Study results: Convalescent plasma

"Convalescent plasma with high antibody titers applied in the first days of illness transforms COVID-19 into a bad cold in the elderly." A randomized, double-blind, and placebo-controlled study conducted by the INFANT Foundation evaluated the efficacy of early administration of convalescent plasma with high antibody titers in older adults with mild disease and observed that its application decreases by 60% the possibility that these patients need oxygen during illness. The study, conducted by a team of scientists led by Dr. Fernando Polack (Director of the INFANT Foundation), showed that convalescent plasma administered to infected people over 65 years of age with comorbidities and in all those over 75 years of age is effective to prevent COVID-19 from developing into a serious respiratory illness, as long as it is administered within the first 72 hours of the onset of symptoms. In this way, and in line with the use of plasma derivatives -such as hyperimmune gamma globulin- and antiviral drugs in other diseases-, antibody-rich plasma acts at the beginning of the disease, preventing it from advancing, unlike the tests carried out in serious patients where stopping the progression of COVID-19 becomes more difficult and conclusive benefits have not been found in its use. “Plasma is just a vehicle that carries antibodies. 28% of people have, according to our study, the amount of antibodies necessary to donate plasma for this treatment. By restricting donors to those with higher antibody concentrations, it is possible to further improve plasma yield. Although this leaves a group of convalescents out of donation, between 4 and 8 recovered patients have the necessary antibodies to be a donor. Patients who had pneumonia or needed hospitalization tend to produce the most antibodies, "Polack explained. The researchers identified the desirable amounts of protective antibodies in the plasma bags using the COVIDAR antibody assay developed by the Leloir Institute in Buenos Aires. This information is an extremely important tool for the design of public policies, since it will allow the design of donation campaigns that directly aim to identify the correct donors, optimizing time, effort and resources. "This study describes the first strategy in the world to stop the progression of SARS-COV2 with an economic, universal, non-patent, proven safe intervention that can be administered on an outpatient basis in care units without the need for hospitalization," Polack said. The trial, which was carried out between the months of June and last October, involved 160 adults over 65 years of age with at least one comorbidity (hypertension, diabetes, obesity, kidney failure and / or chronic obstructive pulmonary disease), and all the elderly over 75 years of age. The program articulated efforts from the public and private sectors, bringing together hospitals in the province of Buenos Aires and sanatoriums in the capital city, and had the support of the respective Ministry and Secretary of Health, PAMI, the Military Hospital, including various other actors in the health area and hundreds of volunteers. An independent Data and Safety Monitoring Committee (DSMB) oversaw the study by monitoring the quality and the well-being of the patients. The study was funded by a grant from the Bill & Melinda Gates Foundation and the INFANT Foundation Pandemic Fund, which brings together numerous national companies and private donors. The research was carried out with the collaboration of the Instituto de Efectividad Clínica y Sanitaria (IECS) and the Fundación Hematológica Sarmiento at the Hospital Dr. Carlos Bocalandro, Hospital San Juan de Dios, Hospital Simplemente Evita, Hospital Central de San Isidro Dr. Melchor Ángel Posse, Clinica Olivos and a network of geriatric care units linked to PAMI in the province of Buenos Aires. Also in the Hospital Militar Central, Centro Gallego, Sanatorio de los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado Corazón, Sanatorio Anchorena and Sanatorio Finochietto in the city of Buenos Aires. The design of this study was randomized, double-blind, and placebo-controlled. This means that half of the patients randomly received high antibody titer plasma and the remaining half placebo (physiological solution), without doctors or participants knowing which substance was administered to each individual. This method is used to ensure impartiality in the evaluation of the results.

About the Study

Once all the recruited patients received plasma or placebo, the evolution of the disease in both groups was compared. Of the patients actually treated with plasma, only 9 needed oxygen compared to 23 who received treatment with placebo. It is estimated that one in 6 people treated with plasma who would have had severe disease if they had not received it, did not develop it. “This is the only study in the world against SARS-COV2 that was done with this rigorous methodology of early comparison of one group against another and, therefore, provides evidence that the disease did not progress due to the administration of plasma and not for other reasons ”, explained Dr. Romina Libster, one of the main authors of the work, a pediatrician who specializes in vaccines and a researcher at the INFANT Foundation. For this study to be possible, the work required the detection of plasma donors, the identification of patients in the nursing homes of the Province and Capital of elderly people with mild early symptoms, their rapid testing at home by swabbing for SARS CoV2 in the laboratory of the Central Military Hospital, and the transfer of those infected who wish to participate to the study institutions by a mobile group provided free of charge by Swiss Medical that traveled through the region for months. There, a team from the Fundación Hematológica Sarmiento coordinated the administration of plasma or placebo, taking care that no one knew who received each product. This continued with daily monitoring of the participants for up to 25 days and the analysis of all the information by a group of research and statistics experts from INFANT and the IECS. During the first weeks of May, against the clock, and in the midst of a pandemic with enormous uncertainty, the INFANT team of researchers trained more than 200 doctors from the participating health centers in the protocol. The goal was to reduce the chances of error in all procedures. At the same time, a large group of volunteers were actively looking for donors. Every day they called a hundred people recovered from COVID-19 to invite them to participate in the program and make them aware of the importance that this contribution could have for new patients. More than 100 volunteers were trained, who helped day and night in the identification of possible patients to enroll in the study, coming from their homes and nursing homes in the suburbs of Buenos Aires, referred through the collaboration of PAMI, or coming through consultations in the clinics in the Federal Capital. "During all stages, the project, which involved around 400 people, required meticulousness to assemble the different links and cover both scientific and logistical needs," said Gonzalo Pérez Marc, pediatrician, deputy director of the Departamento Materno Infantil del Hospital Militar Central and also one of the main authors of the work. This study, carried out with Argentine scientists, is the first evidence in the world, of a universal, accessible and safe treatment that can save lives until vaccines are available.