Posts Tagged ‘COVID-19’

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The world needs mass at-home serological testing for antibodies elicited by SARS-CoV-2, and rapid and frequent point-of-care testing for the presence of the virus’ RNA in selected populations.

How did we end up here? Two ways. Gradually, then suddenly. Ernest Hemingway’s passage is a fitting description for humanity’s perception of the exponential growth of COVID-19 cases and deaths (Fig. 1). The worldwide spread of a highly infectious pathogen was only a matter of time, as long warned by many epidemiologists, public health experts, and influential and prominent voices, such as Bill Gates. Yet most of the world was unprepared for such a pandemic; in fact, most Western countries (prominently the United States1) fumbled their response for weeks. Singapore, Hong Kong and Taiwan have shown the world that, to contain the propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), governments need to quickly implement aggressive testing (by detecting the viral RNA through polymerase chain reaction (PCR)), the isolation of those infected and the tracing and quarantining of their contacts, while educating their citizens about the need for physical distancing and basic public health measures (in particular, frequent hand-washing and staying at home if feeling unwell). When outbreaks are not detected and acted upon sufficiently early, drastic physical distancing — of the sort implemented by China at the end of January and maintained for months — can eventually suppress the outbreak (Fig. 1). It is however unclear whether Western countries that have implemented strict physical-distancing measures later in their infection curve will be able to gradually release such lockdowns, let alone see their outbreaks controlled.

Fig. 1: Early mass testing and early containment measures save lives.
figure1
COVID-19 confirmed cases and deaths for selected countries in a 10-day window ending at each data point (successive data points on a line denote consecutive days). Numbers in colour are the estimated number of total PCR tests per million people up to the data point indicated; stars indicate when strict lockdowns were enacted. Deaths lag with respect to confirmed cases, according to the estimated two-to-three week interval10 between the onset of symptoms and death. Case fatality rates — that is, the fractions of total confirmed cases that become deaths — mostly depend on the extent of testing, on the capacity of a country’s healthcare system, on its demographics and on the availability of drugs that can significantly dampen the severity of COVID-19 in those infected. Even with mass testing, the case fatality rate of COVID-19 is expected to be a multiple of that for seasonal flu in the United States (0.1%). Countries that deployed tests for detecting SARS-CoV-2 RNA early and widely (such as South Korea), that applied contact tracing and targeted physical distancing measures for detected cases (such as South Korea and Japan), or that enacted early, strict lockdowns (such as China) are more likely to contain the disease outbreak earlier. In fact, Singapore, Hong Kong and Taiwan have contained COVID-19 outbreaks and have managed to limit COVID-19-related deaths to less than 10 (hence, these countries are not included in the figure). Data updated 6 April 2020. Individual data points can be affected by reporting errors and delays, by wilful underreporting and by location-specific definitions (and changes to them) for confirmed cases and deaths. Data sources: European Center for Disease Control and Prevention11 (cases and deaths); Our World in Data12, various government sources (tests). A regularly updated version of this graph is available13.

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Such non-pharmacological interventions aim to ‘flatten’ the infection curve by reducing the number of transmission chains and thus the virus’ basic reproduction number — that is, the average number of new cases generated by a case in an immunologically naive population. In the absence of a safe and effective vaccine — which, if current efforts end up being successful, is unlikely to become widely available within the next two years — non-pharmacological interventions will need to remain in place to reduce the threat of secondary outbreaks by maintaining the basic reproduction number below 1. However, the type and degree of the interventions could be better tailored if governments knew who are currently infected and who have been infected and recovered. For this, the world needs to see the mass deployment of serological testing for SARS-CoV-2 antibodies (which appear to be highly specific2), and frequent testing for SARS-CoV-2 RNA in those likely to be exposed to the virus (especially healthcare workers) or at a higher risk for severe respiratory disease (such as the elderly and younger individuals with relevant comorbidities).

Medical-device companies and government and research laboratories around the world have rushed to adapt and scale up nucleic acid tests (mostly employing PCR, but also CRISPR-based detection and loop-mediated isothermal amplification) to detect the virus’ RNA, and government agencies are scrambling to assess them via emergency routes (such as the Emergency Use Authorization program3 by the United States Food and Drug Administration (FDA)). Point-of-care PCR kits — based on lateral-flow technology or cartridge-based instruments for sample preparation, nucleic acid amplification and detection — also require RNA extraction from nasal or throat swabs (or both) but can speed up the time-to-result from a few hours to roughly 30 minutes4 (and in one test, positive results can be obtained in five minutes5), with near-perfect sensitivity and specificity if sample acquisition and preparation and device operation are carried out appropriately by trained personnel. This limits the usefulness of these kits for at-home use, which would significantly raise the fraction of false negatives. Immunoassays incorporating monoclonal antibodies specific for SARS-CoV-2 antigens (for instance, a domain of the virus’ spike protein) should be amenable to home use, yet they are more difficult to develop (the antibodies are typically obtained via the immunization of transgenic animals) and are less accurate than nucleic acid testing.

Lateral flow immunoassays (akin to the pregnancy test) and enzyme-linked immunosorbent assays to detect antibodies elicited by the virus are also being rapidly developed (mostly by Chinese companies thus far). Tens of at-home lateral-flow devices6 are already being commercialized, having obtained the European Union’s CE mark or been authorized for emergency use by the FDA or the Chinese FDA. In many of these kits, the recombinant viral antigens bind to SARS-CoV-2-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) within 15 min; hence, these tests can also detect early-stage infection (of which IgM levels are a marker), but at the expense of sensitivity and accuracy (which can exceed 90% and 99% for IgG7. The real-world performance of such serology tests, which is currently unknown, will depend on the actual prevalence of COVID-19 in the population. For example, at a 5% pre-test probability of having the disease, a test with 99% sensitivity and 95% specificity would lead to as many true positives as false positives. Hence, before wide deployment, governments need to ensure that these finger-prick antibody tests are clinically validated8.

The world should roll out both antibody and nucleic acid tests on a wide scale. Widely available and inexpensive serological testing would help governments to tailor non-pharmacological interventions to specific locations and populations, to decide when to relax them and to permit citizens immune to the virus to help those who remain susceptible to it. Mass testing would also provide valuable data to pressing unknowns: what are the infection rates across locations and populations? What fraction of the population is immune? How long does immunity last and how does it depend on age and on the severity of infection? Wider deployment of nucleic acid tests would also provide clues about the prevalence of a wider range of COVID-19 symptoms, the role of children in spreading the disease, and the epidemiological characteristics of superspreaders9 and of those who were infected and asymptomatic. Testing should be complemented by privacy-minded digital surveillance, via phone apps, aiding contact tracing and permitting lighter levels of physical distancing — as done in Singapore, South Korea and Taiwan. The downside is that any invasion of privacy via the tracking of people can last longer than necessary. De-identified and aggregated health data, such as heart rate and activity levels collected via commercial wearables, might also predict (https://detectstudy.org) the emergence and location of outbreaks.

In our globalized world, the risk of further waves of COVID-19 outbreaks, and thus of prolonged drastic economic consequences, will remain substantial as long as any outbreak anywhere remains. It is in the world’s best interest that richer countries provide test kits, technical and public-health knowledge, personnel, personal protective equipment and, eventually, the necessary vaccine doses to poorer countries to assist them in their efforts to reduce and contain the spread of SARS-CoV-2. This is humanity’s next test.

References
1.
Shear, M. D. et al. The lost month: how a failure to test blinded the U.S. to Covid-19. The New York Times https://www.nytimes.com/2020/03/28/us/testing-coronavirus-pandemic.html (2020).

2.
Ju, B. et al. Preprint at https://doi.org/10.1101/2020.03.21.990770 (2020).

3.
Emergency Use Authorization (U.S. Food & Drug Administration, 2020); https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations

4.
Accula test: SARS-CoV-2 test. U.S. Food & Drug Administration https://www.fda.gov/media/136355/download (2020).

5.
Abbott realtime SARS-CoV-2 assay. Abbott https://www.molecular.abbott/us/en/products/infectious-disease/RealTime-SARS-CoV-2-Assay (2020).

6.
SARS-CoV-2 Diagnostic Pipeline (Find, 2020); https://www.finddx.org/covid-19/pipeline/

7.
COVID-19 Coronavirus rapid test casette. SureScreen Diagnostics https://www.surescreen.com/products/covid-19-coronavirusrapid-test-cassette (2020).

8.
The Associated Press. Virus test results in minutes? Scientists question accuracy. The New York Times https://www.nytimes.com/aponline/2020/03/27/world/europe/bc-virus-outbreakscramble-for-tests.html (2020).

9.
Hu, K. et al. Preprint at https://doi.org/10.1101/2020.03.19.20026245 (2020).

10.
Verity, R. et al. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(20)30243-7 (2020).

11.
Today’s Data on the Geographic Distribution of COVID-19 Cases Worldwide (European Centre for Disease Prevention and Control, 2020); https://www.ecdc.europa.eu/en/publications-data/download-todays-data-geographic-distribution-covid-19-cases-worldwide

12.
Roser, M., Ritchie, H. & Ortiz-Ospina, E. Coronavirus Disease (COVID-19) – Statistics and Research (Our World in Data, 2020); https://ourworldindata.org/coronavirus

13.
Pàmies, P. Tracking COVID-19 cases and deaths. Nature Research Bioengineering Community https://bioengineeringcommunity.nature.com/users/20986-pep-pamies/posts/64985-tracking-covid-19-cases-and-deaths (2020).

https://www.nature.com/articles/s41551-020-0553-6?utm_source=Nature+Briefing&utm_campaign=5907ab71f9-briefing-dy-20200408&utm_medium=email&utm_term=0_c9dfd39373-5907ab71f9-44039353


The antihypertension drugs called ARBs disrupt the pathway that leads to blood vessel constriction by preventing angiotensin II from binding to the AT1 receptor. This now-available angiotensin is then processed by ACE2 (not shown) into the form that leads to blood vessel dilation. ACE inhibitors work by blocking the production of angiotensin II.


A coronavirus spike protein (red) binds to an ACE2 receptor (blue).

For the past few weeks, research journals have been publishing reports on the connection between medications that reduce high blood pressure and COVID-19. The concern is that the medications might increase the abundance of the receptor that SARS-CoV-2—the virus that causes COVID-19—uses to enter cells. Boosting levels of these ACE2 receptors on lung and heart cells could give the virus more cellular entry points to target and potentially make symptoms of the disease more severe.

It’s a hypothesis that is important to test, notes Carlos Ferrario, a professor of general surgery at Wake Forest School of Medicine who specializes in research on antihypertensive drugs.

So far, the data supporting the connection between blood pressure medications—specifically, angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)—and COVID-19 are scant. Yet media coverage of the connection has led patients prescribed the drugs to call their doctors asking if they should stop taking them. In response, several medical associations—including the American College of Cardiology, the American Heart Association, the Heart Failure Society of America, and the European Society of Cardiology—have issued guidelines saying patients should not stop taking the antihypertensive drugs because there’s no evidence to support the claim that they cause more-severe SARS-CoV-2 infections.

In support of that recommendation, Ankit Patel, a clinical and research fellow focusing on the kidneys at Brigham and Women’s Hospital in Boston, and his Brigham colleague Ashish Verma dug into the literature to address the confusion and reported March 24 in JAMA that there’s no definitive evidence to suggest ACE inhibitors and ARBs increase the severity of COVID-19. Another team of doctors, writing in the March 30 issue of the New England Journal of Medicine, came to the same conclusion.

Instead of making COVID-19 symptoms worse, some antihypertensive drugs may actually reduce the severity of infections, and could therefore be used to treat the disease, both sets of doctors say. A closer look at the underlying mechanisms of the medications has also buoyed another idea for how to treat COVID-19—give patients the enzyme ACE2 as a decoy to direct SARS-CoV-2 away from their cells. A biotech company developing such an approach using recombinant ACE2 received regulatory approval today (April 2) to start clinical trials on COVID-19 patients.

“It’s a very interesting idea,” David Kass, a cardiologist at Johns Hopkins School of Medicine tells The Scientist. “Obviously, if the virus binds to this form of ACE2 that’s floating around in the bloodstream and not attached to a cell, it won’t be able to multiply and damage the cells.”

How ACE2 acts in the body

The ACE2 decoy idea can be traced back to early work on the receptor by Josef Penninger, a molecular immunologist at the University of British Columbia. Roughly 20 years ago, he was working as a researcher at the Ontario Cancer Institute when he cloned ACE2 and started probing what it does.

A senior investigator in the lab thought the work was a waste of time, Penninger recalls, telling him that scientists already knew everything they needed to know about the renin–angiotensin system, which regulates blood pressure and fluid and electrolyte balance. The senior researcher added that ACE2, which is associated with the system, was so boring Penninger should stop working on it before he ruined his career. At the time, it was a painful comment to hear, but it made Penninger even more determined to understand ACE2’s biological function. “It’s funny now,” he says.

Over time, he and others started to unravel how ACE2 operates within the renin–angiotensin system. The system starts with a hormone secreted by the kidneys called renin that cleaves the peptide hormone angiotensinogen into angiotensin I. That cleavage product is then converted into a version of angiotensin II by ACE, the angiotensin-converting enzyme. That version binds to the angiotensin II type 1 (AT1) receptor, on the surface of blood vessels, lung, and heart cells among other cells in the body. Where those molecules meet, blood vessels constrict and blood pressure rises, which can contribute to acute respiratory distress syndrome.

This is where ACE2 comes in. The enzyme cleaves an amino acid off angiotensin II to create angiotensin 1-7, which dilates blood vessels, reduces inflammation, and inactivates angiotensin II before it gets to a cell’s AT1 receptor.

“Whenever there is a hormone that has a certain interaction in the body, there’s often another hormone to counteract it,” Patel says. ACE2 counterbalances ACE, and “the body tries to maintain those two in balance to keep things in check.”

Doctors prescribe ACE inhibitors to people with high blood pressure and other heart problems to prevent ACE from converting angiotensin I into the form of angiotensin II that constricts blood vessels, leading to lower blood pressure. ARBs prevent angiotensin II from binding to AT1 receptors so ACE2 metabolizes it, also lowering blood pressure.

“We actually know a lot about ACE2 and its biology,” Penninger says. “We should follow the data.”

An ACE2 boost might distract the coronavirus

Penninger published his work on ACE2 biology in 2002, just before the outbreak of SARS in 2003. After the virus infected humans and started to spread, a team from Boston published the first clues to how SARS-CoV targets ACE2 to gain entry into human cells. There were other receptors proposed as entry points at that time, but the mention of ACE2 caught Penninger’s attention.

He started a study in mice, and in 2005 published the first definitive evidence that SARS-CoV uses ACE2 to infect its host’s cells. In the same study, Penninger and his colleagues showed that the virus reduces ACE2 abundance, which results in ramped-up angiotensin II levels, in turn causing acute lung failure. The work revealed what made SARS-CoV so deadly, he says.

Based on the data, Penninger’s team argued that administering a recombinant ACE2 protein could trick the virus into binding with it, rather than actual ACE2 receptors. This could then protect endogenous receptors and allow them to continue to function in counterbalancing ACE, and, ideally, protect the lung and heart from damage during a viral infection.

Penninger has been working on developing a recombinant ACE2 protein therapy for 15 years. He first tested it in mice after they’d inhaled acid; treatment with ACE2 prevented the animals from developing acute lung injury. Other studies showed the recombinant proteins could be used to treat heart failure, and eventually the research led to clinical trials to test ACE2’s safety in humans.

So far, early clinical trials of the drug have shown it does not have any harmful side effects in healthy humans or in patients with lung failure. (Penninger was not involved in conducting the clinical trial).

The next step is to see if the recombinant enzyme can intervene in a SARS-CoV-2 infection. In a study published today in Cell, Penninger’s group shows the drug can reduce the viral load of SARS-CoV-2 in experimental models by a factor of 1,000 to 5,000. Today, Apeiron Biologics, the biotech company Penninger founded in 2005, was also awarded regulatory approval to start clinical trials to test the drug in patients with severe COVID-19 symptoms, which, he says, could happen as early as the end of next week.

Ramping up ACE2 using ARBs instead

Penninger’s early work on SARS-CoV is part of what prompted the discussion among physicians about the safety of ACE inhibitors and ARBs, which regulate levels of angiotensin II directly or via its cell receptor. Another study related to the antihypertensive drugs that got the doctors’ attention was one done by Ferrario more than a decade ago. Administering ACE inhibitors or ARBs to rats led to increased ACE2 activity in the animals’ hearts, exactly where scientists and physicians wouldn’t want more ACE2 receptors for SARS-CoV-2 to target. Or at least, that’s what one might think.

But Penninger’s preliminary work from 2005 implies that increasing ACE2 levels through antihypertensive drugs might treat symptoms of SARS-CoV-2 infection, with ARBs showing more promise than ACE inhibitors.

ACE inhibitors lower levels of angiotensin II, and when they do, there’s less substrate for ACE2 to metabolize, which could leave the enzyme idle and therefore open to attack by SARS-CoV-2. That’s part of the argument some researchers were making about ACE inhibitors contributing to COVID-19 infection. However, there are no data to show that happens, Penninger says. Still, he argues, the way ACE inhibitors work in the body, freeing up ACE2 on cells for viral targeting rules them out as potential COVID-19 treatments.

Using ARBs to combat the virus is a more promising approach. As Penninger’s team showed, SARS-CoV reduced the abundance of ACE2, causing hypertension and lung failure in mice. If ARBs boost ACE2 expression, that might counteract the effects of the infection. The hypothesis is preliminary at this point, says David Gurwitz, a geneticist with a background in pharmacology at Tel Aviv University. He described the idea, which seems paradoxical, March 4 in a review article published in Drug Development Research. The main difference between ACE inhibitors and ARBs is that the former just frees up existing ACE2 receptors, while the latter leads to an increase in the number of receptors, allowing more angiotensin II to be converted to angiotensin 1-7. That would dilate blood vessels and reduce inflammation, countering any hypertensive state caused by a viral infection.

In clinical analyses designed to ensure that ARBs don’t harm COVID-19 patients, researchers in China have published preliminary data on medRxiv supporting the hypothesis. In the study, the team tracked the health outcomes of 511 patients taking medications for heart conditions who then became infected with SARS-CoV-2. The patients took either ACE inhibitors, ARBs, or other drugs that lowered their blood pressure. The results showed that patients over age 65 taking ARBs were at a lower risk of developing severe lung damage than age-matched patients not taking the medications, but there weren’t enough data to do a similar analysis for ACE inhibitors. The work reveals there was no hazard for ARBs, and there may be benefits, but as always, more data are needed, Kass says.

One way to collect those data on a larger scale, Gurwitz explains, would be to analyze many more COVID-19 patients’ health records to see if they’ve been taking ARBs prior to SARS-CoV-2 infection, then comparing the severity of infection in those patients and how well they recovered with the symptoms of COVID-19 patients not taking the medications.

Gurwitz also recommends researchers compare the percentage of people chronically medicated with different antihypertensive medications in the general population with the percentage of them among hospital admissions for COVID-19. These types of analyses could also be done with many other approved drugs, he notes, not just ARBs.

Already, physicians at University Hospital Zurich have begun a patient registry to do these types of health informatics analyses, and physicians and researchers at Johns Hopkins School of Medicine and other public health schools in the US have been discussing the feasibility of starting these studies.

“Unfortunately for the country, we’re going to have lots of COVID-19 cases,” Kass says. “Groups are now trying to get these epidemiological studies started so we can get answers.”

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Viruses like the novel coronavirus are shells holding genetic material

As the novel coronavirus causing COVID-19 spreads across the globe, with cases surpassing 284,000 worldwide today (March 20), misinformation is spreading almost as fast.

One persistent myth is that this virus, called SARS-CoV-2, was made by scientists and escaped from a lab in Wuhan, China, where the outbreak began.

A new analysis of SARS-CoV-2 may finally put that latter idea to bed. A group of researchers compared the genome of this novel coronavirus with the seven other coronaviruses known to infect humans: SARS, MERS and SARS-CoV-2, which can cause severe disease; along with HKU1, NL63, OC43 and 229E, which typically cause just mild symptoms, the researchers wrote March 17 in the journal Nature Medicine.

“Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” they write in the journal article.

Kristian Andersen, an associate professor of immunology and microbiology at Scripps Research, and his colleagues looked at the genetic template for the spike proteins that protrude from the surface of the virus. The coronavirus uses these spikes to grab the outer walls of its host’s cells and then enter those cells. They specifically looked at the gene sequences responsible for two key features of these spike proteins: the grabber, called the receptor-binding domain, that hooks onto host cells; and the so-called cleavage site that allows the virus to open and enter those cells.

That analysis showed that the “hook” part of the spike had evolved to target a receptor on the outside of human cells called ACE2, which is involved in blood pressure regulation. It is so effective at attaching to human cells that the researchers said the spike proteins were the result of natural selection and not genetic engineering.

Here’s why: SARS-CoV-2 is very closely related to the virus that causes severe acute respiratory syndrome (SARS), which fanned across the globe nearly 20 years ago. Scientists have studied how SARS-CoV differs from SARS-CoV-2 — with several key letter changes in the genetic code. Yet in computer simulations, the mutations in SARS-CoV-2 don’t seem to work very well at helping the virus bind to human cells. If scientists had deliberately engineered this virus, they wouldn’t have chosen mutations that computer models suggest won’t work. But it turns out, nature is smarter than scientists, and the novel coronavirus found a way to mutate that was better — and completely different— from anything scientists could have created, the study found.

Another nail in the “escaped from evil lab” theory? The overall molecular structure of this virus is distinct from the known coronaviruses and instead most closely resembles viruses found in bats and pangolins that had been little studied and never known to cause humans any harm.

“If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness,” according to a statement from Scripps.

Where did the virus come from? The research group came up with two possible scenarios for the origin of SARS-CoV-2 in humans. One scenario follows the origin stories for a few other recent coronaviruses that have wreaked havoc in human populations. In that scenario, we contracted the virus directly from an animal — civets in the case of SARS and camels in the case of Middle East respiratory syndrome (MERS). In the case of SARS-CoV-2, the researchers suggest that animal was a bat, which transmitted the virus to another intermediate animal (possibly a pangolin, some scientists have said) that brought the virus to humans.

In that possible scenario, the genetic features that make the new coronavirus so effective at infecting human cells (its pathogenic powers) would have been in place before hopping to humans.

In the other scenario, those pathogenic features would have evolved only after the virus jumped from its animal host to humans. Some coronaviruses that originated in pangolins have a “hook structure” (that receptor binding domain) similar to that of SARS-CoV-2. In that way, a pangolin either directly or indirectly passed its virus onto a human host. Then, once inside a human host, the virus could have evolved to have its other stealth feature — the cleavage site that lets it easily break into human cells. Once it developed that capacity, the researchers said, the coronavirus would be even more capable of spreading between people.

All of this technical detail could help scientists forecast the future of this pandemic. If the virus did enter human cells in a pathogenic form, that raises the probability of future outbreaks. The virus could still be circulating in the animal population and might again jump to humans, ready to cause an outbreak. But the chances of such future outbreaks are lower if the virus must first enter the human population and then evolve the pathogenic properties, the researchers said.

https://www.livescience.com/coronavirus-not-human-made-in-lab.html?utm_source=Selligent&utm_medium=email&utm_campaign=15588&utm_content=20200321_Coronavirus_Infographic+&utm_term=3675605&m_i=Y78%2BcYxf2Qsne7KyAz%2Bro3S%2BCTo6VIPlVFATrnaXXtdOBEIZH%2BPO_hNXo7rq5mPCFLKyREQpjzGdZOYb2pvbuvu8nQp0tu

On Wednesday, Gregory Rigano, an advisor to the Stanford University School of Medicine, claimed that a world-renowned French researcher had tested a promising cure for coronavirus.

He tweeted: “Full peer-reviewed study has been released by Didier Raoult MD, PhD. After 6 days 100% of patients treated with HCQ + Azithromycin were virologically cured.”

Appearing on Fox News Wednesday night, Rigano followed up by stating:

And I’m here to report that as of this morning, about 5:00 this morning, a well-controlled peer-reviewed study carried out by the most eminent infectious disease specialist in the world—Didier Raoult, MD, PhD—out of the south of France, in which he enrolled 40 patients, again, a well-controlled peer review study, that showed a 100 percent cure rate against coronavirus. The study was released this morning on my Twitter account, @Riganoesq as well as our most recent website, @covidtrial.io. The study was recently accepted to the International Journal of Antimicrobial Agents by Elsevier.

Rigano continued, “In fact to be able to cure a virus was said to be mathematically impossible, and the first company that did it was a small biotech called Pharmacet that was acquired by Gilead Sciences in a cure for hepatitis C. What we’re here to announce is a second cure to a virus of all time.”

On Monday, The Daily Wire reported that an Australian team had announced they might have found a cure for coronavirus, and it was in a similar vein:

According to infectious disease experts at the University of Queensland in Brisbane, Australia, they may have found a treatment that could possibly eliminate the coronavirus. “University of Queensland Centre for Clinical Research director Professor David Paterson told news.com.au today they have seen two drugs used to treat other conditions wipe out the virus in test tubes,” News.com.aureported Monday.

The two medications Paterson referred to are Chloroquine, an anti-malarial drug, and HIV-suppressing combination lopinavir/ritonavir. Paterson told the outlet that it seemed reasonable to call the drugs “a treatment or a cure … It’s a potentially effective treatment. Patients would end up with no viable coronavirus in their system at all after the end of therapy.”

According to covidtrial.io, here are the backgrounds for Didier Raoult and another doctor involved in the study:

Didier Raoult created the Rickettsia Unit at Aix-Marseille University. Since 2008, Dr. Raoult has served as the director of URMITE (Research Unit in Infectious and Tropical Emergent Diseases), collaborating with CNRS (National Center for the Scientific Research), IRD (Research for the Development Institute), INSERM (National Institute of Health and Medical Research) and Aix Marseille University. His laboratory employs more than 200 people, including nearly 100 active researchers who publish between 250 and 350 papers per year and have produced over 50 patents.

Dr. Chandra Duggirala has a bio that states:

He founded Novobionics, a medical device company to treat diabetes and obesity non-invasively and invented it’s double sleeve technology. He lead the company through preclinical trials and several US and international patents. He is also the Principal Investigator of the Reset-Youth trial, one of the largest clinical trials for investigating the reversibility of epigenetic markers of aging. He also founded a software company at the intersection of nutritional biology and A.I.

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By Rachael Rettner

A small Italian town appears to have drastically reduced coronavirus infections — reaching zero cases last week — after implementing an aggressive tactic to curb spread, according to news reports.

The town, Vo Euganeo, in northern Italy, saw a cluster of cases of the new coronavirus disease (COVID-19) in the third week of February and was home to the country’s first death from COVID-19, on Feb. 21, according to The Straits Times.

Following this death, the town was put on lockdown, and all 3,300 residents were tested for coronavirus, according to Sky News.

This mass testing revealed that about 3% of residents were infected with the virus, and of these, about half did not show any symptoms, according to ProMarket, the blog of the Stigler Center at the University of Chicago Booth School of Business. After two weeks of a strict lockdown and quarantine of cases, only 0.25% of residents were infected. The town isolated these last few cases and has since reopened.

Vo Euganeo has not reported any new cases since Friday (March 13), according to Sky News.

“The lesson we learned is that isolating all positive cases, whether they were sick or not, we were able to reduce transmission by 90 percent,” Andrea Cristani, a professor of microbiology at the University of Padua in Italy who helped carry out the testing, told RFI.

This message echoes a recent statement from the World Health Organization (WHO). “We have a simple message to all countries — test, test, test,” Tedros Adhanom Ghebreyesus, director-general of WHO, said at a news briefing Monday (March 16). “All countries should be able to test all suspected cases. They cannot fight this pandemic blindfolded.”

COVID-19 cases in the rest of Italy have soared in recent weeks. The country has reported more than 35,700 cases and nearly 3,000 deaths as of Wednesday (March 18).

https://www.livescience.com/small-italian-town-cuts-coronavirus-cases-testing.html?utm_source=Selligent&utm_medium=email&utm_campaign=15489&utm_content=20200319_Coronavirus_Infographic+&utm_term=3675605&m_i=OguKUMtlVZ2XR0FtmKzVwy23qhJljQ_ECDHOF9yeeiliWl1lAhbCDeG8red8tr52pB6GdMdlKqG0SWmT4cwSI4C0qaXToh


Fifteen-year-old Shaivi Shah donated more than 150 hygiene kits to the homeless.

By Lauren Lee

The teenager and her parents made the purchases and now it was time to pack them up.

Shaivi Shah, 15, recruited her fellow Tesoro High School honor society members to assemble kits of hand sanitizer, antibacterial soap, lotion and reusable masks for distribution to help people experiencing homelessness in the middle of a pandemic.

“They don’t have necessities right now that are crucial to remain clean and stay germ-free,” Shaivi told CNN.


Shah assembles the kits at home.

California Gov. Gavin Newsom’s recent speech about the state’s homeless problem sparked her idea. So far, the efforts of the passionate student has led to the delivery of more than 150 low-cost sanitation kits to three Los Angeles shelters.

A vulnerable population

According to the US Interagency Council on Homelessness, on any given day, more than 150,000 Californians are living in homelessness — the most of any US state. Shaivi feared they might be forgotten in this time of social distancing.

“A lot of people are just focusing on themselves and their families,” she said.

The altruistic teen from Rancho Santa Margarita started a GoFundMe account to raise funds to expand her program throughout California and the US.

https://www.gofundme.com/f/covid19-sanitation-kit-for-the-homeless-community

“These people that are living on the streets, they have no protection, so even a small amount could help.”

A call to service

Shah hopes that her actions will encourage others to step in to help in their own ways during the pandemic.

“It’s important for people to step in and just do whatever they can, even if it helps just one person.”

Shah is no stranger to community service. Last year, she raised thousands of dollars for a homeless shelter through a dance recital. Her duty to help people experiencing homelessness comes from a feeling of gratitude.

“Imagine yourself in their shoes, without a house, without clothes, without any sanitation,” she says.

“That’ll make you be grateful for what you have, and possibly donate and do something good for the other people.”

https://www.cnn.com/2020/03/19/us/teen-donates-sanitization-kits-to-homeless-iyw-trnd/index.html

By Elise Ma

One day after the U.S. began the first human trial of an mRNA vaccine candidate for COVID-19 on March 16, China said Tuesday evening that it had approved the first clinical trial of a vaccine candidate developed by domestic researchers.

The vaccine candidate, known as Ad5-nCoV, is a recombinant novel coronavirus vaccine. It was jointly developed by Tianjin-based Cansino Biologics Inc. and the Institute of Biotechnology of the Academy of Military Medical Sciences. The clinical trial will enroll 108 subjects and take place at Tongji Hospital in Wuhan, the epicenter of COVID-19.

Cansino said Ad5-nCoV is a genetically engineered vaccine candidate with the replication-defective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein. The vaccine candidate is intended to be used to prevent the disease caused by the novel coronavirus infection.

Backed by the state, the company has also obtained support from the Tianjin Science and Technology Bureau through the Project on Emergency Prevention and Control of COVID-19 Infection to develop the vaccine.

On March 17, the company said it has started to prepare for clinical trials of Ad5-nCoV and the pre-screening of healthy volunteers.

Cansino CEO Xuefeng Yu said the company and the academy have been collaborating closely since late January to develop Ad5-nCoV and generate sound scientific data to support its IND filing. “Having committed to providing unconditional support to fight against the global epidemic, Cansino is determined to launch our vaccine product candidate as soon as possible, with no compromises in quality and safety,” he added.

According to the Chinese Clinical Trial Registry, it is a single-center, open and dose-escalation phase I trial testing safety and tolerance of Ad5-nCoV in healthy adults, ages 18 to 60. The low-, middle- and high-dosage groups will each see 36 patients, who will receive 5e10vp, 1E11vp and 1E11vp of Ad5-nCoV, respectively.

The primary indicator is to see whether there are adverse reactions seven days after injection, and the secondary indicators are whether adverse reactions are observed 28 days after injection or severe adverse reactions six months after the injection.

Researchers will also look for anti-S antibody immunoglobulin G, neutralizing antibodies against SARS-CoV-2, neutralizing antibodies against Ad5 and specific T-cell responses as secondary indicators.

Ad5-nCoV is developed with Cansino’s adenovirus-based viral vector vaccine technology platform, which utilizes adenoviruses as viral vectors to deliver vaccine antigens to the human cell. Previously, the technology platform was key in enabling Cansino to translate its Ebola virus disease vaccine, Ad5-EBOV, from a concept to an approved product in merely three years.

A forerunner in China’s vaccine space, Cansino came to the industry’s attention when its Ad5-EBOV became the first approved Ebola virus vaccine in China for emergency use and as part of the national stockpile in October 2017.

Leveraging the existing technology platform, Cansino said results from preclinical animal studies of Ad5-nCoV show that the vaccine candidate can induce strong immune responses in animal models. The preclinical animal safety studies demonstrated a good safety profile.

“We have completed the necessary preclinical steps for vaccine R&D. To date, the GMP clinical batches have passed quality testing and are ready for the phase I clinical trial,” the company said.

Stepping carefully

A cautious scientist, Yu stressed the importance of safety in vaccine development and warned that there is more to think of than just the speed of development.

“We need speed, but we still need quality. We d

on’t want to introduce a second harm to people. It is critically important to check every step,” Yu said in a webinar organized by Chinese CRO Wuxi Apptec last month.

He said although the existing technology platform can speed up the development of a vaccine, there are issues to address before applying any vaccine to a human. Animal models should be available before moving any vaccine candidates into human trials so as to produce a vaccine that will eventually work without concerns such as disease enhancement.

“Even though we have learned from MERS and SARS, COVID-19 is still a new virus that behaves very differently, so we should really get some basic understanding,” Yu said.

And in developing a vaccine for emergency response, Yu said it would be ideal to require just one dose, and developers need to consider the manufacturability of the vaccine in order to benefit more people.

On March 16, the NIH said a phase I trial has begun in Seattle. The vaccine candidate, known as mRNA-1273 and co-developed by NIH and Moderna Inc., encodes viral spike (S) protein for prevention of COVID-19.

https://www.bioworld.com/articles/433791-china-approves-first-homegrown-covid-19-vaccine-to-enter-clinical-trials?id=433791-china-approves-first-homegrown-covid-19-vaccine-to-enter-clinical-trials