Curing COVID-19 with Live Medications

Cure COVID-19 with live drugs. This is the bet of the CRIS Unit for Research and Advanced Therapies of La Paz, with a pioneering approach in the world. It is an experimental therapy, which is in phase II, for severe COVID-19 patients. These are patients admitted to hospital, with acute respiratory failure due to pneumonia and in need of ventilation.

Reactivation of viruses

But to explain this research you have to start at the beginning. Reactivations of viruses -cytomegalovirus, adenovirus, influenza or coronavirus- in children who have undergone a bone marrow transplant is one of the complications that can arise after the intervention. Until the patient fully recovers the immune system is considered vulnerable to viral infections. In fact, these infections in bone marrow transplantation are estimated to cause approximately 20-25 percent of transplant deaths.

To avoid them there are few alternatives. Keep in mind that for an antiviral to be effective, the virus must replicate. “Only in the replication phase are viruses sensitive to any activity”, aim Antonio Pérez-Martínez, head of Oncohematology at Hospital Universitario La Paz.

Immunocompetent donors

After several years of research, cell therapy has become a good alternative. It is the world of live medicines against viral infections.

“The immunocompetent donors they have a cellular immunity that protects against these viral infections, which are very common, because especially adults, we have had exposure to viruses ”, explains Pérez-Martínez. In this way, the donor lymphocytes and its administration in patients during the vulnerable period can protect them from the development of viral infections. “That 20 percent of mortality related to viruses has begun to decrease dramatically and we have improved survival,” he says.

With this experience and its results, a few months ago the experts thought about extrapolating it outside of the transplant … To the COVID patient. This is the clinical trial that the CRIS Unit of La Paz. The question is simple: memory T lymphocytes against the virus may act in the same way as memory T lymphocytes in other infections in the context of transplantation.

Extrapolation to COVID

COVID-19, says Pérez-Martínez, despite being an infection with a nasopharyngeal route of entry, generates a systemic disease, characterized by producing lymphopenia. “The linfopemia generates in patients a state of cellular immunity very similar to the children we transplant. Therefore, we already have the first situation for our treatment to be carried out: our patients with COVID-19 have lymphopenia, and also the more pronounced it is, the more serious the patient is ”.

Second, these candidates must have lymphocytes that react against COVID peptides, that is, memory lymphocytes, that have cellular immunity and that share, at least, a human leukocyte antigen (HLA). At the moment it is unknown if that memory is lasting, says the expert, but what is known is that whoever has it eliminates the disease.

The cytokine storm

Cell therapy sometimes generates a cytokine storm or an inflammatory condition, at first there was fear on the part of the scientific community that it could worsen. However, with this cell therapy it was unlikely as it did not use a conventional lymphocyte. The memory lymphocyte, which has a marker called 45RO or 45RA-, is biologically non-proliferative.

The clinical trial

Child Hemato-Oncology Service of Hospital La Paz_Advanced cell therapies
Antonio Pérez-Martínez, Head of Oncohematology at Hospital Universitario La Paz.

However, the first phase of the clinical trial was carried out to find out if it is possible to obtain lymphocytes from a convalescent donor; see if it is possible to generate a lymph library that covers the HLA of the Spanish population; and to know what doses to administer and what are the possible adverse effects of those doses. “We have seen that we have been able to identify this cell population in donors. In addition, we have been able to create the biobank or lymph library that we are generating. And we have administered to patients without finding a single adverse effect ”.

In addition, a dose escalation design has been made with three cohorts: low, medium and high. “In none of the three have we found any adverse effect related to the treatment “.

In phase II, which is where they are currently, they have started the maximum cohort dose. There is already an arm of standard of care, and another of standard of care plus therapy. “To demonstrate effectiveness we have to recruit around 80-85 patients per arm. We currently have 15 patients in two weeks “, says Pérez-Martínez.

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