To treat his Covid-19, President Trump has started receiving dexamethasone, a common steroid that has been shown to be helpful in people with severe cases of the disease but that doctors warn should not be used early in the course of the illness.
The announcement from Trump’s medical team Sunday morning that the president is on dexamethasone is sure to increase speculation about the president’s illness and was at odds with the generally upbeat description of his condition provided by his physicians. His doctors said Trump had not had a fever since Friday morning and did not have any shortness of breath. One even said that, if Trump “continues to feel and look as well as he does today,” their goal was for him to return to the White House on Monday.
Dexamethasone is generally reserved for patients who have serious disease. The National Institutes of Health’s treatment guidelines for Covid-19 say dexamethasone should be used only in hospitalized patients who are on ventilators or who require supplemental oxygen, and specifically “recommends against using dexamethasone for the treatment of Covid-19 in patients who do not require supplemental oxygen.”
Trump’s doctors confirmed that the president received oxygen for about an hour on Friday after a temporary drop in his oxygen levels — something they danced around saying during a Saturday briefing. Sean Conley, the president’s physician, told reporters on Sunday outside Walter Reed National Military Medical, where Trump is being treated, that the president also experienced a “transient” drop in oxygen levels Saturday but said that he wasn’t sure if oxygen was given.
Conley said that drop in Trump’s oxygen saturation to 93% on Saturday morning prompted the decision to initiate the steroid therapy, believing “the potential benefits early on in the course” outweighed any downsides.
“Our plan is to continue that for the time being,” Brian Garibaldi, another of Trump’s doctors, said about the dexamethasone.
Ethan Weiss, a cardiologist at the University of California, San Francisco, who went to New York to treat critically ill Covid-19 patients during the city’s surge, told STAT, “Nothing matches up.” Weiss said that Trump’s medical team had “an impossible job,” but that “you can’t say he’s fine and he’s going home tomorrow and by the way he’s getting dexamethasone, which was shown in [a clinical trial] to be helpful in only the sickest patients.”
The concern with dexamethasone is that it can suppress the immune system’s activity broadly. While that can be helpful in severe illness — which is typically caused by the immune system overreacting to the infection, not the virus itself — giving the steroid too soon could hinder the immune system from fighting the virus in the first place.
“You don’t want to give it to a patient too early,” Nahid Bhadelia, the medical director of Boston Medical Center’s Special Pathogens Unit, told STAT Friday about dexamethasone. “It’s a blunt instrument, so it may suppress a good immune response as well as a bad one.”
In a clinical trial, dexamethasone reduced deaths by a third in patients hospitalized with Covid-19, but the benefit differed depending how sick patients were. In patients not receiving supplemental oxygen, the study showed no benefit and potential harm.
“Those patients who were not requiring oxygen actually had a statistical trend toward worse outcomes — the dexamethasone was only beneficial in patients who were requiring oxygen,” said C. Michael Gibson, a professor of medicine at Harvard Medical School. He also noted that the effect for dexamethasone was only seen in patients who had been sick for longer than seven days. Trump started feeling sick Thursday, his doctors have said.
Trump is also in the middle of a five-day course of the intravenous antiviral remdesivir. His doctors said the president could continue receiving the infusions at the White House if he were discharged from Walter Reed.
Overall, Trump’s medical team continued to portray Trump in good spirits and relatively good health. But as during a Saturday press briefing, Conley answered questions about certain aspects of Trump’s condition vaguely. He was asked several times about potential damage to the president’s lungs and said “there are some expected findings” without giving additional details.
Conley was also asked why he had avoided saying during the Saturday briefing whether Trump had ever been given supplemental oxygen.
“I was trying to reflect the upbeat attitude the team, the president through his course of illness has had,” Conley said. “I didn’t want to give any information that might steer the course of illness in another direction, and in doing so it came off that we were trying to hide something, which wasn’t necessarily true.”
Damian Garde and Matthew Herper contributed reporting.
THURSDAY, Oct. 1, 2020 (HealthDay News) — A newly approved drug for the leading form of the number one cancer killer, lung cancer, does improve patient survival, a new study confirms.
The immunotherapy drug Tecentriq (atezolizumab) was approved earlier this year by the U.S. Food and Drug Administration to treat patients with newly diagnosed non-small cell lung cancers (NSCLC), which comprise up to 85% of all lung tumors.
Tecentriq targets a protein known as PD-L1 that lies on the surface of tumor cells. Normally, this protein signals the body’s immune system T cells not to attack. However, by targeting PD-L1, Tecentriq unleashes the body’s natural T cells to target and destroy these cancer cells, researchers at Yale Cancer Center explained.
Tecentriq “has already shown excellent activity in patients who progress on frontline chemotherapy, but this study confirmed that the drug is active in selected patients who have not yet received any treatment for lung cancer,” said medical oncologist Dr. Nagashree Seetharamu, who treats lung cancer patients but wasn’t involved in the new study. She practices at Northwell Health Cancer Institute in Lake Success, N.Y.
The new study was funded by Tecentriq’s maker, Genentech, and the results were published Sept. 30 in the New England Journal of Medicine.
The study included 554 patients with stage 4 metastatic NSCLC tumors. All patients had tumors lacking mutations in the EGFR or ALK genes: As the researchers explained in a Yale news release, tumors with those mutations are better treated with other drugs.
Among 205 patients whose tumors had high cellular expression of PD-L1, the median overall survival was 20 months for those who received Tecentriq versus 13 months for those who received standard platinum-based chemotherapy.
Median progression-free survival — the time from treatment to the disease beginning to worsen — was eight months for patients who received Tecentriq versus five months for those on standard chemotherapy, the researchers found.
“These are exciting results that could be life-changing for many patients,” said study lead author Dr. Roy Herbst. He is chief of medical oncology at the Yale Cancer Center as well as the Smilow Cancer Hospital.
“Lung cancer is the most common cancer worldwide, with more than 1.5 million patients diagnosed each year. Half of patients are diagnosed with metastatic disease, and they could be a candidate for this drug,” Herbst said in the news release.
“Also encouraging is that [Tecentriq] was generally well tolerated,” said Herbst, who is also associate cancer center director for translational research at the Yale Cancer Center in New Haven, Conn. “Side effects for patients were similar to those seen in other trials of the drug, which has been approved for treatments of several types of cancer.”
The trial also assessed how Tecentriq performed among patients with a “high tumor mutational burden,” which means that they had high levels of genetic mutations in scraps of cancer DNA detected in blood tests. In some types of cancers, high mutational burden is tied to better responses to immunotherapy drugs like Tecentriq.
“Among these patients with NSCLC, those with high tumor mutational burden who received [Tecentriq] showed improved progression-free survival of seven months versus four months for those given chemotherapy,” Herbst said. “This finding suggests that the [blood] biomarker should be explored further.”
For her part, Seetharamu noted that “there are many commercially available and experimental drugs that target PD-L1.” And she noted that the study did have one flaw.
Tecentriq “was compared to platinum-based chemotherapy alone, which is now not the most common standard treatment,” Seetharamu pointed out. Instead, oncologists are increasingly using standard chemotherapy plus another type of immunotherapy drug, Keytruda. The new study didn’t present a head-to-head comparison of Tecentriq against chemotherapy-plus-Keytruda, however.
“That is understandable,” Seetharamu said, “since the study started before these new treatments made it into common clinical practice.”
Regardless, she said, “the overall survival of 20 months in selected patients with high PD-L1 expression treated with Tecentriq alone is impressive and may provide yet another non-chemotherapy treatment option for patients diagnosed with PD-L1-high lung cancer.”
Zinc-rich diet may help improve immunity to fight Coronavirus.
A new study suggests zinc deficiency can be deadly for COVID patients.
Low level of zinc in blood may increase death risk.
Here are some zinc-rich foods you must consume to boost immunity.
With no signs of sure-shot COVID-19 cure in sight, the best thing to do – apart from following safety protocols – is to prepare your body to avoid or withstand the deadly virus. It has been proven that a good immune system acts as the body’s first line of defence against all viral diseases. Vitamin C is touted to be the best nutrient to help build immunity, but replenishing your body with just this nutrient is not the only solution. Deficiency of certain other nutrients can make you more vulnerable to Coronavirus. A recent scientific study linked low level of zinc in the body to higher death risk in people grappling with COVID-19.
The study findings were revealed and discussed at length at the online ESCMID Conference on Coronavirus Disease (ECCVID) held from September 23 to 25 September 2020. The study was presented by Dr Roberto Guerri-Fernandez, Hospital Del Mar, Barcelona, Spain, and his associates who discovered that a lower level of zinc in the blood could raise mortality rate in patients with COVID-19.
The researchers did a retrospective analysis of symptomatic Coronavirus patients admitted in a tertiary university hospital in Barcelona, Spain, from March 15, 2020, to April 30, 2020. Fasting plasma zinc levels were measured in all patients admitted to the COVID-19 ward. The team used computer modelling and statistical analysis to assess the impact of zinc on the mortality rate.
Eggs – One large egg contains about 5 percent (0.6 mg) as per United States Department Of Agriculture (USDA) data.
Watermelon Seeds – Dietician Dr Simran Saini suggests consuming around half teaspoon watermelon seeds 2-3 times a week.
Chickpeas – 100 gm of the legume provides 1.53 mg of zinc, according to USDA.
Berries – Blueberries, raspberries and other such fruits are good sources of zinc and antioxidants.
Fish – Dr Anshul Jaibharat recommends eating fish at least twice a week.
Include these foods to your immunity-boosting diet to prepare your body to fight all kinds of illnesses.
About Neha GroverLove for reading roused her writing instincts. Neha is guilty of having a deep-set fixation with anything caffeinated. When she is not pouring out her nest of thoughts onto the screen, you can see her reading while sipping on coffee.
Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
From the first months of the COVID-19 pandemic, scientists baffled by the disease’s ferocity have wondered whether the body’s vanguard virus fighter, a molecular messenger called type I interferon, is missing in action in some severe cases. Two papers published online in Science this week confirm that suspicion. They reveal that in a significant minority of patients with serious COVID-19, the interferon response has been crippled by genetic flaws or by rogue antibodies that attack interferon itself.
“Together these two papers explain nearly 14% of severe COVID-19 cases. That is quite amazing,” says Qiang Pan- Hammarström, an immunologist at the Karolinska Institute.
Tadatsugu Taniguchi, a pioneering interferon scientist and emeritus professor at the University of Tokyo, calls the discoveries “remarkable.” He says they highlight the “critical” role of type I interferons in SARS-CoV-2 infection and the development of potentially lethal COVID-19.
Co-author Isabelle Meyts, a pediatric immunologist at the University Hospitals Leuven, was struck by one paper’s finding that rogue antibodies underlie COVID-19 in 10% of gravely ill patients: “There has never been any infectious disease explained at this level by a factor in the human body. And it’s not an isolated cohort of Europeans. Patients are from all over the world, all ethnicities.” Another finding, that 94% of the patients with interferon-attacking antibodies were male, also helps explain why men face higher risk of severe disease.
The paired studies have immediate practical implications. Synthetic interferons, long used to treat other diseases, might help some at-risk patients, as might other therapies aimed at removing the damaging antibodies. A common kind of antibody test could be readily developed and return answers in hours. Those found to be at high risk of developing severe COVID- 19 could take precautions to avoid exposure or be prioritized for vaccination, says Elina Zuniga, an immunologist who studies interferons at the University of California, San Diego.
The findings also raise a red flag for plasma donations from recovered patients. Because it may be rich in antibodies to the virus, “convalescent plasma” is already given to some patients to fight the infection. But some donations could harbor the interferon-neutralizing antibodies. “You should eliminate these patients from the pool of donors,” Zuniga says. “You definitely don’t want to be transferring these autoantibodies into another person.”
Type I interferons are made by every cell in the body and are vital leaders of the antiviral battle early in infection. They launch an immediate, intense local response when a virus invades a cell, triggering infected cells to produce proteins that attack the virus. They also summon immune cells to the site and alert uninfected neighboring cells to prepare their own defenses.
In one study, Jean-Laurent Casanova, an infectious disease geneticist at Rockefeller University, and his team examined blood samples from 987 gravely ill patients from around the world. In 10.2% of the patients, the researchers identified antibodies that attacked and neutralized the patients’ own type I interferon. A subgroup of affected patients had extremely low or undetectable blood levels of this interferon. Lab studies confirmed the antibodies knocked the interferon out of action and cells exposed to the patients’ plasma failed to fend off invasion by the new coronavirus.
At least 10% of critical COVID-19 is an autoimmune attack.
None of the 663 people in a control group with mild or asymptomatic SARS-CoV-2 infection had those damaging antibodies. The antibodies were also scarce in the general population, showing up in only 0.33% of more than 1200 healthy people tested. “What this means is that at least 10% of critical COVID-19 is an autoimmune attack against the immune system itself,” Casanova says.
The preponderance of male patients was a surprise, because women have higher rates of autoimmune disease. “Our favorite hypothesis is that it is an X-linked recessive trait,” Casanova says. “Women with two X chromosomes are protected and men, with one, are not.” Supporting that suspicion, one woman with a rare condition that silences one X chromosome was among the severely ill patients with autoantibodies.
If these striking results hold up, they might also help explain the increased vulnerability of older people to severe COVID-19: Half the gravely ill patients with autoantibodies were older than 65.
The second paper found genetic flaws in patients that led to the same end result: a grossly inadequate interferon response to SARS-CoV-2 infection. The team sequenced DNA from 659 critically ill COVID-19 patients and from 534 controls with mild or asymptomatic disease. They examined 13 genes, chosen because flaws in them impair the body’s production or use of type I interferon; mutations in the genes underlie life-threatening influenza or other viral illnesses. The researchers found that 3.5% of the critically ill patients harbored rare mutations in eight of those genes. In patients for whom blood samples were available, interferon levels were vanishingly small. No members of the control group carried any of the mutations. “This is the first paper to pin down indisputably disease-causing mutations underlying severe COVID-19,” Pan-Hammarström says.
But it’s “probably the tip of the iceberg,” says Paul Hertzog, an interferon expert at the Hudson Institute of Medical Research. Many other damaging mutations, interferon related and not, may influence the development of severe COVID-19, he says.
Zuniga notes that none of the patients who made antibodies against interferon or had the mutations had a history of life-threatening viral illnesses requiring hospitalization. “This suggests that we are more reliant on type I interferons to protect ourselves against SARS-CoV-2 versus other viral infections,” she says. “That makes it important to try therapies aimed at boosting type I interferon responses.”
Dozens of randomized clinical trials are now deploying interferons against SARS-CoV-2. One, led by Tom Wilkinson at the University of Southampton, reported promising findings in a small group of hospitalized COVID-19 patients. But synthetic interferons won’t help patients who harbor mutations that prevent interferons from working, or those with antibodies that attack them.
Some researchers caution that the interferon-neutralizing antibodies could be a cause, rather than a consequence, of severe COVID-19. “It’s possible that they develop during the disease,” says Miriam Merad, an immunologist at the Icahn School of Medicine at Mount Sinai. That would explain why the patients hadn’t faced life-threatening viral infections before, she says.
But Casanova, who has made a career of discovering mutations that confer susceptibility to infectious diseases, says there is a strong case for causality. He points out that preexisting blood samples from a handful of patients showed they had the antibodies in their blood before contracting SARS-CoV-2. He argues that, in response to infection, it’s unlikely that the body could quickly generate the high levels of anti-interferon antibodies his team saw.
Yanick Crow, a clinical geneticist at the University of Edinburgh who studies interferon signaling, calls the antibody paper “shocking,” in part because men were so much more likely than women to carry the rogue antibodies. Tests screening for the antibodies can and should be rapidly developed, he says, and will quickly reveal whether the new findings hold up. Given tens of millions of cases worldwide, he says, “10% is such a high figure and the implications are very important.”
Researchers have discovered that killer T cells, key immune cells in fighting viral infections, are present at much lower levels in people with COVID-19, compared to influenza or glandular fever, thus lending support to the ‘prime and boost’ vaccine model.
The team from the Peter Doherty Institute for Infection and Immunity (Melbourne, Australia) looked at 22 COVID-19 samples from patients who experienced asymptomatic, mild or moderate illness. Their research concentrated on CD8 T cells (killer T cells), which are integral to mounting an effective and rapid recovery from viruses such as influenza. The team looked at T cells in people who express a protein called human antigen leucocyte (HLA) serotype HLA-A2. HLA proteins are important for T cell recognition and vary across individuals.
“What we found is those key immune cells weren’t stimulated optimally for rapid proliferation and expansion to fight SAR-CoV-2,” said first author, University of Melbourne’s Jennifer Habel, a PhD student at the Doherty Institute. “The magnitude of the killer T cells was only five times higher than those of the naïve immune cells. To give that perspective, it’s 10 times lower than what we see during an influenza or glandular fever response.”
In addition to magnitude, the team also looked at the activation profile of these immune cells and found that not only was activation poor, but in some cases these cells remained largely naïve, as if they had not been exposed to the virus at all. These striking findings support the ‘prime and boost’ vaccine model, according to the researchers.
“Knowing the specific T cells and proteins to target will inform the design of an effective vaccine,” said University of Melbourne Professor Katherine Kedzierska, a laboratory head at the Doherty Institute and a world-leading influenza immunology researcher who led this study. “This research shows that potentially, if a vaccine was able to prime the immune system of killer T cells and then boost them a short time later, the immune response is likely to be much more robust to fight SARS-CoV2.”
“If the SARS-CoV-2 virus is indeed compromising the killer T cell response that can be important for recovery, the best bet may be to get the right vaccine before the virus gets to us” said co-author, Doherty Institute Patron Laureate Professor Peter Doherty.
SCOTCH PLAINS, N.J., Sept. 14, 2020 /PRNewswire-PRWeb/ — Dr. Steven M. Bromley, Dr. Indrani Hightower, and Dr. Keith Preis have started offering telemedicine services to patients of The South Jersey MS Center to accommodate the COVID-19 pandemic. The providers are also actively seeing patients in the office, while meeting and exceeding CDC guidelines for safety and sterility.
The team at the South Jersey MS Center is now working six days per week and extending hours to address the needs of parents who are currently homeschooling their children. The team is also prepared to accommodate the needs of elderly and immunocompromised patients.
“We have implemented social distancing, mask wearing by all who enter the office, regimented hand washing, use of hand sanitizers, and room cleaning protocols,” say the NJ Top Docs of South Jersey MS Center.
Dr. Steven M. Bromley, Dr. Indrani Hightower and Dr. Keith Preis are also excited to now offer their patients several new FDA approved infusions.
For the prevention of migraines they are now offering Vyepti infusions every three months. For the treatment of myasthenia gravis, Soliris treatments can be prescribed for patients, which is a treatment given every other week. For multiple sclerosis and other immunological conditions affecting the nervous system, the South Jersey MS Center continues to provide all cutting edge therapies. Lastly, they are also extending new lines of therapy that are immunoprotective and promote general wellness in their patients.
“We now can offer Nutraceutical infusions, which strengthen the immune system, promote rehydration, promote wellness, and also include anti aging properties,” says Dr. Bromley, the director of the South Jersey MS Center.
Some elective infusions help to boost immune system function and include IV fluids, high doses of vitamin C, zinc, selenium, and B vitamins. The well known Myers’ Cocktail infusion includes electrolytes, high doses of B vitamins, magnesium, calcium and antioxidants.
As a thank you for fighting COVID-19 on the frontlines, the team at the South Jersey MS Center are offering healthcare providers and first responders discounted rates for their first infusion service.
NJ Top Docs is a comprehensive, trusted and exclusive healthcare resource featuring reviewed and approved Top Doctors and Dentists in New Jersey online in an easy to use format. NJ Top Docs only reviews and approves providers based on merit after they have been extensively vetted.
NJ Top Docs is a division of USA Top Docs which allows patients to meet providers online before making their appointment.
Melbourne researchers have discovered that killer T cells, key immune cells in fighting viral infections, are present at much lower levels in people with COVID-19, compared to influenza or glandular fever.
Publishing their findings today in PNAS, the team from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) looked at 22 COVID-19 samples from patients who experienced asymptomatic, mild or moderate illness.
First author, University of Melbourne’s Jennifer Habel, a Ph.D. student at the Doherty Institute, said their research concentrated on CD8 T cells (killer T cells), which are integral to mounting an effective and rapid recovery from viruses such as influenza.
The team looked at T cells in people who express a protein called human antigen leucocyte (HLA) serotype HLA-A2. HLA proteins are important for T cell recognition and vary across individuals.
“What we found is those key immune cells weren’t stimulated optimally for rapid proliferation and expansion to fight SAR-CoV-2,” Ms Habel said.
“The magnitude of the killer T cells was only five times higher than those of the naïve immune cells. To give that perspective, it’s 10 times lower than what we see during an influenza or glandular fever response.”
In addition to magnitude, the team also looked at the activation profile of these immune cells and found that not only was activation poor, but in some cases these cells remained largely naïve, as if they hadn’t been exposed to the virus at all.
University of Melbourne Professor Katherine Kedzierska, a laboratory head at the Doherty Institute and a world-leading influenza immunology researcher who led this study, said these striking findings support the ‘prime and boost’ vaccine model.
“Knowing the specific T cells and proteins to target will inform the design of an effective vaccine,” Professor Kedzierska said. “This research shows that potentially, if a vaccine was able to prime the immune system of killer T cells and then boost them a short time later, the immune response is likely to be much more robust to fight SARS-CoV2.”
Co-author, Doherty Institute Patron Laureate Professor Peter Doherty said: “If the SARS-CoV-2 virus is indeed compromising the killer T cell response that can be important for recovery, the best bet may be to get the right vaccine before the virus gets to us.”
Jennifer R. Habel et al. Suboptimal SARS-CoV-2−specific CD8+ T cell response associated with the prominent HLA-A*02:01 phenotype, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.2015486117
Doherty Institute for Infection and Immunity
Immune cell responses in COVID-19 patients far from optimal (2020, September 11)
retrieved 11 September 2020
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
The immune system functions by using an exclusion barrier––eliminating pathogens, tolerating nonthreatening sources of antigens, and maintaining a memory of immunological encounters.1
Key functions of the immune system include deactivating pathogens, such as bacteria, fungi, parasites, and viruses, and eliminating them; combating the body’s own cells if they change because of an illness, such as cancer; and neutralizing harmful substances from the environment.1 The issue of immune support is a major concern for many because of the coronavirus disease 2019 (COVID- 19) pandemic and the annual, looming cold and influenza season. As some students return to school in the fall, many caregivers and parents are likely to be concerned about ensuring that their children’s immune systems are strong. Health experts are still unsure about the possibility of a second wave of COVID-19 infections. Many individuals are trying to be proactive about their health and electing to use nutritional supplements marketed for immune support. Until a COVID-19 vaccine and/or FDAapproved treatment is available, health experts recommend frequent handwashing, proper hygiene, social distancing, use of facial masks, and keeping the immune system healthy to diminish the risk of infection. Pharmacists are in a pivotal position to educate and guide patients about the various nonprescription immune-boosting supplements on the market.
These supplements may contain 1 or more of the vitamins A, C, D, and E, along with trace elements of selenium and zinc. Some also contain echinacea, ginger, and other herbal ingredients for immune enhancement. Other products marketed for immune support include prebiotics and probiotics. Some contain colostrum, which is rich in antibodies, and immunoglobulins A and E that may provide immune-modulating benefits.2 Many other products marketed for strengthening the immune system contain elderberry.2 Some manufacturers have formulated immune-boosting supplements to address the specific needs for patient populations by age groups, including adult and pediatric formulations.
RECENT NEWS AND CLINICAL STUDIES Evidence linking vitamin D deficiency with COVID- 19 severity is anecdotal but growing.3 Health experts have indicated that healthy blood levels of vitamin D may be beneficial in helping individuals with the illness avoid cytokine storm.3 For example, at Northwestern University, investigators used modeling to estimate that 17% of those deficient in vitamin D would develop a severe COVID-19 infection, whereas only about 14% of those with healthy vitamin D levels would.3 They estimated this association based on a potential link between vitamin D deficiency and C-reactive proteins, a surrogate marker for severe COVID-19.3 Although early research is ongoing, investigators are examining the effectiveness of Vitamin D at preventing or easing COVID-19 infections. A list of the current studies is available at Clinical Trials.gov.
Research regarding the use of vitamin C to decrease inflammation and symptoms associated with COVID-19 continues.4 To date, at least 1 clinical trial (NCT04264533) is underway and is expected to be completed by September 2020. The trial is exploring the use of vitamin C infusion as a treatment for severe COVID-19 pneumonia. Additionally, a 2020 metaanalysis of 9 existing clinical trials compared a group of individuals who received an intravenous infusion with a group of controls. The investigators found that, on average, vitamin C shortened the length of mechanical ventilation by 14%.5 The effect varied from study to study, however, and was greater when members of the control group needed longer periods of ventilation.5
In a June 2020 statement, scientists at Duke University announced that they plan to conduct a double-blind, placebo-controlled, randomized clinical trial for the probiotic Lactobacillus rhamnosus GG in households that have been exposed to COVID-19.6 Their goal is to recruit 1000 participants to ascertain whether probiotics can directly diminish the risk and severity of COVID-19 in caregivers and household contacts of known COVID-19 patients. The trial is expected to be completed by May 2022.6
PHARMACISTS’ ROLE Pharmacists can be influential in assisting patients in the proper selection of these nutritional supplements as well as serve as an excellent resource in identifying possible drug/micronutrient contraindications and interactions. Patients taking other medications and those with chronic medical conditions should always consult their primary health care providers before taking any supplements. Pharmacists can also encourage patients to get sufficient sleep, maintain healthy balanced diets, and reduce stress to keep their immune systems intact.
Yvette C. Terrie, BSPharm, RPh, is a consulting pharmacist and a medical writer in Haymarket, Virginia.
How does the immune system work? National Center for Biotechnology Information. Updated April 23, 2020. Accessed July 23, 2020. https://www.ncbi.nlm. nih.gov/books/NBK279364/
McQueen CE, Orr KK. Natural products. In: Krinsky DL, Ferreri SP, Hemstreet B, et al, eds. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. 19th ed. American Pharmacists Association; 2018:957-994.
Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. The possible role of vitamin D in suppressing cytokine storm and associated mortality in COVID-19 patients. medRxiv. May 18, 2020. Accessed July 23, 2020. https://www. medrxiv.org/content/10.1101/2020.04.08.20058578v4
Villines Z. Can vitamin C prevent or treat COVID-19? Medical News Today. June 8, 2020. Accessed July 23, 2020. https://www.medicalnewstoday.com/articles/canvitamin- c-prevent-or-treat-covid-19
Hemilä H, Chalker E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. J Intensive Care. 2020;8:15. doi:10.1186/s40560-020-0432-y
Daniells S. Culturelle probiotics to be studied in COVID-19 exposed households. NutraIngredients–USA. June 5, 2020. Accessed July 23, 2020. https://www. nutraingredients-usa.com/Article/2020/06/05/Culturelle-probiotics-to-be-studied-in- COVID-19-exposed-households
Radiation causes key changes to immune cells in kidney cancer tumors
T cells in tumors are expanded in blood shortly after radiation, then decrease
Study shows timing of treatments may improve success of cancer immunotherapy
Newswise — BUFFALO, N.Y. — It’s clear that radiation therapy, or radiotherapy, an approach used to treat cancer since the early 20th century, can be an effective companion to newer, immune-stimulating approaches known as immunotherapy. Research from a team from Roswell Park Comprehensive Cancer Center explains how radiation helps boost the immune system’s ability to fight cancer in combination with immune checkpoint inhibitors — and provides new evidence that the timing of these therapies can make a big difference in how effectively they work together.
While more than 100 clinical trials currently underway are exploring the combination of radiation with immunotherapy, little is known regarding radiation’s impact within the tumor microenvironment. Looking to fill that void, the researchers, led by Jason Muhitch, PhD, Jacky Chow, PhD, and Anurag Singh, MD, focused their study on renal cell carcinoma (RCC), a form of kidney cancer that, until a few years ago, was thought to be radiation-resistant.
In new research published today in PNAS, the Proceedings of the National Academy of Sciences of the United States of America, they show for the first time that radiation remodels T cell responses found within patient tumors.
Based on results of high-throughput sequencing of samples from patients with RCC, the researchers found that stereotactic body radiation therapy, or SBRT, led to expansion of peripheral blood T cell clones that were also found within patient tumors — the first report of this dynamic in any cancer type.
“Interestingly, this expansion was short-lived, and we saw contraction or reduction of these T cell clones when we evaluated peripheral blood four weeks after treatment,” notes Dr. Muhitch, Assistant Professor of Oncology in the Departments of Urology and Immunology and the paper’s senior author. “That suggests that we have a window shortly after radiation treatment to improve patient outcomes using combination strategies with immunotherapy.”
The work reveals new dynamics of human immune responses, with two important implications: (1) single-dose radiation is an effective immune-sensitizing agent for patients with RCC, and (2) timing is a critical factor for combination strategies that rely on endogenous T cell responses, or activation of immune cells within organs.
“Our findings help explain how a conventional cancer treatment can bolster immune responses in kidney cancer patients,” says Dr. Muhitch, “and may point the way to better treatment outcomes for more patients — not just in kidney cancer, but for other cancer types too.”
The work involved a multidisciplinary team from the Roswell Park departments of Immunology, Urology and Radiation Medicine. Co-authors are Nicholas Hoffend, Scott Abrams, PhD, and Thomas Schwaab, MD, PhD.
The research was supported by grants from the National Center for Advancing Translational Sciences (project number UL1TR001412, to the University at Buffalo Clinical and Translational Science Institute) and National Cancer Institute (project numbers R01CA172105 and P30CA016056). Additional support was provided by the Roswell Park Friends of Urology, Elsa Kreiner Memorial Fund and Fraternal Order of Eagles.
Roswell Park Comprehensive Cancer Center is a community united by the drive to eliminate cancer’s grip on humanity by unlocking its secrets through personalized approaches and unleashing the healing power of hope. Founded by Dr. Roswell Park in 1898, it is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. Learn more at www.roswellpark.org, or contact us at 1-800-ROSWELL (1-800-767-9355) or ASKRoswell@RoswellPark.org.
When the first critically ill COVID-19 patients started arriving in Australian hospitals, intensive care doctors suspected steroids could be an effective treatment.
New clinical trial data provides further evidence corticosteroid treatments reduce death rates of critically ill COVID-19 patients
The treatments are already being used in Australia for patients who are severely ill from COVID-19
National clinical guidelines for corticosteroid treatments will be updated soon in light of the new trial data
Clinical Professor Ian Seppelt from Nepean Hospital in Sydney said intensive care clinicians used steroid treatments but a lack of evidence from clinical trials made them nervous.
“There were all kinds of weird and wacky therapies that had been proposed for a disease that nobody had heard of last December,” he said.
Since then research into corticosteroid treatments for severe COVID-19 patients has advanced quickly.
“We’ve got a new disease, we’ve got a large number of new patients, but we’ve got scientific collaboration to try and get some answers really quickly, and that’s very exciting,” Professor Seppelt said.
Two recent publications have helped firm up the evidence in favour of corticosteroids.
The early results of that trial were published in June in pre-print form, meaning it had not yet been peer-reviewed, and was referred to by medical researchers as “Recovery”.
Why are steroids helpful?
Corticosteroids are synthetic drugs that suppress the immune system and decrease inflammation, pain and swelling.
Elena Schneider-Futschik from the University of Melbourne said COVID-19 could cause an immune system “hyper-response” in some patients.
“When you have a severe reaction, your own body attacks itself, and that’s what causes the symptoms and death,” Dr Schneider-Futschik said.
“With corticosteroids, it modulates this immune response, and that is really helpful in treating the patient.”
That doesn’t mean everyone who has COVID-19 should be treated with corticosteroids.
The WHO guidance recommends limiting the treatment to people in hospital with severe and critical illness who are being given oxygen-therapy, and the meta-analysis indicated corticosteroids may increase the risk of death in patients with non-severe COVID-19.
“Corticosteroids suppress the immune system and this is actually negative in the case of a mild infection,” Dr Schneider-Futschik said.
“You want that usefulness of the immune system when it gets rid of infections, but it also helps to protect you from other infections, from other pathogens, for example influenza.”
Professor Steven Webb from Monash University believes the use of corticosteroids is now universal in Australian hospitals.
“It’s certainly my strong expectation there would be no [COVID-19] patient in an ICU in Australia who has not been receiving either dexamethasone or hydrocortisone,” he said.
Professor Webb is leading one of the clinical trials that was included in the new meta-analysis.
The REMAP-CAP trial includes 384 adult patients in 200 ICUs around the world, including in Australia.
It has so far found a 93 per cent probability that treating critically ill patients with hydrocortisone improved their chance of survival and recovery.
Professor Webb said the trial showed both hydrocortisone and dexamethasone had similar effectiveness.
“The public health significance of that is there’s quite a bit more hydrocortisone around than there is dexamethasone, and there had started to be concerns about adequacy of supply of dexamethasone,” he said.
“The results of REMAP-CAP and the meta analysis provide confidence that this is a class effect of all corticosteroids, and not something that was restricted narrowly to dexamethasone.”
The executive director of the National COVID-19 Clinical Guidance Taskforce, Associate Professor Julian Elliott, said the taskforce was likely to amend its recommendations for corticosteroid treatment in coming weeks.
“The data that’s available from the trials that have been recently published will give us more information on other drugs in the corticosteroid class and enable us to update our recommendations,” he said.
What do we still need to know?
Professor Seppelt said intensive care clinicians wanted more data about what doses of corticosteroids were most effective and had the least adverse side effects.
He said the dosage of dexamethasone used in the Oxford University Recovery trial was quite small.
“There’s some data suggesting worse outcomes with much large doses of dexamethasone but there’s an ongoing question about whether 6 milligrams is the right dose or whether different doses might be better,” he said.
Dr Schneider-Futschik said more evidence was needed about which corticosteroids were best for treating severe COVID-19.
“So that’s something where we still need further studies to actually pin down which steroid to use and at what concentration,” she said.