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Leaky Gut and Microbial Dysbiosis Could Contribute to Cytokine Storm in Severely Ill COVID-19 Cases

AHA Publisher — Mon, 12 Apr 2021 07:00:13 +0000

Dr. Liji Thomas, MD via News-Medical – As the world approaches the grim milestone of three million deaths from COVID-19 disease, a new preprint research paper posted to the bioRxiv* server shows that the presence of gut bacteria in the plasma may be an indicator of progressive disease. In patients with pre-existing comorbidities, COVID-19 is associated with more severe disease. The gut is a well-established route of infection and target for viral damage by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) symptoms. Hospitalized patients with critical COVID-19 also often have gut complications. Besides the above, venous or arterial thromboembolism [blood clot] of the mesenteric vessels and small bowel ischemia [blockage of blood flow in the small bowel] is reported, especially in patients hospitalized for more extended periods. Study Aims and Details The current study, based in Birmingham, Alabama, in the USA, aimed to capture the presence of plasma biomarkers that indicate breaches of the gut epithelial barrier, and the presence of gut microbes in the plasma. Unfortunately, both could not be tested in the same subset of patients due to the small volume of plasma available. Of the 30 patients enrolled in the study with confirmed SARS-CoV-2 infection, all had diarrhea and nausea along with fever and shortness of breath. The median age was 63 years. Only two patients had a critical disease. Over a third were diabetic, and half experienced blood clots. Of the 30, 23 patients were overweight. Five patients had an in-hospital fatal outcome. Laboratory Results Lymphopenia and anemia were observed in half, and two-thirds of the patients, along with high monocyte counts. Neutrophils were also elevated, in 60% of males compared to 45% of females. This is significant since they are the first responders to any infection. Total leukocyte counts were elevated in about 40% of individuals with COVID-19, but platelet count abnormalities were observed in only 17% of subjects. Only two patients showed high levels of brain natriuretic peptide (BNP), probably due to heart failure. C-reactive peptide, an inflammatory marker, was elevated in all patients, with six patients showing levels consistent with severe inflammation. Eight subjects showed high ferritin levels, with half of them having levels indicative of inflammation. Almost all the patients had high fasting glucose and lactate dehydrogenase (LDH) levels. About two-thirds had anemia, Increased troponin-I levels, suggesting cardiac injury, were found in 80% of male subjects, vs only one female subject. Gut Microbes in Plasma The 14 plasma samples sent for evaluation for the presence of bacteria yielded over 150,000 sequencing reads, with the signal indicating strong bacterial presence in two-thirds of the samples. The total microbial population was comparable between patients with COVID-19. Using polymerase chain reaction, a dysbiosis index was arrived at to measure the abundance of bacterial groups in each sample. All the nine samples which indicated the presence of bacteria showed the same three major phyla, Proteobacteria, Firmicutes, and Actinobacteria, with one patient showing unknown bacteria in more significant numbers among all 14. These are the same that have been found in healthy plasma, as well. The most enriched phylum was Proteobacteria, while Bacteroides were present in very limited numbers. Among the two patients with a fatal COVID-19 outcome, the number of Firmicutes was low. Perhaps the abundance of this phylum may be a biomarker for severity of disease. Both Gram-negative bacteria and lipopolysaccharides (LPS), which is a major endotoxin originating from the cell wall of these bacteria, are higher in the plasma samples from COVID-19 patients. Gut Barrier Breaches The presence of gut microbes in plasma may suggest defects in the gut epithelial barrier, allowing bacteria to migrate through the epithelial cells into the systemic blood vessels. This is an important component in systemic inflammation and underlies the progression of COVID-19 in these patients. As a marker of gut permeability, fatty acid-binding protein-2 (FABP2) levels were measured, as this is a protein found within intestinal epithelial cells to bind free fatty acids, cholesterol, and retinoids. As such, its elevation in plasma indicates mucosal damage in the gut. As expected, FABP2 levels were high in the plasma of COVID-19 patients relative to healthy individuals. Gut microbial peptides in plasma are toxic in that they trigger inflammatory pathways and lead to systemic damage. As a measure of this phenomenon, the researchers observed higher levels of peptidoglycan (PGN) and LPS in COVID-19 plasma, at almost double the levels in healthy controls. What Are the Implications? The translocation of gut microbes, normally found only in feces, into the systemic circulation is a fundamental determinant of immune function and metabolism. The presence of gut microbes in plasma may trigger and also exacerbate inflammatory signaling pathways in the body. Inflammation is key to the pathogenesis of severe and critical COVID-19. This study’s findings may support the theory that this is driven by gut bacterial movement into the body’s circulation in these patients. This, in turn, could be due to higher gut permeability because of epithelial barrier dysfunction. Virus shedding in the feces has been found to persist for up to a month after lung symptoms resolve, indicating that viral colonization of the gut may be of longer duration than of the airways. COVID-19 patients in this sample were more likely to be diabetic and obese relative to the controls. In such patients, the commensal bacteria Lactobacillus are less abundant, and this reduction was found in a small group of nine patients tested at the beginning of hospitalization in this study. Most COVID-19 deaths are due to sepsis. In this study, the abundance of multiple pathogenic species such as Acinetobacter and Pseudomona was higher in the gut. Even after the infection resolved, dysbiosis persisted, indicating that the gut may suffer the effects of this illness over the long term. The plasma metabolome is linked to the gut microbiome in the pathogenesis of many diseases. Failure of the gut barrier leads to the detection of bacterial metabolic products in the plasma, in conditions like ulcerative colitis. The study suggests, “Leaky gut and microbial dysbiosis could contribute to cytokine storm in patients severely ill with COVID -19.” *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. This article has been modified. To read the original article click here.

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Experimental Treatment Offers Hope of Fertility for Early Menopausal Women

AHA Publisher — Fri, 02 Apr 2021 07:00:20 +0000

The North American Menopause Society (NAMS) via EurekAlert – Menopause typically signals the end of a woman’s ability to become pregnant. However, in a small new study, a novel approach of administering platelet-rich plasma and gonadotropins near the ovarian follicles is showing promise in restoring ovarian function. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS). As more women look to build their careers before pursuing motherhood, the average age of conceiving a child continues to be pushed back. For some of these women, however, their hope of becoming pregnant is cut short by the onset of early menopause, which is described as the cessation of ovarian function at or before the age of 45 years. It is estimated that roughly 12.2% of women experience early menopause. For these women, the only chance of becoming pregnant is with donor eggs. Multiple treatment options have previously been investigated, including standard, controlled ovarian stimulation. Platelet-rich plasma has been used in women with primary ovarian insufficiency, but few pregnancies and live births resulted. With the failure of these somewhat traditional treatments, more novel approaches, such as methods for inducing the growth of ovarian follicles, are being pursued. In this new, small-scale pilot study, platelet-rich plasma and gonadotropins were injected into the ovaries of study participants, with some fairly amazing results. After treatment, 11 of the 12 study participants resumed menstruation, and one achieved clinical pregnancy, defined as a pregnancy that is confirmed by ultrasound as well as a fetal heartbeat. Although more research and larger studies are needed, these early results regarding the successful resumption of ovarian function offer hope to women in early menopause who may be able to pursue pregnancy through in vitro fertilization using their own eggs. Results are published in the article “Resumed ovarian function and pregnancy in early menopausal women by whole dimension subcortical ovarian administration of platelet-rich plasma and gonadotropins.” “This pilot study investigating the use of platelet-rich plasma and gonadotropins injected into the ovaries of women with early menopause highlights the promise of regenerative medicine in restoring or prolonging fertility. Additional studies conducted prospectively and involving large numbers of women are needed to determine whether this is truly a viable option for women with early menopause hoping to achieve pregnancy using their own eggs,” says Dr. Stephanie Faubion, NAMS medical director. To read the original article click here.

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As Number of COVID-19 Infections Drop, the President Announces FDA-Authorized Plasma Treatment

AHA Publisher — Tue, 25 Aug 2020 07:00:05 +0000

News Staff via CBN News – There’s some good news in the fight against the Coronavirus. The number of new infections has dropped to the lowest level in two months. The news comes as President Trump and the Food and Drug Administration announced progress Sunday in treating COVID-19. So far, the virus has killed more than 175,000 Americans. The FDA declared emergency use authorization for convalescent plasma for COVID-19 patients, saying its benefits outweigh its risks. Convalescent plasma is blood from people who have survived the virus which is then transfused into people currently fighting it. It’s been used on 70,000 people since the pandemic began. The treatment is a century-old approach to fend off flu and measles before vaccines. It’s a go-to tactic when new diseases come along, and history suggests it works against some, but not all, infections. President Trump said the emergency use authorization will dramatically increase access to the treatment. But the FDA’s chief scientist says the treatment should not be recognized as a new standard for treating Coronavirus patients. In a letter describing the emergency authorization, the chief scientist for the FDA, Denise Hinton, said: “COVID-19 convalescent plasma should not be considered a new standard of care for the treatment of patients with COVID-19. Additional data will be forthcoming from other analyses and ongoing, well-controlled clinical trials in the coming months. According to the Associated Press, the White House had grown agitated with the pace of the plasma approval. The accusations of an FDA slowdown, which were presented without evidence, were just the latest assault from Trump’s team on what he refers to as the “deep state” bureaucracy. White House chief of staff Mark Meadows did not deal in specifics, but said that “we’ve looked at a number of people that are not being as diligent as they should be in terms of getting to the bottom of it.” “This president is about cutting red tape,” Meadows said in an interview Sunday on “This Week” on ABC. “He had to make sure that they felt the heat. If they don’t see the light, they need to feel the heat because the American people are suffering.” To read the original article click here. For more articles from CBN News click here.

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Israel Starts Clinical Trial of Plasma-Derived Covid Drug

AHA Publisher — Tue, 18 Aug 2020 07:00:35 +0000

Abigail Klein Leichman via Israel21c – 12 patients are receiving Kamada’s immunoglobulin for coronavirus disease; so far, three patients were well enough to go home from the hospital. Physicians at Hadassah University Medical Center in Jerusalem report promising early results of a clinical study in which they are treating Covid-19 patients with immunoglobulin (IgG) derived from the plasma of recovered patients found to have high levels of antibodies. The serum is prepared by Rehovot-based biopharmaceutical company Kamada. Three patients have already received the serum and are doing well, according to Dr. Yaron Ilan, chief of internal medicine at Hadassah University Medical Center. “The first patient demonstrated a rapid clinical benefit and went home after previously being in moderate condition.” The other two also have been released from the hospital. Ilan stressed that this experimental treatment, though very encouraging, is in an early phase. Dr. Zeev Rotstein, director general of Hadassah Medical Center, called their recovery “almost a miracle.” Rotstein was among the initiators of the collection of plasma from recovered corona patients. He also revealed to the Jerusalem Post on August 12 that Hadassah will help test a Russian-developed vaccine for coronavirus. For the past three months, Hadassah has been collecting plasma donations from recovered patients with the cooperation of ultra-Orthodox communal organizations. Kamada said additional Israeli hospitals are taking part in this Phase 1/2 clinical trial of the anti-SARS-CoV-2 plasma-derived IgG. “This open-label, single-arm multicenter study was approved by the Ministry of Health in Israel. The trial will assess the safety, pharmacokinetics and pharmacodynamics of the company’s plasma-derived IgG product in hospitalized, non-ventilated Covid-19 patients with pneumonia,” Kamada reported. “A total of 12 eligible patients will be enrolled and receive Kamada’s product at a single dose of 4g within 10 days of initial symptoms. Patients will be followed for 84 days. In parallel, Kamada intends to further explore the potential of its IgG product to prevent Covid-19 disease in healthy subjects at risk in a separate study.” This milestone is part of the global collaboration agreement established in April 2020 between Kamada and its partner Kedrion Biopharma for the development, manufacturing and distribution of a plasma-derived immunoglobulin product as a potential treatment for coronavirus disease. Kamada and Kedrion intend to conduct a pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration soon in anticipation of obtaining FDA approval of the proposed clinical development program. Meanwhile, Kedrion will collect Covid-19 convalescent plasma from recovered American patients. “We are encouraged by the results of the product neutralization activity and we believe our product has the potential to be an effective treatment for hospitalized, non-ventilated COVID-19 patients with pneumonia, and look forward to the results from this trial,” said Amir London, Kamada’s CEO. To read the original article click here. For more articles from Israel21c click here.

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COVID Treatment Offers Instant Immunity, and It’s Already Available

AHA Publisher — Fri, 07 Aug 2020 07:00:17 +0000

Staff at CBN News – Nationwide, new cases of COVID-19 are declining, dropping 14 percent in the last two weeks. But on the local level, cases are still rising in at least 10 states. Meanwhile, there’s some good news on the medical front. By now you’ve probably heard a coronavirus vaccine may be here by Christmas. What you may not know is one treatment offering instant immunity is available now, and another like it could be available within weeks, much sooner than a vaccine will be ready. National Institutes of Health Director Dr. Francis Collins says they both show promise. “One of the things I’m pretty excited about is the opportunity to use convalescent plasma, that is plasma that is donated by people who have survived. So if people who are listening who have survived, I hope that they would look into going to their Red Cross or blood bank and donating a unit of blood because that might save somebody else,” Collins said. “And we can go even further than that and actually purify the antibodies of people who’ve survived, called monoclonal antibodies. Those are about to get tested within the next few weeks to see whether they also provide lifesaving benefits,” he said. Those synthetic monoclonal antibodies could be available next month. The US government has awarded the drug company Regeneron a $450 million contract to begin production of an antibody treatment. Other drug companies are also working on similar treatments. “When a virus infects our bodies, our immune system creates these antibodies,” CBN News Medical Reporter Lorie Johnson explains. “So people with healthy immune systems who have already recovered from COVID-19 still have these wonderful antibodies in their blood, and they’re being asked to donate that blood. So please go to coronavirus.gov and see how you can donate a unit of blood because that blood is full of those wonderful antibodies and can be transfused into people who are very, very sick with COVID-19.” This article has been modified. To read the original article click here. For more articles from CBN News click here.

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68,000+ Americans Recover from Coronavirus – How Survivors Are Giving the Gift of Life

AHA Publisher — Thu, 23 Apr 2020 07:00:16 +0000

Lorie Johnson via CBN News – More than 68,000 Americans have fully recovered from COVID-19. Now they can help others struggling with the virus. These survivors have something that could potentially kill the enemy that’s threatening the lives of hundreds of thousands of more vulnerable Americans. Many people who’ve recovered from COVID-19 feel like they have a new lease on life and are trying to give that same gift to others. The gift is their blood. It’s potentially loaded with antibodies specifically designed to destroy the COVID-19 virus. Elizabeth Schneider lives in the state of Washington and is one of the thousands of survivors who are giving blood. It’s called convalescent plasma. “You know, we have an immune system that happens to fight this off on our own and that’s really really powerful,” she said. Schneider tested positive for COVID-19 back in February. When the virus entered her body, like other survivors, her immune system produced enough antibodies that got rid of the virus. Although the virus is gone, the antibodies remain in her blood and can fight-off the virus again if it ever enters her system, making her immune, according to doctors. Health experts are not sure how long COVID-19 antibodies remain in the blood, effectively protecting a person from becoming re-infected. Some antibodies remain in a person forever, such as those that protect against the chickenpox virus. Others, however, remain only for months. Dr. Rebecca Haley is the Medical Director of Cord Blood Services at Bloodworks Northwest, where Schneider donated her blood. “Each donation that goes for direct transfusion can probably treat three or four people,” she explained. “The protocol from the NIH allows us to collect COVID-recovered donors once a week for up to 20 weeks.” In Fort Worth, Texas, a critically ill COVID-19 patient received convalescent plasma at Texas Harris Methodist Hospital. Doctors say many people who suffer the most severe complications from the virus don’t have robust enough immune systems to produce enough antibodies to effectively defend against the virus. Fort Worth pulmonologist Dr. John Burk said convalescent plasma therapy might help reverse the disease in people who are headed for the worst outcomes. “Patients in need who are on a ventilator or who are about to be on a ventilator might be the best candidates to get a little boost in immunity.” Although Chinese doctors report 15 patients who received convalescent plasma were cured, here in the United States studies on the effectiveness of the treatment are still underway. However, while those studies are being conducted, doctors can prescribe the treatment on a “compassionate use” basis. “It could make a world of difference,” Dr. Burk said. “It could be substantial. The truth is we don’t yet know. It is an unproven, experimental treatment.” In Columbus, Ohio, The Ohio State University Wexner Medical Center has transfused the first patient in central and northern Ohio with plasma from a recovered COVID-19 patient. Emergency room physician Dr. Howard Werman tested positive for COVID-19 in March after traveling. Fortunately, he only experienced mild symptoms such as a runny nose and a sore throat. He’s fully recovered now and donated his blood to help people who are much sicker than he was with the virus. At the University of Chicago, doctors are also testing convalescent plasma on their patients as part of a study of the therapy. The research will include 10 patients and may later expand to include more. The hospital has more than 100 COVID-19 patients. Dr. Maria Lucia Madariaga, a general thoracic and lung transplant surgeon at UChicago Medicine, said plasma therapy could prove effective. “They get a single transfusion of the plasma and then we measure what happens,” she said. Ideally, donors should wait a month after their symptoms go away, according to Dr. Patrick Wilson, PhD., an immunologist at Chicago Medicine. “The amount of antibody that is working against the virus will have peaked at 28 days.” While doctors can’t say for sure whether convalescent plasma works on COVID-19 patients, similar treatments proved successful against the Spanish Flu and other coronaviruses like SARS and MERS. Health experts say if you were diagnosed with COVID-19, have fully recovered and would like to help, contact your nearest blood bank such as the Red Cross. To read the original article click here. For more articles from CBN News click here.

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