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Scientists use human breast milk to treat prolonged COVID-19 in a severely immunodeficient patient

Researchers at the University of Campinas (UNICAMP) in São Paulo state, Brazil, have resorted to a thoroughly unconventional method to treat COVID-19…

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Researchers at the University of Campinas (UNICAMP) in São Paulo state, Brazil, have resorted to a thoroughly unconventional method to treat COVID-19 in a patient with a rare genetic disease that makes her immune system unable to combat viruses and other pathogens. She was instructed to take 30 milliliters of breast milk every three hours for a week. The breast milk was donated by a woman who had been vaccinated against SARS-CoV-2. After testing positive for 120 days by RT-PCR, the patient then tested negative.

Credit: Elza Fiúza/Agência Brasil

Researchers at the University of Campinas (UNICAMP) in São Paulo state, Brazil, have resorted to a thoroughly unconventional method to treat COVID-19 in a patient with a rare genetic disease that makes her immune system unable to combat viruses and other pathogens. She was instructed to take 30 milliliters of breast milk every three hours for a week. The breast milk was donated by a woman who had been vaccinated against SARS-CoV-2. After testing positive for 120 days by RT-PCR, the patient then tested negative.

The case is reported in an article published in the journal Viruses. The authors were supported by FAPESP via four projects (16/00194-818/14372-018/14389-0, and 20/04558-0).

“I’ve followed this patient since she was a child, and I was very concerned when she told me she had COVID-19. The innate immunity error from which she suffers dysregulates her entire defense system. Her inflammatory response is defective, with few cells going to the site of the inflammation and low antibody production. Depending on their virulence, infectious agents can lead to two outcomes in such cases – chronic infection or death,” said pediatrician Maria Marluce dos Santos Vilela, a professor at UNICAMP’s Medical School and last author of the article.

Vilela explained that the immune system in humans and other mammals normally produces five types of immunoglobulin antibody (IgM, IgG, IgA, IgE and IgD). Patients with immune dysregulation syndromes have a deficiency of IgE and in some cases a complete absence of IgA, the main antibody that neutralizes viruses and other pathogens. IgA is usually present in breast milk, as well as respiratory and gastrointestinal secretions. The syndromes also entail very low production of IgG, normally the most abundant antibody in blood and responsible for recognizing and neutralizing antigens with which the organism has had contact before. Only 157 cases of the same kind as this patient’s have been described worldwide, as reported in an article published in the Journal of Allergy and Clinical Immunology, with Vilela among its authors.

“Our strategy was to keep the patient isolated at home, where she was cared for by her mother, who monitored oxygen saturation, body temperature and nutrition. In hospital, she could have caught a bacterial infection, which would have made her condition much worse. Since she was diagnosed with COVID-19, in March 2021, we’ve been keeping track of her progress by videoconference,” Vilela said.

In the first 15 days of the infection, the patient had fever, loss of appetite, coughing and asthenia (lack of energy, weakness), but to Vilela’s surprise and relief, her lungs and other systems remained unaffected. After two months, her condition was the same, and the researchers decided to try treatment with convalescent plasma in collaboration with UNICAMP’s blood center. This entails a transfusion of IgG and other antibodies produced by people who have recovered from COVID-19.

The procedure was performed, and the symptoms improved, with a reduction in blood inflammatory markers. After 15 days, however, the RT-PCR test remained positive, and the patient still had mild symptoms, as well as signs of adynamia, general muscle weakness associated with prolonged infectious processes. 

“We were worried that the infection would persist for a long time, making the patient even weaker and increasing the risk that she would infect other people. At the same time, an article came out showing that breastfeeding women immunized with Pfizer’s COVID-19 vaccine produced milk with a reasonable amount of IgA. We decided on an experimental treatment using breast milk to boost her IgA levels,” Vilela said.

The procedure was possible only because the safety and quality of Brazil’s breast milk banks are assured by strict legislation. Donors must prove they are healthy and supply negative test results for infectious diseases such as AIDS, syphilis and hepatitis, among others. In addition, the system keeps records of vaccinations.

“We asked her to take the milk orally and keep it in her mouth for several minutes. IgA works like a broom in the sense that it sticks to pathogens throughout the gastrointestinal tract so that whatever is improper is eliminated in the feces. We decided on a three-hour interval between doses, except at night, in order not to give the virus a chance to replicate,” Vilela said.

The patient tested negative after a week, and twice again at ten-day intervals. “We continue to do RT-PCR tests for SARS-CoV-2. We’re concerned that she will acquire an asymptomatic infection, given the spread of novel variants,” Vilela said.

Same virus

According to the article, the virus remained active in the patient’s organism for at least 124 days. The UNICAMP researchers made sure it was the same infection and not a series of reinfections by sequencing the genomes of viruses isolated from three samples collected on different dates for diagnostic purposes. They also counted the number of viral particles in two of the samples. This part of the investigation was led by Professor José Luiz Proença-Módena, who heads the university’s Laboratory Emerging Virus Studies (LEVE). 

“The results of the sequencing showed that the patient was infected by the gamma variant [P.1] of SARS-CoV-2, which was first detected in Manaus in late 2020 and caused a collapse in the city’s health service in early 2021,” Módena said. “The data also 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 on samples from the patient collected at different times.”

For Vilela, the trial was only possible thanks to resources provided by the SUS (Sistema Único de Saúde), Brazil’s national health system. “The SUS network enabled us to retrieve samples for genomic analysis,” she said. “It also assured the safety of both the convalescent plasma and breast milk used in the treatment. Because its quality control is the same all over Brazil, I was able to tell a colleague in Acre [a state in the far north of Brazil] how to treat a patient with a similar immunodeficiency.”

Módena also emphasized the importance of “interaction between clinical physicians and researchers doing basic science in the kind of multidisciplinary collaborative translational research project FAPESP so strongly encourages”.

###

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.


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Government

New Hampshire Governor Vetoes Ivermectin Bill

New Hampshire Governor Vetoes Ivermectin Bill

Authored by Alice Giordano via The Epoch Times (emphasis ours),

New Hampshire’s Republican…

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New Hampshire Governor Vetoes Ivermectin Bill

Authored by Alice Giordano via The Epoch Times (emphasis ours),

New Hampshire’s Republican Gov. Chris Sununu vetoed a bill that would have made Ivermectin available without a prescription.

Ivermectin tablets packaged for human use. (Natasha Holt/The Epoch Times)

The Republican governor vetoed the bill on June 24, the same day that the U.S. Supreme Court overturned Roe v. Wade. Some fellow Republicans questioned the timing.

It certainly seemed like a convenient way to bury a veto of a bill that won support from the vast majority of Republicans in New Hampshire,” JR Hoell, co-founder of the conservative watchdog group RebuildNH, told The Epoch Times.

Hoell is a former four-term House Republican planning to seek re-election after a four-year hiatus from the the New Hampshire legislature.

Earlier this year, the New Hampshire Department of Children Youth and Family (DCYF) tried to take custody of Hoell’s 13-year old son after a nurse reported him for giving human-grade ivermectin to the teen months earlier.

Several states have introduced bills to make human-grade ivermectin available without a prescription at a brick and mortar store. Currently, it can be ordered online from another country. In April, Tennessee became the the first state to sign such a measure into law. New Hampshire lawmakers were first to introduce the idea.

Both chambers of the state’s Republican controlled legislature approved the bill.

In his statement explaining the veto, Sununu noted that there are only four other controlled medications available without a prescription in New Hampshire and that each were only made available after “rigorous reviews and vetting to ensure” before being dispensed.

“Patients should always consult their doctor before taking medications so that they are fully aware of treatment options and potential unintended consequences of taking a medication that may limit other treatment options in the future,” Sununu said in his statement.

Sununu’s statement is very similar to testimony given by Paula Minnehan, senior vice president of state government regulations for the New Hampshire Hospital Association, at hearings on the bill.

Minnehan too placed emphasis on the review that went into the four prescription medications the state made available under a standing order. They include naloxone, the generic name for Narcan, which is used to counter opioid overdoses, hormone replacement therapy drugs, and a prescription-version of the morning after pill.

It also includes a collection of smoking cessation therapy drugs like Chantix, which has been linked to suicide, depression, and other neuropsychiatric conditions. Last year, Pfizer, the leading maker of the FDA-approved drug, conducted a voluntarily recall of Chantix. Narcan has also been linked to deaths caused by severe withdrawals that have led to acute respiratory distress.

Rep. Melissa Blasek, a Republican co-sponsor of the New Hampshire ivermectin bill, told The Epoch Times, that one could veto any drug-related bill under the pretense of overdose concerns.

The reality is you can overdose on Tylenol,” she said. “Ivermectin has one of the safest track records of any drug.”

The use of human-grade ivermectin became controversial when some doctors began promoting it for the treatment and prevention of COVID-19. Government agencies including the FDA and CDC issued warnings against its use while groups like Front Line COVID-19 Critical Care Alliance (FLCCC) heavily promoted it.

Some doctors were  disciplined for prescribing human-grade ivermectin for COVID-19 including a Maine doctor whose medical license was suspended by the state.

Read more here...

Tyler Durden Thu, 06/30/2022 - 20:30

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Aging-US | Time makes histone H3 modifications drift in mouse liver

BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone…

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BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.”

Credit: Hillje et al.

BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.”

Aging is known to involve epigenetic histone modifications, which are associated with transcriptional changes, occurring throughout the entire lifespan of an individual.

“So far, no study discloses any drift of histone marks in mammals which is time-dependent or influenced by pro-longevity caloric restriction treatment.”

To detect the epigenetic drift of time passing, researchers—from Istituto di Ricovero e Cura a Carattere Scientifico, University of Urbino ‘Carlo Bo’, University of Milan, and University of Padua—determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. 

“In this study, we used chromatin immunoprecipitation sequencing technology to acquire 108 high-resolution profiles of H3K4me3, H3K4me1, H3K27me3 and H3K27ac from the livers of mice aged between 3 months and 12 months and fed 30% caloric restriction diet (CR) or standard diet (SD).”

The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, reduced the extent of changes occurring during the first year of life in these genomic regions.

“In conclusion, while our data do not establish that the observed changes in H3 modification are causally involved in aging, they indicate age, buffered by caloric restriction, releases the histone H3 marking process of transcriptional suppression in gene desert regions of mouse liver genome most of which remain to be functionally understood.”

DOI: https://doi.org/10.18632/aging.204107 

Corresponding Author: Marco Giorgio – marco.giorgio@unipd.it 

Keywords: epigenetics, aging, histones, ChIP-seq, diet

Sign up for free Altmetric alerts about this article:  https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204107

About Aging-US:

Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Government

FDA asks for COVID boosters to fight Omicron’s BA.4, BA.5 subvariants

The U.S. Food and Drug Administration on Thursday recommended booster doses of COVID-19 vaccines be modified beginning this fall to include components…

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FDA asks for COVID boosters to fight Omicron’s BA.4, BA.5 subvariants

By Michael Erman

June 30 (Reuters) – The U.S. Food and Drug Administration on Thursday recommended booster doses of COVID-19 vaccines be modified beginning this fall to include components tailored to combat the currently dominant Omicron BA.4 and BA.5 subvariants of the coronavirus.

The FDA said manufacturers would not need to change the vaccine for the primary vaccination series, saying the coming year will be “a transitional period when this modified booster vaccine may be introduced.”

FILE PHOTO: Signage is seen outside of the Food and Drug Administration (FDA) headquarters in White Oak, Maryland, U.S., August 29, 2020. REUTERS/Andrew Kelly/File Photo

The new booster shots would be bivalent vaccines, meaning doses would target both the original virus as well as the Omicron subvariants.

The decision follows a recommendation by the agency’s outside advisers to change the design of the shots this fall in order to combat more prevalent versions of the coronavirus. read more

BA.4 and BA.5 are now estimated to account for more than 50% of U.S. infections, according the U.S. Centers for Disease Control and Prevention, and have also become dominant elsewhere.

The FDA said in a statement on Thursday that it hoped the modified vaccines could be used in early to mid-fall.

Pfizer Inc (PFE.N) with partner BioNTech SE (22UAy.DE) and Moderna Inc (MRNA.O) have been testing versions of their vaccines modified to combat the BA.1 Omicron variant that caused the massive surge in cases last winter.

Although they have said those vaccines worked against BA.1 and the more recently circulating variants, they did see a lower immune response against BA.4 and BA.5.

The companies had already been manufacturing their BA.1 vaccines, and said on Tuesday that swapping to a BA.4/BA.5 version could slow the rollout.

Pfizer/BioNTech, which on Wednesday announced a $3.2 billion contract to supply more COVID vaccine doses to the United States, said they would have a substantial amount of BA.4/BA.5 vaccine ready for distribution by the first week of October. read more

Moderna said it would be late October or early November before it would have the newly modified vaccine ready.

Reporting by Michael Erman in New Jersey and Leroy Leo in Bengaluru; Editing by Jonathan Oatis and Bill Berkrot

Our Standards: The Thomson Reuters Trust Principles.

Source: Reuters

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