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Post by Admin on May 14, 2020 19:13:36 GMT
Two new studies have been published that further focus attention on how the renin–angiotensin system — and specifically the ACE2 receptor — may be involved in COVID-19 infection. Leading experts suggest that effects of the virus on the renin–angiotensin system may be the key to understanding why men and individuals with underlying cardiovascular diseases appear to have worse outcomes from COVID-19. One study, published in the European Heart Journal1, found higher plasma levels of the ACE2 receptor/enzyme in men vs women in two large samples of patients with heart failure. Noting that the SARS-CoV-2 virus that causes COVID-19 interacts with the ACE2 receptor, the authors suggest that their findings may explain why men have worse outcomes with the virus. The study also shows that neither ACE inhibitors nor angiotensin-receptor blockers (ARBs) were associated with higher plasma ACE2 concentrations. A second study, published as a letter to the New England Journal of Medicine2, studied the relationship between ACE-inhibitor and ARB use and influenza A infection in a large United Kingdom patient database. The authors note that influenza A has been shown to use the ACE2 receptor to mediate lung damage, similar to that seen in severe acute respiratory syndrome (SARS) with COVID-19. "Understanding the shared mechanism between SARS and influenza may help to address the question as to how ACE inhibitors and ARBs may modulate the manifestations of certain viral respiratory infections," they write. Results showed that during a median 8.7 years of follow-up, individuals who had received a prescription for an ACE inhibitor had a lower risk of influenza than those who had not (adjusted hazard ratio, 0.66). A second analysis found that the longer the duration of ACE-inhibitor use, the lower the risk of influenza infection. Similar results were found for ARBs. "These associations regarding observed susceptibility to influenza may reflect mechanisms that are shared with coronaviruses, including SARS-CoV-2," the researchers conclude. Is COVID-19 Activating the Renin–Angiotensin System? In an editorial accompanying the European Heart Journal publication, Gavin Oudit, MD, University of Alberta, Edmonton, Canada, and Mark Pfeffer, MD, Brigham and Women's Hospital, Boston, Massachusetts, suggest that further work should measure plasma angiotensin peptides and plasma ACE2 levels and activity in COVID-19 patients to provide a direct evaluation of the state of the renin–angiotensin system, which could guide therapeutic interventions. 1. academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa373/58346472. www.nejm.org/doi/full/10.1056/NEJMc2005396?query=main_nav_lg
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Post by Admin on May 15, 2020 2:09:57 GMT
"Ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus," researchers from Johns Hopkins University School of Medicine and Zhongshan Ophthalmic Center of Sun Yat-sen University wrote in a preprint study published in bioRxiv on May 9. The short title of the paper is "ACE2 and TMPRSS2 expression on the human ocular surface," which refers to the two receptors of SARS-CoV-2 are detected in human's conjunctiva, limbus, and cornea. The research also shows that ACE2 is especially prominent staining in the superficial conjunctival and corneal epithelial surface. Since the outbreak of COVID-19 pandemic, there has been different opinions and awareness in the routes of viral infection. Some speculation regarding the ocular surface could be a possible site of virus entry and also as a source of contagious infection have been discussed, according to preprint paper. By analyzing human post-mortem eyes as well as surgical specimens for the expression of ACE2 and TMPRSS2, and collecting data from ten post-mortem human eyes, five non-diabetic controls lacking ocular disease, and five diabetic individuals with diabetic retinopathy, researchers found that "ocular surface cells including conjunctiva and cornea are indeed susceptible to infection by SARS-CoV-2, highlighting the importance of safety practices protecting this region." ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection doi: doi.org/10.1101/2020.05.09.086165Abstract Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.
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Post by Admin on May 16, 2020 1:20:38 GMT
As recently announced, Sorrento aims to generate an antibody cocktail product that would act as a "protective shield" against SARS-CoV-2 coronavirus infection and remain effective even if virus mutations render a single antibody therapy less effective over time. Sorrento has been diligently screening billions of antibodies in its proprietary G-MAB™ fully human antibody library and has so far identified hundreds of antibody candidates that bind the S1 subunit of the SARS-CoV-2 Spike protein. Approximately one dozen of these antibodies have demonstrated the ability to block the S1 protein's interaction with human angiotensin-converting enzyme 2 (ACE2), the receptor used for viral entrance into human cells. These blocking antibodies were further tested for their ability to inhibit SARS-CoV-2 virus infection in an in vitro SARS-CoV-2 virus infection model pursuant to a preclinical testing agreement for COVID-19 therapeutic candidates that was previously announced on March 31, 2020 (Sorrento Therapeutics). Among the antibodies showing neutralizing activity, one antibody stood out for its ability to completely block SARS-CoV-2 infection of healthy cells in the experiments. STI-1499 completely neutralized the virus infectivity at a very low antibody dose, making it a prime candidate for further testing and development. Initial biochemical and biophysical analyses also indicate STI-1499 is a potentially strong antibody drug candidate. Sorrento has determined STI-1499 will likely be the first antibody in the antibody cocktail (COVI-SHIELD™) it is developing, as recently announced. STI-1499 is also expected to be developed as a stand-alone therapy, (COVI-GUARD™) because of the high potency it has exhibited in experiments to date. Sorrento plans to request priority evaluation and accelerated review from regulators to determine the best pathway to make any potential treatment available as soon as possible. Sorrento's existing state-of-the-art cGMP antibody manufacturing facility in San Diego is expected to be able to produce up to two hundred thousand doses per month and the Company intends to produce a million doses at risk while seeking FDA approval for any STI-1499 product candidate. The Company is seeking potential government support and pharmaceutical partners to further scale up STI-1499 manufacturing capacity with a goal of potentially providing tens of millions of doses in a short period of time to meet the vast projected demand. "Our STI-1499 antibody shows exceptional therapeutic potential and could potentially save lives following receipt of necessary regulatory approvals. We at Sorrento are working day and night to complete the steps necessary to get this product candidate approved and available to the waiting public," stated Dr. Henry Ji, Chairman and CEO of Sorrento. About Sorrento Therapeutics, Inc. Sorrento is a clinical stage, antibody-centric, biopharmaceutical company developing new therapies to turn malignant cancers into manageable and possibly curable diseases. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as fully human antibodies ("G-MAB™ library"), clinical stage immuno-cellular therapies ("CAR-T", "DAR-T"), antibody-drug conjugates ("ADCs"), and clinical stage oncolytic virus ("Seprehvir®"). Sorrento is also developing potential coronavirus antiviral therapies and vaccines, including COVIDTRAP™, ACE-MAB™, COVI-MAB™, COVI-GUARD™, COVI-SHIELD™ and COVI-CELL™. Sorrento's commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a first-in-class (TRPV1 agonist) non-opioid pain management small molecule, resiniferatoxin ("RTX"), and ZTlido® (lidocaine topical system) 1.8% for the treatment of post-herpetic neuralgia. RTX is completing a phase IB trial for intractable pain associated with cancer and a phase 1B trial in osteoarthritis patients. ZTlido® was approved by the FDA on February 28, 2018. For more information, visit www.sorrentotherapeutics.comForward-Looking Statements This press release and any statements made for and during any presentation or meeting contain forward-looking statements related to Sorrento Therapeutics, Inc., under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding the potency and potential blocking capabilities of STI-1499 and the impact on SARS-CoV-2, the SARS-CoV-2 Spike protein and viral entry; the expected length of any antiviral protection provided by STI-1499; the potential administration and applications of STI-1499; the potential for STI-1499 to protect against future mutations of coronavirus; the preclinical testing of STI-1499; the safety and efficacy of STI-1499; the readiness of Sorrento's cGMP facilities for large-scale production of STI-1499 for commercialization and Sorrento's expected capacity to produce drug substance; the expected time needed for Sorrento's cGMP facilities to produce doses of STI-1499; the potential inclusion of STI-1499 in the antibody cocktail (COVI-SHIELD™) that Sorrento is developing and its development as a stand-alone therapy; the therapeutic potential of STI-1499 for SARS-CoV-2 and COVID-19 disease and any potential ability to save lives; and Sorrento's potential position in the antiviral industry. Risks and uncertainties that could cause our actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks related to Sorrento's and its subsidiaries', affiliates' and partners' technologies and prospects and collaborations with partners, including, but not limited to risks related to conducting pre-clinical studies and seeking IND regulatory approval for STI-1499; conducting and receiving results of clinical trials for STI-1499; the clinical and commercial success of STI-1499 against preventing and treating SARS-CoV-2 virus infections; the viability and success of STI-1499 in anti-viral therapeutic areas, including coronaviruses; clinical development risks, including risks in the progress, timing, cost, and results of clinical trials and product development programs; risk of difficulties or delays in obtaining regulatory approvals; risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; risks of manufacturing and supplying drug product; risks related to leveraging the expertise of its employees, subsidiaries, affiliates and partners to assist the company in the execution of its COVID-19 therapeutic product candidates strategies; risks related to Sorrento's debt obligations; risks related to the global impact of COVID-19; and other risks that are described in Sorrento's most recent periodic reports filed with the Securities and Exchange Commission, including Sorrento's Annual Report on Form 10-K for the year ended December 31, 2019, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release and we undertake no obligation to update any forward-looking statement in this press release except as required by law.
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Post by Admin on May 17, 2020 7:03:29 GMT
According to the Centers for Disease Control, there is “no evidence” that the virus that causes COVID-19 can be spread to people through the water in pools, hot tubs, spas, or water play areas.
That's because chlorine and other common disinfectants, like bromine, ozone, or UV sanitizers, likely kill SARS-CoV-2 in treated water. Chlorine is thought to disarm microorganisms in as little as 30 minutes.
Charles Gerba is a microbiologist and virologist at the University of Arizona who studies how viruses survive in water. He tells Inverse that chlorine does "an excellent job of killing bacteria and viruses — even viruses that are more difficult to kill than coronaviruses like SAR-CoV-2."
But while chlorine is a potent and popular disinfectant, how the chemical actually deactivates viruses isn't well understood.
It's theorized that chlorine damages viral proteins and nucleic acids, which can keep the virus from infecting a host cell and inhibits their reproduction — effectively rendering them harmless, Blatchley explains.
UV light — from UV pool sanitizers or the sun — also damages bacteria and virus's nuclear material. It's often used in tandem with chlorine to wipe out microorganisms in water. Exposure to sunlight may generally make surfaces around outdoor pools less risky virus-wise compared to indoor pools, Blatchley says.
"But that's going to be different in North Dakota than it's going to be in Miami," he says. "And it's going to be different on a cloudy day than on a sunny day."
Currently, there's no data exploring how common water disinfectants affect the Covid-19 virus specifically, Blatchley says. But data on other viruses with similar structure suggests SARS-CoV-2 would be killed by these disinfectants.
"There's nothing about this virus that I know of that would prevent it from being effectively inactivated by these conventional disinfectants that we use," Blatchley explains. That is, unless there's something "really weird," like a possible resistance to disinfectants in certain parts of the virus.
It's possible that the virus may be more sensitive to chlorine and other common water disinfectants than other viruses because it has an envelope structure. Enveloped viruses tend to be sort of "wimpy viruses," Blatchley says. They're relatively fragile, sensitive to physical or chemical stress, and tend to be inactivated quickly by disinfectants.
Saltwater pools are also likely to be low-risk, because the salt and water react to generate chlorine. Meanwhile, swimming in a river, lake, or ocean isn't likely to be radically different risk-wise to pool water.
"Viruses which infect humans usually survive less in seawater than freshwater — so seawater contamination would be seen as a lower risk," Gerba says.
Some of these venues might also be safer as they tend to be less crowded.
"I don't see the risk really coming from the water itself," Blatchley says. "It's really the things that surround the water that present the risk."
If you're in a crowded area, you have increased your risk of becoming infected, Blatchley says.
"It doesn't matter that you happen to be standing in water or standing at the mall," he points out. "It's really that air that you're breathing that other people are affecting."
IS IT SAFE TO SWIM? — Ultimately, the decision to swim or not to swim is a personal one that depends on a range of factors: if facilities are open, how crowded they may be, and the potential mental and physical benefits of the activity.
If you do decide to jump in, there are key precautions advised by public health authorities: practice social distancing, avoid potentially contaminated surfaces and practice good hand hygiene. This means washing your hands, using hand sanitizer, and avoiding touching your face.
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Post by Admin on May 18, 2020 22:19:33 GMT
Everyone is understandably anxious to get out of the house and resume normal life. But the coronavirus hasn’t left, not at all, and resuming normal life means we have to take precautions. The wide-scale use of face masks is the simplest and most effective step we can take towards ensuring public health. And hamsters are helping prove its worth.
Safely masked “It’s very clear that the effect of masking the infected, especially when they are asymptomatic — or symptomatic — it’s much more important than anything else,” Yuen told reporters Sunday.
“It also explained why universal masking is important because we now have known that a large number of those infected have no symptoms.”
The team claims that their research (not yet published) is the first to test whether masks specifically can stop COVID-19, both symptomatic and asymptomatic, from infecting other individuals.
The authors infected healthy hamsters with the virus and placed these animals in containers. In another container connected to the first one, they placed a healthy hamster, thus creating an opportunity for infection. A fan was used to blow air from the infected rat’s container into the neighboring one.
Then, they placed a surgical face mask in the space connecting these two in order to filter all airflow between them.
According to the results, two-thirds (10 out of a 15 total) of the healthy mice were infected within a week without the masks set in place (and without any direct physical contact between the healthy and unhealthy). However, after the masks were installed, transmission rates went down by as much as 75%.
The findings have been detailed on the Hong Kong Today show and in the South China Morning Post. According to the SCMP,” only two of 12 subjects in the adjoining cage” (16.7%) tested positive for the coronavirus when masks were placed on the infected hamster’s box. When the masks were applied only to the cage with healthy hamsters, 4 out of 12 (33%) became infected.
“Transmission can be reduced by 50% when surgical masks are used, especially when masks are worn by infected individuals,” Professor Yuen explained for SCMP.
Furthermore, hamsters that did become infected during the masked experiments showed lower levels of the virus within their body than those infected without a mask.
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