Published in Viruses: CXCL12 and CXCL13 Cytokine Serum Levels Are Associated with the Magnitude and the Quality of SARS-CoV-2 Humoral Responses

The CARE member, Centre Hospitalier Universitaire Vaudois (CHUV), has published a paper on the differences observed between hospitalised and non-hospitalised patients following SARS-CoV-2 infection in terms of the levels of detectable anti-SARS-CoV-2 neutralising responses and antibodies titres, which were significantly lower in non-hospitalised donors.

The aim of this work was to identify early factors that could predict the severity of SARS-CoV-2 infection. To this end, plasma and peripheral blood mononuclear cells were collected at 6 months post-onset of symptoms from 72 patients with severe COVID-19 who required hospitalization (31 of whom were admitted to intensive care) and 23 individuals who did not require hospitalization.

Blood and serum samples collected at 6 months post-onset of symptoms were used to characterize the ex vivo cellular and serum immune signatures, using mass cytometry and multiplex bead assays, respectively. The overall results suggest that the balance between the cytokines CXCL12 and CXCL13 may be an early predictive marker associated with the magnitude and the quality of SARS-CoV-2 antibody and memory B cell responses.

This work may help to improve the care of infected patients through enabling a better understanding of the immunological markers associated with long-lasting immune responses to SARS-CoV-2.

To learn more, click here: CXCL12 and CXCL13 Cytokine Serum Levels Are Associated with the Magnitude and the Quality of SARS-CoV-2 Humoral Responses

CARE’s Young Researchers – Introducing Collins Owino, Post-doctoral researcher, Utrecht University

Read about how Collins’s work in understanding how the coronavirus hijacks human host factors and processes has provided us with opportunities to develop therapies to inhibit viral replication.

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It comprises 38 partners, from both industry and academia, in a set-up of eight multidisciplinary work-packages (WPs). In this series, we highlight the work of some of the young researchers involved in CARE as part of their PhD or postdoctoral work. Here, we learn how this opportunity has benefited Collins (Utrech University), while simultaneously benefiting CARE and its ambition to help society defeat COVID-19 and future pandemics.

What experience did you have working on a Public Private Partnership before joining CARE? 

I had no experience in Public Private Partnership before joining CARE but members of our team have participated in such projects before.

Why did you decide to get involved in CARE?

I decided to get involved because I had just experienced the devastating effects of the SARS-CoV-2 pandemic during my Ph.D. studies. I wanted to contribute to a better understanding of the interaction between the virus and human host factors towards developing novel antiviral drugs and vaccines.

How did your involvement in CARE come about?

I became involved in CARE because of my experience studying virus-human host interactions, which aimed at identifying host factors regulating viral infection. We wanted to apply different CRISPR screening strategies to identify novel host factors regulating SARS-CoV-2 infection that could be drug and vaccine targets.

What is CRISP? New Scientist.

Tell us about the work you have been doing in the CARE consortium

My role in the CARE consortium involves performing loss of function screens using CRISPR interference (CRISPRi) (a novel approach for targeted silencing of transcription in cells/gene knockdown – see https://www.nature.com/articles/nprot.2013.132) to identify novel host factors regulating SARS-CoV-2 infection and other coronaviruses. We further apply different RNA interference approaches to validate the role of the newly identified host factors during the virus infection cycle. In addition, we work with other collaborators within the consortium to identify small molecules that could inhibit these factors for possible host-targeting antivirals. We are currently at the final stage of validating some top hits.

What highlights can you share from your time in the CARE consortium so far?

Some highlights from my time in CARE include learning how to work together within a collaborative environment to meet the general goals of CARE. It has also been fulfilling to be an integral member of our team that has conducted several CRISPR screens and validated the newly identified hits to develop host-targeting therapies against coronaviruses.

Why does this work matter?

This work matters because understanding how the virus hijacks human host factors/processes provides us a better opportunity to develop therapies to disrupt these interactions, thereby inhibiting viral replication.

What are or were the biggest challenges you have experienced (and how did you overcome them?)

During my Ph.D., I studied the biology of the hepatitis B virus. When I joined the RNA virus virology group at Utrecht University, I experienced a significant shift in the techniques and experimental procedures for the CARE project. I overcame these challenges quickly through the support and mentorship of my colleagues at UU.

How have you benefited from your involvement in CARE?

I have benefited immensely by interacting with experienced industry and academia experts who are willing to mentor and guide the upcoming scientists within the consortium. I have been able to sharpen my technical as well as interpersonal skills since I joined the consortium.

What advice would you give to someone getting involved in a Public Private Partnership? 

I would tell them that PPPs require collaboration, trust, and a shared commitment to achieving positive outcomes for public and private interests. They provide a noble opportunity to learn from the members of different teams in an open, transparent, and collaborative environment. It is a great experience.

CARE – Infographic: Work Package 1 Anti-coronavirus drug discovery in phenotypic virus-cell-based assays.

CARE has 8 Work Packages but do you know what each one does? Here, you can learn about the Work Package 1 team, their objectives, their partners, their breakthrough moments and more.

The infographic is also available here

CARE – Infographic: Research objectives and Operating model

Do you whish to know what we do and how we do it? Check out this infographic for key details on CARE Research objectives and Operating model.

The infographic is also available here

Published in Antiviral Res: A new image-based and high-throughput platform to identify broad-spectrum coronavirus antivirals

The CARE member, Johnson & Johnson Innovative Medicine, developed a high-content imaging platform compatible with high-throughput screening, with the aim of identifying compounds with antiviral activity and to deprioritize those that induce undesirable phenotypes in host cells.

The immunofluorescence-based assay to assess the antiviral compounds against coronaviruses was adapted for high-throughput screening by shortening assay run times, miniaturizing well size and volumes, combining permeabilization and staining steps, and by using automated image analysis. The inclusion of cellular dyes and immunostaining in combination with in-depth image analysis enabled identification of compounds that induced undesirable phenotypes in host cells, such as changes in cell morphology or in lysosomal activity.

This platform was easily adapted to different SARS-CoV-2 variants (B1, Omicron BA.5 and Omicron XBB.1.5), SARS-CoV and human coronavirus 229E using different antibodies and cell types. With the platform, ~900K compounds were screened and hits were triaged in just four weeks, thereby allowing the identification of potential anti-coronaviral compounds carrying broad-spectrum activity with limited off-target effects.

This new platform is broadly applicable as it can be adapted to include various cell types, viruses, antibodies, and dyes. By developing and running the antiviral assay against different coronavirus strains, it was demonstrated that the assay can most likely be efficiently adapted to test against new SARS-CoV-2 variants or new coronavirus species as soon as they emerge. Given the high risk for future coronavirus outbreaks or other pandemics from new zoonotic reservoirs, the flexibility and broad applicability of this assay are of particular interest.

To learn more, click here: A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects