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Archive for the ‘Biomarkers: Inflammation’ Category

Key Immune System Genes Identified to Explain High COVID Deaths and Spread in Northern Italy Versus Fewer Cases and Deaths in the South

Posted in Biomarkers: Inflammation, Coronavirus Gene Expression, COVID-19, COVID-19: Pandemic Surgery Guidance, Economic Impact of Coronavirus Pandemic, number of asymptomatic infections, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV on July 29, 2020| Leave a Comment »

Key Immune System Genes Identified to Explain High COVID Deaths and Spread in Northern Italy Versus Fewer Cases and Deaths in the South

Reporter: Stephen J. Williams, PhD

 

via Key Immune System Genes Identified to Explain High COVID Deaths and Spread in Northern Italy Versus Fewer Cases and Deaths in the South

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Inflammation BioMarker C-Reactive Protein Guides Use of Systemic Glucocorticoids in Patients with COVID-19: The Effects on Mortality or Use of Mechanical Ventilation – (CRP) ≥20 mg/dL was associated with significantly reduced risk of Mortality or Mechanical Ventilation Efficacy

Posted in Biomarkers: Inflammation, COVID-19, Population Health Management, Population Health Management, Genetics & Pharmaceutical, SARS-CoV-2, Treatment Protocols for COVID-19, Virus Infective Acute Respiratory Syndrome: SARS-CoV on July 25, 2020| Leave a Comment »

Inflammation BioMarker C-Reactive Protein Guides Use of Systemic Glucocorticoids in Patients with COVID-19: The Effects on Mortality or Use of Mechanical Ventilation – (CRP) ≥20 mg/dL was associated with significantly reduced risk of Mortality or Mechanical Ventilation Efficacy

Reporter: Aviva Lev-Ari, PhD, RN

 

In patients with high levels of inflammation — at least 20 mg/dL — steroid treatment was associated with a 77% reduction in the risk of needing mechanical ventilation or dying (odds ratio [OR], 0.23).

Importantly, treating with steroids when CRP levels were less than 10 mg/dL was associated with an almost threefold increased risk of going on mechanical ventilation or dying (OR, 2.64).

“The laboratory test could potentially be very helpful,” Keller told Medscape Medical News.

https://www.medscape.com/viewarticle/934571

Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19

J Hosp Med. Published Online First July 22, 2020. DOI: 10.12788/jhm.3497 | DOI 10.12788/jhm.3497
By: Marla J Keller, MD , Elizabeth A Kitsis, MD, MBE, Shitij Arora, MD, Jen-Ting Chen, MD, MS, Shivani Agarwal, MD, MPH, Michael J Ross, MD, Yaron Tomer, MD, William Southern, MD, MS
Article has an altmetric score of 299

Abstract

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.

Glucocorticoids are useful as adjunctive treatment for some infections with inflammatory responses, but their efficacy in COVID-19 is unclear. Prior experience with influenza and other coronaviruses may be relevant. A recent meta-analysis of influenza pneumonia showed increased mortality and a higher rate of secondary infections in patients who were administered glucocorticoids.3 For Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza, some studies have demonstrated an association between glucocorticoid use and delayed viral clearance.4-7 However, a recent retrospective series of patients with COVID-19 and ARDS demonstrated a decrease in mortality with glucocorticoid use.8 Glucocorticoids are easily obtained and familiar to providers caring for COVID-19 patients. Hence their empiric use is widespread.8,9

The primary goal of this study was to determine whether early glucocorticoid treatment is associated with reduced mortality or need for MV in COVID-19 patients.

DISCUSSION

The results of this study indicate that early treatment with glucocorticoids is not associated with mortality or need for MV in unselected patients with COVID-19. Subgroup analyses suggest that glucocorticoid-treated patients with markedly elevated CRP may benefit from glucocorticoid treatment, whereas those patients with lower CRP may be harmed. Our findings were consistent after adjustment for clinical characteristics. The public health implications of these findings are hard to overestimate. Given the global growth of the pandemic and that glucocorticoids are widely available and inexpensive, glucocorticoid therapy may save many thousands of lives. Equally important because we have been able to identify a group that may be harmed, some patients may be saved because glucocorticoids will not be given.

Our study reaffirms the finding of the as yet unpublished Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial that there is a subset of patients with COVID-19 who benefit from treatment with glucocorticoids.10 Our study extends the findings of the RECOVERY trial in two important ways. First, in addition to finding some patients who may benefit, we also have identified patient groups that may experience harm from treatment with glucocorticoids. This finding suggests choosing the right patients for glucocorticoid treatment is critical to maximize the likelihood of benefit and minimize the risk of harm. Second, we have identified patient groups who are likely to benefit (or be harmed) on the basis of a widely available lab test (CRP).

Our results are also consistent with previous studies of patients with SARS-CoV and MERS-CoV, in which no associations between glucocorticoid treatment and mortality were found.7 However, the results of studies examining the effect of glucocorticoids in patients with COVID-19 are less consistent.8,11,12

Few of the previous studies examined the effects of glucocorticoids in subgroups of patients. In our study, the improved outcomes associated with glucocorticoid use in patients with elevated CRPs is intriguing and may be clinically important. Proinflammatory cytokines, especially interleukin-6, acutely increase CRP levels. Cytokine storm syndrome (CSS) is a hyperinflammatory condition that occurs in a subset of COVID-19 patients, often resulting in multiorgan dysfunction.13 CRP is markedly elevated in CSS,14 and improved outcomes with glucocorticoid therapy in this subgroup may indicate benefit in this inflammatory phenotype. Patients with lower CRP are less likely to have CSS and may experience more harm than benefit associated with glucocorticoid treatment.

Several limitations are inherent to this study. Since it was done at a single center, the results may not be generalizable. As a retrospective analysis, it is subject to confounding and bias. In addition, because patients were included only if they had reached the outcome of death/MV or hospital discharge, the sample size was truncated. We believe glucocorticoid use in hospitalized patients excluded from the study reflects increased use with time because of a growing belief in their effectiveness.

Preliminary analysis from the RECOVERY study showed a reduced rate of mortality in patients randomized to dexamethasone, compared with those who received standard of care.10 These results led to the National Institutes for Health COVID-19 Treatment Guidelines Panel recommendation for dexamethasone treatment in patients with COVID-19 who require supplemental oxygen or MV.15 Our findings suggest a role for CRP to identify patients who may benefit from glucocorticoid therapy, as well as those in whom it may be harmful. Additional studies to further elucidate the role of CRP in guiding glucocorticoid therapy and to predict clinical response are needed.

SOURCE

 

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National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Posted in Biomarkers: Inflammation, Coronavirus Gene Expression, Drug Development Process, Economic Impact of Coronavirus Pandemic, FDA, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Inflammatory Pathophysiology, number of asymptomatic infections, Pharmaceutical Discovery, Population genetics, SARS-CoV-2, Systemic Inflammatory Response Related Disorders, Treatment Protocols for COVID-19, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , , , , , on July 19, 2020| Leave a Comment »

National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

Below I am giving a link to an important interview by NPR’s Judy Woodruff with Dr. Anthony Fauci on his thoughts regarding the recent spikes in cases, the potential for a COVID-19 vaccine by next year, and promising therapeutics in the pipeline.  The interview link is given below however I will summarize a few of the highlights of the interview.

 

Some notes on the interview

Judy Woodruff began her report with some up to date news regarding the recent spike and that Miami Florida has just ordered the additional use of facemasks.  She asked Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAD), about if the measures currently in use are enough to bring this spike down.  Dr. Fauci said that we need to reboot our efforts, mainly because people are not doing three things which could have prevented this spike mainly

  1. universal wearing of masks
  2. distancing properly from each other
  3. close the bars and pubs (see Wisconsin bars packed after ruling)

It hasn’t been a uniform personal effort

Dr. Fauci on testing

We have to use the tests we have out there efficiently and effectively And we have to get them out to the right people who can do the proper identification, isolation, and do proper contract tracing and need to test more widely in a surveillance way to get a feel of the extent and penetrance of this community spread.  there needs to be support and money for these testing labs

We have a problem and we need to admit and own it but we need to do the things we know are effective to turn this thing around.

On Vaccines

“May be later this year”

His response to Merck’s CEO Ken Frazer who said officials are giving false hop if they say ‘end of year’ but Dr. Fauci disagrees.  He says a year end goal is not outlandish.

What we have been doing is putting certain things in line with each other in an unprecedented way.

Dr. Fauci went on to say that, in the past yes, it took a long time, even years to develop a vaccine but now they have been able to go from sequence of virus to a vaccine development program in days, which is unheard of.  Sixty two days later we have gone into phase 1 trials. the speed at which this is occurring is so much faster.  He says that generally it would take a couple of years to get a neutralizing antibody but we are already there.  Another candidate will be undergoing phase 3 trials by end of this month (July 2020).

He is “cautiously optimistic” that we will have one or more vaccines to give to patients by end of year because given the amount of cases it will be able to get a handle on safety and efficacy by late fall.

Now he says the game changer is that the government is working with companies to ramp up the production of doses of the candidate vaccines so when we find which one works we will have ample doses on hand.  He is worried about the anti vaccine movement derailing vaccine testing and vaccinations but says if we keep on informing the public we can combat this.

Going back to school

Dr. Fauci is concerned for the safety of the vulnerable in schools, including students and staff.  He wants the US to get down to a reasonable baseline of cases but in the US that baseline after the first wave was still significantly higher than in most countries, where the baseline was more like tens of cases not hundreds of cases.

For more information on COVID-19 Please go to our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

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From Cell Press:  New Insights on the D614G Strain of COVID: Will a New Mutated Strain Delay Vaccine Development?

Posted in BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biomarkers: Inflammation, Biotechnology, coronavirus, Coronavirus Gene Expression, COVID-19, COVID-19: Pandemic Surgery Guidance, Drug Development Process, Economic Impact of Coronavirus Pandemic, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Infectious Disease & New Antibiotic Targets, number of asymptomatic infections, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical R&D Investment, Population Health Management, Nutrition and Phytochemistry, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Vaccinology, Viral diseases, Virology - Vector-borne DIsease, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , on July 3, 2020| Leave a Comment »

From Cell Press:  New Insights on the D614G Strain of COVID: Will a New Mutated Strain Delay Vaccine Development?

Reporter: Stephen J. Williams, PhD

Two recent articles in Cell Press, both peer reviewed, discuss the emergence and potential dominance of a new mutated strain of COVID-19, in which the spike protein harbors a D614G mutation.

In the first article “Making Sense of Mutation: What D614G means for the COVID-19 pandemic Remains Unclear”[1] , authors Drs. Nathan Grubaugh, William Hanage, and Angela Rasmussen discuss the recent findings by Korber et al. 2020 [2] which describe the potential increases in infectivity and mortality of this new mutant compared to the parent strain of SARS-CoV2.  For completeness sake I will post this article as to not defer from their interpretations of this important paper by Korber and to offer some counter opinion to some articles which have surfaced this morning in the news.

Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear

 

Nathan D. Grubaugh1 *, William P. Hanage2 *, Angela L. Rasmussen3 * 1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA 2Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA 3Center for Infection and Immunity, Columbia Mailman School of Public Health, New York, NY 10032, USA Correspondence: grubaughlab@gmail.com

 

Abstract: Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

Introduction: Following the emergence of SARS-CoV-2 in China in late 2019, and the rapid expansion of the COVID19 pandemic in 2020, questions about viral evolution have come tumbling after. Did SARS-CoV-2 evolve to become better adapted to humans? More infectious or transmissible? More deadly? Virus mutations can rise in frequency due to natural selection, random genetic drift, or features of recent epidemiology. As these forces can work in tandem, it’s often hard to differentiate when a virus mutation becomes common through fitness or by chance. It is even harder to determine if a single mutation will change the outcome of an infection, or a pandemic. The new study by Korber et al. (2020) sits at the heart of this debate. They present compelling data that an amino acid change in the virus’ spike protein, D614G, emerged early during the pandemic, and viruses containing G614 are now dominant in many places around the world. The crucial questions are whether this is the result of natural selection, and what it means for the COVID-19 pandemic. For viruses like SARS-CoV-2 transmission really is everything – if they don’t get into another host their lineage ends. Korber et al. (2020) hypothesized that the rapid spread of G614 was because it is more infectious than D614. In support of their hypothesis, the authors provided evidence that clinical samples from G614 infections have a higher levels of viral RNA, and produced higher titers in pseudoviruses from in vitro experiments; results that now seem to be corroborated by others [e.g. (Hu et al., 2020; Wagner et al., 2020)]. Still, these data do not prove that G614 is more infectious or transmissible than viruses containing D614. And because of that, many questions remain on the potential impacts, if any, that D614G has on the COVID-19 pandemic.

The authors note that this new G614 variant has become the predominant form over the whole world however in China the predominant form is still the D614 form.  As they state

“over the period that G614 became the global majority variant, the number of introductions from China where D614 was still dominant were declining, while those from Europe climbed. This alone might explain the apparent success of G614.”

Grubaugh et al. feel there is not enough evidence that infection with this new variant will lead to higher mortality.  Both Korber et al. and the Seattle study (Wagner et al) did not find that the higher viral load of this variant led to a difference in hospitalizations so apparently each variant might be equally as morbid.

In addition, Grubaugh et al. believe this variant would not have much affect on vaccine development as, even though the mutation lies within the spike protein, D614G is not in the receptor binding domain of the spike protein.  Korber suggest that there may be changes in glycosylation however these experiments will need to be performed.  In addition, antibodies from either D614 or G614 variant infected patients could cross neutralize.

 

Conclusions: While there has already been much breathless commentary on what this mutation means for the COVID19 pandemic, the global expansion of G614 whether through natural selection or chance means that this variant now is the pandemic. As a result its properties matter. It is clear from the in vitro and clinical data that G614 has a distinct phenotype, but whether this is the result of bonafide adaptation to human ACE2, whether it increases transmissibility, or will have a notable effect, is not clear. The work by Korber et al. (2020) provides an early base for more extensive epidemiological, in vivo experimental, and diverse clinical investigations to fill in the many critical gaps in how D614G impacts the pandemic.

The link to the Korber Cell paper is here: https://www.cell.com/cell/fulltext/S0092-8674(20)30820-5

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

DOI: https://doi.org/10.1016/j.cell.2020.06.043

Keypoints

  • The consistent increase of G614 at regional levels may indicate a fitness advantage

 

  • G614 is associated with lower RT PCR Ct’s, suggestive of higher viral loads in patients

 

  • The G614 variant grows to higher titers as pseudotyped virions

Summary

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

 

References

  1. Grubaugh, N.D., Hanage, W.P., Rasmussen, A.L., Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear, Cell (2020), doi: https:// doi.org/10.1016/j.cell.2020.06.040.
  2. Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E.E., Bhattacharya, T., Foley, B., et al. (2020). Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182.
  3. Endo, A., Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott, S., Kucharski, A.J., and Funk, S. (2020). Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China. Wellcome Open Res 5, 67.
  4. Hu, J., He, C.-L., Gao, Q.-Z., Zhang, G.-J., Cao, X.-X., Long, Q.-X., Deng, H.-J., Huang, L.-Y., Chen, J., Wang, K., et al. (2020). The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. bioRxiv 2020.06.20.161323.
  5. Wagner, C., Roychoudhury, P., Hadfield, J., Hodcroft, E.B., Lee, J., Moncla, L.H., Müller, N.F., Behrens, C., Huang, M.-L., Mathias, P., et al. (2020). Comparing viral load and clinical outcomes in Washington State across D614G mutation in spike protein of SARS-CoV-2. Https://github.com/blab/ncov-D614G.

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A Series of Recently Published Papers Report the Development of SARS-CoV2 Neutralizing Antibodies and Passive Immunity toward COVID19

Posted in Biomarkers: Inflammation, Coronavirus Gene Expression, COVID-19, COVID-19 effects on Human Heart, COVID-19: Pandemic Surgery Guidance, Economic Impact of Coronavirus Pandemic, Human Antibody Response, Immune Modulatory, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Immunology, Infectious Disease & New Antibiotic Targets, number of asymptomatic infections, Population Health Management, Genetics & Pharmaceutical, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, SARS-COV2 Hijacking the Complement and Coagulation Systems, Serology tests for coronavirus antibodies, Synthetic Immunology: Hacking Immune Cells, Treatment Protocols for COVID-19, Vaccinology, Viral diseases, Virology - Vector-borne DIsease, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , , on May 19, 2020| Leave a Comment »

A Series of Recently Published Papers Report the Development of SARS-CoV2 Neutralizing Antibodies and Passive Immunity toward COVID19

Curator: Stephen J. Williams, Ph.D.

 

Passive Immunity and Treatment of Infectious Diseases

The ability of one person to pass on immunity to another person (passive immunity) is one of the chief methods we develop immunity to many antigens.  For instance, maternal antibodies are passed to the offspring in the neonatal setting as well as in a mother’s milk during breast feeding.  In the clinical setting this is achieved by transferring antibodies from one patient who has been exposed to an antigen (like a virus) to the another individual.   However, the process of purifying the most efficacious antibody as well as its mass production is limiting due to its complexity and cost and can be prohibitively long delay during a pandemic outbreak, when therapies are few and needed immediately.  Regardless, the benefits of developing neutralizing antibodies to confer passive immunity versus development of a vaccine are evident, as the former takes considerable less time than development of a safe and effective vaccine.  For a good review on the development and use of neutralizing antibodies and the use of passive immunity to treat infectious diseases please read the following review:

Margaret A. Keller1,* and E. Richard Stiehm. Passive Immunity in Prevention and Treatment of Infectious Diseases. Clin Microbiol Rev. 2000 Oct; 13(4): 602–614. doi: 10.1128/cmr.13.4.602-614.2000

ABSTRACT

Antibodies have been used for over a century in the prevention and treatment of infectious disease. They are used most commonly for the prevention of measles, hepatitis A, hepatitis B, tetanus, varicella, rabies, and vaccinia. Although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism. High-dose intravenous immunoglobulin can be used to treat certain viral infections in immunocompromised patients (e.g., cytomegalovirus, parvovirus B19, and enterovirus infections). Antibodies may also be of value in toxic shock syndrome, Ebola virus, and refractory staphylococcal infections. Palivizumab, the first monoclonal antibody licensed (in 1998) for an infectious disease, can prevent respiratory syncytial virus infection in high-risk infants. The development and use of additional monoclonal antibodies to key epitopes of microbial pathogens may further define protective humoral responses and lead to new approaches for the prevention and treatment of infectious diseases.

TABLE 1

Summary of the efficacy of antibody in the prevention and treatment of infectious diseases

Infection
Bacterial infections
 Respiratory infections (streptococcus, Streptococcus pneumoniae, Neisseria meningitis, Haemophilus influenzae)
 Diphtheria
 Pertussis
 Tetanus
 Other clostridial infections
  C. botulinum
  C. difficile
 Staphylococcal infections
  Toxic shock syndrome
  Antibiotic resistance
  S. epidermidis in newborns
 Invasive streptococcal disease (toxic shock syndrome)
 High-risk newborns
 Shock, intensive care, and trauma
 Pseudomonas infection
  Cystic Fibrosis
  Burns
Viral diseases
 Hepatitis A
 Hepatitis B
 Hepatitis C
 HIV infection
 RSV infection
 Herpesvirus infections
  CMV
  EBV
  HSV
  VZV
 Parvovirus infection
 Enterovirus infection
  In newborns
 Ebola
 Rabies
 Measles
 Rubella
 Mumps
 Tick-borne encephalitis
 Vaccinia

Go to:

A Great Explanation of Active versus Passive Immunity by Dr. John Campbell, one of the pioneers in the field of immunology:Antibodies have been used for over a century in the prevention and treatment of infectious disease. They are used most commonly for the prevention of measles, hepatitis A, hepatitis B, tetanus, varicella, rabies, and vaccinia. Although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism. High-dose intravenous immunoglobulin can be used to treat certain viral infections in immunocompromised patients (e.g., cytomegalovirus, parvovirus B19, and enterovirus infections). Antibodies may also be of value in toxic shock syndrome, Ebola virus, and refractory staphylococcal infections. Palivizumab, the first monoclonal antibody licensed (in 1998) for an infectious disease, can prevent respiratory syncytial virus infection in high-risk infants. The development and use of additional monoclonal antibodies to key epitopes of microbial pathogens may further define protective humoral responses and lead to new approaches for the prevention and treatment of infectious diseases.

 

However, developing successful neutralizing antibodies can still be difficult but with the latest monoclonal antibody technology, as highlighted by the following papers, this process has made much more efficient.  In addition, it is not feasable to isolate antibodies from the plasma of covalescent patients in a scale that is needed for a worldwide outbreak.

A good explanation of the need can be found is Dr. Irina Robu’s post Race to develop antibody drugs for COVID-19 where:

When fighting off foreign invaders, our bodies make antibodies precisely produced for the task. The reason vaccines offer such long-lasting protection is they train the immune system to identify a pathogen, so immune cells remember and are ready to attack the virus when it appears. Monoclonal antibodies for coronavirus would take the place of the ones our bodies might produce to fight the disease. The manufactured antibodies would be infused into the body to either tamp down an existing infection, or to protect someone who has been exposed to the virus. However, these drugs are synthetic versions of the convalescent plasma treatments that rely on antibodies from people who have recovered from infection. But the engineered versions are easier to scale because they’re manufactured in rats, rather than from plasma donors.

The following papers represent the latest published work on development of therapeutic and prophylactic neutralizing antibodies to the coronavirus SARS-CoV2

1.  Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.

Pinto, D., Park, Y., Beltramello, M. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature (2020).                                                                            https://doi.org/10.1038/s41586-020-2349-y

Abstract

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

 

2.  Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells

Yunlong Cao et al.  Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell (2020).

https://doi.org/10.1016/j.cell.2020.05.025

Summary

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 ng/mL and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8Å Cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody’s epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2 neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B-cell sequencing in response to pandemic infectious diseases.

3. A human monoclonal antibody blocking SARS-CoV-2 infection

Wang, C., Li, W., Drabek, D. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 11, 2251 (2020). https://doi.org/10.1038/s41467-020-16256-y

Abstract

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.

Extra References on Development of Neutralizing antibodies for COVID19 {Sars-CoV2} published this year (2020)  [1-4]

  1. Fan P, Chi X, Liu G, Zhang G, Chen Z, Liu Y, Fang T, Li J, Banadyga L, He S et al: Potent neutralizing monoclonal antibodies against Ebola virus isolated from vaccinated donors. mAbs 2020, 12(1):1742457.
  2. Dussupt V, Sankhala RS, Gromowski GD, Donofrio G, De La Barrera RA, Larocca RA, Zaky W, Mendez-Rivera L, Choe M, Davidson E et al: Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. Nature medicine 2020, 26(2):228-235.
  3. Young CL, Lyons AC, Hsu WW, Vanlandingham DL, Park SL, Bilyeu AN, Ayers VB, Hettenbach SM, Zelenka AM, Cool KR et al: Protection of swine by potent neutralizing anti-Japanese encephalitis virus monoclonal antibodies derived from vaccination. Antiviral research 2020, 174:104675.
  4. Sautto GA, Kirchenbaum GA, Abreu RB, Ecker JW, Pierce SR, Kleanthous H, Ross TM: A Computationally Optimized Broadly Reactive Antigen Subtype-Specific Influenza Vaccine Strategy Elicits Unique Potent Broadly Neutralizing Antibodies against Hemagglutinin. J Immunol 2020, 204(2):375-385.

 

For More Articles on COVID-19 Please see Our Coronavirus Portal on this Open Access Scientific Journal at:

https://pharmaceuticalintelligence.com/coronavirus-portal/

and the following Articles on  Immunity at

Race to develop antibody drugs for COVID-19
Bispecific and Trispecific Engagers: NK-T Cells and Cancer Therapy
Issues Need to be Resolved With ImmunoModulatory Therapies: NK cells, mAbs, and adoptive T cells
Antibody-bound Viral Antigens

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Crowdsourcing Difficult-to-Collect Epidemiological Data in Pandemics: Lessons from Ebola to the current COVID-19 Pandemic

Posted in Biomarkers: Inflammation, coronavirus, Coronavirus Gene Expression, COVID-19, Curation, Curation methodology, Economic Impact of Coronavirus Pandemic, Evidence-based decision-making, Evolution of Biology Through Culture, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), number of asymptomatic infections, Population Health Management, Population Health Management, Genetics & Pharmaceutical, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, SARS-COV2 Hijacking the Complement and Coagulation Systems, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , , on May 15, 2020| Leave a Comment »

Crowdsourcing Difficult-to-Collect Epidemiological Data in Pandemics: Lessons from Ebola to the current COVID-19 Pandemic

 

Curator: Stephen J. Williams, Ph.D.

 

At the onset of the COVID-19 pandemic, epidemiological data from the origin of the Sars-Cov2 outbreak, notably from the Wuhan region in China, was sparse.  In fact, official individual patient data rarely become available early on in an outbreak, when that data is needed most. Epidemiological data was just emerging from China as countries like Italy, Spain, and the United States started to experience a rapid emergence of the outbreak in their respective countries.  China, made of 31 geographical provinces, is a vast and complex country, with both large urban and rural areas.

 

 

 

As a result of this geographical diversity and differences in healthcare coverage across the country, epidemiological data can be challenging.  For instance, cancer incidence data for regions and whole country is difficult to calculate as there are not many regional cancer data collection efforts, contrasted with the cancer statistics collected in the United States, which is meticulously collected by cancer registries in each region, state and municipality.  Therefore, countries like China must depend on hospital record data and autopsy reports in order to back-extrapolate cancer incidence data.  This is the case in some developed countries like Italy where cancer registry is administered by a local government and may not be as extensive (for example in the Napoli region of Italy).

 

 

 

 

 

 

Population density China by province. Source https://www.unicef.cn/en/figure-13-population-density-province-2017

 

 

 

Epidemiologists, in areas in which data collection may be challenging, are relying on alternate means of data collection such as using devices connected to the internet-of-things such as mobile devices, or in some cases, social media is becoming useful to obtain health related data.  Such as effort to acquire pharmacovigilance data, patient engagement, and oral chemotherapeutic adherence using the social media site Twitter has been discussed in earlier posts: (see below)

Twitter is Becoming a Powerful Tool in Science and Medicine at https://pharmaceuticalintelligence.com/2014/11/06/twitter-is-becoming-a-powerful-tool-in-science-and-medicine/

 

 

 

 

 

Now epidemiologists are finding crowd-sourced data from social media and social networks becoming useful in collecting COVID-19 related data in those countries where health data collection efforts may be sub-optimal.  In a recent paper in The Lancet Digital Health [1], authors Kaiyuan Sun, Jenny Chen, and Cecile Viboud present data from the COVID-19 outbreak in China using information collected over social network sites as well as public news outlets and find strong correlations with later-released government statistics, showing the usefulness in such social and crowd-sourcing strategies to collect pertinent time-sensitive data.  In particular, the authors aim was to investigate this strategy of data collection to reduce the time delays between infection and detection, isolation and reporting of cases.

The paper is summarized below:

Kaiyuan Sun, PhD Jenny Chen, BScn Cécile Viboud, PhD . (2020).  Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study.  The Lancet: Digital Health; Volume 2, Issue 4, E201-E208.

Summary

Background

As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks.

Methods

In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time.

Findings

We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020.

Interpretation

News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions.

A Few notes on Methodology:

  • The authors used crowd-sourced reports from DXY.cn, a social network for Chinese physicians, health-care professionals, pharmacies and health-care facilities. This online platform provides real time coverage of the COVID-19 outbreak in China
  • More data was curated from news media, television and includes time-stamped information on COVID-19 cases
  • These reports are publicly available, de-identified patient data
  • No patient consent was needed and no ethics approval was required
  • Data was collected between January 20, 2020 and January 31,2020
  • Sex, age, province of identification, travel history, dates of symptom development was collected
  • Additional data was collected for other international sites of the pandemic including Cambodia, Canada, France, Germany, Hong Kong, India, Italy, Japan, Malaysia, Nepal, Russia, Singapore, UK, and USA
  • All patients in database had laboratory confirmation of infection

 

Results

  • 507 patient data was collected with 153 visited and 152 resident of Wuhan
  • Reported cases were skewed toward males however the overall population curve is skewed toward males in China
  • Most cases (26%) were from Beijing (urban area) while an equal amount were from rural areas combined (Shaanzi and Yunnan)
  • Age distribution of COVID cases were skewed toward older age groups with median age of 45 HOWEVER there were surprisingly a statistically high amount of cases less than 5 years of age
  • Outbreak progression based on the crowd-sourced patient line was consistent with the data published by the China Center for Disease Control
  • Median reporting delay in the authors crowd-sourcing data was 5 days
  • Crowd-sourced data was able to detect apparent rapid growth of newly reported cases during the collection period in several provinces outside of Hubei province, which is consistent with local government data

The following graphs show age distribution for China in 2017 and predicted for 2050.

projected age distribution China 2050. Source https://chinapower.csis.org/aging-problem/

 

 

 

 

 

 

 

 

 

 

 

 

The authors have previously used this curation of news methodology to analyze the Ebola outbreak[2].

A further use of the crowd-sourced database was availability of travel histories for patients returning from Wuhan and onset of symptoms, allowing for estimation of incubation periods.

The following published literature has also used these datasets:

Backer JA, Klinkenberg D, Wallinga J: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2020, 25(5).

Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Annals of internal medicine 2020, 172(9):577-582.

Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY et al: Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. The New England journal of medicine 2020, 382(13):1199-1207.

Dataset is available on the Laboratory for the Modeling of Biological and Socio-technical systems website of Northeastern University at https://www.mobs-lab.org/.

References

  1. Sun K, Chen J, Viboud C: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study. The Lancet Digital health 2020, 2(4):e201-e208.
  2. Cleaton JM, Viboud C, Simonsen L, Hurtado AM, Chowell G: Characterizing Ebola Transmission Patterns Based on Internet News Reports. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016, 62(1):24-31.

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Powerful Artificial Intelligence (AI) Tools Being Developed for the COVID-19 Fight

Posted in Artificial Intelligence in Health Care - Tools & Innovations, Artificial Intelligence in Medicine - Application for Diagnosis, Artificial Intelligence in Medicine - Applications in Therapeutics, Big Data, Biomarkers: Inflammation, Cancer Researchers Fighting COVID-19, coronavirus, Coronavirus Gene Expression, COVID-19, COVID-19 effects on Human Heart, COVID-19: Pandemic Surgery Guidance, Disease Biology, Economic Impact of Coronavirus Pandemic, Health Economics and Outcomes Research, HealthCare IT, Image Processing/Computing, Imaging-based Cancer Patient Management, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Intelligent Information Systems, number of asymptomatic infections, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, SARS-COV2 Hijacking the Complement and Coagulation Systems, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Vaccinology, Viral diseases, Virology - Vector-borne DIsease, tagged , , , , , , , , , , , on May 13, 2020| Leave a Comment »

Powerful AI Tools Being Developed for the COVID-19 Fight

Curator: Stephen J. Williams, Ph.D.

 

Source: https://www.ibm.com/blogs/research/2020/04/ai-powered-technologies-accelerate-discovery-covid-19/

IBM Releases Novel AI-Powered Technologies to Help Health and Research Community Accelerate the Discovery of Medical Insights and Treatments for COVID-19

April 3, 2020 | Written by: 

IBM Research has been actively developing new cloud and AI-powered technologies that can help researchers across a variety of scientific disciplines accelerate the process of discovery. As the COVID-19 pandemic unfolds, we continue to ask how these technologies and our scientific knowledge can help in the global battle against coronavirus.

Today, we are making available multiple novel, free resources from across IBM to help healthcare researchers, doctors and scientists around the world accelerate COVID-19 drug discovery: from gathering insights, to applying the latest virus genomic information and identifying potential targets for treatments, to creating new drug molecule candidates.

Though some of the resources are still in exploratory stages, IBM is making them available to qualifying researchers at no charge to aid the international scientific investigation of COVID-19.

Today’s announcement follows our recent leadership in launching the U.S. COVID-19 High Performance Computing Consortium, which is harnessing massive computing power in the effort to help confront the coronavirus.

Streamlining the Search for Information

Healthcare agencies and governments around the world have quickly amassed medical and other relevant data about the pandemic. And, there are already vast troves of medical research that could prove relevant to COVID-19. Yet, as with any large volume of disparate data sources, it is difficult to efficiently aggregate and analyze that data in ways that can yield scientific insights.

To help researchers access structured and unstructured data quickly, we are offering a cloud-based AI research resource that has been trained on a corpus of thousands of scientific papers contained in the COVID-19 Open Research Dataset (CORD-19), prepared by the White House and a coalition of research groups, and licensed databases from the DrugBank, Clinicaltrials.gov and GenBank. This tool uses our advanced AI and allows researchers to pose specific queries to the collections of papers and to extract critical COVID-19 knowledge quickly. Please note, access to this resource will be granted only to qualified researchers. To learn more and request access, please click here.

Aiding the Hunt for Treatments

The traditional drug discovery pipeline relies on a library of compounds that are screened, improved, and tested to determine safety and efficacy. In dealing with new pathogens such as SARS-CoV-2, there is the potential to enhance the compound libraries with additional novel compounds. To help address this need, IBM Research has recently created a new, AI-generative framework which can rapidly identify novel peptides, proteins, drug candidates and materials.

We have applied this AI technology against three COVID-19 targets to identify 3,000 new small molecules as potential COVID-19 therapeutic candidates. IBM is releasing these molecules under an open license, and researchers can study them via a new interactive molecular explorer tool to understand their characteristics and relationship to COVID-19 and identify candidates that might have desirable properties to be further pursued in drug development.

To streamline efforts to identify new treatments for COVID-19, we are also making the IBM Functional Genomics Platform available for free for the duration of the pandemic. Built to discover the molecular features in viral and bacterial genomes, this cloud-based repository and research tool includes genes, proteins and other molecular targets from sequenced viral and bacterial organisms in one place with connections pre-computed to help accelerate discovery of molecular targets required for drug design, test development and treatment.

Select IBM collaborators from government agencies, academic institutions and other organizations already use this platform for bacterial genomic study. And now, those working on COVID-19 can request the IBM Functional Genomics Platform interface to explore the genomic features of the virus. Access to the IBM Functional Genomics Platform will be prioritized for those conducting COVID-19 research. To learn more and request access, please click here.

Drug and Disease Information

Clinicians and healthcare professionals on the frontlines of care will also have free access to hundreds of pieces of evidence-based, curated COVID-19 and infectious disease content from IBM Micromedex and EBSCO DynaMed. Using these two rich decision support solutions, users will have access to drug and disease information in a single and comprehensive search. Clinicians can also provide patients with consumer-friendly patient education handouts with relevant, actionable medical information. IBM Micromedex is one of the largest online reference databases for medication information and is used by more than 4,500 hospitals and health systems worldwide. EBSCO DynaMed provides peer-reviewed clinical content, including systematic literature reviews in 28 specialties for comprehensive disease topics, health conditions and abnormal findings, to highly focused topics on evaluation, differential diagnosis and management.

The scientific community is working hard to make important new discoveries relevant to the treatment of COVID-19, and we’re hopeful that releasing these novel tools will help accelerate this global effort. This work also outlines our long-term vision for the future of accelerated discovery, where multi-disciplinary scientists and clinicians work together to rapidly and effectively create next generation therapeutics, aided by novel AI-powered technologies.

Learn more about IBM’s response to COVID-19: IBM.com/COVID19.

Source: https://www.ibm.com/blogs/research/2020/04/ai-powered-technologies-accelerate-discovery-covid-19/

DiA Imaging Analysis Receives Grant to Accelerate Global Access to its AI Ultrasound Solutions in the Fight Against COVID-19

Source: https://www.grantnews.com/news-articles/?rkey=20200512UN05506&filter=12337

Grant will allow company to accelerate access to its AI solutions and use of ultrasound in COVID-19 emergency settings

TEL AVIV, Israel, May 12, 2020 /PRNewswire-PRWeb/ — DiA Imaging Analysis, a leading provider of AI based ultrasound analysis solutions, today announced that it has received a government grant from the Israel Innovation Authority (IIA) to develop solutions for ultrasound imaging analysis of COVID-19 patients using Artificial Intelligence (AI).Using ultrasound in point of care emergency settings has gained momentum since the outbreak of COVID-19 pandemic. In these settings, which include makeshift hospital COVID-19 departments and triage “tents,” portable ultrasound offers clinicians diagnostic decision support, with the added advantage of being easier to disinfect and eliminating the need to transport patients from one room to another.However, analyzing ultrasound images is a process that it is still mostly done visually, leading to a growing market need for automated solutions and decision support.As the leading provider of AI solutions for ultrasound analysis and backed by Connecticut Innovations, DiA makes ultrasound analysis smarter and accessible to both new and expert ultrasound users with various levels of experience. The company’s flagship LVivo Cardio Toolbox for AI-based cardiac ultrasound analysis enables clinicians to automatically generate objective clinical analysis, with increased accuracy and efficiency to support decisions about patient treatment and care.

The IIA grant provides a budget of millions NIS to increase access to DiA’s solutions for users in Israel and globally, and accelerate R&D with a focus on new AI solutions for COVID-19 patient management. DiA solutions are vendor-neutral and platform agnostic, as well as powered to run in low processing, mobile environments like handheld ultrasound.Recent data highlights the importance of looking at the heart during the progression of COVID-19, with one study citing 20% of patients hospitalized with COVID-19 showing signs of heart damage and increased mortality rates in those patients. DiA’s LVivo cardiac analysis solutions automatically generate objective, quantified cardiac ultrasound results to enable point-of-care clinicians to assess cardiac function on the spot, near patients’ bedside.

According to Dr. Ami Applebaum, the Chairman of the Board of the IIA, “The purpose of IIA’s call was to bring solutions to global markets for fighting COVID-19, with an emphasis on relevancy, fast time to market and collaborations promising continuity of the Israeli economy. DiA meets these requirements with AI innovation for ultrasound.”DiA has received several FDA/CE clearances and established distribution partnerships with industry leading companies including GE Healthcare, IBM Watson and Konica Minolta, currently serving thousands of end users worldwide.”We see growing use of ultrasound in point of care settings, and an urgent need for automated, objective solutions that provide decision support in real time,” said Hila Goldman-Aslan, CEO and Co-founder of DiA Imaging Analysis, “Our AI solutions meet this need by immediately helping clinicians on the frontlines to quickly and easily assess COVID-19 patients’ hearts to help guide care delivery.”

About DiA Imaging Analysis:
DiA Imaging Analysis provides advanced AI-based ultrasound analysis technology that makes ultrasound accessible to all. DiA’s automated tools deliver fast and accurate clinical indications to support the decision-making process and offer better patient care. DiA’s AI-based technology uses advanced pattern recognition and machine-learning algorithms to automatically imitate the way the human eye detects image borders and identifies motion. Using DiA’s tools provides automated and objective AI tools, helps reduce variability among users, and increases efficiency. It allows clinicians with various levels of experience to quickly and easily analyze ultrasound images.

For additional information, please visit http://www.dia-analysis.com.

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Dr. Giordano Featured in Forbes Article on COVID-19 Antibody Tests in Italy and USA

Posted in Biomarkers: Inflammation, Cancer Researchers Fighting COVID-19, Coronavirus Gene Expression, COVID-19, COVID-19, COVID-19 effects on Human Heart, COVID-19: Pandemic Surgery Guidance, Diagnostic Immunology, Diagnostics and Lab Tests, Economic Impact of Coronavirus Pandemic, Evolution of Biology Through Culture, Frontiers in Cardiology and Cardiovascular Disorders, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Interviews with Key Opinion Leaders (KOLs), number of asymptomatic infections, Population Health Management, Population Health Management, Genetics & Pharmaceutical, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, Scientific Publishing, Systemic Inflammatory Diseases as CVD Risk, tagged , , , , , , , , , , on May 10, 2020| Leave a Comment »

Dr. Giordano Featured in Forbes Article on COVID-19 Antibody Tests in Italy and USA

Reporter: Stephen J. Williams, PhD

Article ID #276: Dr. Giordano Featured in Forbes Article on COVID-19 Antibody Tests in Italy and USA. Published on 5/10/2020

WordCloud Image Produced by Adam Tubman

via Dr. Giordano Featured in Forbes Article on COVID-19 Antibody Tests in Italy and USA

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Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on NCI Activities: COVID-19 and Cancer Research 5:20 PM

Posted in Biomarkers: Inflammation, Cancer - General, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Cancer Researchers Fighting COVID-19, Conference Coverage with Social Media, coronavirus, Coronavirus Gene Expression, COVID-19, COVID-19: Pandemic Surgery Guidance, Economic Impact of Coronavirus Pandemic, Funding Opportunities for Cancer Research, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), number of asymptomatic infections, Population Health Management, Genetics & Pharmaceutical, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , , on April 28, 2020| Leave a Comment »

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on NCI Activities: COVID-19 and Cancer Research 5:20 PM

Reporter: Stephen J. Williams, PhD

NCI Activities: COVID-19 and Cancer Research

Dinah S. Singer. NCI-DCB, Bethesda, MD @theNCI

  • at the NCI they are pivoting some of their clinical trials to address COVID related issues like trials on tocilizumab and producing longitudinal cohorts of cancer patients and COVID for further analysis and studies
  • vaccine and antibody efforts at NCI and they are asking all their cancer centers (Cancer COVID Consortium) collecting data
  • Moonshot is collecting metadata but now COVID data from cellular therapy patients
  • they are about to publish new grants related to COVID and adding option to investigators to use current funds to do COVID related options
  • she says if at home take the time to think, write manuscripts, analyze data BE A REVIEWER FOR JOURNALS,
  • SSMMART project from Moonshot is still active
  • so far NCI and NIH grant process is ongoing although the peer review process is slower
  • they have extended deadlines with NO justification required (extend 90 days)
  • also allowing flexibility on use of grant money and allowing more early investigator rules and lax on those rules
  • non competitive renewals (type 5) will allow restructuring of project; contact program administrator
  • she and NCI heard rumors of institutions shutting down cancer research she is stressing to them not to do that
  • non refundable travel costs may be charged to the grant
  • NCI contemplating on extending the early investigator time
  • for more information go to NIH and NCI COVID-19 pages which have more guidances updated regularly

Follow on Twitter at:

@pharma_BI

@AACR

@CureCancerNow

@pharmanews

@BiotechWorld

@theNCI

#AACR20

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Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on COVID-19 and Cancer 9:00 AM

Posted in Biomarkers: Inflammation, Cancer - General, Cancer and Current Therapeutics, Cancer Researchers Fighting COVID-19, Coronavirus Gene Expression, COVID-19, COVID-19: Pandemic Surgery Guidance, Economic Impact of Coronavirus Pandemic, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Vaccinology, Viral diseases, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , , , on April 28, 2020| Leave a Comment »

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on COVID-19 and Cancer 9:00 AM

Reporter: Stephen J. Williams, PhD

 

COVID-19 and Cancer

Introduction

Antoni Ribas
UCLA Medical Center

  • Almost 60,000 viewed the AACR 2020 Virtual meeting for the April 27 session
  • The following speakers were the first cancer researchers treating patients at the epicenters of the pandemic even though nothing was known about the virus

 

The experience of treating patients with cancer during the COVID-19 pandemic in China
Li Zhang, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

  • reporting a retrospective study from three hospitals from Wuhan
  • 2.2% of Wuhan cancer patients were COVID positive; most were lung cancers and most male; 35% were stage four
  • most have hospital transmission of secondary infection; had severe events when admitted
  • 74% were prescribed antivirals like ganciclovir and others; iv IgG was given to some
  • mortailtiy rate of 26%; by April 4 54% were cured and discharged; median time of infection to severe event was 7 days; clinical presentation SARS sepsis, and shock
  • by day 10 in lung cancer patients, see lung path but after supportive therapy improved
  • cancer patients at stage four who did not receive therapy were at higher risk
  • cancer patients who had received chemo in last 14 days had higher risk of infection
  • they followed up with cancer patients on I/O inhibitors;  it seemed there was only one patient that contracted COVID19 so there may not be as much risk with immune checkpoint inhibitors

 

TERAVOLT (Thoracic cancERs international coVid 19 cOLlaboraTion): First results of a global collaboration to address the impact of COVID-19 in patients with thoracic malignancies

Marina Chiara Garassino

@marinagarassino
Fondazione IRCCS Istituto Nazionale dei Tumori

Dr Marina Chiara Garassino is the Chief of the Thoracic Oncology Unit at Istituto Nazionale dei Tumori, Milan, Italy. She leads the strategy for clinical and translational research in advanced and locally advanced NSCLC, SCLC, mesothelioma and thymic malignancies. Istituto Nazionale dei Tumori in Milan is the most important comprehensive cancer in Italy and one of the most important in Europe. As a medical oncologist, she has done research in precision medicine and in immuno-oncology. Her main research interests have been mainly development of new drugs and therapeutical strategies and biomarkers. She has contributed to over 150 peer-reviewed publications, including publications as first or last author in the New England Journal of Medicine, Lancet Oncology, Journal of Clinical Oncology, Annals of Oncology. She has delivered many presentations at international congresses,  including  AACR, ASCO, ECCO, ESMO, WCLC. Her education includes a degree and further specialization in Medical Oncology at Università degli Studi in Milan. She achieved a Master Degree in Oncology management at University of Economics “Luigi Bocconi”. She completed her training with an ESMO Clinical fellowship in 2009 at Christie’s Hospital in Manchester (UK). She was a member of the EMA SAG (Scientific Advisory Group). She is serving as ESMO Council member as the Chair of the National Societies Committee. She was the ESMO National Representative for Italy for 5 years (2011-2017). She is serving on several ESMO Committees (Public Policy extended Committee, Press Committee, Women for Oncology Committee, Lung Cancer faculty, Membership Committee).She used to be an active member of the Young Oncologist Committee. She’s serving on both ESMO, WCLC and ASCO annual congress Lung Cancer Track (2019, and 2020), Chair of ESMO National Societies, from 2019. She is the founder and president of Women for Oncology Italy.

  • 2 million confirmed cases but half of patients are asymptomatic and not tested; pooled prevalance of COVID in cancer patients in Italy was 2%; must take them as high risk patients
  • they were not prepared for pandemic lasting for months instead of days; March 15 in middle of outbreak they started TERAVOLT registry; by March 26 had IRB approval; they are accruing 17 new patients per week; Ontario also joined in and has become worldwide (21 countries involved);  in registry they also included radiologic exams and COVID testing result
  • most patients were males and many smokers; 75% had SCLC; 83% of cases had one comorbility like hypertension and one third had at least one comorbility; 73.9% of patients were on treatment (they see this in their clinic: 30% on chemo or TKI alone; other patients were just on folowup
  • most of symptoms overlap with symptoms of lung cancer like pneumonia and pneumonitits and multi organ failure; most were hospitalized
  • unexpected high mortality among lung cancer patients with COVID19; this mortality seems due to COVID and not to cancer;
  • study had some limitations like short followup and some surgical cases so some bias may be present
  • she stresses don’t go it alone and make your own registry JOIN A REGISTRY

 

Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments
Fabrice Barlesi @barlesi
Gustave Roussy Cancer Campus

Professor Fabrice Barlesi
 As a specialist in lung cancer, precision medicine and cancer immunology, Prof. Fabrice Barlesi is a major contributor to research in the field of novel oncological therapies. He was apppointed General Director of Gustave Roussy in January 2020.
Fabrice Barlesi is Professor of Medicine at the University of Aix-Marseille. He has been head of the Multidisciplinary Oncology and Innovative Therapies Department of the Nord Hospital in Marseille (Marseille Public Hospitals) and the Marseille Centre for Early Trials in Oncology (CLIP2) which were established by him. He holds a doctorate in Sciences and Management with methods of analysis of health care systems, together with an ESSEC (international business school) master’s degree in general hospital management.
Professor Barlesi was also a co-founder of the Marseille Immunopôle French Immunology network, which aims to coordinate immunological expertise in the Aix-Marseille metropolitan area. In this context, he has organised PIONeeR (Investment in the future RHU 2017), the major international Hospital-University research project whose objective is to improve understanding of resistance to immunotherapy – anti-PD1(L1) – in lung cancer and help to prevent and overcome it. He was also vice-chair of the PACA (Provence, Alps and Côte d’Azur) Region Cancer Research Directorate.
Professor Barlesi is the author and co-author of some 300 articles in international journals and specialist publications. In 2018, the European Society of Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC) awarded him the prestigious Heine H. Hansen prize. He appears in the 2019 world list of most influential researchers (Highly cited researchers, Web of Science Group).
  • March 14 started protective measures and at peak had increased commited beds at highest rate
  • 12% of cancer patients tested positive for COVID; (by RTPCR); they curated data across different chemo regimens used
  • they retrospectively collected data; primary endpoint was clinical worsening; median of disease 13 days;
  • they actually had more breast cancer patients and other solid malignancies; 23% of covid cases no symptoms; 83% finally did have the symptoms after followup; diarhea actually in 10% of cases so clinics are seeing this as a symptom
  • CT scan showed 66% cases had pneumonitits like display; 25% patients were managed as outpatient
  • 24% patients worsened during treatment but 75% were able to go home (treated at home or well)
  • I/O did not have negative outcome and you can use these drugs without increasing risk to COVID
  • although many clinical trials have been hindered they are actively recruiting for COVID-cancer studies
  • outcomes with respect to death and symptoms are comparable to worldwide stats

Adapting oncologic practice to COVID19 outbreak: From outpatient triage to risk assessment for specific treatment in Madrid, Spain
Carlos Gomez-Martin
Octubre University Hospital

  • MOST slides were DO NOT POST so as requested data will not be shown; this study will be published soon
  • Summary is that Spain is seeing statistics like other European countries and similar results
  • Tocilizumab, the IL6 antagonists had been suggested as a treatment for cytokine storm and they are involved in a trial with this agent; results will be published

Experience in using oncology drugs in patients with COVID-19

Paolo A. Ascierto
Istituto Nazionale Tumori IRCCS Fondazione Pascale

  • giving surgery only for patients at highest risk of cancer mortality so using neoadjuvant therapy more often
  • telemedicine is a viable strategy for patient consult
  • for metastatic melanoma they are given highest priority for treatment
  • they are conducting a tocilizumab clinical trial and have accrued over 300 patients
  • results are in press so please look for publication soon
  • also can use TNF inhibitor, JAK inhibitor, IL1 inhibitor to treat cytokine storm

COVID-19 and cancer: Flattening the curve but widening disparities
Louis P. Voigt
Memorial Sloan Kettering Cancer Center

  • Sloan has performed about 5000 COVID tests;  78 patients needed hospitilization; 15 died; 40% still in ICU
  • they do see many African American patients
  • mortality rates in US (published) have been around 50-60 % for cancer patients with COVID; Sloan prelim results are lower but still accruing data

Patients with cancer appear more vulnerable to SARS-COV-2: A multi-center study during the COVID-19 outbreak
Hongbing Cai
Zhongnan Hospital of Wuhan University

  • metastatic cancer showed much higher risk than non cancer but non metastatic showed increased risk too
  • main criteria of outcome was ICU admission
  • patients need to be isolated and personalized treatment plans need to be made
  • many comparisons were between non cancer and cancer which was clearest significance; had not looked at cancer types or stage grade or treatment
  • it appears that there are more questions right now than answers so data collection is a priority

Follow on Twitter at:

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For other Articles on the Online Open Access Journal on COVID19 and Cancer please see

https://pharmaceuticalintelligence.com/coronavirus-portal/

Opinion Articles from the Lancet: COVID-19 and Cancer Care in China and Africa

Actemra, immunosuppressive which was designed to treat rheumatoid arthritis but also approved in 2017 to treat cytokine storms in cancer patients SAVED the sickest of all COVID-19 patients

The Second in a Series of Virtual Town Halls with Leading Oncologist on Cancer Patient Care during COVID-19 Pandemic: What you need to know

Responses to the COVID-19 outbreak from Oncologists, Cancer Societies and the NCI: Important information for cancer patients

 

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