COVID-19: Convalescent T cells could protect the vulnerable
An infusion of immune cells from people who have recovered from COVID-19 could shield those with compromised immune systems from the infection responsible for the disease, a lab-based study of cellular cultures suggests.
People who have recently received a bone marrow or organ transplant or are undergoing cancer treatment have reduced immunity. This makes them especially vulnerable to infections with viruses such as SARS-CoV-2, which causes COVID-19.
The Cellular Therapy Program at Children’s National, a hospital in Washington, D.C., uses a technique called “adoptive immunotherapy” to protect those with weakened immune systems from viruses including cytomegalovirus and the Epstein-Barr virus.
The technique involves isolating T cells that target the virus from the blood of someone recovering from the infection. After the cells have been cultured in a lab, healthcare providers inject them into people with weakened immunity, protecting them from the infection.
A team from Children’s National has now investigated the potential of adoptive immunotherapy to protect against COVID-19.
This preclinical research involved testing the immune capabilities of T cells from individuals recovering from the illness.
“We found that many people who recover from COVID-19 have T cells that recognize and target viral proteins of SARS-CoV-2, giving them immunity from the virus because those T cells are primed to fight it,” says Dr. Michael Keller, a pediatric immunology specialist who led the study.
“This suggests that adoptive immunotherapy using convalescent T cells to target these regions of the virus may be an effective way to protect vulnerable people, especially those with compromised immune systems due to cancer therapy or transplantation.”
These individuals’ vulnerability to infection can prevent or delay the treatments they need.
“This approach could serve as a viable option to protect or treat them, especially since their underlying conditions may make vaccines for SARS-CoV-2 unsafe or ineffective,” says Dr. Catherine Bollard, director of the hospital’s Center for Cancer and Immunology Research.
Dr. Bollard is also the senior author of the new study, which has been published in the journal Blood.
For the research, 46 individuals recovering from COVID-19 donated blood. Most had experienced only mild symptoms, and the researchers analyzed the samples around 36 days after the onset of the symptoms.
They identified T cells that recognized parts of proteins in the virus’s membrane, spike, and nucleocapsid, the shell surrounding its genetic material.
The researchers expanded these immune cells in the lab and found that they responded to the viral proteins by producing interferon gamma, a signaling molecule that orchestrates the immune system’s assault on viruses.
Many of the cells targeted a part of the membrane that is highly conserved, meaning that it changes little, if at all, as the virus evolves. This suggests that the virus may not be able to evolve ways to evade this part of the human immune system.
Vaccines currently in development target key parts of the spike proteins that give coronaviruses their characteristic crown-like appearance.
The authors propose that the highly conserved part of the membrane that they have identified might be another worthwhile target. A vaccine that trained T cells to recognize this part of the virus could provide long-lasting protection against the infection.
The study adds to evidence that even if the number of circulating antibodies declines steeply in the months after SARS-CoV-2 infection, as a recently published preprint of one study suggests, T cells may continue to protect against reinfection.
The authors also note that T cell immunity to two closely related coronaviruses — which cause severe acute respiratory syndrome, or SARS, and Middle East respiratory syndrome, or MERS — appears to persist for years.
One important drawback of this study is that it did not directly test the ability of donors’ T cells to inactivate the virus, either in the lab or in humans.
As the researchers acknowledge, future studies will have to evaluate whether adoptive T cell immunotherapy is safe and effective for people at high risk of severe COVID-19.
In addition, they highlight that their sample size was relatively small and that many of the donors had only experienced mild symptoms of the illness. Moreover, not every participant had laboratory-confirmed COVID-19 or a positive antibody test.
Finally, the authors address the possibility that T cell therapy could provoke excessive inflammation that results from a massive release of immune signaling molecules known as cytokines. They note, however, that this “cytokine release syndrome” is associated with cytokines other than interferon gamma in people with COVID-19.
“As other inflammatory complications, such as cytokine release syndrome, are very rare after virus-specific T cell therapy, the risk of inflammatory complications after adoptive T cell therapy for COVID-19, particularly when utilized early and derived from donors who themselves did not have inflammatory disease, are likely low.”
For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.