Scientists characterize T cells that predict recovery from severe COVID-19

Vaccines do the amazing job of delaying the pandemic of COVID-19, but infected people can still die from serious illnesses, delaying the emergence of new drugs to treat them. .. It seems that it is not the virus itself that ultimately kills these patients, but an overreaction of the immune system leads to massive inflammation and tissue damage.

By studying a type of immune cells called T cells, a team of Gladstone scientists have revealed a fundamental difference between patients who have overcome severe COVID-19 and those who have succumbed to it. The team also worked with researchers at the University of California, San Francisco and Emory University to discover that dying patients have a relatively large number of T cells that can infiltrate the lungs. This can contribute to the widespread lung deterioration that is characteristic of the deadly COVID-19. ..

Survey results published in scientific journals Cell report, Can pave the way for new treatments. Currently, patients hospitalized with severe COVID-19 are receiving dexamethasone, a drug primarily used to reduce inflammation.

“Dexamethasone was a lifesaver for many patients,” said Dr. Nadia Lone, senior and corresponding author of the study, Associate Researcher Gladstone. “But that’s not always enough. Our research suggests that it may also be beneficial to directly prevent excess immune cells, including inflammatory T cells, from entering the lungs and causing further damage. This approach may be a good complement to anti-inflammatory treatment. For COVID-19 patients in intensive care rooms. “

This study may also help with the prognosis of the disease.

“Some patients can get seriously ill with the virus,” said Dr. Warner Green, MD, Principal Investigator and Co-author of the study at Gladstone. “We are in desperate need of effective ways to predict the course of the disease and reduce lung damage in people with severe COVID-19.”

T cell imbalance

T cells are an important factor in a successful immune response to many viruses, including SARS-CoV-2, the virus that causes COVID-19. And they are significantly depleted from the blood during severe COVID-19.

To characterize the remaining T cells, scientists obtained blood samples collected from COVID-19 patients in the intensive care unit (ICU). About half of these patients eventually recovered, but the other half died of the disease. By examining samples taken at various times during the patient’s stay in the ICU, scientists were able to identify trends that may be associated with the outcome of the disease.

Much has already been learned about the immune response of COVID-19 patients during or after active infection. For example, studies from convalescent individuals, including Lone’s own previous studies, reveal how the immune system provides long-term immunity. However, it is not very clear how the immune system protects against serious illness, or conversely, how the immune system can deteriorate and lead to death. To understand the cause of death, researchers needed to compare fatal and non-fatal severe cases.

Scientists use CyTOF, a technique implemented in Roan’s lab to distinguish between many types of T cells circulating in the body, to make a big difference in the T cell response of ICU patients to the virus. I found that.

“The response of T cells to SARS-CoV-2 was increased in patients who eventually recovered from the ICU,” said Roan, an associate professor of urology at the University of California, San Francisco. “However, in patients who eventually died, the T cell response could not be detected or the response declined over time.”

The difference also extended to the composition of T cells in patients who recognize the SARS-CoV-2 virus. In particular, surviving patients have an increased number of T cells called Th1, which are known to be important fighters for viral infections. Roan’s team discovered the molecular characteristics of Th1 cells. This may explain why they were able to grow in these patients.

In contrast, they found that deceased patients had an increased number of T cells that secreted inflammatory molecules that contributed to worsening lung condition. These patients also had more regulatory T cells that recognized the virus. Regulatory T cells usually help calm the immune response once the infection has subsided.

“Perhaps in these patients, regulatory T cells were activated too quickly, preventing effector T cells from initiating an appropriate immune response to SARS-CoV-2,” Roan said. .. “This can help explain the patient’s slight response to the virus.”

Based on these findings, physicians may be able to predict the course of the disease from the relative abundance of Th1 cells and regulatory T cells that recognize SARS-CoV-2 in the patient’s blood.

But the loan warns. “Our findings show a correlation, not a cause. The immune system is complex and can interact with many moving parts. To prove the cause of death, Further research is needed. “

Stop the flow of lung homing cells

Another potential cause of death the team discovered was a surge in T cells that could infiltrate the lungs of dying patients. In contrast, these cells decreased over time in patients who recovered.

Scientists call these lung homing cells “bystander T cells.” This is because these are T cells that do not directly recognize the SARS-CoV-2 virus.

“Our study suggests that during severe COVID-19, bystander T cells may be mobilized from the blood to the lungs, where they may contribute to immune pathology,” Roan said. Says.

The cause of the bystander T cell proliferation in severe COVID-19 cases remains unknown, but may be partially mediated by proteins secreted by the lungs that mobilize these cells. Anyway, stopping the flow to the lungs may help reduce lung damage and accelerate the recovery of patients with severe illness.

This approach is particularly promising, as drugs that antagonize molecules on the surface of bystander T cells have already been approved for the treatment of metastatic cancer.

“Our next step is to test these drugs in a mouse model of severe COVID-19,” says Roan. “We hope that after further scrutiny, such drugs will be quickly tested as adjuvant therapy for COVID-19.”

reference: Neidleman J, Luo X, George AF, and other SARS-CoV-2 specific T cell features predict recovery from severe COVID-19. Cell person in charge.. 2021: 109414. Doi: 10.1016 / j.celrep.2021.109414

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