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Placenta lacks molecules required for COVID-19 infection

Posted in Allergy and Infectious Diseases, Biochemical pathways, Biomarkers & Medical Diagnostics, Biotechnology, Cancer Researchers Fighting COVID-19, Clinical Diagnostics, Coronavirus Gene Expression, COVID-19, Economic Impact of Coronavirus Pandemic, Enzymes and isoenzymes, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, number of asymptomatic infections, Placenta, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , on July 16, 2020| Leave a Comment »

Placenta lacks molecules required for COVID-19 infection

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 10 million people, including pregnant women. To date, no consistent evidence for the vertical transmission of SARS-CoV-2 has been found. The placenta serves as the lungs, gut, kidneys, and liver of the fetus. This fetal organ also has major endocrine actions that modulate maternal physiology and, importantly, together with the extraplacental chorioamniotic membranes shield the fetus against microbes from hematogenous dissemination and from invading the amniotic cavity.

 

Most pathogens that cause hematogenous infections in the mother are not able to reach the fetus, which is largely due to the potent protective mechanisms provided by placental cells (i.e. trophoblast cells: syncytiotrophoblasts and cytotrophoblasts). Yet, some of these pathogens such as Toxoplasma gondii, Rubella virus, herpesvirus (HSV), cytomegalovirus (CMV), and Zika virus (ZIKV), among others, are capable of crossing the placenta and infecting the fetus, causing congenital disease.

 

The placental membranes that contain the fetus and amniotic fluid lack the messenger RNA (mRNA) molecule required to manufacture the ACE2 receptor, the main cell surface receptor used by the SARS-CoV-2 virus to cause infection. These placental tissues also lack mRNA needed to make an enzyme, called TMPRSS2, that SARS-CoV-2 uses to enter a cell. Both the receptor and enzyme are present in only miniscule amounts in the placenta, suggesting a possible explanation for why SARS-CoV-2 has only rarely been found in fetuses or newborns of women infected with the virus, according to the study authors.

 

The single-cell transcriptomic analysis presented by the researchers provides evidence that SARS-CoV-2 is unlikely to infect the placenta and fetus since its canonical receptor and protease, ACE2 and TRMPSS2, are only minimally expressed by the human placenta throughout pregnancy. In addition, it was shown that the SARS-CoV-2 receptors are not expressed by the chorioamniotic membranes in the third trimester. However, viral receptors utilized by CMV, ZIKV, and others are highly expressed by the human placental tissues.

 

Transcript levels do not always correlate with protein expression, but the data of the present study indicates a low likelihood of placental infection and vertical transmission of SARS-CoV-2. However, it is still possible that the expression of these proteins is much higher in individuals with pregnancy complications related with the renin-angiotensin-aldosterone system, which can alter the expression of ACE2. The cellular receptors and mechanisms that could be exploited by SARS-CoV-2 are still under investigation.

 

References:

 

https://www.nih.gov/news-events/news-releases/placenta-lacks-major-molecules-used-sars-cov-2-virus-cause-infection

 

https://pubmed.ncbi.nlm.nih.gov/32662421/

 

https://pubmed.ncbi.nlm.nih.gov/32217113/

 

https://pubmed.ncbi.nlm.nih.gov/32161408/

 

https://pubmed.ncbi.nlm.nih.gov/32335053/

 

https://pubmed.ncbi.nlm.nih.gov/32298273/

 

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Updates on the Oxford, AstraZeneca COVID-19 Vaccine

Posted in COVID-19, Drug Delivery Platform Technology, FDA, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, Small Molecules in Development of Therapeutic Drugs, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , on June 16, 2020| Leave a Comment »

Updates on the Oxford, AstraZeneca COVID-19 Vaccine

Reporter: Stephen J. Williams, PhD

AstraZeneca’s CEO states that their COVID-19 vaccine, codeveloped with Oxford University, should provide protection for a year.

AstraZeneca’s potential coronavirus vaccine is likely to provide protection against contracting Covid-19 for about a year, the company’s chief executive told a Belgian radio station on Tuesday.

The British drugmaker has already begun human trials of the vaccine developed by the University of Oxford, with a phase I trial in Britain due to end soon and a phase III trial already begun, Pascal Soriot told broadcaster Bel RTL.

“We think that it will protect for about a year,” Soriot said.

AstraZeneca said on Saturday that it had signed contracts with France, Germany, Italy and the Netherlands to supply the European Union with up to 400 million doses of the potential vaccine.

It has also agreed deals with Britain and the United States.

“If all goes well, we will have the results of the clinical trials in August/September. We are manufacturing in parallel. We will be ready to deliver from October if all goes well,” Soriot said.

Source: https://www.cnbc.com/2020/06/16/astrazeneca-covid-19-vaccine-likely-to-protect-for-a-year-ceo-says.html

 

 

From In The Pipeline (Derek Lowe’s regular column in Science)

Criticism of the Oxford Coronavirus Vaccine

By Derek Lowe 18 May, 2020

This piece at Forbes by Bill Haseltine has set off a lot of comment – it’s a look at the Oxford group’s vaccine candidate as compared to the SinoVac candidate, and you may recall (background here) that these are the two teams that have separately reported that their vaccines appear to protect rhesus monkeys from infection after exposure to the coronavirus. Haseltine has some criticisms of the Oxford data, and as you will see from that link to his name, his opinions deserve to be taken seriously. So what’s going on? Update: here’s the take on this at BioCentury.

Looking at the preprint on the Oxford results, Haseltine has a problem with the claim that the monkeys were protected from infection by a dose of ChAdOx1 nCoV-19. The key data are in the preprint’s Figure 3. The Oxford team checked for viral RNA several different ways. One was using bronchoaveolar lavage (BAL fluid), a sampling technique that involves running a bronchoscope down into the lungs and washing out aveolar spaces – a pretty darn invasive assay, which is why you don’t hear about it all that much compared to the still-not-so-nonivasive nose swabs. BAL fluid of the virus-exposed unvaccinated animals showed coronavirus genomic RNA throughout the study, and viral subgenomic RNA (more indicative of active replication) at days 3 and 5 after exposure. Meanwhile, the vaccinated animals showed the genomic RNA in only two monkeys, and no subgenomic RNA at all.

So far, so good. But both vaccinated and unvaccinated monkeys showed the same amount of viral genomic RNA from nose swab samples (Figure 3c). That’s the test that’s used out in the human population, and that means that the vaccinated animals would still be declared as positive for the coronavirus after being exposed to it. And the other thing that Haseltine notes is that the amount (the “titer”, in the lingo) of neutralizing antibodies in the blood of the vaccinated animals does not appear to be that high. You’d like to be able to dilute the blood antibody samples down by hundreds of times or even a thousandfold and still see antiviral activity in an in vitro assay, but in the Oxford case the activity started disappearing at about fortyfold dilution (Figure 2b).

On the positive side, 2/3 of the unvaccinated animals showed clear evidence of viral pneumonia at autopsy, but none of the vaccinated ones did. The conclusion is that the vaccinated animals were indeed infected – the vaccine did not protect against that – but that the disease was definitely less severe. But these results mean that the virus might well still be transmissible from people who had been so vaccinated, even if the disease course itself was not as deadly. You’d want to do better than that, if you can. Haseltine’s take is “Time will tell if this is the best approach. I wouldn’t bet on it.”

Haseltine compares these results to the SinoVac inactivated virus vaccine, and finds that that one looks better – at its highest dose, no viral RNA was recovered from the tissues of the vaccinated animals, for example. This sort of “sterilizing immunity” is what you’d want to aim for – it gives the virus nowhere to go in the human population if you can vaccinate enough people. But it’s worth noting that the SinoVac results were from three doses of their vaccine (versus one of the Oxford candidate), and the viral exposure challenge was about half as strong (total viral particles) as what the Oxford paper used. The Oxford group also inoculated their monkeys in both the upper and lower respiratory tract, while the SinoVac team used a single inoculation in the trachea. So I agree with that tweet linked from AndyBiotech; I don’t think that a head-to-head comparison is fair. But Haseltine’s point stands, that the results as we have them from the ChAdOx1 nCoV-19 vaccine did not actually protect monkeys from infection.

Source: https://blogs.sciencemag.org/pipeline/archives/2020/05/18/criticism-of-the-oxford-coronavirus-vaccine

 

Please see other Articles on COVID-19 on our Coronavirus Portal Including Late Breaking News at:

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

 

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SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Posted in COVID-19, Population Health Management, Genetics & Pharmaceutical, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, SARS-CoV-2, Treatment Protocols for COVID-19, Virus Infective Acute Respiratory Syndrome: SARS-CoV on June 1, 2020| Leave a Comment »

SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Reporter: Aviva Lev-Ari, PhD, RN – Bold face and colors are my addition

From: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>

Reply-To: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>

Date: Tuesday, June 2, 2020 at 8:50 AM

To: Aviva Lev-Ari <aviva.lev-ari@comcast.net>

Subject: Re: Coronavirus May Be a Vascular Disease, Which Explains Everything | Elemental

“I don’t think the conclusion is fully validated. I would want to see autopsy reports, like that found in China. It can be done safely, and the tools could be discarded.”

Larry

UPDATED on 3/1/2021

COVID Clot Prevention Evidence Beginning to Bud

— Randomized prophylaxis trials have struggled, but some now near initial read-out

by Crystal Phend, Senior Editor, MedPage Today December 28, 2020

Three adaptive platform partner trials — ACTIV-4, REMAP-CAP, and ATTACC — just halted therapeutic anticoagulation for prophylactic use in ICU patients after interim data showed futility in seeking a reduction in need for organ support and possible safety concern.

“It is terrific gain of knowledge to have results from randomized trials, even if they have to be stopped early,” said Stephan Moll, MD, a hematologist-oncologist involved in setting the prophylaxis protocols for the University of North Carolina at Chapel Hill. “This is refreshing news after all the retrospective, limited data of the first 9 months of the COVID-19 pandemic.”

ACTIV-4, REMAP-CAP, and ATTACC data are “urgently” undergoing additional analyses to be made available as soon as possible, according to trial leadership. Non-ICU subgroups, and a range of other treatment arms in those trials, are also ongoing.

SOURCE

UPDATED on 6/29/2020

Another duality and paradox in the Treatment of COVID-19 Patients in ICUs was expressed by Mike Yoffe, MD, PhD, David H. Koch Professor of Biology and Biological Engineering, Massachusetts Institute of Technology. Dr. Yaffe has a joint appointment in Acute Care Surgery, Trauma, and Surgical Critical Care, and in Surgical Oncology @BIDMC

on 6/29 at SOLUTIONS with/in/sight at Koch Institute @MIT

How Are Cancer Researchers Fighting COVID-19? (Part II)” Jun 29, 2020 11:30 AM EST

Mike Yoffe, MD, PhD 

In COVID-19 patients: two life threatening conditions are seen in ICUs:

  • Blood Clotting – Hypercoagulability or Thrombophilia
  • Cytokine Storm – immuno-inflammatory response
  • The coexistence of 1 and 2 – HINDERS the ability to use effectively tPA as an anti-clotting agent while the cytokine storm is present.

Mike Yoffe’s related domain of expertise:

Signaling pathways and networks that control cytokine responses and inflammation

Misregulation of cytokine feedback loops, along with inappropriate activation of the blood clotting cascade causes dysregulation of cell signaling pathways in innate immune cells (neutrophils and macrophages), resulting in tissue damage and multiple organ failure following trauma or sepsis. Our research is focused on understanding the role of the p38-MK2 pathway in cytokine control and innate immune function, and on cross-talk between cytokines, clotting factors, and neutrophil NADPH oxidase-derived ROS in tissue damage, coagulopathy, and inflammation, using biochemistry, cell biology, and mouse knock-out/knock-in models.  We recently discovered a particularly important link between abnormal blood clotting and the complement pathway cytokine C5a which causes excessive production of extracellular ROS and organ damage by neutrophils after traumatic injury.

SOURCE

https://www.bidmc.org/research/research-by-department/surgery/acute-care-surgery-trauma-and-surgical-critical-care/michael-b-yaffe

 

SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Mandeep Mehra, MD, medical director of the Brigham and Women’s Hospital Heart and Vascular Center.

“All these Covid-associated complications were a mystery. We see blood clotting, we see kidney damage, we see inflammation of the heart, we see stroke, we see encephalitis [swelling of the brain],” says William Li, MD, president of the Angiogenesis Foundation. “A whole myriad of seemingly unconnected phenomena that you do not normally see with SARS or H1N1 or, frankly, most infectious diseases.”

“If you start to put all of the data together that’s emerging, it turns out that this virus is probably a vasculotropic virus, meaning that it affects the [blood vessels],”

Mehra explains. “Then it starts to infect endothelial cell after endothelial cell, creates a local immune response, and inflames the endothelium.”

Benhur Lee, MD, a professor of microbiology at the Icahn School of Medicine at Mount Sinai:

“In SARS1, the protein that’s required to cleave it is likely present only in the lung environment, so that’s where it can replicate. To my knowledge, it doesn’t really go systemic,” Lee says. “[SARS-CoV-2] is cleaved by a protein called furin, and that’s a big danger because furin is present in all our cells, it’s ubiquitous.”

Sanjum Sethi, MD, MPH, an interventional cardiologist at Columbia University Irving Medical Center:

“The endothelial cell layer is in part responsible for [clot] regulation, it inhibits clot formation through a variety of ways, If that’s disrupted, you could see why that may potentially promote clot formation.” Damage to endothelial cells causes inflammation in the blood vessels, and that can cause any plaque that’s accumulated to rupture, causing a heart attack. “Inflammation and endothelial dysfunction promote plaque rupture. Endothelial dysfunction is linked towards worse heart outcomes, in particular myocardial infarction or heart attack.”

https://elemental.medium.com/coronavirus-may-be-a-blood-vessel-disease-which-explains-everything-2c4032481ab2

Endothelial cell dysfunction: pre-existing conditions like high blood pressure, high cholesterol, diabetes, and heart disease are at a higher risk for severe complications from a virus that’s supposed to just infect the lungs. Why ventilation often isn’t enough to help many Covid-19 patients breathe better. Moving air into the lungs, which ventilators help with, is only one part of the equation. The exchange of oxygen and carbon dioxide in the blood is just as important to provide the rest of the body with oxygen, and that process relies on functioning blood vessels in the lungs.

William Li, MD, president of the Angiogenesis Foundation:

“If you have blood clots within the blood vessels that are required for complete oxygen exchange, even if you’re moving air in and out of the airways, [if] the circulation is blocked, the full benefits of mechanical ventilatory support are somewhat thwarted,” “We were observing virus particles filling up the endothelial cell like filling up a gumball machine. The endothelial cell swells and the cell membrane starts to break down, and now you have a layer of injured endothelium.” “Endothelial cells connect the entire circulation [system], 60,000 miles worth of blood vessels throughout our body,” says Li. “Is this one way that Covid-19 can impact the brain, the heart, the Covid toe? Does SARS-CoV-2 traffic itself through the endothelial cells or get into the bloodstream this way? We don’t know the answer to that.”

https://elemental.medium.com/coronavirus-may-be-a-blood-vessel-disease-which-explains-everything-2c4032481ab2

If Covid-19 is a vascular disease, the best antiviral therapy might not be antiviral therapy

“I suspect from what we see and what our preliminary data show is that this virus has an additional risk factor for blood clots, but I can’t prove that yet,” Sethi says. An alternative theory is that the blood clotting and symptoms in other organs are caused by inflammation in the body due to an over-reactive immune response — the so-called cytokine storm

SARS-CoV-2 virus can infect the endothelial cells that line the inside of blood vessels. Endothelial cells protect the cardiovascular system, and they release proteins that influence everything from blood clotting to the immune response. In the paper, the scientists showed damage to endothelial cells in the lungs, heart, kidneys, liver, and intestines in people with Covid-19.

Treatment Protocol for COVID-19

The good news is that if Covid-19 is a vascular disease, there are existing drugs that can help protect against endothelial cell damage. In another New England Journal of Medicine paper that looked at nearly 9,000 people with Covid-19, Mehra showed that the use of statins and ACE inhibitors were linked to higher rates of survival. Statins reduce the risk of heart attacks not only by lowering cholesterol or preventing plaque, they also stabilize existing plaque, meaning they’re less likely to rupture if someone is on the drugs.

“It turns out that both statins and ACE inhibitors are extremely protective on vascular dysfunction,” Mehra says. “Most of their benefit in the continuum of cardiovascular illness — be it high blood pressure, be it stroke, be it heart attack, be it arrhythmia, be it heart failure — in any situation the mechanism by which they protect the cardiovascular system starts with their ability to stabilize the endothelial cells.”

  • The best therapy might actually be a drug that stabilizes the vascular endothelial.

Endothelial cell infection and endotheliitis in COVID-19

Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.
SARS-CoV-2 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. ACE2 receptors are also expressed by endothelial cells.
Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. Intriguingly, SARS-CoV-2 can directly infect engineered human blood vessel organoids in vitro.
Here we demonstrate endothelial cell involvement across vascular beds of different organs in a series of patients with COVID-19 (further case details are provided in the appendix).
Patient 1 was a male renal transplant recipient, aged 71 years, with coronary artery disease and arterial hypertension. The patient’s condition deteriorated following COVID-19 diagnosis, and he required mechanical ventilation. Multisystem organ failure occurred, and the patient died on day 8.

Post-mortem analysis of the transplanted kidney by electron microscopy revealed viral inclusion structures in endothelial cells (figure A, B). In histological analyses, we found an accumulation of inflammatory cells associated with endothelium, as well as apoptotic bodies, in the heart, the small bowel (figure C) and lung (figure D). An accumulation of mononuclear cells was found in the lung, and most small lung vessels appeared congested.

See Figures in https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext

Findings
We found evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation. Although the virus uses ACE2 receptor expressed by pneumocytes in the epithelial alveolar lining to infect the host, thereby causing lung injury, the ACE2 receptor is also widely expressed on endothelial cells, which traverse multiple organs.
Recruitment of immune cells, either by direct viral infection of the endothelium or immune-mediated, can result in widespread endothelial dysfunction associated with apoptosis (figure D).
The vascular endothelium is an active paracrine, endocrine, and autocrine organ that is indispensable for the regulation of vascular tone and the maintenance of vascular homoeostasis.
Endothelial dysfunction is a principal determinant of microvascular dysfunction by shifting the vascular equilibrium towards more vasoconstriction with subsequent organ ischaemia, inflammation with associated tissue oedema, and a pro-coagulant state.
Our findings show the presence of viral elements within endothelial cells and an accumulation of inflammatory cells, with evidence of endothelial and inflammatory cell death. These findings suggest that SARS-CoV-2 infection facilitates the induction of endotheliitis in several organs as a direct consequence of viral involvement (as noted with presence of viral bodies) and of the host inflammatory response. In addition, induction of apoptosis and pyroptosis might have an important role in endothelial cell injury in patients with COVID-19.
COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. This hypothesis provides a rationale for therapies to stabilise the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins., , , ,
This strategy could be particularly relevant for vulnerable patients with pre-existing endothelial dysfunction, which is associated with male sex, smoking, hypertension, diabetes, obesity, and established cardiovascular disease, all of which are associated with adverse outcomes in COVID-19.

References

    • Zhou F
    • Yu T
    • Du R
    • et al.
    Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

    Lancet.2020; 395: 1054-1062

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    • Horton R
  2. Offline: COVID-19—bewilderment and candour.

    Lancet.2020; 3951178

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    • Ferrario CM
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  3. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2.

    Circulation.2005; 111: 2605-2610

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    • Monteil V KH
    • Prado P
    • Hagelkrüys A
    • et al.
  4. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.

    Cell.2020; (published online in press.)

    https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00739.pdf

    Date accessed: April 17, 2020

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    • Flammer AJ
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  5. The assessment of endothelial function: from research into clinical practice.

    Circulation.2012; 126: 753-767

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    • Lerman LO
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  6. Endothelial dysfunction – a marker of atherosclerotic risk.

    Arterioscl Throm Vas.2003; 23: 168-175

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    • Anderson TJ
    • Meredith IT
    • Yeung AC
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    N Engl J Med.1995; 332: 488-493

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    • Virdis A
    • Ghiadoni L
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    • Salvetti A
  8. Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients.

    J Hypertens.1998; 16: 447-456

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    • Flammer AJ
    • Sudano I
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    • et al.
  9. Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis.

    Circulation.2008; 117: 2262-2269

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    • Hurlimann D
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  10. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.

    Circulation.2002; 106: 2184-2187

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    • Feldmann M
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  11. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed.

    Lancet.2020; (published online April 9.)

    https://doi.org/10.1016/S0140-6736(20)30858-8

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SOURCE

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext

Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

List of authors.

  • Mandeep R. Mehra, M.D.,
  • Sapan S. Desai, M.D., Ph.D.,
  • SreyRam Kuy, M.D., M.H.S.,
  • Timothy D. Henry, M.D.,
  • and Amit N. Patel, M.D.

Metrics

Abstract

BACKGROUND

Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context.

METHODS

Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020.

CONCLUSIONS

Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)

As the coronavirus disease 2019 (Covid-19) pandemic has spread around the globe, there has been growing recognition that persons with underlying increased cardiovascular risk may be disproportionately affected.1-3 Several studies of case series have noted cardiac arrhythmias, cardiomyopathy, and cardiac arrest as terminal events in patients with Covid-19.1-4 Higher incidences of cardiac arrhythmias, acute coronary syndromes, and heart failure–related events have also been reported during seasonal influenza outbreaks, which suggests that acute respiratory infections may result in activation of coagulation pathways, proinflammatory effects, and endothelial cell dysfunction.5 In addition, however, concern has been expressed that medical therapy for cardiovascular disease might specifically contribute to the severity of illness in patients with Covid-19.6,7

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Covid-19, has been shown to establish itself in the host through the use of angiotensin-converting enzyme 2 (ACE2) as its cellular receptor.8 ACE2 is a membrane-bound monocarboxypeptidase found ubiquitously in humans and expressed predominantly in heart, intestine, kidney, and pulmonary alveolar (type II) cells.7,9 Entry of SARS-CoV-2 into human cells is facilitated by the interaction of a receptor-binding domain in its viral spike glycoprotein ectodomain with the ACE2 receptor.10

ACE2 is counterregulatory to the activity of angiotensin II generated through ACE1 and is protective against detrimental activation of the renin–angiotensin–aldosterone system. Angiotensin II is catalyzed by ACE2 to angiotensin-(1–7), which exerts vasodilatory, antiinflammatory, antifibrotic, and antigrowth effects.11 It has been suggested that ACE inhibitors and angiotensin-receptor blockers (ARBs) may increase the expression of ACE2, which has been shown in the heart in rats,12 and thereby may confer a predisposition to more severe infection and adverse outcomes during Covid-19.6,7 Others have suggested that ACE inhibitors may counter the antiinflammatory effects of ACE2. However, in vitro studies have not shown direct inhibitory activity of ACE inhibitors against ACE2 function.9,13

Despite these uncertainties, some have recommended cessation of treatment with ACE inhibitors and ARBs in patients with Covid-19.6 However, several scientific societies, including the American Heart Association, the American College of Cardiology, the Heart Failure Society of America, and the Council on Hypertension of the European Society of Cardiology, have urged that these important medications should not be discontinued in the absence of clear clinical evidence of harm.14,15 We therefore undertook a study to investigate the relationship between underlying cardiovascular disease and Covid-19 outcomes and to evaluate the association between cardiovascular drug therapy and mortality in this illness.

Discussion

Our investigation confirms previous reports of the independent relationship of older age, underlying cardiovascular disease (coronary artery disease, heart failure, and cardiac arrhythmias), current smoking, and COPD with death in Covid-19. Our results also suggest that women are proportionately more likely than men to survive the infection. Neither harmful nor beneficial associations were noted for antiplatelet therapy, beta-blockers, or hypoglycemic therapy. It is important to note that we were not able to confirm previous concerns regarding a potential harmful association of either ACE inhibitors or ARBs with in-hospital mortality in this clinical context.

In viral infections such as influenza, older age is associated with an increased risk of cardiovascular events and death.5 In the 2003 epidemic of severe acute respiratory syndrome (SARS, caused by SARS-CoV-1 infection), sex differences in the risk of death similar to those we observed were noted.17 Women have stronger innate and adaptive immunity and greater resistance to viral infections than men.18 In animal models of SARS-CoV-1 infection, higher susceptibility of male mice to SARS-CoV-1 and greater accumulation of macrophages and neutrophils in the lungs have been described.19 Ovariectomy or the use of estrogen-receptor antagonists increased mortality from SARS-CoV-1 infection in female animals. Furthermore, the difference in risk between the sexes increased with advancing age.19 These findings may support the observation in our investigation that suggested an association between survival and female sex, independent of older age.

Infection with SARS-CoV-2 is a mild disease in most people, but in some the disease progresses to a severe respiratory illness characterized by a hyperinflammatory syndrome, multiorgan dysfunction, and death.20 In the lung, the viral spike glycoprotein of SARS-CoV-2 interacts with cell-surface ACE2, and the virus is internalized by endocytosis. The endocytic event up-regulates the activity of ADAM metallopeptidase domain 17 (ADAM17), which cleaves ACE2 from the cell membrane, resulting in a loss of ACE2-mediated protection against the effects of activation of the tissue renin–angiotensin–aldosterone system while mediating the release of proinflammatory cytokines into the circulation.21 The stress of critical illness and inflammation may unite in destabilizing preexisting cardiovascular illness. Vascular endothelial cell dysfunction, inflammation-associated myocardial depression, stress cardiomyopathy, direct viral infection of the heart and its vessels, or the host response may cause or worsen heart failure, demand-related ischemia, and arrhythmias.22 These factors may underlie the observed associations between cardiovascular disease and death in Covid-19.

In our analyses, use of either ACE inhibitors or statins was associated with better survival among patients with Covid-19. However, these associations should be considered with extreme caution. Because our study was not a randomized, controlled trial, we cannot exclude the possibility of confounding. In addition, we examined relationships between many variables and in-hospital death, and no primary hypothesis was prespecified; these factors increased the probability of chance associations being found. Therefore, a cause-and-effect relationship between drug therapy and survival should not be inferred. These data also offer no information concerning the potential effect of initiation of ACE inhibitor or statin therapy in patients with Covid-19 who do not have an appropriate indication for these medications. Randomized clinical trials evaluating the role of ACE inhibitors and statins will be necessary before any conclusion can be reached regarding a potential benefit of these agents in patients with Covid-19.

In this multinational observational study involving patients hospitalized with Covid-19, we confirmed previous observations suggesting that underlying cardiovascular disease is independently associated with an increased risk of in-hospital death. We were not able to confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital mortality in this clinical context.

Supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital. The development and maintenance of the Surgical Outcomes Collaborative database was funded by Surgisphere.

This article was published on May 1, 2020, and updated on May 8, 2020, at NEJM.org.

Author Affiliations

From Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston (M.R.M.); Surgisphere, Chicago (S.S.D.); Baylor College of Medicine and Department of Veterans Affairs, Houston (S.K.); Christ Hospital, Cincinnati (T.D.H.); the Department of Biomedical Engineering, University of Utah, Salt Lake City (A.N.P.); and HCA Research Institute, Nashville (A.N.P.).

References

1. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020 March 3 (Epub ahead of print).

2. Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020 March 25 (Epub ahead of print).

3. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020 March 27 (Epub ahead of print).

4. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020 March 19 (Epub ahead of print).

5. Nguyen JL, Yang W, Ito K, Matte TD, Shaman J, Kinney PL. Seasonal influenza infections and cardiovascular disease mortality. JAMA Cardiol 2016;1:274-81.

6. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020;8(4): e21.

7. Nicin L, Abplanalp WT, Mellentin H, et al. Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. Eur Heart J 2020 April 15 (Epub ahead of print).

8. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181(2):271.e8-280.e8.

9. Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J 2004;383: 45-51.

10. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARSCoV-2 spike glycoprotein. Cell 2020; 181(2):281.e6-292.e6.

11. Li XC, Zhang J, Zhuo JL. The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res 2017;125:21-38.

12. Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005;111: 2605-10.

13. Patel AB, Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? JAMA 2020 March 24 (Epub ahead of print).

14. American College of Cardiology. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. March 17, 2020 (https://www .acc.org/latest-in-cardiology/articles/ 2020/03/17/08/59/hfsa-acc-aha-statement -addresses-concerns-re-using-raas -antagonists-in-covid-19).

15. European Society of Cardiology. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. March 13, 2020 (https://www.escardio.org/Councils/ Council-on-Hypertension-(CHT)/News/ position-statement-of-the-esc-council-on -hypertension-on-ace-inhibitors-and-ang).

16. World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance. March 13, 2020 (https://www.who.int/docs/default -source/coronaviruse/clinical -management-of-novel-cov.pdf).

17. Karlberg J, Chong DSY, Lai WYY. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol 2004;159:229- 31. The New England Journal of Medicine Downloaded from nejm.org on June 1, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved. 8 n engl j med nejm.org The new england journal o f medicine

18. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016;16:626-38.

19. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection. J Immunol 2017;198: 4046-53.

20. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant 2020;39:405-7.

21. Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: a double edged sword. Circulation 2020 March 26 (Epub ahead of print).

22. Mehra MR, Ruschitzka F. COVID-19 illness and heart failure: a missing link? JACC Heart Fail (in press). Copyright © 2020 Massachusetts Medical Society

 

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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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Blood Clots Tied to Coronavirus Problems

Posted in 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, tagged , , , , on May 11, 2020| Leave a Comment »

Blood Clots Tied to Coronavirus Problems

Reporter: Irina Robu, PhD

Frequent complications of COVID-19 include purple rashes, swollen legs, clogged catheters and sudden death. Anyone with a severe illness is at risk of developing clots, but hospitalized patients with COVID-19 appear to be more susceptible. Blood clots in the deep veins of the body can occur due to injury/damage, inactivity, surgery, chemotherapy for cancer. Injuries like bone fractures or muscle tears can cause damage to blood vessels, leading to clots. Yes, due to long periods of inactivity, gravity causes blood to stagnate in the lowest areas of your body.

Yet, blood clots can form a variety of reasons. One of the most known blood clots that form in veins is pulmonary embolism caused by deep vein thrombosis. In some cases, a pulmonary embolism can be difficult to diagnose when you have an underlying lung or heart condition. It is possible that anything that gets in the bloodstream and then lodges in the smaller pulmonary arteries can be a pulmonary embolism.

Research from Netherlands and France suggest that clots appear in 20% to 30% of critically ill COVID-19 patients. Researchers have a few credible hypotheses to explain the phenomenon and they are starting to launch studies aimed at gaining mechanistic visions. But with the death toll rising, they are also scrambling to test clot-curbing medications. Common anticoagulant blood thinners such as warfarin and enoxaparin don’t reliably avert clotting in people with COVID-19 and young people are dying of strokes caused by the blockages in the brain. It is indicated that patients in the hospital have extremely elevated levels of a protein fragment called D-dimer, which is generated when a clot breaks down. High levels of D-dimer appear to be a powerful predictor of mortality in hospitalized patients infected with coronavirus.

Jeffrey Laurence, a hematologist at Weill Cornell Medicine in New York City studied lung and skin samples from three people infected with COVID-19 and found that the capillaries were clogged with clots. Even with all the research, how clotting occurs is still a mystery. One probability is that SARS-CoV-2 is unswervingly attacking the endothelial cells that line the blood vessels, which harbor the same ACE2 receptor that the virus uses to enter lung cells. This is confirmed by researchers from University Hospital Zurich in Switzerland and Brigham and Women’s Hospital in Boston, Massachusetts, who observed SARS-Cov-2 in endothelial cells inside kidney tissue.

Clotting can also be affected by the virus effects, because in some people COVID-19 prompts immune cells to release a torrent of chemical signals that ramps up inflammation. As the virus appears to activate the complement system, it then sparks clotting which acts a defense mechanism. People with the COVID-19 disease who become hospitalized usually have a number of risk factors for clotting such as high blood pressure, diabetes and/or genetic predisposition to clotting.

While researchers initiate how clotting occurs in people with COVID-19, they’re hurrying to test new therapies meant at preventing and busting clots. Blood-thinning medications are usually the standard of care for patients in the intensive-care unit and patients with COVID-19 are no exception. Similar trials are planned for scientists at Beth Israel Deaconess Medical Center have started enrolment for a clinical trial to evaluate an even more powerful clot-busting medication, tissue plasminogen activator. TPK is a drug more potent that carries higher risks of serious bleeding than do blood thinners. Scientists anticipate that these trials and others will deliver the data required to help physicians to make difficult treatment decisions.

SOURCE

https://www.scientificamerican.com/article/blood-clots-are-mysteriously-tied-to-many-coronavirus-problems/?fbclid=IwAR2SsBh00fkPjSqgCYyFpwCu6FlZbmnsYtSDYHqZ7xW_Dw2yP7f9HaLUhTE

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Special COVID-19 Christopher Magazine

Posted in Cardiovascular and Vascular Systems, coronavirus, Coronavirus Gene Expression, COVID-19, Evolution of Biology Through Culture, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Interviews with Key Opinion Leaders (KOLs), Interviews with Scientific Leaders, Population genetics, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, 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, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , on May 10, 2020| Leave a Comment »

Reporter: Stephen J. Williams, PhD

via Special COVID-19 Christopher Magazine

 

Special COVID-19 Christopher Magazine

 / KARLSMALLEY
Article ID #277: Special COVID-19 Christopher Magazine. Published on 5/10/2020

WordCloud Image Produced by Adam Tubman

Christopher-cover

Antonio Giordano, MD, PhD. explains what COVID is and how to contain the infection, pointing also to what will require attention next.

Please see this special release at http://online.fliphtml5.com/qlnw/zgau/#p=1

 

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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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