When on August 25, Doctor of Science Tania Crombet Ramos presented to the country’s leadership part of the partial results of the use of the humanized monoclonal antibody Nimotuzumab, in patients with severe COVID-19 disease. More than 600 kilometers from Havana, in the municipality of Guáimaro, Camagüey province, Marlon Silva Acosta was about to receive the benefits of a drug that does not hesitate to assure “saved his life.”
Then, in the weekly meeting that took place almost two years ago with scientists and experts who participate in science and technological innovation activities in the confrontation with SARS-CoV-2, Dr. Crombet Ramos reported: “The monoclonal antibody was safe in the treatment of these patients, demonstrating an improvement in ventilatory function, a decrease in inflammation markers, and a radiological improvement or stabilization of multifocal interstitial pneumonia in 80% of the patients at seventh day of treatment. It also showed evidence of prevention or improvement of fibrotic lesions and a high recovery rate in seriously ill patients”.
Everything that Marlon Silva would experience since August 15, when he began with respiratory symptoms and on the advice of the doctor from the family doctor’s office, a rapid test was carried out on the 18th, it would corroborate the data provided by the scientist on this product biotechnology, developed by the Center for Molecular Immunology (CIM). “Right there I was positive.
Then they referred me to the field hospital of the Guáimaro ESBEC suspect center, “Marlon told Cubadebate almost two months after he went through that “nightmare”. He was there until the 22nd, because up to that moment no lung sounds had been detected when he was auscultated. He received a first dose of Interferon and began treatment with Azithromycin, he said.
“That same day the clinician, at the visitation pass, detected crackling noises at the base of the lung and sent me to the hospital, but the covid room was fully occupied. That is why, they took me to the field hospital of Guáimaro hotel, for better care, ” he recalled. “I had already presented, in addition to the fever, loss of appetite, taste and smell, but above all the fever was very high and, the respiratory sounds detected by the clinician were maintained.”
It was at the hotel that Marlon began to feel short of breath. On the 25th, after taking the first X-ray, he was immediately sent to the Municipal Hospital of Guáimaro, “Manuel Enrique Cardoso”. Maybe, this is how Marlon remembers the name of the doctor who was on duty that night when he entered. “They started hydration immediately, they started giving me the second-generation antibiotic Cefuroxime, in addition to Dexamethasone, and they continued to administer Azithromyzine,” he said.
On the 26th, at the changing of the guard, Dr. Daniel informed him of the possibility of treating him with the drug Nimotuzumab. “I had already received two doses of interferon. The doctor explains to me that, due to my serious condition, he qualified for the emergency use of Nimotuzumab, but he had to give my consent. We did the formalities and started the treatment with this drug and thank God I assimilated it well. I must also thank the speed with which this doctor “moved,” as Cubans say, and began treatment with that monoclonal antibody, “he confessed.
On the 25th, after taking the first X-ray, he was immediately sent to the Municipal Hospital of Guáimaro,
(Photo: Courtesy of the interviewee.)
If the final X-ray is observed at the time of discharge, with respect to the previous X-ray, it can be seen that the white mottling, which is a sign of an ongoing inflammatory process, has improved and disappeared. Photo: Courtesy of the interviewee.
The improvement, he said, was not long in coming. Two days after this first dose, “the lack of air was not so great, I had good oxygen saturation in my blood and I was thus able to leave the ICU towards another room, in the same COVID area, but now out of danger.”
“On August 29th they gave me the second dose of Nimotuzumab and on the first of September the third. Then they make me the badge. That day in the afternoon they gave me the medical discharge, of course, with the complementary tests carried out and a negative rapid test”, said Marlon. “I have just turned 37 years old. I do not have any underlying disease and of the adverse effects that I read in the form that was given to me to give my consent and that would be associated with the medication, I did not present any. Neither dizziness, nor nausea, nor loss of appetite, all were, thank God, blessings and recovery, ” he pointed out.
The story is now told by this young man from The Bahamas, where he works as a collaborator, for the Ministry of Education. When he became ill, he was not vaccinated and he hopes in December, when he returns to Cuba, to be able to receive his booster dose with some of the island’s immunogens. Of those “serious” days and the uncertainty of suffering the ravages of a deadly virus, he also remembers fear and anguish. “We all get sick at home, including my nine-year-old son, but luckily only I made it worse.” Luckily, he added, there is Nimotuzumab.
A fortress for the Cuban protocol against covid “In a patient with pneumonia, the results are formidable,” says Dr. Leonor Porto Franco, a first-degree specialist in Geriatrics and Gerontology, master’s degree in Longevity and assistant professor at the Faculty of Medicine of the Amalia Simoni Hospital, in the city of Camagüey, when we inquired about their experience in the use of this antibody. “We started using Nimotuzumab at the end of July and so far its results are excellent, few adverse reactions that have been solved without medication.The important thing about its administration is that it must be early, ” said the specialist.
According to Porto Franco, the drug has been used in a total of 110 cases and very few patients died. “All these people arrived in a frank inflammatory period with an advanced disease, I think that the success of the treatment is in its precociousness and the correct application of the protocol,” she insisted. Dr. Leonor agrees with Dr. Raity Hernández Fernández, specialist in intensive care and emergency at the Matanzas Mario Muñoz Monroe military hospital. “The Nimotuzumab arrived at our hospital in July. In a context in which the situation in the country and especially in Matanzas was very complex. Many cases are diagnosed daily, with a large number arriving directly from the house to the intensive care room and the intensive care unit room ”, recalled the interviewee. The ICU occupancy rate was very high, responding to a difficult phenomenon of hyperinflammation and development of critical severe forms and death in many patients from multi-organ damage and thrombotic phenomena, he said.
The specialist said that as a scientific strategy and taking into account the imperative need for a drug to stop said hyperinflammation, it was decided to carry out a clinical trial with this monoclonal antibody. After evaluating the clinical improvement in severe cases, given by the non-progression to critical states, it was decided to include it in the national protocol, she said. “In our center, until October 20, Nimotuzumab has been used in 172 patients, with 120 of them already discharged. The drug is very safe, with few adverse reactions, generally mild. It is easy to administer by peripheral venous access and does not need intensive monitoring for its administration”, explained Dr. Hernández Fernández. “The earlier the better the cases, always taking into account the criteria for use,” he emphasized. Favorable clinical evolution in a short time.
The experience regarding the use of the monoclonal antibody that arrived in his province at a critical time due to the rise in infections, is just as satisfactory for Dr. Yaikiel Díaz Morales, clinician, deputy director of the military hospital in the province of Villa Clara. “Our hospital was a pioneer in confronting covid-19 when the pandemic began last year, as well as in the use of some innovative drugs in our country, such as the monoclonal antibody Itolizumab, from the Center for Molecular Immunology (CIM) that it gave us very good results. We were able to start using them in minimal care wards for patients who were high risk, ”he said.
According to the specialist, Itolizumab was introduced in the province from a local transmission event in a Nursing Home. “We set ourselves the task of starting to use it in those patients who were very delicate patients, with many risk factors and who were covid-positive. This monoclonal had a great impact at that time in Villa Clara and, as a result, new studies with this product have emerged and we have increased its use. Then, at the country level, it becomes a drug approved in the covid care protocols that were modified in the course of the epidemic,” recalled the clinician.
Faced with the hyperinflammatory syndrome, a suspicion from a clinical and radiological point of view, “that was the moment to use that monoclonal we had in our hands: Itolizumab”.
In the first, second and even the third regrowth, the main results we had were undoubtedly to prevent patients with moderate forms of the disease from evolving to severe or critical forms of it and having to move from minimal care rooms to nursing homes. intensive therapy. We treat with this drug and it was our main weapon to stop this hyperinflammatory response along with the rest of the drugs in the protocol and get the patient to be discharged without aggravating ”, he commented. Then – he said – we reached the most critical moment of the pandemic, “the most terrible and one that has claimed the most Cuban lives since the epidemic began, as a result of the circulation throughout the country of other variants of the virus.”
HASTA AQUI “The clinical, radiological and humoral evolution of these patients did not resemble the clinical evolution that the patients had last year, since they evolved to serious or critical forms faster. We still saw the markers rise faster than at other times during the pandemic. It is then that Nimotuzumab joins the protocol that we have been working on, ”said Dr. Yaikiel. This monoclonal antibody, he said, was not unknown. “We are a collective made up of working groups where there are specialists in internal medicine, nephrology, obstetrics, pediatrics and many of us, especially internists, had already read something about Nimotuzumab, especially in aspects related to the specialty of pulmonology, in the treatment of pulmonary fibrosis and other lung conditions ”.
“It arrived at a critical moment in the epidemic, with a hospital practically collapsed, with all the hospitalization beds occupied, an intensive care unit whose occupational rate fluctuated practically every day at 100%, and it was the right decision,” he said. For Dr. Yaikiel, the idea that the main research centers in the country are interrelated with health institutions in the different territories was strategic at this time. “
We have maintained a very close relationship with the CIM. Both by telephone and by videoconference they trained us on how to use the product, what were its characteristics, indications and mechanisms of action ”, he said. He referred the specialist that its use began first in eight patients, and to date around 60 patients with moderate forms of the disease, bronchopneumonic processes and based on clinical, complementary and radiological criteria have been treated with Nimotuzumab. “We were struck by the fact that, unlike the other monoclonal, in this one its use is more feasible, its administration is in a short time, the adverse reactions are practically nil and if they appear they are slight, since they are controlled quickly. We did not report serious adverse reactions in any patient, “he said.
The interviewee stressed that the results are very positive. “When we get feedback with the specific results that the CIM offers us on the studies that are being carried out, we realize that what they describe is precisely the clinical evolution of the patients. In other words, the clinical improvement that we see in patients translates into a reduction of several markers that the MIC is seeing later in the studies of these same patients from us and from other hospitals that they collect.
It is observed how the levels of interleukin and other cytokines that are the cause of this hyperinflammatory syndrome decrease ”, explained Dr. Yaikiel Díaz Morales. He added that it is evident from a clinical point of view how patients with a bronchopneumonic picture, saturation and oxygenation drop, altered respiratory rate, when receiving a first dose of Nimotuzumab, show a clinical improvement 48 or 72 hours after using this medicine. “We have also observed at work in our hospital how patients after the second dose (they are applied at 72 hour intervals) have a clinical improvement and from the radiological point of view. Many of them have had to use a third dose, others have not. The minority, just four patients, have had to use a fourth dose, “he explained. “For the community of our hospital, Nimotuzumab — like Itolizumab — is undoubtedly a blessing for the treatment of COVID-19. This disease has taught each of us professionals to face it with all the phenomena and complications that it causes from a microvascular point of view. Without having these weapons, the Nimotuzumab and also the Itolizumab, we would not have saved so many lives. These drugs, along with anticoagulation, other anti-inflammatories and of course the rest of the Cuban protocol, are undoubtedly the tools to face this complex disease ”, he considered.
For the specialist, when faced with a patient who from a clinical point of view is evolving into severe or critical forms of the disease, “having an antibody like Nimotuzumab on hand gives us security and confidence. We are hopeful that this drug is capable of reducing that terrible hyperinflammatory response to prevent that patient from dying or not going on a good path, as we say in the room. ” Dr. Yaikiel appreciates the opportunity to have this monoclonal within the therapeutic arsenal and also thanks its developers. “In the most critical moments we had the support of the CIM, having the call of Professor Mayra, Professor Tania, at times when the epidemiological situation in our province was very difficult to give us support, confidence, to exchange on occasions about a specific patient has given us encouragement and strength to continue. Our collective is ready to continue to be handsome until the pandemic is eradicated or taken to the minimum of its expression, ”he said.
What does the scientific evidence say about Nimotuzumab? Doctor of Science Tania Crombet Ramos, director of Clinical Research at the Center for Molecular Immunology, is clear in her explanation: “Unlike other innovative molecules that we have used in covid, this antibody could have not only an important anti-inflammatory role ”.
“Nimotuzumab could also impact on the improvement of the coagulation disorder that accompanies covid, or it could prevent or reverse pulmonary fibrosis, since the EGF receptor (epidermal growth factor) is one of the central proteins that participate in the cell proliferation and tissue repair that has to occur as a consequence of the damage caused by the virus ”, he said.
But what is Nimotuzumab? The scientist explained that it is a monoclonal antibody that blocks or inhibits epidermal growth factor, which is a highly validated target in oncology. As a consequence of this blockade, there is an inhibition of the uncontrolled proliferation of tumor cells, of the formation of new vessels, of metastasis, which is tumor spread, in addition to the induction of apoptosis, which is nothing more than death. of tumor cells. The monoclonal also activates the immune system. “Unlike other molecules that recognize the same target, Nimutozumab is a very safe molecule.
This is one of its great advantages, as it preferentially recognizes tumor cells and not normal tissue, which has a lower expression of the EGF receptor and can be used in combination with other cancer therapies such as irradiation and chemotherapy, although it can also be used as monotherapy ”, added the expert. Since 2002, Nimotuzumab obtained its health registration in the indication of advanced head and neck cancer. It is also registered in other indications such as nasopharyngeal tumors, which is a differentiated subsite within head and neck cancer, esophageal tumors, pancreatic cancer, and non-small cell lung cancer.
Patients with brain tumors can also benefit from this product, particularly those classified as glioblastomas multiformes or anaplastic astrocytoma, and brain stem tumors in the case of the pediatric population. “According to the annual consumption demand of the Ministry of Public Health, our estimate is that more than 5000 oncology patients are treated annually with Nimotuzumab. It is also registered in 24 other countries and has a special sales permit in fifteen European territories and in other countries such as Malaysia and Singapore ”, said Crombet Ramos.
Regarding the use of this monoclonal in patients with covid-19, he explained that a clinical trial was carried out between the months of May and June at the Julio Trigo and Salvador Allende hospitals in the capital, and at the end of this investigation Nimotuzumab was incorporated into the protocol Cuban management of covid-19. “Currently it is used in the treatment of the severe patient and the moderate patient at high risk of aggravation, who has evidence of lung lesions,” she said. She said that global estimates show that more than 5,000 patients have been treated with Nimotuzumab between the months of July and September, precisely at the peak of the pandemic in Cuba.”
The most important results of our research show that monoclonal was very safe in the management of patients with covid-19 in serious condition and moderate stage, at risk of passing to severe forms of the disease. There was an improvement in ventilatory function, a reduction or stabilization of the concentration of interleukin 6, which is one of the most pathogenic cytokines that affects the hyperinflammatory state that occurs in covid-19, was demonstrated. There was also a radiological improvement or stabilization of the pneumonia lesions.
He said that global estimates show that a number of more than 5000 patients have been treated with Nimotuzumab between the months of July and September, precisely at the peak of the pandemic in Cuba. “The most important results of our research show that monoclonal was very safe in the management of patients with covid-19 in serious condition and moderate stage, at risk of passing to severe forms of the disease. There was an improvement in ventilatory function, a reduction or stabilization of the concentration of interleukin 6, which is one of the most pathogenic cytokines that affects the hyperinflammatory state that occurs in covid-19, was demonstrated. There was also a radiological improvement or stabilization of multifocal interstitial pneumonia lesions in 80% of the patients on the seventh day after the first dose ”. “We also have preliminary evidence of prevention or reversal of fibrotic lesions by computerized axial tomography and a high recovery rate of more than 80% was achieved in the case of severe patients and greater than 90% in the case of moderate patients with very high risk.
In summary, Nimotuzumab is a very safe molecule, which also shows a high recovery rate and allows the reduction of pulmonary sequelae ”, said the scientist. The best of the evidence is there, in stories like Marlon’s, or in the many accumulated battles of Leonor, Yaikiel and Raity, who from within the red zone have seen in the Nimotuzumab the science of a laboratory translated into hope and safety in saving lives.
Source: Cubadebate
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