John Parkinson

Scientists can harvest T-cells from the blood of recovered COVID-19 patients and multiplied in the lab and maintain the ability to target proteins that are key to the virus's function, according to a new study.

The study’s findings were published in the journal 

"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," study leader Michael Keller, MD, a pediatric immunology specialist at Children's National Hospital, said. "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."

Investigators from the Cellular Therapy Program at Children’s National believed that the expanded group of COVID-19 virus-targeting T-cells could be infused into immunocompromised patients, helping them build an immune response before exposure to the virus and therefore protecting the patient from a serious or life-threatening infection.

This hypothesis came after previous research done looking at the safety of T-cells with antiviral activity in a phase 1 trial looking at adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, Human Herpesvirus 6 and human parainfluenza-3.

The T-cells were mainly grown from the peripheral blood of donors who were seropositive for SARS-CoV-2. The study also identified that SARS-CoV-2 directed T-cells have adapted to predominantly target specific parts of the viral proteins found on the cell membrane, revealing new ways that the immune system responds to COVID-19 infection.

“In this study, we demonstrate that ex vivo expanded CSTs may be easily generated from convalescent patients, following recovery from COVID-19, and recognize multiple immunodominant epitopes within membrane protein, which represent class II restricted T-cell epitope “hot spots”, the investigators wrote.

In addition, the authors note that using T-cells to develop a vaccine may offer another viable option for researchers. The current development has been targeting the spike proteins.

The Cell Therapy Program is now seeking approval from the U.S. Food and Drug Administration for a phase 1 trial that will track safety and effectiveness of using COVID-19-specific T-cells to boost the immune response in patients with compromised immune systems, particularly for patients after bone marrow transplant.

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These vital cells that are recovered from COVID-19 patients might be able to help people with compromised immune systems due to cancer therapy or transplantation.

Harnessing T Cells to Potentially Protect the Vulnerable from COVID-19  

Based upon updated dataset from the ACTIV-3 trial, which was reviewed yesterday, Eli Lilly decided to end that study.

All other studies with bamlanivimab are ongoing, according to Lilly. The have 3 other trials related to COVID-19. ACTIV-2 trial is examining recently diagnosed mild to moderate COVID-19 patients. 

The BLAZE-1, phase 2 trial in people recently diagnosed with COVID-19 in the ambulatory (non-hospitalized) setting is studying bamlanivimab as monotherapy and in combination with etesevimab. Earlier this month, interim data from the trial showed it was associated with a reduced viral load, symptoms, and hospitalizations or emergency room visits associated with COVID-19.

The BLAZE-2 study is a phase 3 trial examining bamlanivimab for the prevention of COVID-19 in residents and staff at long-term care facilities.

Based on data from BLAZE-1, Lilly submitted a request in early October for  an Emergency Use Authorizatio for bamlanivimab for the treatment of recently diagnosed mild to moderate COVID-19 in high-risk patients.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the company said in a statement.

While they decided to discontinue this trial in hospitalized COVID-19 patients, Lilly is continuing their other trials with the medication for COVID-19 treatment.

Lilly Ends ACTIV-3 Trial Using Bamlanivimab

Johnson & Johnson (J&J) announced it is preparing to resume their COVID-19 vaccine trial. While they did not set a timetable, this signals a return to their study after a pause to their trial back in mid-October.

They paused their trial a couple of weeks ago due to an unexplained illness in a vaccine participant. “We have temporarily paused further dosing in all our COVID-19 vaccine candidate clinical trials, including the phase 3 ENSEMBLE trial,” the company said in a statement at that time.

The company did not offer any more information about the illness when it happened. “We must respect this participant’s privacy. We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information.”

And in the latest statement the company still did not disclose the illness. “After a thorough evaluation of a serious medical event experienced by one study participant, no clear cause has been identified,” the company said in a statement. “There are many possible factors that could have caused the event. Based on the information gathered to date and the input of independent experts, the Company has found no evidence that the vaccine candidate caused the event.”

The independent Data Safety and Monitoring Board (DSMB) overseeing J&J’s Trial has recommended resuming trial recruitment. Following consultation with the U.S. Food and Drug Administration, preparations to resume the trial in the United States, including submissions for approval by the Institutional Review Boards, are now underway. Discussions with other regulators around the world to resume the clinical trial program are progressing.

J &J’s ENSEMBLE trial is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a single dose of a vaccine versus placebo in up to 60,000 adults 18 years old and older, including significant representation from those who are over age 60.

The company is planning to move forward after receiving a recommendation from the DSMB to start up the trial again.

J&J Prepares to Resume COVID-19 Vaccine Trial 

A patient in Vienna, Austria was admitted to a local hospital. The 45 year old woman had a 7 day history of cough, weakness, myalgia, fever, and dyspnoea. She also had a 4 day history of nausea and diarrhea.

The next day after admittance, her condition worsened, and the patient was put on a ventilator.

In discussing potential treatment options, the attending physicians, family, and infectious disease experts decided upon a course of treatment for compassionate use.

An investigational therapy, APN01, developed by Austria-based Apeiron was started with intravenous infusion for 5 min twice daily. The investigators reported the patient became afebrile within hours.

APN01 is a recombinant form of the human angiotensin-converting enzyme 2 (rhsACE2), and this compound is the crucial severe acute respiratory syndrome SARS-CoV-2 receptor and protects multiple tissues, including the lung from injury as a regulator of the renin—angiotensin system.

The next day the patient’s temperature rose suggesting bacterial pneumonia. She was treated with cefuroxime.

The patient also was diagnosed dealt with methicillin-sensitive 

The patient was released after 57 days in the hospital.

The study’s lead author Alexander Zoufaly, MD, Department of Infectious Diseases/Clinic Favoriten spoke with 

 about the specifics of the case and offered some insights into the investigational therapy.

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A case study examines a treatment for a hospitalized case of the virus.

Author | John Parkinson

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