COVID-19 and the Heart: Cedars-Sinai Doctors Treat Patients With Heart Cell Therapy
Cedars-Sinai has been recognized nationally for how it manages COVID-19 patients. Particularly, at the medical center, some critically ill patients received an experimental treatment of lab-grown human heart tissue and, consequently, showed significant improvement.
CAP-1002 is the name of the experimental heart-cell therapy that was previously used in clinical research focused on the treatment of heart failure. The therapeutic contains cardiosphere - derived cells (CDCs) from heart tissue, which are grown in the laboratory. According to previous studies, in several diseases, the intravenously given cells had intense benefits for inflammation and the immune system.
CAP-1002 May Help Patients Fight Off a Fatal Immune Response
With this heart-cell therapy, Cedars-Sinai may be getting to the core of widespread inflammation caused by the body's immune response, which is a common reaction triggered by COVID-19. This therapy could be a key difference in helping patients overcome the disease.
In what is believed to be the first peer-reviewed report on cell therapy in critically ill COVID-19 patients, researchers at Cedars-Sinai reported on the therapy in 6 patients critically ill with the disease. 4 of them, suffering from respiratory failure, recovered well enough within 4 days of the infusions, and within less than 3 weeks they were discharged from the hospital.
The other 2 patients who received the treatment remained in intensive care. None of the patients showed adverse effects from the heart-cell therapy.
According to hospital officials, by comparison around the same time, among a group of 34 COVID-19 patients treated in the intensive care unit who did not receive cell therapy, 6 people died.
The cell therapy was used by the hospital with Food and Drug Administration approval for emergency compassionate use. Each patient, or their legal representative, gave written informed consent and each case was approved by the Cedars-Sinai Institutional Review Board.
Doctors conducted the emergency use treatment in collaboration with Capricor Therapeutics, the biotechnology company which manufactured the CAP-1002 cells. The researchers, together with the manufacturers, reported their findings in a paper titled Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series, published in the journal Basic Research in Cardiology.
According to investigators, patient outcomes, although encouraging, are not sufficient to prove that the CAP-1002 administration is effective and safe for treating COVID-19 without a clinical trial and control group. A future randomized clinical trial also needs to look into how some COVID-19 patients get better on their own with standard treatments.
Randomized Clinical Trial to Establish CAP-1002 Efficacy
The compassionate use study has an immediate successor in the Cytokine Storm in Covid Syndrome Trial. This expanded access protocol continues to evaluate the clinical and biochemical effects of CAP-1002 administration in patients with severe or critical COVID-19 infection.
The first peer-reviewed report grew out of the discovery that, for those critically ill with COVID-19, it's the body's overreaction that often delivers the fatal blow and not the infection itself.
The body is overwhelmed with infection-fighting proteins after its immune system unleashes cytokine upregulation and an exaggerated yet maladaptive inflammatory response. These proteins can trigger multiple-organ failure and death. The increasing severity of illness is associated with more than 50% mortality rates in critically ill patients.
COVID-19 is predominately defined by respiratory symptoms. Although most cases are mild to moderate in severity, about 15% develop severe pneumonia, and nearly 5% progress to:
The Cedars-Sinai researchers evaluated the safety and impact of allogeneic CDCs, formulated for intravenous infusion as CAP-1002, and now believe that by countering immune overreaction, the cells could stop or treat acute respiratory distress and myocarditis.
The cell therapy's anti-inflammatory effect could be a critical boost. According to previous studies, CDCs have intense benefits for the immune system and inflammation by secreting exosomes. These are nanoscale vesicles with various active contents that travel widely throughout the body.
CDCs have been tested in clinical trials in more than 200 patients for:
These studies, along with more extensive preclinical evaluation, have also demonstrated that a majority of IV CDCs are retained in the lungs and may lead to local benefits within the lung parenchyma.
Meanwhile, another collaborative study between the Marbán lab and the Regenerative Medicine Institute - published in Cell Reports Medicine - shows that COVID-19 may infect cardiac cells. The cardiac complications include:
Many COVID-19 patients experience heart problems, but the reasons behind the complications are not yet completely clear. Until now, only limited evidence showed that the heart's muscle cells are directly infected by the virus. All the conditions implicated:
Findings from this line of research may help prevent heart infections. A number of immunomodulatory therapies are under investigation for COVID-19 and are awaiting validation in large-scale randomized trials, including:
Given the body of evidence confirming relevant disease-modifying bioactivity and the safety record of CDCs in humans, applicability to the hyperinflammatory stage of COVID-19 seems compelling.