Тема о КОРОНАВИРУСУ... све на једном месту

[Tanja M]

Investigational Drugs and Biologics

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Examples of prospective treatments are discussed below.

Antiviral Agents

Remdesivir

The broad-spectrum antiviral agent remdesivir (GS-5734; Gilead Sciences, Inc) is a nucleotide analog prodrug. It has been shown to inhibit replication of other human coronaviruses associated with high morbidity in tissue cultures, including severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. Efficacy in animal models has been demonstrated for SARS-CoV and MERS-CoV. In addition, remdesivir is in clinical trials for Ebola virus infections. ^[37]

 

Several phase 3 clinical trials are underway for testing remdesivir for use in COVID-19 in the United States, South Korea, and China.

An in vitro study showed that the antiviral activity of remdesivir plus interferon beta (IFNb) was superior to that of lopinavir/ritonavir (LPV/RTV; Kaletra, Aluvia; AbbVie Corporation). Prophylactic and therapeutic remdesivir improved pulmonary function and reduced lung viral loads and severe lung pathology in mice, whereas LPV/RTV-IFNb slightly reduced viral loads without affecting other disease parameters. Therapeutic LPV/RTV-IFNb improved pulmonary function but did not reduce virus replication or severe lung pathology. ^[38]

Lopinavir/ritonavir

Unconfirmed media reports from China reported lopinavir/ritonavir to be effective for COVID-19 treatment. A press release by AbbVie indicated that Chinese clinical information was not accessible to the company, so accuracy has not been confirmed. AbbVie is working with global health authorities to determine efficacy and safety of lopinavir/ritonavir for the treatment of COVID-19. ^[39] A combination of lopinavir/ritonavir plus IFNb treatment improved clinical parameters in marmosets and mice infected with MERS-CoV. ^[37]

Rintatolimod

The toll-like receptor 3 (TLR-3) agonist rintatolimod (Poly I:Poly C12U; Ampligen; AIM ImmunoTech) is being tested as a potential treatment for COVID-19 by the National Institute of Infectious Diseases (NIID) in Japan and the University of Tokyo. ^[40] It is a broad-spectrum antiviral agent. ^[41]

Other investigational antivirals

Other investigational antivirals being tested for efficacy against COVID-19 include azvudine (nucleoside reverse transcriptase inhibitor), danoprevir (NS3/4A HCV protease inhibitor), and favipiravir (viral RNA polymerase inhibitor).

 

Immunomodulators and Other Investigational Therapies

Interleukin-6 inhibitors

 

Interleukin-6 (IL-6) inhibitors may ameliorate severe damage to lung tissue caused by cytokine release in patients with serious COVID-19 infections.

 

On March 16, 2020, Sanofi and Regeneron announced initiation of a phase 2/3 trial of the IL-6 inhibitor sarilumab (Kevzara). The United States–based component of the trial will be initiated in New York. The multicenter, double-blind, phase 2/3 trial has an adaptive design with two parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infection across approximately 16 US sites, and will evaluate the effect of sarilumab on fever and the need for supplemental oxygen. The second, larger, part of the trial will evaluate improvement in longer-term outcomes, including preventing death and reducing the need for mechanical ventilation, supplemental oxygen, and/or hospitalization. ^[42]

 

Another IL-6 inhibitor, tocilizumab (Actemra; Genentech/Roche) is being studied in China, and the manufacturer is in active communication with the FDA to explore a clinical trial. ^[43]

 

An anti-interleukin-6 receptor monoclonal antibody (TZLS-501; Tiziana Life Sciences and Novimmune) is currently being developed. ^[44]

 

Hydroxychloroquine and chloroquine

 

Hydroxychloroquine and chloroquine are widely used antimalarial drugs that elicit immunomodulatory effects and are therefore also used to treat autoimmune conditions (eg, systemic lupus erythematosus, rheumatoid arthritis). Published reports stemming from the COVID-19 Chinese outbreak have evaluated the potential usefulness of these drugs in controlling cytokine release syndrome in critically ill patients. ^{[45, 46]}

 

According to a consensus statement from a multicenter collaboration group in China, chloroquine phosphate 500-mg twice daily in tablet form for 10 days may be considered in patients with COVID-19 pneumonia. ^[35] Wang et al reported that chloroquine effectively inhibits SARS-CoV-2 in vitro. ^[36]

 

The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic models (PBPK) were conducted for each drug. Hydroxychloroquine was found to be more potent than chloroquine in vitro. Based on PBPK models, the authors recommend a loading dose of hydroxychloroquine 400 mg PO BID, followed by 200 mg BID for 4 days. ^[45]

 

Corticosteroids

 

A study describing clinical outcomes of patients diagnosed with COVID-19 was conducted in Wuhan China (N = 201). Eighty-four patients (41.8%) developed ARDS, and of those, 44 (52.4%) died. Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). ^[47]

 

An open-label prospective trial is planned to study clinical improvement in patients treated with methylprednisolone IV. ^[48]

 

Nitric oxide

 

Published findings from the 2004 SARS-CoV infection suggest the potential role of inhaled nitric oxide (iNO; Mallinckrodt Pharmaceuticals, plc) as a supportive measure for treating infection in patients with pulmonary complications. Treatment with iNO reversed pulmonary hypertension, improved severe hypoxia, and shortened the length of ventilatory support compared with matched control patients with SARS. ^[49]

 

A phase 2 study of iNO is underway in patients with COVID-19 with the goal of preventing disease progression in those with severe ARDS. ^[50]

 

Other immunomodulators and investigational therapies

 

Table 1. Additional Immunomodulators and Other Investigational Therapies (Open Table in a new window)

Therapy	Proposed Use	Description/Comments
Ifenprodil (NP-120; Algernon Pharmaceuticals) [51]	ARDS/lung injury	N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist. NMDA is linked to inflammation and lung injury. An injectable and long-acting oral product are under production to begin clinical trials for COVID-19 and acute lung injury.
Remestemcel-L (Mesoblast Ltd) [52]	ARDS/lung injury	Allogeneic mesenchymal stem cell (MSC) product candidate being investigated as a treatment for ARDS associated with COVID-19.
TJM2 (I-MAB Biopharma) [53]	Cytokine storm	TJM2 is a neutralizing antibody against human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in acute and chronic inflammation.
Anti-SARS-CoV-2 polyclonal hyperimmune globulin [54]	Immunoglobulin	Under development to treat high-risk patients.
CEL-SCI Corporation [55]	Immunotherapy	Preferentially directed immunotherapy using ligand antigen epitope presentation system (LEAPS) peptide technology to reduce COVID-19 viral load and consequent lung damage.
Brilacidin (Innovation Pharmaceuticals) [56]	Immunotherapy	Defensin-mimetic that mimics the immune system and disrupts the pathogen membrane, leading to cell death. It is undergoing clinical-stage testing at a US regional biocontainment laboratory.
Monoclonal antibodies (Regeneron) [57]	Antibody-directed therapy	Mab cocktail slated by mid-April, with the goal of initiating human trials by early summer.
Vir Biotechnology and NIH [58]	Antibody-directed therapy	Human monoclonal antibodies against coronaviruses, including COVID-19.
Antibodies (Eli Lilly and AbCellera) [59]	Antibody-directed therapy	Antibody treatment from more than 500 unique antibodies isolated from one of the first US patients to recover from COVID-19.
Vascular leakage therapy [60]	Reduction of endothelial dysfunction	Targets the angiopoietin-Tie2 signaling pathway to reduce endothelial dysfunction.

 

Vaccines

Table 2. Investigational Vaccines (Open Table in a new window)

Vaccine	Comments
INO-4800 (Inovio Pharmaceuticals) [61]	Phase 1 human clinical trials are expected to begin in April 2020. In addition, Inovio has received a grant from the Bill and Melinda Gates Foundation to accelerate testing and scale up a smart device (Cellectra 3PSP) for large-scale intradermal vaccine delivery.
mRNA-1273 (Moderna Inc) [62]	A phase 1 study has been initiated in 45 healthy volunteers as of March 16, 2020 at Kaiser Permanente Washington Health Research Instituted in Seattle.
mRNA vaccine (CureVac) [63]	Vaccine is in development and not yet ready for human testing as of March 16, 2020.
COVID-19 S-Trimer (GlaxoSmithKline [GSK] and Clover Biopharmaceuticals) [64]	Preclinical development is underway using GSK’s adjuvants (compounds that enhance vaccine efficacy) and Clover’s proprietary proteins, which stimulate an immune response.
SARS-CoV-2 vaccine (Johnson & Johnson [J&J]) [65]	Partnering with the Biomedical advanced Research and Development Authority (BARDA) to utilize Janssen’s AdVac and PER.C6 technologies, which provide rapid upscale production of an optimal vaccine candidate.
rDNA vaccine (Sanofi) [66]	Collaborating with BARDA to develop a vaccine using their recombinant DNA platform.
Saponin-based Matrix-M adjuvant vaccine (Novavax) [67]	Stimulates the entry of antigen-presenting cell into the injection site and enhances antigen presentation in local lymph nodes to boost the immune response.
Live-attenuated vaccine (Codagenix) [68]	Codagenix, a clinical-stage biotechnology company, is collaborating with the Serum Institute of India to co-develop a live-attenuated vaccine.
PCR-based DNA vaccine (Applied DNA Sciences and Takis Biotech) [69]	The collaboration has designed four COVID-19 vaccine candidates utilizing PCR-based DNA manufacturing systems for preclinical testing in animals.
Intranasal COVID-19 vaccine (Altimmune, Inc) [70]	Design and synthesis has been completed and is advancing toward animal testing.

 

Coronavirus Disease 2019 (COVID-19): Practice Essentials, Background

EMEDICINE.MEDSCAPE.COM

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[uomo del Ve.Te.]

АлександраВ и  Milica Bajic  немојте само револвере да потежете ако море (може) икако барем сад за време поста.... 

[Justin Waters]

Evo čisto jedan pokušaj procjene kada će biti vrhunac u Italji, nakon čega će dolaziti do pada broja aktivno zaraženih, što će pratiti manji broj smrtnih slučajeva.

Kriva će imati oblik gausovog zvona, pa uzimajući sadašnji trend par prijedloga kako će se ta kriva formirati:

Ako bude žuta, onda će vrhunac biti oko 8 aprila sa cca 61000 slučajem

Zelena oko 18 aprila sa 72000 slučajeva 

Plava oko 25 aprila sa 90000 slučajeva. 

Po obliku krive se vidi uticaj karantene, čime je suzbijeno da se pojavi veći broj što bi učinio da bude strmija i sa mnogo većom ordinatom na vrhuncu. 

 

[Milica Bajic]

пре 15 минута, uomo del Ve.Te. рече

АлександраВ и  Milica Bajic  немојте само револвере да потежете ако море (може) икако барем сад за време поста.... 

Hvala, u pravu si. Totalno je bezveze.

[grigorije22]

Evo šta se kopira na tzv. Pravoslavnim fb grupama.

[Justin Waters]

 

[Justin Waters]

пре 4 минута, grigorije22 рече

Evo šta se kopira na tzv. Pravoslavnim fb grupama.

Moram priznati da su baš maštoviti...neki ljudu prosipaju svoje talente, a mogli bi biti scenaristi ili pisci naučne fantastike. 

[grigorije22]

пре 1 минут, Justin Waters рече

Moram priznati da su baš maštoviti...neki ljudu prosipaju svoje talente, a mogli bi biti scenaristi ili pisci naučne fantastike. 

I naravno neki famozni naučnik koji dokazuje da virusi ne postoje i daje alternativno objašnjenje. 
 

 

[Justin Waters]

пре 17 минута, grigorije22 рече

I naravno neki famozni naučnik koji dokazuje da virusi ne postoje i daje alternativno objašnjenje. 

Nije negirao viruse nego se izlupetao u vezi njihove prirode i kako djeluju na živi svijet. Nije naučnik, aktivista bio..za hranjenje "zdravom hranom" itd....

Aajonus Vonderplanitz - Wikipedia

EN.WIKIPEDIA.ORG

 

[grigorije22]

пре 3 минута, Justin Waters рече

Nije negirao viruse nego se izlupetao u vezi njihove prirode i kako djeluju na živi svijet. Nije naučnik, aktivista bio..za hranjenje "zdravom hranom" itd....

Aajonus Vonderplanitz - Wikipedia

EN.WIKIPEDIA.ORG

 

Zašto se izlupetao? Zbog čega je njegovo alternativno objašnjenje besmisleno?

[Justin Waters]

Управо сада, grigorije22 рече

Zašto se izlupetao? Zbog čega je njegovo alternativno objašnjenje besmisleno?

Zato što govori da su virusi odgovor organizma na prisustvo toksina u tijelu...govori o virusima kao o "sapunu" rastvoru kako ga on naziva koga generišu same ćelije da očiste nastalu situaciju usljed trovanja.

Postoji čitava nauka koja se bavi virusima i zove se "virologija" i koja je klasifikovala 5000 virusa u živom svijetu i to u detalje i kakav im je mehanizam. Dok ovaj nije vidio virusa pod mikroskopom. 

Metod obrazlaganja mu je slična kreacionističko - ravnozemljaškoj metodologiji. Negira postojeće nalaze nauke, a objašnjenja koja nudi nisu uopšte utemeljena na sopstevnim istraživanjima nego na pričam ti priču, "iskustvu" itd...

 

[Tumaralo.]

@grigorije22

Misliš da će svaki Indijanac iz Amazonije i svaki afrički Bušman i Pigmej primiti "žig zveri" pre dolaska Antihrista?

[Tanja M]

A doctor in eastern Ontario has improvised a way to double his small hospital's ventilator capacity in preparation for a possible COVID-19 outbreak.

Anesthetist Alain Gauthier, who has a PhD in respiratory mechanics and works in Perth, west of Ottawa, spotted the idea in a YouTube video.

 

In basic terms, the rig involves running two hoses from one ventilator and doubling the power.

In just 10 minutes and with the help of some extra tubing, Gauthier made it possible to double the number of patients ventilated in the hospital at once, if needed.

But there's a catch: the two patients attached to the same ventilator need to be of similar size and lung capacity. And if one patient declines, things will need to be adjusted.

It's not perfect, but as Gauthier put it, "if it comes to last resort, I'm prepared to use it."

Gauthier said the population the Perth and Smiths Falls District Hospital serves may be at greater risk if hit with the COVID-19 outbreak. Many of the 60,000 people in the region are older, with underlying health conditions such as diabetes and chronic pulmonary disease.

• Coronavirus: Here's what's happening in Canada and around the world on Wednesday

His hospital recently received four new ventilators, and keeps four old ones that are still functioning in reserve. Those older machines can't be repaired if they break down, however.

In a rural health-care setting, the hospital's ability to increase its surge capacity may be limited in the event of a widespread outbreak.

Learning from YouTube

The idea to double up patients on a single ventilator was studied in theory by American doctors Greg Neyman and Charlene Babcock in 2006. It was tried once, successfully, in the aftermath of the 2017 mass shooting of the Route 91 Harvest music festival in Las Vegas.

Babcock, an emergency physician in Michigan, created a how-to video on YouTube to help doctors around the world respond to COVID-19. That's where Gauthier got the idea.

The goal, Gauthier said, is to avoid the kinds of difficult ethical decisions facing Italian physicians who have had to choose which critical patients should get a ventilator, because there aren't enough to go around.

His efforts speak to the lengths doctors across the country are going to prepare their hospitals and staff for the worst-case scenario, a sudden onslaught of COVID-19 cases, he said.

"We are concerned, we're trying to get ready as much as possible," he said.

His colleagues were incredibly enthusiastic about his ability to potentially double the ventilator capacity of the hospital, he said.

• Why Italy was hit so hard and so fast by COVID-19

Dr. Alan Drummond, an emergency physician at the hospital, said he even broke social distancing protocol to give Gauthier a hug.

But Gauthier said he wants no credit. He said he's only doing what every Canadian health-care worker is doing right now: trying to brace for what's to come.

"A lot of work is being done by pretty much everyone," he said.

The federal government is also ordering additional ventilators, which will be distributed to provincial and territorial health authorities.

CBC's Journalistic Standards and Practices|About CBC News

Perth doctor rigs up solution to feared ventilator shortage | CBC News

WWW.CBC.CA

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A doctor in eastern Ontario has improvised a way to double his small hospital's ventilator capacity in preparation for a possible...

 

 

[grigorije22]

пре 1 сат, Justin Waters рече

Zato što govori da su virusi odgovor organizma na prisustvo toksina u tijelu...govori o virusima kao o "sapunu" rastvoru kako ga on naziva koga generišu same ćelije da očiste nastalu situaciju usljed trovanja.

Postoji čitava nauka koja se bavi virusima i zove se "virologija" i koja je klasifikovala 5000 virusa u živom svijetu i to u detalje i kakav im je mehanizam. Dok ovaj nije vidio virusa pod mikroskopom. 

Metod obrazlaganja mu je slična kreacionističko - ravnozemljaškoj metodologiji. Negira postojeće nalaze nauke, a objašnjenja koja nudi nisu uopšte utemeljena na sopstevnim istraživanjima nego na pričam ti priču, "iskustvu" itd...

 

Evo ti na primer odgovor
Савремени научници су, част изузецима протуве, које ће за шаку долара, под присилом разних претњи да говоре како елити одговара. Зато неки од нас не верују научницима, јер више нема независне науке, ако је икада и постојала. Ти верујеш свему што ти сервирају, јер ми те истине не можемо да знамо, можемо само да верујемо људима научницима, а људи су врло кварљива роба.

I ovo
Сећаш ли се подсмеха од пре десетак година на приче разних духовника о течном чипу, о наночипу који се може аплицирати на разне начине, дакле, подметнути?
А шта је Кина сад урадила? Произвела баш то, понудила и уграђује у своје људе ради превентиве болести и ране дијагностике тобоже. И не само она, него и Русија, Шведска, Иран и још понека земља. Та прича се на наше очи обистињава, а тек ћемо да видимо шта се још спрема.

[Justin Waters]

пре 3 минута, grigorije22 рече

Evo ti na primer odgovor
Савремени научници су, част изузецима протуве, које ће за шаку долара, под присилом разних претњи да говоре како елити одговара. Зато неки од нас не верују научницима, јер више нема независне науке, ако је икада и постојала. Ти верујеш свему што ти сервирају, јер ми те истине не можемо да знамо, можемо само да верујемо људима научницима, а људи су врло кварљива роба.

Imam osjećaj da si kopirao moju poruku negdje na taj zilotski mediji koji pratiš i da si tražio pojašenjenje. 

Odgovor je vrh, decidan, jasan, s kontra argumentima nemam dalje