If I Have Cancer, Dementia or MS, Should I Get the Covid Vaccine? – Kaiser Health News

By Judith Graham January 27, 2021

This story also ran on CNN. It can be republished for free.

As public demand grows for limited supplies of covid-19 vaccines, questions remain about the vaccines appropriateness for older adults with various illnesses. Among them are cancer patients receiving active treatment, dementia patients near the end of their lives and people with autoimmune conditions.

Recently, a number of readers have asked me whether older relatives with these conditions should be immunized. This is a matter for medical experts, and I solicited advice from several. All strongly suggested that people with questions contact their doctors and discuss their individual medical circumstances.

Experts advice may be helpful since states are beginning to offer vaccines to adults over age 65, 70 or 75, including those with serious underlying medical conditions. Twenty-eight states are doing so, according to the latest survey by The New York Times.

Q: My 80-year-old mother has chronic lymphocytic leukemia. For weeks, her oncologist would not tell her yes or no about the vaccine. After much pressure, he finally responded: It wont work for you, your immune system is too compromised to make antibodies. She asked if she can take the vaccine anyway, just in case it might offer a little protection, and he told her he was done discussing it with her.

First, some basics. Older adults, in general, responded extremely well to the two covid-19 vaccines that have received special authorization from the Food and Drug Administration. In large clinical trials sponsored by drugmakers Pfizer and Moderna, the vaccines achieved substantial protection against significant illness, with efficacy for older adults ranging from 87% to 94%.

But people 65 and older undergoing cancer treatment were not included in these studies. As a result, its not known what degree of protection they might derive.

Dr. Tobias Hohl, chief of the infectious diseases service at Memorial Sloan Kettering Cancer Center in New York City, suggested that three factors should influence patients decisions: Are vaccines safe, will they be effective, and what is my risk of becoming severely ill from covid-19? Regarding risk, he noted that older adults are the people most likely to become severely ill and perish from covid, accounting for about 80% of deaths to date a compelling argument for vaccination.

Regarding safety, there is no evidence at this time that cancer patients are more likely to experience side effects from the Pfizer-BioNTech and Moderna vaccines than other people. Generally, we are confident that these vaccines are safe for [cancer] patients, including older patients, said Dr. Armin Shahrokni, a Memorial Sloan Kettering geriatrician and oncologist.

The exception, which applies to everyone, not just cancer patients: people who are allergic to covid-19 vaccine components or who experience severe allergic responses after getting a first shot shouldnt get covid-19 vaccines.

Efficacy is a consideration for patients whose underlying cancer or treatment suppresses their immune systems. Notably, patients with blood and lymph node cancers may experience a blunted response to vaccines, along with patients undergoing chemotherapy or radiation therapy.

Even in this case, we have every reason to believe that if their immune system is functioning at all, they will respond to the vaccine to some extent, and thats likely to be beneficial, said Dr. William Dale, chair of supportive care medicine and director of the Center for Cancer Aging Research at City of Hope, a comprehensive cancer center in Los Angeles County.

Balancing the timing of cancer treatment and immunization may be a consideration in some cases. For those with serious disease who need therapy as quickly as possible, we should not delay [cancer] treatment because we want to preserve immune function and vaccinate them against covid, said Hohl of Memorial Sloan Kettering.

One approach might be trying to time covid vaccination in between cycles of chemotherapy, if possible, said Dr. Catherine Liu, a professor in the vaccine and infectious disease division at Fred Hutchinson Cancer Research Center in Seattle.

In new guidelines published late last week, the National Comprehensive Cancer Network, an alliance of cancer centers, urged that patients undergoing active treatment be prioritized for vaccines as soon as possible. A notable exception: Patients whove received stem cell transplants or bone marrow transplants should wait at least three months before getting vaccines, the group recommended.

The American Cancer Societys chief medical and scientific officer, Dr. William Cance, said his organization is strongly in favor of cancer patients and cancer survivors getting vaccinated, particularly older adults. Given vaccine shortages, he also recommended that cancer patients who contract covid-19 get antibody therapies as soon as possible, if their oncologists believe theyre good candidates. These infusion therapies, from Eli Lilly and Co. and Regeneron Pharmaceuticals, rely on synthetic immune cells to help fight infections.

Q: Should my 97-year-old mom, in a nursing home with dementia, even get the covid vaccine?

The federal government and all 50 states recommend covid vaccines for long-term care residents, most of whom have Alzheimers disease or other types of cognitive impairment. This is an effort to stem the tide of covid-related illness and death that has swept through nursing homes and assisted living facilities 37% of all covid deaths as of mid-January.

The Alzheimers Association also strongly encourages immunization against covid-19, both for people [with dementia] living in long-term care and those living in the community, said Beth Kallmyer, vice president of care and support.

What I think this question is trying to ask is Will my loved one live long enough to see the benefit of being vaccinated? said Dr. Joshua Uy, medical director at a Philadelphia nursing home and geriatric fellowship director at the University of Pennsylvanias Perelman School of Medicine.

Potential benefits include not becoming ill or dying from covid-19, having visits from family or friends, engaging with other residents and taking part in activities, Uy suggested. (This is a partial list.) Since these benefits could start accruing a few weeks after residents in a facility are fully immunized, I would recommend the vaccine for a 97-year-old with significant dementia, Uy said.

Minimizing suffering is a key consideration, said Dr. Michael Rafii, associate professor of clinical neurology at the University of Southern Californias Keck School of Medicine. Even if a person has end-stage dementia, you want to do anything you can to reduce the risk of suffering. And this vaccine provides individuals with a good deal of protection from suffering severe covid, he said.

My advice is that everyone should get vaccinated, regardless of what stage of dementia theyre in, Rafii said. That includes dementia patients at the end of their lives in hospice care, he noted.

If possible, a loved one should be at hand for reassurance since being approached by someone wearing a mask and carrying a needle can evoke anxiety in dementia patients. Have the person administering the vaccine explain who they are, what theyre doing and why theyre wearing a mask in clear, simple language, Rafii suggested.

Q: Im 80 and I have Type 2 diabetes and an autoimmune disease. Should I get the vaccine?

There are two parts to this question. The first has to do with comorbidities having more than one medical condition. Should older adults with comorbidities get covid vaccines?

Absolutely, because theyre at higher risk of becoming seriously ill from covid, said Dr. Abinash Virk, an infectious diseases specialist and co-chair of the Mayo Clinics covid-19 vaccine rollout.

Pfizers and Modernas studies specifically looked at people who were older and had comorbidities, and they showed that vaccine response was similar to [that of] people who were younger, she noted.

The second part has to do with autoimmune illnesses such as lupus or rheumatoid arthritis, which also put people at higher risk. The concern here is that a vaccine might trigger inflammatory responses that could exacerbate these conditions.

Philippa Marrack, chair of the department of immunology and genomic medicine at National Jewish Health in Denver, said theres no scientifically rigorous data on how patients with autoimmune conditions respond to the Pfizer and Moderna vaccines.

So far, reasons for concern havent surfaced. More than 100,000 people have gotten these vaccines now, including some who probably had autoimmune disease, and theres been no systematic reporting of problems, Marrack said. If patients with autoimmune disorders are really worried, they should talk with their physicians about delaying immunization until other covid vaccines with different formulations become available, she suggested.

Last week, the National Multiple Sclerosis Society recommended that most patients with multiple sclerosis another serious autoimmune condition get the Pfizer or Moderna covid vaccines.

The vaccines are not likely to trigger an MS relapse or to worsen your chronic MS symptoms. The risk of getting COVID-19 far outweighs any risk of having an MS relapse from the vaccine, it said in a statement.

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If I Have Cancer, Dementia or MS, Should I Get the Covid Vaccine? - Kaiser Health News

L-MIND Trial Results Show CD19 Antibody Is Reasonable in R/R DLBCL – Targeted Oncology

During a Targeted Oncology Case Based Peer Perspectives Roundtable event, Loretta J. Nastoupil, MD, associate professor, director, Lymphoma Outcomes Database, section chief, New Drug Development, in the Department of Lymphoma/Myeloma, Division Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discussed the case of a 74-year-old patients with diffuse large B-cell lymphoma.

Targeted OncologyTM: What are the potential second- and third-line therapy options for this patient at this point in their treatment?

NASTOUPIL: The current NCCN [National Comprehensive Cancer Network] guidelines...look like a laundry list of a number of different therapeutic options and [do] not necessarily provide an algorithm for what might be the preferred choice based [on] certain patient characteristics.1 It just signifies that there may be several different chemoimmuno-therapy approaches and then even some potential targeted therapy approaches.

Then in the third line, CAR [chimeric antigen receptor] T-cell therapy becomes an option for patients.

Why is the tafasitamab and lenalidomide regimen listed in this poll? What is the rationale for combining these agents?

For those who may not be familiar, tafasitamab is a naked CD19 antibody, not a CAR T therapy. Its not an antibody-drug conjugate but a naked antibody engineered for enhanced ADCC [anti- body-dependent cellular cytotoxicity].

Tafasitamab and lenalidomide were approved in July 2020 for the treatment of DLBCL.2 Its an interesting label in that it is approved for patients who are not transplant candidates, and so that raises the question of how you define a nontransplant candidate. Its approved in combination withlenalidomide, 25 mg dosed 1 through 21 of a 28-day cycle; the lenalidomide is continued for a maximum of 12 cycles, but the tafasitamab is continued as monotherapy until disease progression or intolerance.

Tafasitamab was engineered for enhanced ADCC and direct cell death. Investigators saw encouraging activity in a phase 1 trial as a single agent. Then the rationale for combination with lenalidomide is because of the enhanced ADCC and because of activity seen with rituximab [Rituxan] and lenalidomide across a number of B-cell lymphoma subtypes. It was felt that this might be an interesting synergistic combination, and then [investigators] set out to explore it further in this phase 2 study in relapsed/refractory DLBCL.

Which trial looked at this combination, and what was the design?

The L-MIND study [NCT02399085] was an open-label, multi-center study.3 [Investigators] evaluated patients with relapsed/ refractory DLBCL. Now some important eligibility criteria are worth noting. They restricted eligibility to patients who had had 1 to 3 prior lines of therapy, so this is not a heavily pretreated patient population.

Patients who were ineligible for high-dose chemotherapy or autologous stem cell transplant were evaluated. There are not agreed-upon criteria for whos not a transplant candidate, other than failing to have chemotherapy-sensitive disease. But because this [trial] would enroll patients whod only had 1 prior line of therapy, that opens the discussion to how you would define a nontransplant candidate. This was done in a number of European sites where age alone is a factor, so generally patients over the age of 70 are deemed not appropriate candidates for stem cell transplant; its one of the more common criteria that were applied for defining this patient population.

The study schema outlined the dosing of lenalidomide at 25 mg [daily], which is standard in multiple myeloma studies. Its a bit higher than the standard dosing done in most Hodgkin or non-Hodgkin lymphoma studies and speaks to the evolution of treatment over time, particularly when weve combined [lenalidomide] with other agents. Most of the time were starting at 20 mg, but for the purposes of this study, in the schema it was 25 mg of lenalidomide.

Its also important to note that there was an induction phase with the combination, and particularly during cycle 1, tafasitamab was dosed weekly with an additional loading dose on day 4 of cycle 1 and then continued weekly up to all 3 cycles so 12 weeks of treatment. Beyond cycle 3, it was dosed every other week or every 2 weeks until disease progression or intolerance. The primary end point of the study was objective response rate [ORR] as assessed by independent central review, and then key secondary end points included progression-free survival [PFS], duration of response [DOR], and overall survival [OS], in addition to safety.

There were 81 patients enrolled on the single-arm phase 2 study, and that speaks to the fact that lymphoma is a rare tumor type. The median age was 72, again [considering] that age over 70 was one of the most common criteria utilized to define a nontransplant candidate. About 51% of the patient population had an IPI risk score of 3 or higher, 75% had advanced-stage disease, median number of prior lines of therapy was 2, and primary refractory [disease] comprised only about 19% of the patient population. These patients generally were not primary refractory, though [the trial] did include some. Prior stem cell transplant patients might be a poor transplant candidate because theyve already had transplant; [these patients comprised] about 11% of the patient population.

What were the efficacy data seen in the L-MIND study?

The ORR determined by the independent central review was quite notable. The ORR in patients with relapsed/refractory DLBCL was 60%, and the complete response rate was 43%. Probably even more important is that it appeared to be durable. The median DOR was 21.7 months. It was not reached among those patients who achieved a complete response, which was almost half the study population....DOR for patients who had a partial response [was markedly lower at] only 4.4 months, and 72% of [all] patients had an ongoing response beyond 12 months.

Importantly, there was a PFS in this patient population of 12.1 months, and median OS had not been reached. At 18 months, 64% of the patient population was still alive. I think this is important because if you put this into context, prior to the introduction of CAR T, if we look at the SCHOLAR-1 datawhich were of a retrospective analysis of patients treated at MD Anderson Cancer Center, at Mayo Clinic, and in the Lysa group, which is a large French group the median OS...was 6 months for patients with relapsed/ refractory DLBCL in second line or later.4 Again, this is a marked improvement over that.

The median PFS is also quite notable at 12 months [at 50%] because the median PFS for the CAR T population was only about 6 months. Now this probably reflects a specific patient population in that most of these patients were not as heavily pretreated as the CAR T population. A small percent- age were primary refractory.

Are other studies in the DLBCL setting looking at this regimen?

There were data reported at the 2020 American Society of Clinical Oncology Annual Meeting [from] the RE-MIND study [NCT04150328]....They essentially compared [the L-MIND] results with a synthetic control where they captured retrospective data of single-use lenalidomide in relapsed/refractory DLBCL and then tried to match that in terms of baseline characteristics.5

It looks like [the combination] was at least a significant improvement over lenalidomide monotherapy. Then the question is really: Is it better than the other options currently available in the relapsed DLBCL space? And that hasnt been answered. Its moving into front line. The phase 1b data were reported. Theres a randomized study that is launching, so that will then raise the question of how we sequence treatment in DLBCL.

What was the toxicity profile of tafasitamab and lenalidomide for these patients?

The most common adverse events [AEs] were neutropenia, anemia, and thrombocytopenianot surprising to me because again this is an antibody in combination with lenalidomide.3 Grade 3 or higher neutropenia occurred in 48% of patients and grade 3 or higher thrombocytopenia in 17% of patients. Fortunately, febrile neutropenia was not high. There was 10% with grade 3 and 2% with grade 4. Growth factor use was at the discretion of the treating physician. It was not built into the protocol in terms of prophylactic use.

For the most common AEs that were nonhematologic, [what was noticeable was] the vast majority were grade 1/2, though about 9% of patients had a grade 3 rash, which is not unusual for lenalidomide in lymphoma. One percent had grade 3 diarrhea, and about 5% had hypokalemia. Some of that might be related to diarrhea and some nausea. Cough was about 1% at grade 3 or higher, and bronchitis was 1% at grade 4. Fatigue was another common AE, with 15% at grade 1 or 2.

Serious AEs occurred in 51% of the study population, although 19% were attributed to the study drug; 12% discontinued therapy as a result of toxicity, and then 9% had an AE of special interest. The AEs of special interest included tumor flare in 3 patients, and 1 patient with grade 2 basal cell carcinoma. Grade 3 [allergic dermatitis] occurred in 3 patients. There were 13% who had a treatment-emergent AE that led to death; however, according to the [investigators], none [of the deaths] were thought to be related to study treatment. The severity and incidence of the toxicities after lenalidomide was discontinued decreased, suggesting that a lot of the toxicity was due to the combination and not the CD19 monotherapy.

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L-MIND Trial Results Show CD19 Antibody Is Reasonable in R/R DLBCL - Targeted Oncology

Profile of T Cells, Broadly Neutralizing Antibodies, Anti-Viral Targets: COVID-19 Updates – Bio-IT World

January 29, 2021 I COVID-19 may become seasonal, severe infection associated with myeloid immune cells, potential Achilles heel of coronaviruses identified, melatonin synthesized in lungs could have protective effect, and plitidepsin outperforms remdesivir in preclinical trials. Plus: NSAID use during COVID-19 is time-dependent on its harm or benefit and NAU to test Allarity drug against Coronavirus Variant B117.

Research News

COVID-19 may be seasonal, like the flu, suggests a new paper published in Evolutionary Bioinformatics. Authors of the paper show that COVID-19 cases and mortality rates, among other epidemiological metrics, are significantly correlated with temperature and latitude across 221 countries. They also explain that our own immune systems could be partially responsible for the pattern of seasonality. For example, our immune response to the flu can be influenced by temperature and nutritional status, including vitamin D, a critical nutrient to our immune defenses. The researchers add that it is, however, too soon to say how seasonality and our immune systems interact in the case of COVID-19. DOI:10.1177/1176934321989695

SARS-CoV-2 independently entered Russia at least 67 times, primarily at the end of February and beginning of March 2020, according to a new study published in Nature Communications. Researchers of the study used 211 virus genomes, which were sequenced at Smorodintsev Research Institute of Influenza, and all genomes had been obtained from patients from 25 Russian regions during mid-March to April 2020. They determined that the vast majority of introductions came from European countries, and no cases of introduction from China were registered, which they attribute to the timely closure of borders with the country. Currently, nine local virus lineages are circulating in Russia, which are not present elsewhere in the world. DOI:10.1038/s41467-020-20880-z

Research led at Vanderbilt University Medical Center has discovered a proofreading exoribonuclease, called nsp14-ExoN, which can correct errors in the RNA sequence that occur during replication, when copies of a virus are generated. They believe that this may be the Achilles heel of the coronavirus, a finding that could help close the door on COVID-19 and possibly head off future pandemics. Using cutting-edge technologies and novel bioinformatics approaches, the researchers discovered that this ExoN also regulates the rate of recombination, which is the ability of the coronavirus to shuffle parts of its genome and even pull genetic material from other viral strains while it replicates in order to gain evolutionary advantage. These patterns of recombination are conserved across multiple coronaviruses, including SARS-CoV-2. They believe that the coronavirus ExoN is therefore a conserved, important target for inhibition and attenuation in the ongoing pandemic. This research is published in PLOS Pathogens. DOI:10.1371/journal.ppat.1009226

Also at Vanderbilt University Medical Center (VUMC), researchers have identified genetic factors that increase the risk for developing pneumonia to help identify patients with COVID-19 at greatest risk for this life-threatening complication. The researchers conducted genome-wide association studies (GWAS) of more than 85,000 patients whose genetic information is stored in VUMCs BioVU biobank. They identified nearly 9,000 cases of pneumonia in patients of European ancestry and 1,710 cases in patients of African ancestry. After further analysis, the research team linked the gene that causes cystic fibrosis (CF) and European ancestry and the mutation that causes sickle cell disease (SCD) in patients of African ancestry as the strongest pneumonia associations. After removing patients with CF and SCD, they then pinpointed a pneumonia-associated variation in a gene called R3HCC1L in patients of European ancestry, and one near a gene called UQCRFS1 in patients of African ancestry. They believe these findings could be applied to identifying patients with high risk of severe pneumonia to enable early interventions. They have published this work in the American Journal of Human Genetics. DOI:10.1016/j.ajhg.2020.12.010

Melatonin produced in the lungs acts as a barrier against SARS-CoV-2, blocking the expression of genes that encode proteins in cells serving as viral entry points, finds researchers at the University of So Paulo (USP). The hormone, therefore, prevents infection of these cells by the virus and inhibits the immune response so that the virus remains in the respiratory tract for a few days and then leaves the host, say the researchers. They used RNA sequencing data to quantify the level of expression of 212 COVID-19 signature genes in 288 samples from healthy human lungs. The researchers correlated these gene expression levels with a gene index that estimated the capacity of the lungs to synthesize melatonin (MEL-index). They then were able to determine that when the MEL-index was high, the entry points for the virus in the lungs were closed, and vice-versa. The research team suggests the potential for nasal administration of melatonin to prevent disease from developing in pre-symptomatic COVID-19 patients. This study is published in Melatonin Research. DOI:10.32794/mr11250090

In a new study, published in Cell Reports Medicine, La Jolla Institute for Immunology (LJI) researchers suggest that T cells can mount attacks against many SARS-CoV-2 targets, beyond the key sites on the viruss spike protein. They believe that by attacking the virus from many angles, the body is equipped to potentially recognize different SARS-CoV-2 variants. The researchers examined T cells from 100 people who had recovered from COVID-19 to take a closer look at the genetic sequence of the virus to separate the potential epitopes from the epitopes that these T cells would recognize. Their analysis revealed that not all parts of the virus induce the same strong immune response in everyone, and T cells can recognize dozens of epitopes on SARS-CoV-2 that vary from person to person. They determined that each study participant had the ability to recognize about 17 CD8+ T cell epitopes and 19 CD4+ T cell epitopes. DOI:10.1016/j.xcrm/2021/100202

John Hopkins Medicine researchers, in collaboration with Immunoscape, have published a complete profile of the response of T cells in people who have recovered from SARS-CoV-2 infection. The paper, published in The Journal of Clinical Investigation, better defines which T cells interact with which specific portion of the SARS-CoV-2 virus and how those interactions can provide long-lasting immunity against COVID-19. The researchers collected blood samples from 30 convalescent patients who had recovered from mild cases of COVID-19 and the Immunoscape team, a U.S.-Singapore biotechnology company, used its highly sensitive human leukocyte antigen (HLA)-SARS-CoV-2 tetramers to tag and identify the types of virus-recognizing CD8+ T cells. The researchers found that as levels of neutralizing antibodies increased in the convalescent plasma, so did the number of memory CD8+ T cells that recognized SARS-CoV-2 epitopes. They believe this means lasting protection against reinfection, and this knowledge will guide COVID-19 vaccine design to produce a strong immune response that could provide years of protection. DOI:10.1172/JCI145476

Severe COVID-19 patients have significantly elevated levels of a certain type of immune cell in their blood, call monocytic myeloid-derived suppressor cells (M-MDSC), according to a new study published in the Journal of Clinical Investigation. Karolinska Institutet researchers studied 147 patients with mild to fatal COVID-19 who were sampled repeatedly from blood and respiratory tract. These samples were then compared with patients who had influenza and healthy individuals. They found that the patients with severe COVID-19 had significantly higher levels of M-MDSCs in their blood when compared to milder cases and healthy participants. COVID-19 patients also had fewer T cells in their blood than healthy individuals that showed signs of impaired function. Additionally, their analysis revealed that the levels of M-MDSCs early in the course of infection seemed to reflect subsequent disease severity. DOI:10.1172/JCI44734

Researchers have engineered an antibody that effectively neutralizes SARS-CoV-2 and that also acts against multiple SARS-like viruses. Their antibody, ADG-2, was studied in mice. To engineer this broadly neutralizing antibody (bnAb), the researchers started with antibodies from the memory B cells of a 2003 SARS survivor that cross-neutralized multiple SARS-related viruses with modest potency. They then selectively engineered the binding affinities of several of these bnAbs, creating improvements in their abilities to bind the virus. The researchers then studied the engineered antibodies for SARS-CoV-2 neutralizing activity in mouse cell lines. ADG-2 was particularly effective. It showed broad binding activity to more than a dozen SARS-related coronaviruses. This research is published in Science. DOI:10.1126/science.abf4830

Plitidepsin has shown a potent efficacy against SARS-CoV-2 in preclinical trials, outperforming the antiviral remdesivir. These results, published in Science, show that in studies in human cells, plitidepsin demonstrated potent anti-SARS-CoV-2 activity: 27.5-fold more so than remdesivir as tested in the same cell line. In a model of human lung cells, plitidepsin greatly reduced viral replication. In further experiments involving both plitidepsin and remdesivir in vitro, the researchers suggest that plitidepsin has an additive effect with the approved drug and would be a potential candidate for a combined therapy. Authors of the research article believe that this promising treatment, which has limited clinical approval for the treatment of multiple myeloma, should be strongly considered for expanded clinical trials for the treatment of COVID-19. DOI:10.1126/science.abf4058

Oregon Health & Science University (OHSU) researchers have demonstrated that antibodies generated by the SARS-CoV-2 virus react to other strains of coronavirus and vice-versa. They determined, however, that antibodies generated by the 2003 SARS outbreak had only limited effectiveness in neutralizing SARS-CoV-2. The researchers believe that these findings have implications on both vaccine effectiveness and diagnosis of COVID-19. They believe that more work needs to be done to determine the lasting effectiveness of COVID-19 vaccine, given the speed of mutations. The team believes their study also suggests that efforts to accurately discern a previous COVID-19 infection, by analyzing antibodies in the blood, may be complicated by the presence of antibodies reacting to other strains of coronavirus including the common cold. This study is published in Cell Reports. DOI:10.1016/j.celrep.2021.108737

A new method to mapping viral mutations that escape leading clinical antibodies against COVID-19 has revealed mutations in the SARS-CoV-2 virus that allow it to evade treatments, including a single amino-acid mutation that fully escapes Regenerons antibody cocktail. University of Washington researchers and colleagues developed this scanning method to map how mutations to the receptor-binding domain (RBD) affect its recognition by antibodies. Their maps identified mutations that escape antibody binding, including a single mutation that escapes both antibodies in the Regeneron antibody cocktail. To further investigate, the team examined deep sequencing data from a persistently infected patient who was treated with the antibody cocktail at day 145 after diagnosis with COVID-19, and their analysis identified resistance mutations that arose in the patient. Furthermore, after they examined all human-derived SARS-CoV-2 sequences available as of mid-January 2021, the researchers report a substantial number of RBD mutations that escaped one or more of the antibodies that are in circulation. This paper is published in Science. DOI:10.1126/science.abf9302

Monash University researchers have discovered two new molecules that provide profound protection in experimental models of asthma, as well as protection from acute respiratory distress syndrome (ARDS) that is seen in some patients with severe COVID-19. In their study, originally designed to investigate how the immune system impacts gut bacteria, the researchers found that p-cresol sulfate (PCS), a gut bacteria by-product, led to a striking protection against asthma. They then determined that PCS was produced by enhanced bacterial metabolism of L-tyrosine, a well-known amino acid found in dietary supplements. The researchers saw significant protection against lung inflammation in mice given either L-tyrosine or PCS, as well as protection from ARDS. The researchers now aim to test one of the molecules in a clinical trial in asthmatics this year. These new findings are published in Nature Immunology. DOI:10.1038/s41590-020-00856-3

Non-steroidal anti-inflammatory drugs (NSAIDs) reduced both antibody and inflammatory responses to SARS-CoV-2 infection in mice, a new study finds that is published in the Journal of Virology. The authors of the study highlight that the timing of NSAID use during COVID-19 is important. They explain that NSAIDs anti-inflammatory activity could be detrimental early in SARS-CoV-2 infection because inflammation is usually helpful during this stage. This changes at later stages of COVID-19, particularly if the patient experiences intense inflammation known as cytokine storm. The researchers also note that a reduction in neutralizing antibodies caused by NSAIDs could be benign, or it might hinder the immune systems ability to fight the infection in its early stages. It could also reduce the magnitude or duration of protection from either natural infection or vaccination. DOI:10.1128/JVI.00014-21

Rhesus macaque monkeys infected with SARS-CoV-2 developed protective immune responses that could be reproduced with a vaccine, according to University of California, Davis (UC Davis) researchers. The team infected eight rhesus macaques at the California National Primate Research Center (CNPRC) with SARS-CoV-2 virus isolated from the first human patient treated at UC Davis, and they followed the immune responses in the monkeys over two weeks. The animals showed signs of lasting immunity and, most importantly, structures called germinal centers developed in the lymph nodes near the lungs. These germinal centers contained cells call T follicular helper (Tfh) cells. Germinal centers and Tfh cells are associated with generating plasma cells that remain in the body for many years to produce antibodies against pathogens the immune system has seen before, the researchers explain. They believe these results suggest that vaccines that induce this response will support immunity against COVID-19. This study is published in Nature Communications. DOI:10.1038/s41467-020-20642-x

Patients who have recovered from severe COVID-19 infection could be left with more protective T cells needed to fight reinfection, finds a team of researchers led at La Jolla Institute for Immunology (LJI). For their study, published in Science Immunology, the team analyzed CD8+ T cells from 39 COVID-19 patients and 10 individuals who had never been exposed to the virus. Of the COVID-19 patients, 17 had a mild case that did not require hospitalization, 13 had been hospitalized, and nine needed intensive care support. Surprisingly, the researchers saw weaker CD8+ T cell responses in patients with milder COVID-19 cases and saw the strongest CD8+ T cell responses in the patients who required hospitalization or intensive care. The team now hopes to study how T cells in tissues hit hardest by SARS-CoV-2, such as the lungs, react to the virus. They explain the importance of this as the memory T cells that provide long-term immunity need to live in the tissues. DOI:10.11260/sciimmunol.abe4782

In a new study published in Science Signaling, scientists discovered that SARS-CoV-2 may enter and replicate in human cells by exploiting newly identified sequences within cell receptors. They also suggest that these sequences could potentially serve as targets for new therapies against COVID-19. After analyzing the Eukaryotic Linear Motif database, the team of scientists discovered that ACE2 and various receptors contained several short linear motifs (SLiMs), or small amino acid sequences, that they predict plays a role in endocytosis and autophagy, or the entering of human cells and cellular housekeeping. The team determined that two SLiMs in ACE2 bound to endocytosis-related proteins, and one SLiM in the integrin beta-3 (3) bound to two proteins involved in autophagy. They believe that their prediction models could help identify similar SLiMs that assist with the replication of not only SARS-CoV-2, but other viruses that cause disease. DOI:10.1126/scisignal.abd0334

Ohio University researchers have published the first structural biology analysis of a section of the COVID-19 viral RNA called the stem-loop II motif, which they believe could be a potential target for anti-viral drugs to combat the virus. The research team identified this non-coding section of the RNA that is likely key to SARS-CoV-2 replication. Interestingly, they determined that the structural flexibility of this noncoding RNA motif differs by only a single nucleotide when compared to that in the early 2000s SARS-CoV outbreak, and the team also identified FDA-approved drugs that bind to the RNA motif and alter its flexibility. Since the structure and flexibility of noncoding RNA affects its function, the researchers suggest that it may be possible to develop antiviral drugs that specifically target this RNA motif to battle the virus. This research is published in Biochemical and Biophysical Research Communications. DOI:10.1016/j.bbrc.2021.01.013

Innate immunity may play a larger role in controlling SARS-CoV-2 viral load than adaptive immunity, according to a new study published in ACS Pharmacology & Translational Science. Researchers of the study developed a mathematical model that predicts viral load over time in organs that express the ACE2 receptor, which allows SARS-CoV-2 entry into human cells. They then used this model to simulate different conditions to determine this key role for innate immunity in controlling viral load. The researchers suggest the importance of starting antiviral or interferon therapy as soon as possible after the onset of COVID-19 symptoms. DOI:10.1021/acsptsci.0c00183

Industry News

Allarity Therapeutics in Denmark plans to further test the antiviral activity of stenoparib, its Poly ADP-Ribose Polymerase (PARP) inhibitor, against the B.1.1.7 variant of SARS-CoV-2. Stenoparib is a small molecule, targeting inhibitor of PARP, a key DNA damage repair enzyme active in tumors, which was originally developed by the pharmaceutical company Eisai. Results of previous pre-clinical studies for SARS-CoV-2 demonstrated that stenoparib inhibits SARS-CoV-2 as a single agent, and stenoparib in combination with remdesivir was active in inhibiting coronavirus in vitro. Allarity will now work with scientists at Northern Arizona Universitys Pathogen and Microbiome Institute (PMI) to test the similar ability of stenoparib to block the infection and replication of Coronavirus Variant B117. Press Release

Clear Labs announced the availability of the Clear Dx Whole Genome Sequencing (WGS), the first automated WGS solution that determines the complete RNA sequence of the SARS-CoV-2 genome in less than 24-hours with only minutes of hands-on time. The Clear Dx platform is powered by next generation sequencing (NGS), robotics and cloud-based analytics, and as a result, their WGS can more easily determine the nature of virus transmission by differentiating virus strains and monitoring mutations that lead to variants. In addition to WGS, the platform also features the Clear Dx SARS-CoV-2 Diagnostic Assay, which has received EUA, that allows labs to perform diagnostic screening and genomic surveillance simultaneously. Press Release

Originally posted here:
Profile of T Cells, Broadly Neutralizing Antibodies, Anti-Viral Targets: COVID-19 Updates - Bio-IT World

HealthLynked’s The Future of Healthcare Summit Brings Healthcare Experts and Technology Innovators from Around the World to Naples, Florida – WFMZ…

NAPLES, Fla., Jan. 29, 2021 /PRNewswire/ -- HealthLynked Corp. (OTCQB: HLYK), a global healthcare network focused on care management of its members and a provider of healthcare technologies that connects doctors, patients and medical data, today announced that it will host the first annual Future of Healthcare Summit that will convene the top leaders in the $5 trillion healthcare industry at Arthrex's corporate campus that features a 30,000-SF fitness center and 200,000-SF Innovation Hotelin Naples, Florida from March 15-17th.

The summit is an invitation only event for healthcare providers. The event features world-class CEOs, innovators and industry experts who will come together to present a series of lectures on a wide range of healthcare topics and explore what can be done to both catalyze innovation and improve healthcare.

Dr. Michael Dent, HealthLynked's CEO has developed an agenda that focuses on genomics, functional medicine, anti-aging, stem cells, artificial intelligence, diagnostic advances, telemedicine, intellectual property, tissue regeneration, cancer treatments and medical devices.

The summit venue will be open to the public on Tuesday, March 16th, where a series of Ted Talk style lectures will cover the latest healthcare trends, technology, and treatments. This open forum will allow the public the opportunity to learn about the latest advances in healthcare and how they are being applied today and what to expect in future.

HealthLynked has confirmed a world-class slate of speakers including:

Attendees of the summit include doctors, hospital executives, academics, researchers, venture capitalists, pharmaceutical firms, policymakers, philanthropists, and future leaders. The seating for the summit will follow COVID-19 spacing guidelines and Arthrex campus facilities are equipped with Synexisair purification systems that kill airborne COVID-19 to add an additional layer of safety for the attendees.

For a look at the full agenda, as well as speaker bios, please visit the 2021 Healthcare Summitwebsite. For additional sponsorship opportunities please email summitsponsors@healthlynked.com.

Dr. Michael Dent, Chief Executive Officer of HealthLynked stated, "The next 15 years will bring a wave of medical breakthroughs in new therapies, medicines, medical devices and data analytics. We have achieved new milestones in gene editing, cancer immunotherapy and artificial intelligence. All of these advances will allow us to more effectively treat disease and find cures that have eluded us. Our goal is to provide an informative series of lectures to show the future of healthcare and create an environment for innovate thought leaders to turn ideas into actionable solutions."

About HealthLynked Corp.

HealthLynked Corp. provides a solution for both patient members and providers to improve healthcare through the efficient exchange of medical information. The HealthLynked Network is a cloud-based platform that allows members to connect with their healthcare providers and take more control of their healthcare. Members enter their medical information, including medications, allergies, past surgeries and personal health records, in one convenient online and secure location, free of charge. Participating healthcare providers can connect with their current and future patients through the system. Benefits to in-network providers include the ability to utilize the HealthLynked patent pending patient access hub "PAH" for patient analytics. Other benefits for preferred providers include HLYK marketing tools to connect with their active and inactive patients to improve patient retention, access more accurate and current patient information, provide more efficient online scheduling and to fill last minute cancelations using the Company's "real time appointment scheduling" all within its mobile application. Preferred providers pay a monthly fee to access these HealthLynked services. For additional information about HealthLynked Corp., please visit http://www.healthlynked.com and connect with HealthLynked on Twitter, Facebook, and LinkedIn.

Forward Looking Statements

Forward-Looking Statements in this press release, which are not historical facts, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Our actual results, including as a result of any acquisitions, performance or achievements may differ materially from those expressed or implied by these forward-looking statements. In some cases, you can identify forward-looking statements by the use of words such as "may," "could," "expect," "intend," "plan," "seek," "anticipate," "believe," "estimate," "predict," "potential," "continue," "likely," "will," "would" and variations of these terms and similar expressions, or the negative of these terms or similar expressions. Such forward-looking statements are necessarily based upon estimates and assumptions that, while considered reasonable by our management, and us are inherently uncertain. We caution you not to place undue reliance on any forward-looking statements, which are made as of the date of this press release. We undertake no obligation to update publicly any of these forward-looking statements to reflect actual results, new information or future events, changes in assumptions or changes in other factors affecting forward looking statements, except to the extent required by applicable laws. If we update one or more forward-looking statements, no inference should be drawn that we will make additional updates with respect to those or other forward-looking statements. Certain risks and uncertainties applicable to our operations and us are described in the "Risk Factors" section of our most recent Annual Report on Form 10-K and in other filings we have made with the U.S. Securities and Exchange Commission. These reports are publicly available at http://www.sec.gov.

Contacts:

George O'Leary

Chief Financial Officer

goleary@healthlynked.com

(800) 928-7144, ext. 103

Investor Relations Contacts:

Jim Hock

Hanover International Inc.

jh@hanoverintlinc.com

760-564-7400

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SOURCE HealthLynked Corp.

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HealthLynked's The Future of Healthcare Summit Brings Healthcare Experts and Technology Innovators from Around the World to Naples, Florida - WFMZ...