Researchers explore the reason why Covid-19 severity differs in people

Prashasti Awasthi Mumbai | Updated on October 09, 2020 Published on October 09, 2020

As the world has marked 10 months into the pandemic, scientists and researchers are still trying to wrap their minds around how the virus causes more harm to some and less harm to others.

In order to solve this complex problem, scientists at La Jolla Institute for Immunology (LJI), The University of Liverpool, and the University of Southampton led the first of its kind study to give a detailed snapshot of how the body’s CD4+ T cells respond to the SARS-CoV-2 virus.

The study was titled “Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in Covid-19.”

Their study, published in the journal Cell, suggested that coronavirus develops a novel T cells subset that can kill B cells, which play a vital role in antibodies production, and cause severity.

Researchers believe that their study can lay an important foundation for further detailed analysis. It also demonstrated the power of a cutting-edge technique called single-cell RNA sequencing (RNA-seq).

The lead author of the study, LJI Associate Professor Pandurangan Vijayanand, M.D., Ph.D., said in a statement: “This study employs single-cell RNA-seq to analyze RNA molecules expressed by CD4+ T cells that specifically recognize SARS-CoV-2”

Another study author, Christian H Ottensmeier, M.D., Ph.D., FRCP, professor at the University of Liverpool and adjunct professor at LJI wrote: “This lets us show, for the first time, the complete nature of the cells that respond to this virus.”

“This is the beginning. We needed to have a reference to look back at for further studies, and this work is novel, timely, detailed, innovative — and open,” Ottensmeier added.

Vijayanand and his colleagues at LJI have launched the use of single-cell RNA-sequence in immunology. For their new study, the researchers focused on CD4+ T cells, which play a vital role in fighting any infection.

Vijayanand and Ottensmeier had planned to use single-cell RNA-seq to analyse CD4+ T cells from patients hospitalised for influenza this year.

“We were collecting appropriate samples very early on in the pandemic,” says Vijayanand.

For their study, the researchers examined samples from 40 Covid-19 patients in two groups.

The hospitalised group included 22 patients (with nine treated in the ICU). The non-hospitalised group had 18 patients who had experienced milder Covid-19 symptoms.

The scientists used single-cell RNA-seq to analyse the types of CD4+ T cells that respond to SARS-COV-2 in these patients.


The authors of the study found that one reason that leads to severe cases of the virus is the higher levels of “cytotoxic” TFH cells in hospitalised patients, which could potentially make an infection worse.

The researchers then studied SARS-CoV-2-specific antibody concentrations in patients. Those with dysfunctional TFH cells also had fewer antibodies.

The study aims to lead the scientific community to explore CD4+ T cell responses to SARS-CoV-2, and the work establishes a baseline for comparing responses in people over time or with different disease severities.

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Published on October 09, 2020
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