Highlights of the Crick's response to the COVID-19 pandemic

Key researchers

Content

Summary

  • The Crick’s decision to become a rapid testing hub for North London hospitals helps drive a government policy change on testing healthcare staff

  • Two approaches to biomarker discovery predict severity of COVID-19 disease

  • Important insights into the humoral and cell-mediated responses to SARS-CoV-2

  • Structural analysis of the SARS-CoV-2 viral spike protein aids understanding of viral mutation, infectivity and vaccine efficacy

Testing

In March 2020, when many NHS staff were falling ill with COVID-like symptoms without any ability to access NHS COVID testing, Crick Group Leaders Steve Gamblin, Sonia Gandhi and Charles Swanton met to discuss whether Crick facilities could be repurposed to set up a SARS-CoV-2 testing laboratory for NHS healthcare workers and patients.

Testing

Biomarkers for immune pathology

The enormous heterogeneity of COVID-19 patients in terms of age, sex, ethnicity, clinical presentation and underlying health conditions meant that in the early stages of the pandemic, it was not clear whether an immune signature flagging predisposition to serious illness would exist.

Such a signature was important: as hospitals were overwhelmed, there was intense interest in early stratification of those patients most likely to recover rapidly, to enable critical care decisions to be made.

Biomarkers for immune pathology

Host response to infection

SARS-CoV-2 entered the human population from an animal reservoir in 2019, and has spread rapidly in its new human hosts, due to a lack of immunity. In a paper published in December 2020, George Kassiotis and colleagues suggested that this immune deficit may not be universal (Ng et al, 2020a).

Cross-reactive antibodies

Caveats and benefits of interferon λ therapy

In the early scramble to find treatments to combat COVID-19, many existing antiviral medications were tested for efficacy. The use of different types of interferon (IFN) as antiviral agents seemed promising, as they are central to antiviral immunity. Type I IFNs (IFN-α and IFN-β) are widely expressed, as is their receptor, and prolonged responses can result in harmful proinflammatory effects. However, the type III IFN receptor is largely limited to epithelia, and consequently type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces, conferring localised antiviral protection without inducing a damaging systemic response, and making IFN-λ a potential anti-SARS-CoV-2 therapeutic.

Interferon lambda therapy

Viral structure

Steve Gamblin and colleagues are renowned for their work on the influenza virus surface glycoprotein hemagglutinin, which mediates receptor binding and membrane fusion in influenza infections, and they were quickly able to apply their existing expertise to the challenge presented by the SARS-CoV-2 outbreak.

Viral structure

Peer reviewed Crick research publications on SARS-CoV-2 and COVID-19