Essential Nutritional Tips for Patients with COVID-19

Essential Nutritional Tips for Patients with COVID-19

  • March 31, 2021

As with many illnesses, good nutrition plays an important role to speed recovery from COVID-19. Smart food choices help to provide the proper anti-inflammatory nutrients needed to support essential bodily processes, improve immunity, and protect against loss of energy and diminished muscular strength.

Both macro- and micronutrients are key drivers for a healthy immune response, particularly for higher-risk populations.

Even for those who have not been diagnosed with COVID-19, poor nutrition can compromise immune function and increase the risk of becoming infected. Here is a look at how important it is to educate home-based care providers on nutritional support principles, along with the top tips needed to make sure patients with COVID-19 stay as healthy and strong as possible, as outlined by Certified Nutrition Support Clinician, Lisa Logan of McKesson Medical-Surgical.

Fluids: 2-3 liters per day

It is critical that patients stay hydrated, Logan says. Fluid requirements must be individualized based on a range of factors, including body weight, age, gender, medical conditions and body temperature. According to American Society of Parenteral and Enteral Nutrition, patients should drink water or clear liquids every hour. Ideally, they should consume at least two to four ounces of fluid every 15 minutes. If the patient has gastrointestinal issues, such as vomiting or diarrhea, then he or she must consume oral hydration solutions along with water.

“The important thing is to monitor seniors for signs of dehydration,” Logan says. Signs of dehydration can include increased thirst, fever, dizziness, lightheadedness, decreased urine output, dark colored urine color and an increased heart rate.

Logan has four sample recommendations for caregivers:

– Keep liquids visibly available for patients, including at the bedside

– Offer a variety of liquids to avoid taste fatigue

– Remember to include foods with a high fluid content, such as melons, soups and stews

– Select the appropriate liquid supplement as recommended by a registered dietitian who understands the patient’s medical conditions

“The type of liquid you drink will depend on the situation,” Logan says. “Water or clear liquid drinks with electrolytes are fine. But there are many patients who are malnourished and would benefit from a high-calorie, high-protein supplement if they have a diagnosis of malnutrition. The drink selected should be based upon a clinical evaluation and assessment.”

Calories: 1,500 to 2,000 calories daily — normal maintenance

Due to increased stress from COVID-19, an individual often needs an additional 400 to 500 calories each day, over their normal dietary requirements. In some cases, home-based care providers should aim for patients to consume between 2,000 and 2,500 calories per day. Utilizing the expertise of a dietitian can help formulate a diet plan with high calorie and high protein supplements, so that patients can achieve their nutritional goals.

Along with the calorie count, seniors must focus on an anti-inflammatory diet.

“COVID is an inflammatory process and improper dietary choices can adversely impact the immune system,” Logan says. “Therefore, consuming an anti-inflammatory diet is essential. You want more of a plant-based diet, eliminating refined foods, sugar, saturated fats and processed meat. The food that you give your loved one, or a patient, should be healthy.”

Protein: 75 to 100 grams per day

One major focus for caregivers helping patients with COVID-19 is addressing malnutrition.

“Malnutrition is a risk factor causing many issues relating to functional and physiologic decline, along with organ dysfunction that leads to increased rates of morbidity and mortality,” Logan says. “There is emerging evidence that one’s nutritional status clearly impacts immunity. If your immune system is not up to par, you can’t fight off infection. It is important to identify malnutrition early on so that nutrition support can be implemented immediately to improve health and quality of life.”

To avoid malnutrition, caregivers should use a reliable malnutrition screening tool, one that provides a score to address the severity of malnutrition. The MNA (Mini Nutrition Assessment) by Nestlé Nutrition Institute is an example of a tool that clinicians can use. It addresses key factors such as recent weight loss, appetite and body mass index to help determine the degree of nutritional impairments.

The caregiver must also encourage a diet that is adequate in protein, which is required to maintain muscle mass. Most patients require at least one gram of protein per kilogram of ideal body weight, which can total 75 to 100 grams of protein per day.

While requirements will vary with conditions such as kidney and liver disease, some standard protein sources include: 

– Peanut or nut butters

– Dairy (milk, eggs, yogurt, cheese)

– Meat (fish, poultry)

– Protein shakes

However, one should consider getting dietary protein from plant- based alternatives like soy products (tofu, tempeh, and edamame), lentils, chickpeas, almonds and Quinoa.

Supplements for immunity boost

Along with promoting protein and high calorie diets, liquid supplements taken between meals can provide an extra immunity boost and maintain the flow of nutrients into the body. Logan cites the work of Dr. Gina Serraiocco, who recommends a variety of supplements that can help the immune function, so it is more equipped to fight inflammation.

“Patients who are vitamin D-deficient have a higher chance of getting COVID,” Logan says.

She adds that zinc, vitamin C, melatonin, turmeric and Omega-3 fatty acids can all serve as anti-inflammatory and immune-supportive agents. For many of these recommendations, Logan credits Dr. Serraiocco, an integrative and functional medicine physician at Sutter’s Palo Alto Medical Center, whose research is industry-leading in this area. Dr. Serraiocco has made it her focus to educate patients and health care workers on the best life-style approaches and supplements needed to help during this horrible pandemic.

This article is sponsored by McKesson Medical-Surgical, which works with health systems, physician offices, extended care providers, in-home patients, labs, payers and others across the spectrum of care to build healthier organizations that deliver better care to patients in every setting. For more information, visit mms.mckesson.com.

Cancer Research Institute and RevImmune Announce Dosing of First Patient in New Phase 2 Study Assessing Therapeutic Benefit of Interleukin-7 in Patients with Cancer and COVID-19

Cancer Research Institute and RevImmune Announce Dosing of First Patient in New Phase 2 Study Assessing Therapeutic Benefit of Interleukin-7 in Patients with Cancer and COVID-19

  • March 30, 2021

NEW YORK and BETHESDA, Maryland, March 30, 2021 — The Cancer Research Institute (CRI), a nonprofit organization dedicated to the discovery and development of powerful immunotherapies for all cancers and RevImmune, Inc., a privately held biotech company focused on T-cell technology and development, announced today the dosing of the first patient in a new study designed to assess the therapeutic benefit of interleukin-7 (IL-7) in cancer patients with COVID-19. This stems from a new understanding that patients with severe COVID-19 have low levels of T cells and exhausted T cells, and these patients benefit from therapies that focus on augmenting the cellular immune response, rather than solely therapies that dampen the immune system.

The Phase 2 multi-center clinical trial called “ILIAD-7-US-O” will evaluate the clinical benefit of RevImmune’s product candidate CYT107 in approximately 48 patients living with cancer. CYT107 is a therapeutic form of the master growth factor for human T cells, IL-7, and this is the first study to test an IL-7 drug specifically in people with cancer who also have COVID-19. The clinical trial is funded by CRI’s Clinical Accelerator, a program that supports and coordinates early-phase clinical trials of promising immuno-oncology combination therapies.

“This partnership allows CRI to apply RevImmune’s promising IL-7 agent in a novel setting of patients with both cancer and COVID-19, potentially offering a way to strengthen the immune system’s ability to fend off the SARS-CoV-2 coronavirus, mitigate symptoms of COVID-19, and improve overall outcomes for people living with cancer and COVID,” said Jay Campbell, managing director of CRI’s Venture Fund and Anna-Maria Kellen Clinical Accelerator.

Common cancer treatment regimens can compromise a patient’s immune system, including reductions in lymphocyte counts, such as T cells, a condition known as lymphopenia. Similarly, COVID-19 can lead to dysregulation of the adaptive immune system, which can also result in patients becoming lymphopenic. The profound and protracted lymphopenia experienced in COVID-19 patients has been correlated with increased secondary infections and death. Furthermore, surviving lymphocytes have severely impaired anti-viral function and are exhausted, ultimately resulting in immune system collapse.

IL-7 has been shown to provide a rapid and durable restoration of functional immune cells, predominantly CD4+ and CD8+ T cells, which are able to fight the primary viral infection and secondary infections. In previous clinical studies, CYT107 has demonstrated the ability to quickly restore immune function, such as increasing the number and diversity of T cells in patients, including those with low and exhausted T cell levels. CYT107 has been shown to be safe and well-tolerated and patients experienced durable long-lasting responses.

Researchers involved in the ILIAD-7 study hope CYT107 will provide the same benefit to cancer patients with COVID-19, with the aim of reducing risk of progressing to severe stages of COVID-19.

“The medical community has learned a great deal about COVID-19 as a disease this past year and has come to realize that patients who develop severe COVID-19 symptoms have impaired immune systems, including exhausted and depleted T-cells,” said Michel Morre, D.V.M., M.Sc., chief scientific officer at RevImmune. “Therapies like IL-7 reinvigorate and expand the cellular immune response to the infection, and we are excited for the opportunity to continue to follow the science and evaluate a potential treatment option for those affected by both COVID-19 and cancer.”

About the ILIAD-7-US-O Study
The ILIAD-7-US-O study tests RevImmune’s recombinant interleukin-7 product, CYT107, on patients with cancer and lymphopenic (with low lymphocyte counts) COVID-19. The trial aims to compare the effects of CYT107 versus placebo at producing immune reconstitution by restoring lymphocyte function and increasing lymphocyte proliferation in oncology patients, where their cancer is being or has been treated with standard of care therapies. The trial hopes to observe a possible clinical improvement as patients with restored lymphocyte counts should better eliminate invading pathogens such as SARS-CoV-2. Approximately 48 patients will be randomized 1:1 to receive either CYT107 or placebo at two trial sites: Memorial Sloan Kettering Cancer Center in New York City and The University of Texas MD Anderson Cancer Center in Houston, Texas, with Stephen Pastores, M.D., and Cristina Gutierrez, M.D., as Principal Investigators, respectively. The clinical trial is funded by the CRI Anna-Maria Kellen Clinical Accelerator, a program that supports and coordinates early-phase clinical trials of promising immuno-oncology combination therapies.

About the Cancer Research Institute
The Cancer Research Institute (CRI), established in 1953, is a top-rated U.S. nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 27 members of the National Academy of Sciences, CRI has invested $445 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org.

About the CRI Anna-Maria Kellen Clinical Accelerator
CRI’s clinical program, the Anna-Maria Kellen Clinical Accelerator, is a unique academia-nonprofit-industry collaboration model that serves as an “incubator” that delivers multi-center clinical trials for promising new immunotherapy combinations. CRI’s venture philanthropy fund supports clinical trials within this program, which fosters a collaborative environment that enables scientists to advance their most ambitious research ideas and accelerates studies that one group or company could not do alone. To learn more about the CRI Anna-Maria Kellen Clinical Accelerator, go to cancerresearch.org/clinical-accelerator.

About RevImmune
RevImmune is a privately held biotech company based in France, the U.S. and the U.K. RevImmune is in multiple Phase II trials with CYT107 for treatment of sepsis, certain infectious diseases, and certain cancers. Over 500 patients have been treated with CYT107 in RevImmune’s prior and current trials for multiple different viral diseases and sepsis. CYT107 showed an excellent safety profile and encouraging results in those trials. To learn more, go to revimmune.com.

Media Contacts:
For Cancer Research Institute: Brian Brewer, +1-212-688-7515 x242, bbrewer@cancerresearch.org
For RevImmune: Michel Morre, +33 6 03 35 70 60, mmorre@revimmune.com

 

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Natural Drug Approved for White Blood Cell Recovery Can Be Repurposed To Improve Cognition in Alzheimer’s Patients

Natural Drug Approved for White Blood Cell Recovery Can Be Repurposed To Improve Cognition in Alzheimer’s Patients

  • March 29, 2021

A Phase II clinical trial shows the innate immune system is a viable target for therapeutic intervention in Alzheimer’s disease.

The clinical trial data reported in the article “Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer’s disease” published in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions, by scientists from the University of Colorado Alzheimer’s and Cognition Center at the University of Colorado Anschutz Medical Campus (CU Anschutz), shows a man-made version (Sargramostim) of a natural protein (granulocyte-macrophage colony stimulating factor, GM-CSF) may have both disease-modifying and cognition-enhancing activities in Alzheimer’s disease patients.

“The goal of the clinical trial was to examine the impact of a natural human protein called granulocyte-macrophage colony stimulating factor (GM-CSF) on people living with Alzheimer’s disease. We tested GM-CSF because people with rheumatoid arthritis tend not to get Alzheimer’s disease and we had previously found this protein, which is increased in the blood of people with rheumatoid arthritis, reduced amyloid deposition in Alzheimer’s mice and returned their poor memory to normal after a few weeks of treatment. Thus, naturally increased levels of GM-CSF in people with rheumatoid arthritis may be one reason that they are protected from Alzheimer’s disease,” says Huntington Potter, PhD, director of the CU Alzheimer’s and Cognition Center, who together with Jonathan Woodcock, MD, Timothy Boyd, PhD, and collaborators carried out the new trial.

Patients with Alzheimer’s disease exhibit markers of inflammation in their brains, cerebrospinal fluid and serum. Targeting inflammation using non-steroidal anti-inflammatory drugs however, have not yielded any beneficial responses in patients with Alzheimer’s disease or mild cognitive impairment (MCI) in earlier trials.

Sargramostim/GM-CSF is prescribed to boost white blood cells after cancer treatments or exposure to radiation. The protein stimulates the bone marrow to make more macrophages and granulocytes, specific types of white blood cells, and progenitor cells that repair blood vessels. These white blood cells circulate throughout the body and remove cells, bacteria and amyloid deposits and also repairing blood vessels.

The current data reveals Sargramostim/GM-CSF is also effective in treating and improving memory in people with mild-to-moderate Alzheimer’s disease.

“Human GM-CSF is the active compound in the known human drug Sargramostim, and we are the first to study its effect on people with Alzheimer’s disease,” says Potter.

The team carried out a randomized, double-blind, placebo-controlled Phase II trial (NCT01409915) to test the safety and efficacy of Sargramostim treatment in participants with mild-moderate Alzheimer’s disease.

Study participants were either administered Sargramostim at the standard FDA dose of 250 μg/m2/day by subcutaneous injection, or saline for five days a week for three weeks. The study included 20 participants in the test and placebo group. Most participants in the study were recruited and treated at CU Anschutz with a few from the University of South Florida. The CU Anschutz researchers then conducted and studied multiple neurological, neuropsychological, cell, cytokine, Alzheimer’s pathology biomarkers and neuroimaging assessments.

The investigators found that short-term Sargramostim treatment increased innate and other immune cells, modulated cytokine measures, and was safe and well-tolerated by participants. They also found cognition memory improved by almost two points in the 30 point Mini-Mental State Exam. Brain amyloid, tangles, neurodegeneration, and measures of blood biomarkers of Alzheimer’s disease, all improved toward normal.

“These results suggest that short-term Sargramostim treatment leads to innate immune system activation, cognition and memory improvement, and partial normalization of blood measures of amyloid and tau pathology and neuronal damage in participants with mild-to-moderate Alzheimer’s disease,” says Potter. “This surprising finding that stimulating the innate immune system and modulating inflammation may be a new treatment approach and induced us to start a larger trial of Sargramostim in Alzheimer’s disease with more participants treated over a longer time.”

The larger trial will be funded by the Alzheimer’s Association/Part The Cloud, the University of Colorado, the Global Down Syndrome Foundation, and by a large grant recently awarded from the National Institute on Aging.

Should recovered patients get COVID-19 jab?

Should recovered patients get COVID-19 jab?

  • March 26, 2021

As COVID-19 vaccines become more and more available to the general public questions on who should get the jab also have been rising, most prominently whether people who have been infected with coronavirus should also be inoculated – most scientists agree that the answer is “yes.”

Regardless of previous infection, the United States Centers for Disease Control and Prevention says people should plan on getting vaccinated when it’s their turn. “It’s a pretty straightforward question,” Johns Hopkins infectious disease specialist Dr. Amesh Adalja told The Associated Press (AP). “Yes, you need to get vaccinated.”

Professor Mustafa Gerek from the University of Health Sciences told Demirören News Agency (DHA) that after infection “it is likely that you have enough antibodies at which stage you may not need vaccination” but it is unclear how long immunity lasts.

After someone recovers, their immune system should keep them from becoming sick again right away. “Your immune system is able to identify the virus, and protect itself,” said Dr. Saskia Popescu, an infectious disease expert at George Mason University.

Scientists still do not know exactly how long this immunity lasts or how strong it is, though recent research suggests the protection could last for several months.

It’s impossible to know how long a person might be immune, said Dr. Prathit Kulkarni, an infectious disease expert at Baylor College of Medicine. “There’s no way to calculate that.”

Vaccines, by contrast, are designed to bring about a more consistent and optimal immune response. They also should boost whatever preexisting immunity a person might have from an infection, experts say.

The Turkish Health Ministry, on its COVID-19 information platform, lists health care workers who previously had the infection as eligible for the vaccine one month after they have suffered from the coronavirus, as they are considered the highest risk group. Other risk groups can, and are encouraged to, be vaccinated six months after infection.

“Since we’re in this pandemic, and don’t have a handle on it, the safer approach is to vaccinate,” Kulkarni said. “You don’t lose anything and you stand to benefit.”

If you have been infected in the last three months, the U.S. Centers for Disease Control and Prevention (CDC) says vaccination can be delayed if you want to let others go first while supplies are limited.

“All things being equal you would want the person with no protection to go first,” Adalja said.

Study results strengthen the case for using Regeneron’s antibody cocktail in high-risk Covid patients.

Study results strengthen the case for using Regeneron’s antibody cocktail in high-risk Covid patients.

  • March 23, 2021

A monoclonal antibody treatment developed by the drug maker Regeneron sharply cut the risk of hospitalization and death when given to high-risk Covid-19 patients in a large clinical trial, the company announced on Tuesday.

The results are the latest in a growing flurry of evidence that the infused drugs, meant to mimic the antibodies that the immune system generates naturally in fighting the coronavirus, can help infected patients avoid the worst outcomes if given early.

Regeneron’s treatment, a cocktail of two antibody drugs, was given last fall to President Donald J. Trump shortly after he got sick with Covid-19 and is now one of three such therapies available in the United States.

The new results come from a Phase 3 trial that enrolled more than 4,500 patients beginning in late September, around the time virus cases began to climb dangerously in the United States. The study found that patients who got the infused treatment within 10 days of developing symptoms or testing positive had a roughly 70 percent reduced risk of being hospitalized or dying compared with patients who were infused with a placebo.

“I think these are exciting data,” said Dr. Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital who was not involved in the study.

Even as vaccinations speed up, antibody treatments are expected to be helpful for high-risk people who still get sick for many months at least, and longer still if the virus can’t be wiped out. While there are signs that emerging virus variants may in some cases make antibodies less potent, Regeneron’s cocktail has not shown such vulnerability in laboratory tests.

In the new findings, Regeneron’s treatment worked equally well when given at half the dosing at which it was authorized. Regeneron said that it planned to request that the Food and Drug Administration allow the treatment to be given at that reduced strength.

Such a change would bring several advantages: While the cocktail is safe, getting it at a lower dose reduces the odds of side effects, such as an infusion reaction.

It would also allow Regeneron to increase the supply it can provide the United States. The company said that it had expected to supply the country with about 750,000 doses at the originally authorized higher strength by the end of June. If the lower strength is authorized, the company expects to provide about 1.25 million doses by then.

The antibody treatments from Regeneron and the drug maker Eli Lilly, which makes the other two such drugs authorized in the United States, were expected to be in high demand and to serve as a bridge in fighting the pandemic before vaccinations ramped up. Instead, they ended up sitting on refrigerator shelves in many places even during recent surges.

Many patients and their doctors did not know to ask for them or where to find them. Overwhelmed hospitals lacked the bandwidth to prioritize giving out the treatments. And some doctors were unconvinced by the relatively weak evidence available last fall supporting their use.

That picture is gradually shifting, thanks to improved logistics and more awareness. And more solid evidence, like the new data from Regeneron, also appears to be helping the drugs get used more widely. “As the data get stronger and stronger, I would expect that use will increase,” Dr. Gandhi said.

BioAge Initiates Phase 2 Trial of BGE-175 to Treat COVID-19 by Reversing Immune Aging, a Key Cause of Morbidity and Mortality in Older Patients

BioAge Initiates Phase 2 Trial of BGE-175 to Treat COVID-19 by Reversing Immune Aging, a Key Cause of Morbidity and Mortality in Older Patients

  • March 22, 2021

RICHMOND, Calif.–()–BioAge Labs, Inc., a clinical-stage biotechnology company developing medications that target aging to treat severe diseases, today announced that it has commenced a Phase 2 clinical trial of BGE-175, a potent oral inhibitor of prostaglandin D2 (PGD2) DP1 signaling with a safety database comprising > 2400 patients, for treating COVID-19 patients aged 60 or older. Top-line results are expected in 2021.

COVID-19 has devastated elderly populations around the world, largely because the immune system declines with age, making older people much more vulnerable to infection,” said Kristen Fortney, Ph.D., Chief Executive Officer of BioAge. “By reversing age-related dysregulation of critical immune mechanisms, BGE-175 could allow older patients to more effectively fight off COVID-19. Our strongly encouraging preclinical data show that BGE-175 almost completely protects older mice against lethality from infection with SARS-CoV-2, the virus that causes COVID-19. In addition, BGE-175 dramatically decreases viral load in lung tissue, which is correlated with both disease severity and transmission of the virus.”

The preclinical data were obtained in collaboration with coronavirus expert Stanley Perlman, M.D., Professor of Microbiology and Immunology at the University of Iowa.

DP1 signaling becomes dysregulated with aging and adversely affects the immune response of older animals to SARS-CoV-2 and other viral challenges. We have shown that BGE-175 can dramatically improve outcomes in mouse models of COVID-19,” said Dr. Perlman. “Because some of the rapidly spreading variants of SARS-CoV-2 are vaccine-resistant, it is critically important to develop COVID-19 treatments, like BGE-175, that are likely to be equally effective against infections with these more contagious and potentially more lethal strains.”

About the Phase 2 trial

The randomized, placebo-controlled, parallel-group, multicenter, double-blind study will recruit patients ≥ 60 years old hospitalized for COVID-19 who are not yet in respiratory failure. A total of 132 participants will receive daily doses of BGE-175 or placebo (66 in each group) for up to 14 days. The study medication will be administered orally or, in patients who cannot swallow, via nasogastric tube. The trial is being conducted in the US, Argentina, and Brazil.

The primary endpoint is the proportion of patients who die or progress to respiratory failure within 28 days after receiving the first dose of BGE-175. Secondary endpoints include viral load, clinical improvement or worsening, incidence and duration of supplementary oxygen or ventilation, time to discharge or rehospitalization, and intensive care unit (ICU) admission, all over a 57-day period after the first dose. The study will also measure PGD2 DP1 signaling activity and the levels of inflammatory markers. Full details of the trial are available at ClinicalTrials.gov.

Some cases of COVID-19 are associated with uncontrolled inflammation, which increases disease severity and morbidity. Hence, the trial will also measure BGE-175’s effect on levels of inflammatory markers, including cytokines, CD4+ and CD8+ T cells, and total lymphocytes. The resultant data will provide insight into BGE-175’s ability to restore normal regulation of the immune system.

The drug’s mechanism could be useful against diseases beyond COVID-19. “By targeting immune aging directly, BGE-175 has the potential to boost immune cell function while preventing dangerous overreaction,” said Paul Rubin, M.D., Chief Medical Officer of BioAge. “PGD2 DP1 signaling is associated with increased susceptibility to infection and risk of mortality. A correlation between inhibition of PGD2 DP1 and patient response in this trial would provide evidence that BGE-175 has the potential to reverse age-related decline in immune mechanisms that are critical for host defense against major viral challenges such as COVID-19, SARS, and pandemic influenza.”

COVID-19 and aging

Aging is the largest risk factor for COVID-19 morbidity and mortality: people over 80 are hundreds of times more likely to die of the disease than those under 40.1 Older people are at higher risk in part because the aging immune system becomes less efficient and prone to hyperinflammation. Rejuvenating the immune system by treating age-related deterioration directly could help to lessen the severity of COVID-19 infection and boost protection by vaccines.2

About BGE-175

BGE-175 is a potent, orally administered small-molecule inhibitor of the PGD2 DP1 pathway, which BioAge’s platform identified as a key target for immune aging. DP1 signaling is associated with elevated susceptibility to infection and higher risk of mortality from infectious disease. Inhibition of DP1 affects immune function in multiple ways, activating dendritic and natural killer (NK) cells while attenuating neutrophil migration. Together, these effects counteract immunosenescence and improve aspects of both adaptive and innate immunity.

Multiple Phase 1–3 clinical trials of BGE-175 for allergic rhinitis, conducted by Shionogi & Co., Ltd., demonstrated that the drug was safe and well-tolerated in more than 2,400 study participants.

About the BioAge Platform

The BioAge platform identifies key drug targets that impact aging. The Company’s proprietary human aging cohorts include archived longitudinal blood samples collected up to 50 years ago, with participant -omics data that is tied to extensive medical follow-up records including detailed future healthspan, lifespan, and disease outcomes. BioAge has built a systems biology and AI platform that leverages these rich datasets to generate hypotheses about the determinants of healthy human aging and identify the molecular drivers of age-related pathology. BioAge’s pipeline of development candidates targeting these key pathways has the potential to address significant unmet medical needs of the aging population.

About BioAge

BioAge is a biotechnology company that develops proprietary drugs to treat aging and aging-related diseases. Since its founding in 2015, the Company has raised more than $127 million in venture capital funding from Andreessen Horowitz, Kaiser Foundation Hospitals, Khosla Ventures, Felicis Ventures, and others to back its AI-driven approach of mapping the molecular pathways that impact human longevity. BioAge’s mission is to develop a pipeline of therapeutic assets that target aging to treat severe diseases.

References

1 Nature 2020; 584:430–436

2 Nature 2020; 586:352–354

Source: BioAge Labs, Inc.

Pfizer vaccine provides less protection in cancer patients after a single dose, study finds

Pfizer vaccine provides less protection in cancer patients after a single dose, study finds

  • March 12, 2021

The Pfizer/BioNTech Covid-19 vaccine provides less protection in cancer patients than healthy individuals following a single dose, a new real-world study in the UK suggests, raising questions about whether the UK’s strategy to delay second doses should apply to such patients.

A second dose of the vaccine at three weeks, however, boosted their protection significantly, with the researchers calling for earlier boosts in this group in the UK. The UK’s vaccine strategy currently involves a 12-week gap between doses of the coronavirus vaccines; Pfizer recommends 21 days between doses.

The study analyzed the impact of the Pfizer-BioNTech vaccine on 205 participants — 54 healthy volunteers and 151 elderly patients with solid cancers, such as breast or prostate cancer, and haematological (blood) cancers, such as leukemia. The preprint study has not yet been peer-reviewed or published.

The researchers looked for levels of antibodies and T cells in their blood to identify the level of immune response generated against the coronavirus.

Three weeks after one dose of the vaccine, an antibody response was found in 39% of solid cancer patients and just 13% of people with blood cancer. The response in healthy volunteers was 97%.

In the solid cancer patients who received a second dose three weeks after the first, the antibody response shot up to 95% within two weeks of the boost. There were not enough booster vaccines given to blood cancer patients to determine the response in that group.

Further evidence of the need for a boost was shown by the fact that antibody levels only increased to 43% in people with solid cancers and 8% in those with blood cancer five weeks after their first dose. It was 100% in healthy volunteers.

“Our data provides the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations. We show that following first dose, most solid and haematological cancer patients remained immunologically unprotected up until at least five weeks following primary injection; but this poor one dose efficacy can be rescued with an early booster at day 21,” said Dr. Sheeba Irshad, a senior clinical lecturer from the School of Cancer & Pharmaceutical Sciences who led the research.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place such as social distancing and shielding when attending hospitals, even after vaccination,” Irshad added in a statement.

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, highlighted that certain limitations needs to be taken into account.

“The change in UK policy around delaying a second dose of vaccine allowed for the authors to make some comparisons between those who received a second dose within 21 days and those who did not. They have not yet provided data on those who received a second dose after a 12 week delay,” he said in a statement to the UK’s Science Media Centre.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” he added.

“All of these findings are consistent with our understanding of the immune system function in cancer patients.,” said Shoba Amarnath, Newcastle University research fellow at the Newcastle University Centre for Cancer. “We know that the immune system within cancer patients is compromised as compared to healthy controls. Hence, a 2nd vaccine boost prepares the dysregulated immune system to function at the same efficiency as healthy controls.

“The data in the study supports the notion that in solid cancer patients a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

For High-Risk Cancer Patients, Experts Consider Any Vaccine-Induced Covid-19 Protection Beneficial

For High-Risk Cancer Patients, Experts Consider Any Vaccine-Induced Covid-19 Protection Beneficial

  • March 9, 2021

Going through cancer treatment during a pandemic can be an anxiety-provoking process—from concerns over treatment delays to the risk of contracting the coronavirus. Add in the sense of isolation that comes while trying to avoid the virus, and the situation can become dire.

The growing availability of approved Covid-19 vaccines is providing hope that the pandemic will wane. But cancer patients have questions about their place in the vaccine line (which can vary considerably by location), as well as their ability to mount the immune response needed for vaccine-induced protection from future SARS-CoV-2 exposures.

After all, chemotherapy and other treatments used to beat back tumor cells can lead to a temporary dip in immune function, while other cancer treatments are designed to turn off immune “checkpoints” that otherwise stop the immune system from attacking some tumor cells.

“The goal of immunotherapy or checkpoint blockade is to actually stimulate the immune system. So there may be different effects on vaccine-induced immunity. Many of us are studying that to try to understand whether it’s detrimental or perhaps even beneficial,” explained John Wherry, director of the University of Pennsylvania’s Institute of Immunology and chair of its systems pharmacology and translational therapeutics department.

In the meantime, though, Wherry and other experts say most cancer patients on treatment should get a Covid-19 shot as soon as it is available to them, since even lower-than-usual response to the vaccines is expected to offer protection.

“In general, the vast majority of patients with cancer — even those who are receiving treatment — should receive the vaccine and will benefit from it,” Jia Luo, a fellow in medical oncology at Memorial Sloan Kettering Center, said in an e-mail. “Patients should speak to their oncologist about their specific case and the timing of their vaccination.”

Though research is needed to tease out vaccine efficacy for individuals on active treatment for cancer (and those treatments can vary considerably by cancer type, subtype, and stage), the vaccines appear to be safe for cancer patients. And there is reason to believe they will offer much needed protection, even in individuals that have immune deficiencies due to treatment or cancer itself.

“The question is whether [Covid-19 vaccines] work as well in people having cancer treatment like chemotherapy and radiation,” Luo noted. “A few cancer treatments reduce how well a person’s immune system responds. It’s possible that the vaccines might not be as effective in those people. Even so, having some protection is key.”

Based on the data on hand and strong immune responses they induce, Wherry believes the available vaccines will likely offer some protection to immune compromised individuals by kicking both antibody-producing B cells and T immune cells into gear

B cells make secreted proteins—as antibodies—that interact with viral surface structures in a lock-and-key manner keep viral intruders out of our cells. But viruses that do manage to make it into the cell still have to contend with T cells, which take down infected cells that are starting to make copies of the virus. 

T cells that have been primed by a vaccine are “ready to go,” Wherry said, and “can eliminate that infection locally before it ever has a chance to spread and maybe before you know that you got a small infection.” 

Those strong immune responses can come with temporary side effects, he added, so a few days of feeling poorly is a normal response to the vaccine.

The immune landscape gets more complicated for cancer patients who have their antibody-producing B cells destroyed as part of the treatment process, including individuals with hematological malignancies such as leukemia or lymphoma that arise in those very cells, he explained. But there is a good change that vaccines can still boost Covid-19 immunity by readying T cells against SARS-CoV-2.

“If we need to now vaccinate you and we’ve just eliminated all of your B cells, we now have a problem that you’re not going to generate antibodies as well,” Wherry said. “The hope, in many of these cancer patients, is that we will be able to generate T cells that will provide at least some degree of protection from severe disease, even though they may not prevent initial infection.”

Beyond benefits that vaccination can offer high-risk cancer patients and survivors, experts like Wherry noted that vaccinating individuals with reduced immune function might protect the broader community by preventing long-term infections implicated in the emergence of new SARS-CoV-2 mutations. 

“There’s not a large collection of data about this that allows us to think statistically, but there are a large number of anecdotes that have been reported about this. Most of the time when you see these prolonged infections, they’re leukemia or lymphoma patients,” Wherry explained. “When patients can’t get immune control that leads to long virus replication with perhaps a very weak immune response, which is a perfect scenario to drive mutation and viral evolution.”

At an online meeting on Covid-19 and cancer, organized by the AACR in February, oncologists and patient advocates participating in a vaccination-focused panel touched on such questions, as well as the burden being placed on unvaccinated cancer patients trying to avoid SARS-CoV-2. They also took stock of the grim outcomes that have been documented for cancer patients who contract Covid-19—the subject of countless studies over the past year.

For a retrospective analysis published in JAMA Oncology in December, for example, investigators at Case Western Reserve University considered health records for millions of individuals with or without cancer who were treated at US hospitals since 1999. 

That study, which included data for more than 273,000 individuals diagnosed with cancer in the year leading up to August of 2020, suggested newly diagnosed cancer patients were more prone to contracting SARS-CoV-2 than people without cancer, though the risk varied with cancer type and patient ethnicity.

The Case Western team found that nearly 48 percent of adult or senior cancer patients who contracted Covid-19 landed up in hospital. In contrast, cancer-free people with Covid-19 were hospitalized just over 24 percent of the time and just over 12 percent of Covid-19-free adults and seniors were hospitalized.

Having both cancer and Covid-19 also increased the risk of death to nearly 15 percent, compared to a case fatality rate of around 4 percent in the cancer-only group and just over 5 percent in the Covid-19-only group. 

Likewise, in a review article published in the journal Cancer Discovery last month, investigators with the AACR Covid-19 and Cancer Task Force estimated that the risk of death doubles in SARS-CoV-2-infected people with cancer compared to their cancer-free counterparts — findings that contributed to recommendations from AACR and other groups to prioritize Covid-19 vaccination in individuals with cancer and cancer survivors.

Covid-19 outcomes appear to be particularly poor in individuals being treated for hematological malignancies (leukemia, lymphoma, and the like) and people with thoracic malignancies such as lung cancer.

At the Montefiore Medical Center and Albert Einstein College of Medicine in the Bronx, investigators saw a case fatality rate of 25 percent for individuals with solid cancer types who contracted SARS-CoV-2 early on in the pandemic. That jumped to a 37 percent in the small group of people treated for hematologic malignancies during the same time frame, from mid-March to early April of 2020.

As the pandemic raged through New York City last spring, Luo and other investigators at Memorial Sloan Kettering found themselves poised to look at whether lung cancer treatments that target the immune system might make Covid-19 more severe and, if so, whether treatments should be delayed in these patients. That was not the case.

Though she and her colleagues found that patients with blood cancer and lung cancer were more likely to experience severe Covid-19, lung cancer treatment did not appear to impact that risk. In a subsequent analysis, the team spelled out some of the most important risk factors for individuals with lung cancer, including age, smoking history, and other chronic medical, Luo explained, which all increased severe Covid-19 risk more profoundly than cancer-related factors like lung cancer subtype, cancer stage, or treatment type.

“Based on our research, rather than delaying or withholding treatment, we advocated for focusing on safely treating lung cancer during the pandemic,” Luo said.

“The most important thing to remember during this pandemic is that patients with cancer should continue treatment,” she added. “Cancer care is essential care, and we don’t want our patients to put their life-saving treatments on hold.”

Long COVID patients say they feel better after getting vaccinated

Long COVID patients say they feel better after getting vaccinated

  • March 3, 2021

Daniel Griffin wasn’t sure what to expect when his patients with chronic COVID-19 symptoms started getting vaccinated. There was some concern that the shots might make things worse by triggering the immune system. Luckily, the opposite seemed to be true.

“I started getting texts and calls from some of my colleagues saying hey, are your patients with long COVID reporting that they’re feeling better after the vaccine?” says Griffin, an infectious diseases clinician and researcher at Columbia University. When he started talking with patients, he saw that they were. “It’s not 100 percent, but it does seem like to be around a third,” he says.

Early reports from Griffin and others hint that people with persistent symptoms may improve after getting vaccinated. Information is still limited, and the data is largely anecdotal — but if the pattern holds, it could help researchers understand more about why symptoms of COVID-19 persist in some people, and offer a path to relief.

Many of Griffin’s patients who improved had significant side effects after their first shot of either the Moderna or Pfizer / BioNTech vaccine. That’s common in people who’ve had COVID-19 before — they already have some level of antibodies, so the first shot acts more like a second booster. Then, his patients with chronic symptoms started to report that their sense of smell was improving or that they weren’t as fatigued. “For some of them it was short lived. But for a chunk, it actually persisted — they went ahead, got their second shot out, and are saying, wow, they really feel like there’s light at the end of the tunnel,” Griffin says.

A number of people who catch COVID-19 experience symptoms — like fatigue, shortness of breath, or loss of smell — months after their initial illness. For some, those symptoms are debilitating. Many people who got sick during the first wave of the pandemic a year ago still aren’t fully recovered. Doctors like Griffin are learning more about what’s being called “long COVID,” but answers are still limited. Any hint of a path toward relief “would be nothing short of a miracle,” says Diana Berrent, founder of the COVID-19 survivors and long-haulers group Survivor Corps.

Some patient surveys are trying to get an early read on how widespread improvement is. Director Gez Medinger, who covers long COVID on his YouTube channel, surveyed nearly 500 people in various long-hauler support groups on Facebook. Around a third of people surveyed said that they felt slightly or entirely better when they were at least two weeks out from vaccination.

Dozens of people who responded to a poll in the Facebook group for Survivor Corps said that their symptoms improved slightly or went away almost completely. “We were really concerned that people were going to have bad reaction. It never occurred to us that they would actually improve,” Berrent says. Another survivors group, Patient-Led Research, is also surveying people with long COVID who have been vaccinated.

There are limitations to these types of surveys — they’re small, and they’re limited to people who seek out and participate in support groups. They can’t prove that the vaccine was what led to any symptom improvement. But they can point researchers toward useful research questions.

There are plausible biological reasons vaccination could help people with long COVID, says Akiko Iwasaki, an immunologist at Yale University. Scientists still don’t know for sure why some people have chronic symptoms, but one theory is that the virus or fragments of the virus stick around in their body. They’re not contagious, but the leftovers continue to irritate the immune system. Vaccination could clear those out. “Potentially, those remnants are removed because you’re generating a lot of antibodies,” Iwasaki told The Verge.

Another theory is that, for some people, COVID-19 triggers long-lasting changes in the immune system, and it could turn on healthy cells and tissues. In that case, the vaccine might help by giving a jolt to the immune system. “It can reset some of those existing responses,” Iwasaki says. In that case, symptom improvement would probably be short-lived and only last as long as the vaccine’s kick does.

There’s a lot more to learn about the relationship between long COVID and vaccines. It’ll take more and more rigorous, survey data to understand exactly what portion of people feel better after they get vaccinated. There are studies underway that monitor certain inflammatory proteins in the blood of people with chronic symptoms, and researchers could compare levels in people who are and aren’t vaccinated, Griffin says.

Research should also check if one type of vaccine is more effective at reducing chronic symptoms than the others. Even though Moderna, Pfizer / BioNTech, and Johnson & Johnson vaccines work equally well at preventing severe infection, they might vary in how well they could help people with long COVID. “Once we know that, we can recommend among COVID people to get different vaccines,” Iwasaki says.

That data would also help clarify the reasons people have chronic symptoms. If a significant number of people have long-term improvement after they get vaccinated, Iwasaki says she’d lean toward the viral remnants theory. “For that, once you get rid of the virus, that’s it — you don’t suffer from this anymore.” She notes, though, that everyone has different experiences with the disease. “It’s not a one size fits all.”

Berrent still thinks it’s too early to say for sure how much vaccines can actually help people with long COVID. “I think this is all very interesting,” she says. “I feel like we’re still gathering data here.” It is encouraging, though, to see that they aren’t having bad reactions to the vaccine, and any minor improvement is exciting.

The early reports are a good push for people with chronic COVID-19 symptoms to get vaccinated, Griffin says. “It doesn’t look harmful, and it may be therapeutic. I think it’s encouraging for people with long COVID to get signed up as soon as they can.”

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Fecal Transplants Are Showing Promise as a New Treatment For a Type of Skin Cancer

  • February 8, 2021

The effect of a drug, or impact of a treatment like chemotherapy, doesn’t just depend on your body. The success of a particular medicine also depends on the trillions of bacteria in your gut.

 

The 100 trillion bacteria that live within the human digestive tract – known as the human gut microbiome – help us extract nutrients from food, boost the immune response and modulate the effects of drugs.

Recent research, including my own, has implicated the gut microbiome in seemingly unconnected states, ranging from the response to cancer treatments to obesity and a host of neurological diseases, including Alzheimer’s, Parkinson’s disease, depression, schizophrenia and autism.

What underlies these apparently discrete observations is the unifying idea that the gut microbiota send signals beyond the gut and that these signals have broad effects on a large swathe of target tissues.

I am a medical oncologist whose research involves developing novel therapies for melanoma. To evaluate whether altering the microbiome could benefit cancer patients, my colleagues and I evaluated the transfer of fecal matter from melanoma patients who responded well to immunotherapy to those patients for whom immunotherapy failed.

Just published in the journal Science, our results reveal that this treatment helped shrink the tumors of advanced melanoma patients when other therapies hadn’t worked.

 

What connects cancer and gut bacteria?

Gut microbiota have been linked to to the success and failure of multiple cancer treatments, including chemotherapy and cancer immunotherapy with immune checkpoint inhibitors such as nivolumab and pembrolizumab.

In the more recent studies, the species and relative populations of gut bacteria determined the probability that a cancer patient would respond to drugs known as “immune checkpoint inhibitors.”

This research showed that differences in the gut microbiome between individual patients were associated with various outcomes to these drugs. But the precise mechanisms underlying microbiome-immune interactions remain unclear.

Can fecal microbes help drugs reach hard to treat melanoma?

Oncologists often treat patients with advanced melanoma using immunotherapies targeting specific proteins on the surface of immune cells known as PD-1 and CTLA-4. These work in a subset of patients, however – 50-70 percent of patients have cancers that get worse despite treatment.

No medical treatments have been approved to treat melanoma patients who have failed PD-1 immunotherapies.

To investigate whether certain types of microbes could boost the efficacy of PD-1 immunotherapies, my colleagues and I developed a study in which we collected fecal microbes from patients who had responded well to this therapy and administered these to cancer patients who didn’t benefit from the checkpoint drugs.

We chose stool from patients who responded well to immunotherapy based on the hunch that they would have greater quantities of bacteria implicated in helping shrink the cancer.

file 20210204 24 1wpdow3(Diwakar Davar/CC BY-ND)

As it is difficult to identify one or two species of bacteria that are responsible for the beneficial response to these therapies, we used the entire bacterial community – hence fecal microbe transplant.

Transplant recipients were patients whose melanoma had never responded to immunotherapy. Both recipients and donors underwent screening for diseases to ensure that no infectious agents would be transmitted during the transplant.

 

Following a biopsy of their tumor, patients received a fecal microbe transplant from patients who benefited from immunotherapy along with a drug called called pembrolizumab, which was continued every three weeks.

My colleagues and I assessed the fecal microbe transplant 12 weeks after the treatment. Patients whose cancers had shrunk or remained the same size after the fecal microbe transplant continued to receive pembrolizumab for up to two years.

Results of novel clinical trial

file 20210204 20 lkqki8(Diwakar Davar/CC BY-ND)

Following this fecal microbe transplant treatment, tumors of six out of 15 patients in the study had tumors that shrank or remained the same. The treatment was well tolerated, though some of the patients experienced minor side effects including fatigue.

When we analyzed the gut microbiota of treated patients, we observed that the six patients whose cancers had stabilized or improved showed increased numbers of bacteria that had previously been associated with responses to immunotherapy.

My colleagues and I also analyzed the blood and tumors from responders. In doing so, we observed that the responders had lower levels of adverse immune cells termed myeloid cells, and higher levels of memory immune cells. Additionally, by analyzing proteins in the blood serum of treated patients, we observed reductions in levels of key immune system molecules associated with resistance in responders.

These results suggest that introducing certain intestinal microorganisms into a patient’s colon may help the patient respond to drugs that enhance the immune system’s ability to recognize and kill tumor cells.

Ultimately we hope to move beyond fecal microbe transplants to specific collections of microbes in cancers besides melanoma, paving the way for standardized microbe-based drug therapy to treat immunotherapy-resistant tumors. The Conversation

Diwakar Davar, Assistant Professor of Medicine, University of Pittsburgh.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

 

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