Sarah Teichmann and Muzlifah Haniffa use Human Cell Atlas to shed light on COVID-19

Current Lister Fellow Professor Muzlifah Haniffa, Professor of Dermatology and Immunology at Newcastle University and Associate Faculty at the Wellcome Sanger Institute and former Fellow Dr Sarah Teichmann, Head of Cellular Genetics and Senior Group Leader at the Wellcome Sanger Institute, are two of the researchers collaborating on the Human Cell Atlas initiative.

This ambitious project – co-founded by Dr Sarah Teichmann – aims to characterise every cell type in the human body to create a collection of biological maps that describe and define the cellular basis of health and disease.

When the COVID-19 pandemic began, the Human Cell Atlas team turned their attention to working out how the SARS-CoV-2 virus enters and interacts with human cells (Sungnak et al., Nature Medicine, 2020).

“It has been an incredible year and a half for science, and the collaborative, creative and concerted effort by the Human Cell Atlas community in the UK, and globally, who have risen to the challenge and are a credit to the field,” says Sarah.

Explaining the differences between disease severity

Sarah and Muzlifah are both authors on a Nature Medicine paper, published on April 20th, 2021. In one of the most detailed studies of immune responses in COVID-19 to date, the paper reports on how researchers used Human Cell Atlas data to identify key differences in the responses of immune cells in people who had no symptoms compared to those who experienced severe symptoms.

The study analysed blood from 130 people and sequenced over 780,000 individual immune cells from these samples.

In asymptomatic people and those with mild symptoms, they found raised levels of B cells, which produce antibodies in places such as the nose, and helper T-cells, which fight infection. They also showed people with more serious symptoms had not only lost these protective B cells but had gained inflammatory cells. High levels of these monocytes and killer T-cells can cause lung inflammation. Those with severe disease also had raised levels of platelet-producing cells, which cause blood to clot.

These findings could be used to identify potential targets for developing therapies. With further research, it may be possible to develop treatments that decrease platelet production or reduce the number of killer T-cells produced by people infected with SARS-CoV-2.

Understanding the effect of COVID-19 on specific cells

Other aspects of Human Cell Atlas COVID-19 research have focused on specific cells. Back in March 2021, Sarah was a co-author on a paper that showed how the virus infects specific ductal cells in the salivary gland, which are released from the glands into saliva with live virus inside them.

This work sheds light on how COVID-10 causes a loss of taste in some people and outlines how the virus may travel via saliva in the mouth to other parts of the body and be responsible for transmission between people.

A new testing strategy proposal

In February, Sarah also contributed to a paper in Science Advances that presented a new COVID-19 testing strategy, INSIGHT. It combines point-of-care diagnosis with central lab-based next-generation sequencing and can be undertaken in two stages. The first stage allows for a result in 1 to 2 hours, and the second stage confirms this result while collating data in a centralized repository helping to inform epidemiological efforts.

The Teichmann group hosts the COVID-19 Cell Atlas portal at the Sanger Institute, providing centralised online access to datasets such as the ones described above and many more gathered generated by researchers around the world.