Scientists use breast milk to treat prolonged Covid-19 in patient with severe immunodeficiency

Researchers at the State University of Campinas (Unicamp) used an unconventional method to treat Covid-19 in a patient with a rare genetic disease that makes her immune system unable to fight viruses and other pathogens. For a week, she was instructed to ingest 30 milliliters of breast milk – from a donor vaccinated against SARS-CoV-2 – every three hours. After this period, the result of the RT-PCR test – which had been indicating the presence of viral RNA for more than 120 days – finally came back negative.

The case was reported in an article published in the journal Viruses. The authors received support from FAPESP through four projects (16/00194-8, 18/14372-0, 18/14389-0 and 20/04558-0).

“I have been following this patient since she was a child and when she told me she had Covid-19 I was very apprehensive. The innate error of the immunity that she presents leaves her defense system all deregulated. Her inflammatory response is deficient, there are few cells mobilizing to the inflammation site and low antibody production. The virulence characteristics of the infectious agents can lead to two outcomes in these cases: chronic infection or death”, says pediatrician Maria Marluce dos Santos Vilela, professor at the Faculty of Medical Sciences (FCM- Unicamp) and lead author of the article.

The researcher explains that the human and other mammalian immune systems normally produce five types of antibodies: immunoglobulins IgM, IgG, IgA, IgE and IgD. Carriers of this disease – known as immunoderegulation syndrome – usually have little IgE and, in some cases, a complete absence of IgA, the main neutralizing antibody for viruses and other pathogens, which is usually present in breast milk, respiratory and gastrointestinal secretions. In addition, there is a very low production of IgG, normally the most abundant antibody in the blood and responsible for recognizing and neutralizing antigens with which the organism has had previous contact. There are only 157 such cases described in the world, characterized in a study published in the Journal of Allergy and Clinical Immunology, of which Vilela is a co-author.

“Our strategy was to keep the patient isolated at home, under the care of her mother – who monitored oxygenation, body temperature and nutrition. In the hospital she could contract a bacterial infection, which would make the situation even more serious. , in March 2021, we periodically followed her by video”, says the doctor.

In the first 15 days of infection, the patient presented fever, loss of appetite and weight, cough and indisposition. But to Vilela’s surprise and relief, the lung and other systems remained unchanged. Two months later, the condition remained the same and the group then decided to test, in partnership with Unicamp’s Hemocentro, the treatment with convalescent plasma, that is, the transfusion of antibodies produced by people who had been cured of Covid-19, mainly those of the IgG type.

The procedure was performed and promoted improvement of symptoms and reduction of inflammatory markers in the blood. But, after 15 days, the RT-PCR test remained positive and the patient continued to present mild symptoms and signs of what doctors call adynamia, which is a great muscle weakness associated with prolonged infectious processes.

“We were concerned that the infection would last for a long time, which would weaken it further and increase the risk of infecting other people. At the same time, the results of a study came out showing that lactating women immunized with the Pfizer vaccine produced milk with a reasonable amount of IgA. We then decided to carry out the assistance experience of replacing IgA via breast milk”, says Vilela.

The researcher says that it was only possible to carry out the test because there is strict legislation in the country that guarantees the safety of milk banks. Only healthy women with negative tests for infectious diseases such as AIDS, syphilis and hepatitis, among others, can donate. And the system also lets you know if the donor has been immunized.

“We recommend that she consume milk orally, because IgA works like a ‘broom’, that is, it sticks to pathogens throughout the gastrointestinal tract and everything that is inappropriate is eliminated in the feces. hours between doses – except at night – was designed to not give the virus a chance to continue replicating”, says the pediatrician.

The test was negative after a week and two other tests, performed at intervals of ten days each, also did not detect the presence of SARS-CoV-2. “And we are still doing RT-PCR tests for SARS-CoV-2. Our concern is that, with the new variants, she will acquire an asymptomatic infection”, says the doctor.

always the same virus

According to data in the article, the patient remained at least 124 days with the virus active in her body. To make sure it was the same pathogen and not successive infections, the Unicamp researchers sequenced the SARS-CoV-2 genome isolated from three samples collected at different times for diagnostic purposes. In two samples it was also possible to quantify the number of viral particles. This part of the investigation was led by Professor José Luiz Proença Módena, coordinator of the Laboratory for the Study of Emerging Viruses (Leve).

“The sequencing results showed that the patient was infected by the gamma variant (P.1) of SARS-CoV-2, the one that emerged in Manaus in late 2020 and caused a collapse in the health system there in early 2021. In addition, the data showed that the patient was chronically infected by the same virus and not successively infected by different viruses, since no mutations in the viral genome were found in the three sequencing reactions performed with samples from the patient collected at different times”, reports Modena.

In Vilela’s assessment, the trial was only possible thanks to the resources offered by the Unified Health System (SUS). “It was the SUS network that allowed the retrieval of samples for genomic analyses. And, in addition, it guaranteed the safety of both convalescent plasma and breast milk used in the treatment. And as the network’s quality control is the same in country, I was able to instruct a colleague from Acre to care for a patient with a similar immunodeficiency”, he says.

Modena also highlighted the importance of “interaction between clinical and basic areas, through collaborative, multidisciplinary and translational research, greatly encouraged by FAPESP”.