE also has the capacity to act as a fulcrum in the long-term visibility and foresight of what is being developed and researched for future pandemics.

Prof Yuka Manabe (YM): CARE could become a model for accelerating pandemic response and preparedness; academia has many innovative ideas that can be accelerated to impactful products if paired with industry partners who understand quality, reproducibility and commercialization.

Prof. Raffaele De Francesco (RDF): The World Health Organization (WHO) declared COVID-19 to be no longer a global health emergency in May 2023 however, the attention paid to COVID-19 should remain very high. New variants of the virus are constantly emerging, and some of these variants may be more transmissible or severe than previous variants. In this scenario, the activities of the Care consortium remain highly relevant.

What are your observations of the programme over the past three years?

 JM: It is clear that there has been a great deal of progress in CARE since inception. We have observed greater data sharing, interaction and communication between the work packages. While there are less lead compounds than anticipated in CARE, the repurposing work and working with compounds from outside the consortium and combination drugs offers promising alternative strategies.

YM: after a predictable period of framework development for how to engage, there has been measurable growth of CARE with increasing productivity and better cross fertilization across work packages.

RDF: CARE has made significant progress towards its goal to develop new drugs to fight Covid-19 and future pandemics, through building a very strong network that has the potential to make a major impact. The Consortium has shown how academia and industry can work together effectively to accelerate drug discovery and development.

What hopes do you have for the remaining period of CARE?

JM: CARE is offering very interesting integrative work in the systems biology approach from the molecular to clinical approaches which will be key and may have a great impact in the clinical trial developments. In the last few years of CARE, there is very interesting ancillary work planned such as the interactions related to the regulatory aspect with EMA with data from GDPR and ethics studies. The consortium systems modelling is also novel and may have a wider impact on other consortium and such IMI funding models. In my opinion this should be of interest to the Innovative Health Initiative (IHI) Steering Committee for to enable CARE learnings to be applied or adapted for other viral work.

YM: I hope that the funders continue to realize the value of seeing the collaboration through and considering how this vibrant network can be leveraged for future work. There have been many basic science discoveries in addition to novel and robust pipelines built to test new compounds. Expanding the work from just Europe to low- and middle-income countries in future iterations would also be welcome.

RDF: I hope and expect to see additional groundbreaking discoveries as well as substantial progress of existing candidates, eventually leading to the development of new important therapeutic and preventive agents.