What is the antibody recovered patients have in common?

Some important questions for Covid-19 researchers around the world.

1. How many people recovered from the Covid-19 disease?

2. What gives some children strong antibody protection against Covid-19

3. What is the particular antibody that recovered patients have in common?

4. Can researchers isolate this particular antibody found in the blood of recovered patients?

5. Why is it taking so long to isolate the common denominator that helped people around the world recover from Covid-19?

6. Can vaccines be made from the blood of recovered patients?

A Utube lecture that provides some important information.
https://www.youtube.com/watch?v=Fqw-9yMV0sI

Important information on Covid-19

UPDATED INFORMATION ON THE COVID-19 PANDEMIC.

THE CORONA COVID-19 DISEASE WITH THE SARS-CoV-2 VIRUS.

What I understand so far...
1. It is a powerful and deadly virus for people with weak immune systems: for people with high blood pressure, with sleep Apnia, and those who already suffer from lung problems, Early testing for the SARSCOV2 virus is vitally important! Every person, young and old, should be tested and a possible solution for those with the virus is a blood cleansing dialysis to stop the progress of the disease. Ask your doctor.
2. People over Seventy years of age are the most vulnerable.
3. Young or old, a medical respirator is the extreme last resort for keeping you alive. It means your lungs have filled with fluids and you cannot breathe on your own. You absolutely do not want to reach the Third Stage of the Covid-19 disease where you will need the life-maintaining respirator. Your lungs may already be destroyed.
4. Every hospital in Canada must have enough testing equipment kits to help locate the virus. The general population outside of hospitals also need to be tested and I recommend the government mail self-testing return- by- mail laboratory kits to every household in Canada.
  For the desperate 3% who desperately need them, hospitals need enough medical respirators to help keep Covid-19 patients alive. One Respirator can service Two (2) patients.

 Testing kits must be prioritized by the Canadian government before the virus expands into the general population. They must be quickly manufactured and dispensed throughout Canada.
5. The steps we as individuals need to take include refraining from joining groups over Ten people and also, cleaning our hands with strong hand soap. Look at the bottom of this page for a cheap but powerful hand cleanser.
6. If you must go to a shopping center for groceries, wear gloves and a mask. If there are registered cases of the virus in your area, I suggest wearing a surgical mask if available but if not, a construction mask may be the next best thing or simply use a thin scarf to protect your face.
7. If possible, get yourself tested for the virus and if a medical authority quarantines you, obey without question.
8. If you have recovered from the SARS-CoV-2 virus and you feel strong enough, donate a litre of your blood to a blood bank because somewhere around the world, a smart scientist may use your plasma to create a Vaccine against Covid-19.
9. For those countries that do not have enough respirators, it is possible to use one respirator for two patients by creating a Y in the tubing leading from the respirator to the patients. A Respirator, however, is the last resort effort to save a life and if the virus is located fast enough during its first stage, it can be stopped before becoming dangerous.
10.  If you have one or more of these Covid-19 symptoms, go and have yourself tested.
      1. A loss of smell and of taste.
      2. Headaches that come and go.
      3. Higher than normal body temperature.
      4. A dry cough and sore throat.

 One early-stage drug being tested is called APNO1 and it works during the early stage of the COVID-19 disease. Testing kits and faster action to attack the virus is the priority!
I will visit a laboratory to understand more about the Covid-19 disease containing the SARS-CoV-2 virus which causes the disease, then I will report back.
Good luck!
Signed: N.J. Raglione.

Hello Gentle People. Here is more information on the Covid-19 epidemic.

April 05, 2020
We need early detection and preventive measures for everybody in Canada and around the world because the drug APNO1 WORKS IN THE EARLY STAGE but may not work in the late stage of the Covid-19 disease.
Testing early for everybody becomes imperative!  Detecting the virus early allows the drug a chance to inhibit the disease. Early detection and early treatment is imperative! Do not wait until it is too late!
The Chinese government tested absolutely everybody in Wuhan as quickly and as early as possible. We Canadians have to do the same!
The drug APNO1 is effective if administered in the early stages of the disease but researchers do not promise that it will work in the later stages of Convid-19. This leads me to believe we need more early testing and then early-stage treatment.
With Covid-19, waiting at home or in a nursing home during the late-stage of this disease, often results in death for vulnerable elders.
N.J.R..

" Research shows that the SARS-CoV-2 virus causing the COVID-19 DISEASE EPIDEMIC is spread through close contact with an infected person and it is most contagious before and during the first week of symptoms. The disease has three (3) stages and the last stage is the most dangerous.

"Autopsies have confirmed that the lungs are filled with clear liquid jelly, much resembling the lungs of wet drowning. Although the nature of the clear jelly has yet to be determined, hyaluronan (HA) is associated with ARDS; moreover, during SARS infection, the production and regulation of hyaluronan is defective. The levels of inflammatory cytokines (IL-1, TNF) are high in the lungs of COVID-19 patients and these cytokines are strong inducers of HA-synthase-2 (HAS2) in CD31+ endothelium, EpCAM+ lung alveolar epithelial cells, and fibroblasts. Importantly, HA has the ability to absorb water up to 1000 times its molecular weight. Therefore, reducing the presence or inhibiting the production of HA holds a great promise in helping COVID-19 patients breathe."

Infection can occur in two ways, droplet and contact.
Droplets' mean respiratory droplets produced by an infected person's sneeze or cough. These can travel up to 6 feet or (1.8 meters). A person becomes infected when droplets from a cough or sneeze directly enter the body through the eyes, mouth, or nose.
Contact means touching a person directly or object directly, such as door handles that have droplets on them from an infected person's cough or sneeze. Unwashed hands contaminated with COVID-19 can introduce the virus to your body when you touch your eyes, mouth or nose. Washing your hands often and avoiding touching your face are two very important ways to help prevent the spread of COVID-19"
SUNNYBROOK...HEALTH SCIENCES CENTRE.
=======
Hello again!
Here is a quick and easy way to disinfect your hands. Fill a plastic pump bottle with Vinegar and squirt in some dish soap. Except for the pump bottle which you can buy at any Dollar store, the Vinegar and dish soap are handy kitchen products usually found in most homes. You will be surprised how well this works not only cleaning your hands but your dishes and almost anything you want to keep clean around the house...and it is cheap to make.
Now for some potential life saving good news! During the early stage of the disease, you can help your lungs fight the infection by taking Vitamin B3 tablets and also by eating foods containing B3. What foods are high in b3? Good sources of vitamin B3, also known as Niacin, include yeast, meat, poultry, redfish (e.g., tuna, salmon), cereals, legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide some niacin.
Don't forget to call an ambulance if the disease climbs up to level 2 and things get rough!

In a new study in the journal Nature Medicine, researchers from the University of Melbourne at the Peter Doherty Institute for Infection and Immunity in Australia have outlined how the human immune system mounts its response to the new coronavirus.

The scientists were able to conduct a case study using information about one of the first hospital patients with a SARS-CoV-2 infection in Australia. This was a 47-year-old female who had traveled to Melbourne from Wuhan, China.

Keep clean and good luck in your struggle against the Covid-19 epidemic. N.J. Raglione. Dir. The World Friendly Peace and Ecology Movement.

(From what I read and learn, the drug APNO1 is effective if administered in the early stages of the disease but researchers do not promise that it will work in the later stages of Convid-19. This leads me to believe we need more early testing and then early-stage treatment.
Possibly with the drug called APNOI or hrsACE2) N.J.R.

HEADLINE NEWS...

"“Our new study provides direct evidence that a drug – called APN01 (human recombinant soluble angiotensin-converting enzyme 2 – hrsACE2) – soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19,” said University of Toronto Dr. Art Slutsky, also a scientist at Toronto’s Keenan Research Centre for Biomedical Science at St. Michael’s Hospital. 

What the researchers found through cell cultures is that the drug inhibited the coronavirus load. Using engineered replicas of human blood vessel and kidneys – “organoids” grown from human stem cells – the researchers demonstrated the virus can directly infect and duplicate itself in such tissues."=============================




A UBC researcher claims to have found a COVID-19 trial drug.
“There is hope for this horrible outbreak,” the researcher says.
Jeremy Hainsworth / Glacier News
APRIL 4, 2020 11:32 AM

Coronavirus-narvikk-iStock
Photograph By NARVIKK/ISTOCK
University of British Columbia researchers say they have found a trial drug that blocks the cellular door the virus uses to infect people with COVID-19.

“There is hope for this horrible outbreak,” said UBC Life Sciences Institute director Dr. Josef Penninger.

Penninger said the drug might soon be ready for testing.

He said a global team’s work provides new insights into the SARS-CoV-2 virus and its interactions on a cellular level, as well as how the virus can infect blood vessels and kidneys.

“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented outbreak,” he said.

Meanwhile, the World Health Organization (WHO) said March 20 that Thailand , Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain and Switzerland will be involved in a multi-country clinical study for potential treatments for COVID-19, part of a rapid global search for drugs to treat COVID-19.

Penninger’s team’s findings were published in the science journal Cell Friday.

Penninger said the finding holds some promise for a treatment capable of stopping early infection of the novel coronavirus that, as of April 4, has affected more than 1.16 million people and claimed the lives of 62,491people worldwide.

The study has involved researchers from Vancouver, Toronto, Spain and Sweden.

Penninger explained that cell membrane-surface protein ACE2 plays a key role in the outbreak.

In earlier work, Penninger and colleagues at the University of Toronto and the Institute of Molecular Biology in Vienna identified ACE2 as the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003.

What the new finding means, Penninger said, is that “the absence of a clinically proven antiviral therapy or a treatment specifically targeting the critical SARS-CoV-2 receptor ACE2 on a molecular level has meant an empty arsenal for health care providers struggling to treat severe cases of COVID-19.”

“Our new study provides direct evidence that a drug – called APN01 (human recombinant soluble angiotensin-converting enzyme 2 – hrsACE2) – soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19,” said University of Toronto Dr. Art Slutsky, also a scientist at Toronto’s Keenan Research Centre for Biomedical Science at St. Michael’s Hospital.

What the researchers found through cell cultures is that the drug inhibited the coronavirus load. Using engineered replicas of human blood vessel and kidneys – “organoids” grown from human stem cells – the researchers demonstrated the virus can directly infect and duplicate itself in such tissues.

What can be drawn from that, they said, is key information on the disease’s development and that severe cases of COVID-19 can lead to with multi-organ failure and cardiovascular damage.

“Clinical grade hrsACE2 also reduced the SARS-CoV-2 infection in these engineered human tissues,” they said.

“Using organoids allows us to test in a very agile way treatments that are already being used for other diseases, or that are close to being validated,” said Prof. Núria Montserrat of the Institute for Bioengineering in Catalonia, Spain.

“In these moments in which time is short, human organoids save the time that we would spend to test a new drug in the human setting,” Montserrat said.

“The virus causing COVID-19 is a close sibling to the first SARS virus,” Penninger said. “Our previous work has helped to rapidly identify ACE2 as the entry gate for SARS-CoV-2, which explains a lot about the disease, he said.

“Now, we know that a soluble form of ACE2 could be indeed a very rational therapy that specifically targets the gate the virus must take to infect us.

The WHO team’s work, dubbed Solidarity, will test four different drugs or combinations – remdesivir, a combination of two drugs, lopinavir and ritonavir, the two drugs plus interferon beta, and chloroquine – and will compare their effectiveness to what is called standard of care – the regular support hospitals treating COVID-19 patients.

“This global problem requires urgent global solutions,” said WHO’s representative to Thailand, Daniel Kertesz. “The goal is to identify medicines that will save lives in the global battle to fight this virus.”

Research by Penninger’s team was supported in part by the Canadian federal government through emergency funding focused on accelerating the development, testing and implementation of measures to deal with the COVID-19 outbreak.



jhainsworth@glaciermedia.ca

@jhainswo

UPDATED INFORMATION ON THE COVID-19 PANDEMIC.

THE CORONA COVID-19 DISEASE WITH THE SARS-CoV-2 VIRUS.

What I understand so far...
1. It is a powerful and deadly virus for people with weak immune systems.
2. People over Seventy years of age are the most vulnerable.
3. A medical respirator is a necessary life-saver for those in the fourth stage of the disease.
4. Every hospital in Canada may need a minimum of five hundred medical respirators before the virus expands into the general population. Respirators should be prioritized by the Canadian government and then quickly manufactured and dispensed throughout Canada. One respirator can service Two (2) patients.
5. The steps we as individuals need to take include refraining from joining groups over Ten people and also, cleaning our hands with a strong hand soap. Look at the bottom of this page for a cheap but powerful hand cleanser.
6. If you must go to a shopping center for groceries, wear gloves and a mask. If there are registered cases of the virus in your area, I suggest wearing a surgical mask if available but if not, a construction mask may be the next best thing or simply use a thin scarf to protect your face.
7. If possible, get yourself tested for the virus and if a medical authority quarantines you, obey without question.
8. If you have recovered from the SARS-CoV-2 virus and you feel strong enough, donate a litre of your blood to a blood bank because somewhere around the world, a smart scientist may use your plasma to create a Vaccine against Covid-19.
9. For those countries that do not have enough respirators, it is possible to use one respirator for two patients by creating a Y in the tubing leading from the respirator to the patients.
I will visit a laboratory to understand more about the Covid-19 disease containing the SARS-CoV-2 virus which causes the disease, then I will report back.
Good luck!
Signed: N.J. Raglione.

Hello Gentle People. Here is more information on the Covid-19 epidemic.

April 05, 2020
We need early detection and preventive measures for everybody in Canada and around the world. The drug APNO1 WORKS IN THE EARLY STAGE but may not work in the late stage of the Covid-19 disease.
Testing early for everybody becomes imperative and to detect the virus early allows the drug a chance to inhibit the disease. Early detection and early treatment is imperative!
The Chinese government tested absolutely everybody in Wuhan to detect the virus as quickly and as early as possible. We Canadians have to do the same!
The drug APNO1 is effective if administered in the early stages of the disease but researchers do not promise that it will work in the later stages of Convid-19. This leads me to believe we need more early testing and then early-stage treatment.
To wait at home for the late-stage often results in death.
N.J.R..

" Research shows that the SARS-CoV-2 virus causing the COVID-19 DISEASE EPIDEMIC is spread through close contact with an infected person and it is most contagious before and during the first week of symptoms. The disease has three (3) stages and the last stage is the most dangerous.

"Autopsies have confirmed that the lungs are filled with clear liquid jelly, much resembling the lungs of wet drowning. Although the nature of the clear jelly has yet to be determined, hyaluronan (HA) is associated with ARDS; moreover, during SARS infection, the production and regulation of hyaluronan is defective. The levels of inflammatory cytokines (IL-1, TNF) are high in the lungs of COVID-19 patients and these cytokines are strong inducers of HA-synthase-2 (HAS2) in CD31+ endothelium, EpCAM+ lung alveolar epithelial cells, and fibroblasts. Importantly, HA has the ability to absorb water up to 1000 times its molecular weight. Therefore, reducing the presence or inhibiting the production of HA holds a great promise in helping COVID-19 patients breathe."

Infection can occur in two ways, droplet and contact.
Droplets' mean respiratory droplets produced by an infected person's sneeze or cough. These can travel up to 6 feet or (1.8 meters). A person becomes infected when droplets from a cough or sneeze directly enter the body through the eyes, mouth, or nose.
Contact means touching a person directly or object directly, such as door handles that have droplets on them from an infected person's cough or sneeze. Unwashed hands contaminated with COVID-19 can introduce the virus to your body when you touch your eyes, mouth or nose. Washing your hands often and avoiding touching your face are two very important ways to help prevent the spread of COVID-19"
SUNNYBROOK...HEALTH SCIENCES CENTRE.
=======
Hello again!
Here is a quick and easy way to disinfect your hands. Fill a plastic pump bottle with Vinegar and squirt in some dish soap. Except for the pump bottle which you can buy at any Dollar store, the Vinegar and dish soap are handy kitchen products usually found in most homes. You will be surprised how well this works not only cleaning your hands but your dishes and almost anything you want to keep clean around the house...and it is cheap to make.
Now for some potential life saving good news! During the early stage of the disease, you can help your lungs fight the infection by taking Vitamin B3 tablets and also by eating foods containing B3. What foods are high in b3? Good sources of vitamin B3, also known as Niacin, include yeast, meat, poultry, redfish (e.g., tuna, salmon), cereals, legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide some niacin.
Don't forget to call an ambulance if the disease climbs up to level 2 and things get rough!

Keep clean and good luck in your struggle against the Covid-19 epidemic. N.J. Raglione. Dir. The World Friendly Peace and Ecology Movement.

COVID-19 and the Edward Jenner approach.

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Published: 23 March 2020
COVID-19 infection: the perspectives on immune responses
Yufang Shi, Ying Wang, Changshun Shao, Jianan Huang, Jianhe Gan, Xiaoping Huang, Enrico Bucci, Mauro Piacentini, Giuseppe Ippolito & Gerry Melino
Cell Death & Differentiation (2020)Cite this article

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More than 100 years since the outbreak of the 1918 influenza pandemic, we now seem to face another pandemic. The outbreak of the new coronavirus (SARS-CoV-2) infection is spreading to every continent, forcing us to live with this virus for perhaps a long time. Scientists and clinicians have learned much of coronavirus disease 2019, COVID-19, and its pathogenesis [1]: not all people exposed to SARS-CoV-2 are infected and not all infected patients develop severe respiratory illness. Accordingly, SARS-CoV-2 infection can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load [2]. From the point of view of prevention, individuals at stage I, the stealth carriers, are the least manageable because, at least on some occasions, they spread the virus unknowingly: indeed, the first asymptomatic transmission has been reported in Germany [3]. The role of asymptomatic SARS-CoV-2 infected individuals in disseminating the infection remains to be defined.

Among over 1000 patients analyzed in Wuhan, except occasionally in children and adolescence, it infects all the other age groups evenly. About 15% of the confirmed cases progress to the severe phase, although there is a higher chance for patients over 65 to progress into the severe phase [1]. One of the biggest unanswered questions is why some develop severe disease, whilst others do not. Clearly, conventional wisdom based on the overall immunity of the infected patients cannot explain this broad spectrum in disease presentation.

Two-phase immune responses induced by COVID-19 infection
Clinically, the immune responses induced by SARS-CoV-2 infection are two-phased. During the incubation and non-severe stages, a specific adaptive immune response is required to eliminate the virus and to preclude disease progression to severe stages. Therefore, strategies to boost immune responses (anti-sera or pegylated IFNα) at this stage are certainly important. For the development of an endogenous protective immune response at the incubation and non-severe stages, the host should be in good general health and an appropriate genetic background (e.g. HLA) that elicits specific antiviral immunity. Genetic differences are well-known to contribute to individual variations in the immune response to pathogens. However, when a protective immune response is impaired, virus will propagate and massive destruction of the affected tissues will occur, especially in organs that have high ACE2 expression, such as intestine and kidney. The damaged cells induce innate inflammation in the lungs that is largely mediated by pro-inflammatory macrophages and granulocytes. Lung inflammation is the main cause of life-threatening respiratory disorders at the severe stage [4]. Therefore, good general health may not be advantageous for patients who have advanced to the severe stage: once severe lung damage occurs, efforts should be made to suppress inflammation and to manage the symptoms.

Alarmingly, after discharge from the hospital, some patients remain/return viral positive and others even relapse. This indicates that a virus-eliminating immune response to SARS-CoV-2 may be difficult to induce at least in some patients and vaccines may not work in these individuals. Those recovered from the non-severe stage should be monitored for the virus together with T/B cell responses. These scenarios should be considered when determining the strategies of vaccine development. In addition, there are many types or subtypes of coronavirus. Thus, if vaccines directly targeting SARS-CoV-2 prove to be difficult to develop, the Edward Jenner approach should be considered.

Cytokine storm and lung damage
The cytokine release syndrome (CRS) seems to affect patients with severe conditions. Since lymphocytopenia is often seen in severe COVID-19 patients, the CRS caused by SARS-CoV-2 virus has to be mediated by leukocytes other than T cells, as in patients receiving CAR-T therapy; a high WBC-count is common, suggesting it, in association with lymphocytopenia, as a differential diagnostic criterion for COVID-19. In any case, blocking IL-6 may be effective. Blocking IL-1 and TNF may also benefit patients. Although various clinical sites in China have announced the use of mesenchymal stromal/stem cells (MSCs) in severe cases with COVID-19 infection, solid results have yet to be seen. One caveat is that MSCs need to be activated by IFNγ to exert their anti-inflammatory effects, which may be absent in severely affected patients as T cells are not well activated by SARS-CoV-2 infection. To enhance effectiveness, one could consider employing the “licensing-approach”: pretreat MSCs with IFNγ with/without TNF or IL-1 [5]. Such cytokine-licensed MSCs could be more effective in the suppression of hyperactive immune response and promotion of tissue repair, as licensed-MSCs are effective in LPS-induced acute lung damage [6].

Lung damage is a major hurdle to recovery in those severe patients. Through producing various growth factors, MSCs may help repair the damaged lung tissue. It is important to mention that various studies have shown that in animal models with bleomycin-induced lung injury, vitamin B3 (niacin or nicotinamide) is highly effective in preventing lung tissue damage [7]. It might be a wise approach to supply this food supplement to COVID-19 patients.

HLA haplotypes and SARS-CoV-2 infection
The major-histocompatibility-complex antigen loci (HLA) are the prototypical candidates for genetic susceptibility to infectious diseases [8, 9]. Haplotype HLA-loci variability results from selective pressure during co-evolution with pathogens. Immunologists have found that T-cell antigen receptors, on CD4+ or CD8+ T cells recognize the conformational structure of the antigen-binding-grove together with the associated antigen peptides. Therefore, different HLA haplotypes are associated with distinct disease susceptibilities. The repertoire of the HLA molecules composing a haplotype determines the survival during evolution. Accordingly, it seems advantageous to have HLA molecules with increased binding specificities to the SARS-CoV-2 virus peptides on the cell surface of antigen-presenting cells. Indeed, the susceptibility to various infectious diseases such as tuberculosis, leprosy, HIV, hepatitis B, and influenza is associated with specific HLA haplotypes. Particular murine MHC class II haplotypes are associated with the susceptibility to influenza. In man, HLA class I is also associated with H1N1 infections: HLA-A*11, HLA-B*35, and HLA-DRB1*10 confer susceptibility to influenza A(H1N1)pdm09 infection [10]. Therefore, it is imperative to study whether specific HLA loci are associated with the development of anti-SARS-CoV-2 immunity and, if so, to identify the alleles, either class I or II, that demonstrate induction of protective immunity. Once the dominant alleles are identified, simple detection kits can be developed. Such information is critical for (1) strategic clinical management; (2) evaluation of the efficacy of vaccination in different individuals in the general population; (3) assignment of clinical professional and managerial teams amid interactions with COVID-19 patients.

Hyaluronan: a potential cause of fatalities
The innate immune response to tissue damage caused by the virus could lead to acute respiratory distress syndrome (ARDS), in which respiratory failure is characterized by the rapid onset of widespread inflammation in the lungs and subsequent fatality [4]. The symptoms of ARDS patients include short/rapid breathing, and cyanosis. Severe patients admitted to intensive care units often require mechanical ventilators and those unable to breath have to be connected to extracorporeal membrane oxygenation (ECMO) to support life [11]. CT images revealed that there are characteristic white patches called “ground glass”, containing fluid in the lungs [2]. Recent autopsies have confirmed that the lungs are filled with clear liquid jelly, much resembling the lungs of wet drowning [4]. Although the nature of the clear jelly has yet to be determined, hyaluronan (HA) is associated with ARDS [12]; moreover, during SARS infection, the production and regulation of hyaluronan is defective. The levels of inflammatory cytokines (IL-1, TNF) are high in the lungs of COVID-19 patients and these cytokines are strong inducers of HA-synthase-2 (HAS2) in CD31+ endothelium, EpCAM+ lung alveolar epithelial cells, and fibroblasts [13]. Importantly, HA has the ability to absorb water up to 1000 times its molecular weight. Therefore, reducing the presence or inhibiting the production of HA holds a great promise in helping COVID-19 patients breathe. Doctors can simply provide patients with medical-grade hyaluronidase to reduce the accumulation of HA and thus to clear the jelly in the lung. In animal models, influenza-induced breathing difficulties can be relieved by the intranasal administration of hyaluronidase. Doctors can also use a clinically approved bile therapy drug, Hymecromone (4-Methylumbelliferone, 4-MU), an inhibitor of HAS2 [14]. LPS-induced lung inflammation can be relieved by 4-MU. 4-MU or its chemical derivatives exist widely in various herbs used in traditional Chinese medicine, which may explain the observed effectiveness of combined herbal medicine in some patients.

Overall, this synopsis is based on some clinical common sense. We propose some simple but largely ignored, approaches to the treatment of COVID-19 patients (Fig. 1). We believe that the two-phase division is very important: the first immune defense-based protective phase and the second inflammation-driven damaging phase. Doctors should try to boost immune responses during the first while suppressing it in the second phase. Since Vitamin B3 is highly lung-protective, it should be used as soon as coughing begins. When breathing difficulty becomes apparent, hyaluronidase can be used intratracheally and at the same time, 4-MU can be given to inhibit HAS2. Of course, HLA typing will provide susceptibility information for strategizing prevention, treatment, vaccination, and clinical approaches. We hope that some of the above ideas can be employed to help combat this deadly contagious disease of increasing incidence around the world.

Fig. 1: Schematic representation of the progression of COVID-19 infection and potential adjuvant interventions.
figure1
After an incubation period, the invading COVID-19 virus causes non-severe symptoms and elicits protective immune responses. The successful elimination of the infection relies on the health status and the HLA haplotype of the infected individual. In this period, strategies to boost immune response can be applied. If the general health status and the HLA haplotype of the infected individual do not eliminate the virus, the patient then enters the severe stage, when a strong damaging inflammatory response occurs, especially in the lungs. At this stage, inhibition of hyaluronan synthase and elimination of hyaluronan can be prescribed. Cytokine activated mesenchymal stem cells can be used to block inflammation and promote tissue reparation. Vitamin B3 can be given to patients starting to have lung CT image abnormalities.

Full size image
References
1.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. The New England journal of medicine. 2020. https://doi.org/10.1056/NEJMoa2002032.

2.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama. 2020. https://doi.org/10.1001/jama.2020.1585.

3.
Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. The New England journal of medicine. 2020;382:970-1. https://doi.org/10.1056/NEJMc2001468.

Article
PubMed
Google Scholar
4.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory medicine. 2020. https://doi.org/10.1016/S2213-2600(20)30076-X.

5.
Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014;15:1009–16. https://doi.org/10.1038/ni.3002.

CAS
Article
PubMed
Google Scholar
6.
Wang G, Cao K, Liu K, Xue Y, Roberts AI, Li F, et al. Kynurenic acid, an IDO metabolite, controls TSG-6-mediated immunosuppression of human mesenchymal stem cells. Cell death and differentiation. 2018;25:1209-23. https://doi.org/10.1038/s41418-017-0006-2.

CAS
Article
PubMed
Google Scholar
7.
Nagai A, Matsumiya H, Hayashi M, Yasui S, Okamoto H, Konno K. Effects of nicotinamide and niacin on bleomycin-induced acute injury and subsequent fibrosis in hamster lungs. Experimental lung research. 1994;20:263-81. https://doi.org/10.3109/01902149409064387.

CAS
Article
PubMed
Google Scholar
8.
Blackwell JM, Jamieson SE, Burgner D. HLA and infectious diseases. Clin Microbiol Rev. 2009;22:370–85. https://doi.org/10.1128/CMR.00048-08.

CAS
Article
PubMed
PubMed Central
Google Scholar
9.
Matzaraki V, Kumar V, Wijmenga C, Zhernakova A. The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biol. 2017;18:76. https://doi.org/10.1186/s13059-017-1207-1.

Article
PubMed
PubMed Central
Google Scholar
10.
Dutta M, Dutta P, Medhi S, Borkakoty B, Biswas D. Polymorphism of HLA class I and class II alleles in influenza A(H1N1)pdm09 virus infected population of Assam, Northeast India. J Med Virol. 2018;90:854–60. https://doi.org/10.1002/jmv.25018.

CAS
Article
PubMed
Google Scholar
11.
MacLaren G, Fisher D, Brodie D. Preparing for the most critically Ill patients with COVID-19: the potential role of extracorporeal membrane oxygenation. JAMA. 2020. https://doi.org/10.1001/jama.2020.2342.

12.
Hallgren R, Samuelsson T, Laurent TC, Modig J. Accumulation of hyaluronan (hyaluronic acid) in the lung in adult respiratory distress syndrome. Am Rev Respir Dis. 1989;139:682–7. https://doi.org/10.1164/ajrccm/139.3.682.

CAS
Article
PubMed
Google Scholar
13.
Bell TJ, B O, Morgan DJ, Salek-Ardakani S, Jagger C, Fujimori T, et al. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biol. 2018;80:14–28.

Article
Google Scholar
14.
Collum SD, Chen NY, Hernandez AM, Hanmandlu A, Sweeney H, Mertens TCJ, et al. Inhibition of hyaluronan synthesis attenuates pulmonary hypertension associated with lung fibrosis. British journal of pharmacology. 2017;174:3 284–301. https://doi.org/10.1111/bph.13947.

Article
Google Scholar
Download references

Acknowledgements
The work has been partially supported by grants from the National Key R&D Program of China (2018YFA0107500), the Scientific Innovation Project of the Chinese Academy of Sciences (XDA16020403), Suzhou 2020 Emergency Innovation Funding on COVID-19 Infection, the National Natural Science Foundation of China (81530043, 81861138015, 31771641 and 81571612), PANDORA-ID-NET (to GI), the European & Developing Countries Clinical Trials Partner-ship, supported under Horizon 2020 to GI), Italian Ministry of Health (RC, 1 to MP and GI).

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The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Medical College, Suzhou, China
Yufang Shi, Changshun Shao, Jianan Huang, Jianhe Gan & Xiaoping Huang
Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China
Yufang Shi & Ying Wang
Sbarro Health Research Organization, Temple University, Philadelphia, PA, 19122, USA
Enrico Bucci
Resis Srl, 10010, Samone, TO, Italy
Enrico Bucci
National Institute for Infectious Diseases ‘Lazzaro Spallanzani” IRCCS, 00149, Rome, Italy
Mauro Piacentini & Giuseppe Ippolito
Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy
Gerry Melino
Medical Research Council (MRC) Toxicology Unit, University of Cambridge, Cambridge, CB2 1QP, UK
Gerry Melino
Corresponding author
Correspondence to Yufang Shi.

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Shi, Y., Wang, Y., Shao, C. et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ (2020). https://doi.org/10.1038/s41418-020-0530-3

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Received01 March 2020

Revised10 March 2020

Accepted10 March 2020

Published23 March 2020

DOIhttps://doi.org/10.1038/s41418-020-0530-3

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Infectious diseases

Today:
Many Pharmacies and grocery stores provide Purell hand disinfectant and or water and soap to customers before the customer, young or old, enters their establishment. In China, where Elders are venerated, authorities provide their elders with face masks and gloves and happily for people around the world in the province where it all started, the Covid-19 epidemic is almost over. People are now being slowly allowed to leave and also to enter Wuhan.
I have just heard that the government of Quebec has removed the onerous requirement of limiting our elders to a couple of hours of grocery shopping too damn early in the morning! It should never have been introduced in the first place as it screams of human rights abuse. Young people are not immune to the SARS-CoV-2 virus and the Covid-19 disease it causes and should be taking the same precautions as our older and more vulnerable population.

If you survived Covid-19, donate blood for Vaccine research.

THE CORONA COVID-19 DISEASE WITH THE SARS-CoV-2 VIRUS.

What I understand so far...
1. It is a powerful and deadly virus for people with weak immune systems.
2. People over Seventy years of age are the most vulnerable.
3. A medical respirator is a necessary life-saver for those infected by the virus.
4. Every hospital in Canada may need a minimum of five hundred medical respirators and they should be prioritized by the Canadian government and then quickly manufactured and dispensed throughout Canada before the virus expands into the general population.
5. The steps we as individuals need to take include refraining from joining groups over Ten people and also, cleaning our hands with a strong hand soap. Look at the bottom of this page for a cheap but powerful hand cleanser.
6. If you must go to a shopping center for groceries, wear gloves. If there are registered cases of the virus in your area, I suggest wearing a surgical mask if available but if not, a construction mask may be the next best thing.
7. If possible, get yourself tested for the virus and if a medical authority quarantines you, obey without question.
8. If you have recovered from the SARS-CoV-2 virus and you feel strong enough, donate a litre of your blood. Somewhere around the world a smart scientist may use your plasma to create a Vaccine against Covid-19.
I will visit a laboratory to understand more about the Covid-19 disease containing the SARS-CoV-2 virus which causes the disease, then I will report back.
Good luck!
Signed: N.J. Raglione.

Hello Gentle People. Here is more information on the Covid-19 epidemic.
" Research shows that the SARS-CoV-2 virus causing the COVID-19 DISEASE EPIDEMIC is spread through close contact with an infected person and it is most contagious before and during the first week of symptoms.
Infection can occur in two ways, droplet and contact.
Droplets' mean respiratory droplets produced by an infected person's sneeze or cough. These can travel up to 6 feet or (1.8 meters). A person becomes infected when droplets from a cough or sneeze directly enter the body through the eyes, mouth, or nose.
Contact means touching a person directly or object directly, such as door handles that have droplets on them from an infected person's cough or sneeze. Unwashed hands contaminated with COVID-19 can introduce the virus to your body when you touch your eyes, mouth or nose. Washing your hands often and avoiding touching your face are two very important ways to help prevent the spread of COVID-19"
SUNNYBROOK...HEALTH SCIENCES CENTRE.
=======
Hello again!
Here is a quick and easy way to disinfect your hands. Fill a plastic pump bottle with Vinegar and squirt in some dish soap. Except for the pump bottle which you can buy at any Dollar store, the Vinegar and dish soap are handy kitchen products usually found in most homes. You will be surprised how well this works not only cleaning your hands but your dishes and almost anything you want to keep clean around the house...and it is cheap to make.
Now for some potential life saving good news! During the early stage of the disease, you can strengthen your body and help your lungs fight the infection by taking Vitamin B3 tablets and also by eating foods containing B3. They won't cure the infection but might help save your energy and keep you alive during your immune system's fight against the SARScoV2. 
What foods are high in b3? Good sources of vitamin B3, also known as Niacin, include yeast, meat, poultry, redfish (e.g., tuna, salmon), cereals, legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide some niacin.
Don't forget to call an ambulance if the disease climbs up to level 2 and things get rough!

Keep clean and good luck in your struggle against the Covid-19 epidemic. N.J. Raglione. Dir. The World Friendly Peace and Ecology Movement.
----------------------------
POTENTIAL CURES FOR COVID-19
-----------------------------------------------
THE SHORT VERSION: REPURPOSING DRUGS.
Three existing anti-virus drugs may have a chance against the Covid-19 virus. They are:
1. REMDESIVIR... A viral inhibitor. It seems to be the best so far and is undergoing testing in China.
2. ACE2... A human protein inhibitor which may decoy the Covid virus by glomming on to the virus and preventing it from getting into cells. Adding extra ACE2 may help protect the existing ACE2 in protecting the cells which cover the lungs.
3. CHLOROQUINE...It is an anti-malaria drug that inhibits the ability of the new virus to infect and grow in Monkey cells. Combining Chloroquine with Remdesivir is also under testing in China.
4. The H.I.V. drug Kaletra, also called Aluvia, is a combination of two Protease inhibitors: Lopinavir and Ritonavir. Kaletra is being tested in China.
5. High doses of Lopinavir combined with Ritonavir worked to cure a 70-year-old lady in Bankok.

=================================================================
THE PRECISE VERSION:
"Repurposed drugs may help scientists fight the new coronavirus.
Work on similar viruses is giving researchers clues to develop drugs against the disease.
A patient who recovered from COVID-19 is discharged from a Wuhan hospital on February 18. His plasma may help to create a vaccine against the Coronavirus: Covid-19.

STR/AFP/GETTY IMAGES

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By Tina Hesman Saey

MARCH 10, 2020 AT 7:00 AM

As the new coronavirus makes its way around the world, doctors and researchers are searching for drugs to treat the ill and stop the spread of the disease, which has already killed more than 3,800 people since its introduction in Wuhan, China, in December.

The culprit virus is in the same family as the coronaviruses that caused two other outbreaks, severe acute respiratory syndrome, and the Middle East respiratory syndrome. But the new coronavirus may be more infectious. In early March, the number of confirmed cases of the new disease, called COVID-19, had exceeded 100,000, far surpassing the more than 10,600 combined total cases of SARS and MERS.

Health officials are mainly relying on quarantines to try to contain the virus’ spread. Such low-tech public health measures were effective at stopping SARS in 2004, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, said January 29 in Arlington, Va., at the annual American Society for Microbiology’s Biothreats meeting.

But stopping the new virus may require a more aggressive approach. In China alone, about 300 clinical trials are in the works to treat sick patients with standard antiviral therapies, such as interferons, as well as stem cells, traditional Chinese medicines including acupuncture, and blood plasma from people who have already recovered from the virus.

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GO
Researchers are not stopping there. They also are working to develop drugs to treat infections and vaccines to prevent them (SN: 3/14/20, p. 6). But creating therapies against new diseases often takes years, if not decades. With this new coronavirus, now known as SARS-CoV-2, nobody wants to wait that long. Thanks to their experience developing treatments against the MERS coronavirus, as well as other diseases, such as HIV, hepatitis C, influenza, Ebola and malaria, researchers are moving quickly to see what they can borrow to help patients sooner.

“Repurposing drugs is absolutely the best thing that could happen right now.”

Karla Satchell, Northwestern University Feinberg School of Medicine
Finding new uses for old drugs is a good strategy, especially when racing to fight a fast-moving disease for which there is no treatment, says Karla Satchell, a microbiologist, an immunologist at Northwestern University Feinberg School of Medicine in Chicago.

“Repurposing drugs is absolutely the best thing that could happen right now,” Satchell says. Potentially, drugs that combat HIV or hepatitis C might be able to put the new coronavirus in check, too. “Those drugs exist. They’ve been produced. They’ve been tested in patients,” she says. Although these drugs aren’t approved to treat the new coronavirus disease, they’re a great place to start. One of the most promising candidates, however, hasn’t yet been approved for any disease.

Early focus
Scientists have been quick to reveal the new corona­virus’ secrets. When SARS emerged in 2002, researchers took about five months to get a complete picture of the virus’s genetic makeup, or genome. With the new virus, Chinese health officials first reported a cluster of mysterious pneumonia cases in Wuhan to the World Health Organization on December 31. By January 10, the new coronavirus’s full genome was made available to researchers worldwide in public databases.

A virus’s genome is one of the most valuable tools scientists have for understanding where the pathogen came from, how it works and how to fight it. The first thing that coronaviruses have in common is that their genetic material is RNA, a chemical cousin to DNA.

Researchers immediately began comparing the new coronavirus’s genome with SARS and MERS viruses and other RNA viruses to determine whether drugs developed to combat those disease-­causing organisms would work against the new threat. As a result, some potential Achilles’ heels of SARS-CoV-2 have already come to light.

One target is the virus’s main protein-cutting enzyme, called M protease. RNA viruses often make one long string of proteins that later get cut into individual proteins to form various parts of the virus. In the new coronavirus, the M protease is one of 16 proteins that are linked like beads on a string, says Stephen Burley, an oncologist and structural biologist at Rutgers University in Piscataway, N.J.


DAVID S. GOODSELL/RCSB PROTEIN DATA BANK
M protease (model is shown) is a key enzyme for the new corona­virus’ survival and may be an Achilles’ heel. Drugs (blue) might be able to nestle into the enzyme and stop viral replication.
The virus can mature and infect new cells only if M protease can snip the string of proteins free, he says. Stop the protease from cutting and the virus can’t reproduce or replicate.

Existing drugs might be able to stop the virus’s M protease, two research groups proposed online January 29 at bioRxiv.org. One group suggested four drugs, including one used to treat hepatitis C and two aimed at HIV. A second group named 10 candidates, including an anti-nausea medication, an antifungal drug, and some cancer-fighting drugs.

HIV and hepatitis C are both RNA viruses that need a protease to cut proteins free from long chains. Drugs that inhibit those proteases can reduce levels of HIV and hepatitis C viruses to undetectable. Some of those drugs are now being tested against the new coronavirus in clinical trials in China.

The HIV drug Kaletra, also called Aluvia, is a combination of two protease inhibitors, lopinavir, and ritonavir. Kaletra’s maker, the global pharmaceutical company AbbVie, announced on January 26 that it is donating the drug to be tested in COVID-19 patients in China. Kaletra will be tested alone or in combination with other drugs. For instance, researchers may combine Kaletra with Arbidol, a drug that prevents some viruses from fusing with and infecting human cells. Arbidol may be tested on its own as well.

See all our coverage of the 2019 novel coronavirus outbreak
But the HIV drugs may not work against the new virus because of two differences in the proteases. The coronavirus protease cuts proteins in different spots than does the HIV protease say: Guangdi Li of the Xiangya School of Public Health of Central South University in Changsha, China, and Erik De Clercq, a pioneer in HIV therapy at KU Leuven in Belgium. Secondly, the HIV drugs were designed to fit a pocket in HIV’s protease that doesn’t exist in the new coronavirus’s protease, the researchers reported February 10 in Nature Reviews Drug Discovery.

Yet a few anecdotal accounts suggest the HIV drugs may help people with COVID-19 recover. Doctors at Rajavithi Hospital in Bangkok reported in a news briefing February 2 that they had treated a severely ill 70-year-old woman with high doses of a combination of lopinavir and ritonavir and the anti-influenza drug oseltamivir, which is sold as Tamiflu. Within 48 hours of treatment, the woman tested negative for the virus.

Her recovery may be due more to the HIV drugs than to oseltamivir. In 124 patients treated with oseltamivir at Zhongnan Hospital of Wuhan University, “no effective outcomes were observed,” doctors reported on February 7 in JAMA. Clinical trials in which these drugs are given to more people in carefully controlled conditions are needed to determine what to make of those isolated reports.

Viral weak spots
Researchers may be able to exploit a second weakness in the virus: its copying process, specifically the enzymes known as RNA-dependent RNA polymerases that the virus uses to make copies of its RNA. “Those enzymes are absolutely essential,” says Mark Denison, an evolutionary biologist at Vanderbilt University School of Medicine in Nashville. If the enzyme doesn’t work, “you can’t make new virus.”

Denison and colleagues have been testing molecules that muck with the copying machinery of RNA viruses. The molecules mimic the nucleotides that RNA polymerases string together to make viral genomes. Researchers have tested chemically altered versions of two RNA nucleotides — adenosine and cytidine — against a wide variety of RNA viruses in test tubes and in animals. The molecules “get incorporated into the viral RNA and either stop it from growing or they damage it by introducing mutations,” Denison says.

One of the molecules that researchers are most excited about is an experimental drug called Remdesivir. The drug is being tested in people with COVID-19 because it can stop the MERS virus in the lab and in animal studies. The drug has also been used in patients with Ebola, another RNA virus.

Remdesivir has been given to hundreds of people infected with Ebola, without causing serious side effects, but the drug hasn’t been as effective as scientists had hoped, virologist Timothy Sheahan of the University of North Carolina at Chapel Hill said January 29 at the Biothreats meeting. In a clinical trial in Congo, for example, about 53 percent of Ebola patients treated with remdesivir died, researchers reported November 27 in the New England Journal of Medicine. That’s better than the 66 percent of infected people killed in the ongoing Ebola outbreak, but other drugs in the trial were more effective.

Repurposed drugs that might treat COVID-19
Several drugs are in testing to target various parts of the new coronavirus.

Remdesivir
Designed to treat: RNA viruses (MERS, Ebola)
Evidence for: Lab tests against the COVID-19 virus; animal tests against MERS; tests in people with Ebola
Evidence against: Not as helpful as other drugs against Ebola
Lopinavir/ritonavir
Designed to treat: HIV
Evidence for: HIV and the new virus have a similar enzyme; anecdotal evidence in COVID-19 patients
Evidence against: The enzymes work differently; the new virus doesn’t have the pocket that the HIV drugs fit into to block the enzyme
Chloroquine
Designed to treat: Malaria
Evidence for: Lab tests against COVID-19
Evidence against: No data
APN01 (ACE2 protein decoy)
Designed to treat: SARS
Evidence for: Tests in animals infected with other viruses; tests in people with lung damage
Evidence against: It didn’t completely protect people with acute respiratory distress syndrome
Several tests of Remdesivir in lab animals infected with MERS have researchers still hopeful when it comes to the new coronavirus. In studies in both rhesus macaques and mice, Remdesivir protected animals from lung damage whether the drug was given before or after infection. Molecular pathologist Emmie de Wit of NIAID’s Laboratory of Virology in Hamilton, Mont., and colleagues reported the monkey results February 13 in the Proceedings of the National Academy of Sciences.

“Remdesivir appears to be one of the most promising antiviral treatments tested in a nonhuman primate model to date,” the team wrote. The results also suggest Remdesivir given before infection might help protect health care workers and family members of infected people from getting severe forms of the disease, Sheahan says.

Denison, Sheahan, and colleagues tested Remdesivir on infected human lung cells in the lab and in mice infected with MERS. Remdesivir was more potent at stopping the MERS virus than HIV drugs and interferon-beta, the researchers reported January 10 in Nature Communications.

But the question is still open about whether Remdesivir can stop the new coronavirus.

In lab tests, it can. Both Remdesivir and the antimalaria drug chloroquine inhibited the new virus’s ability to infect and grow in monkey cells, virologist Manli Wang of the Wuhan Institute of Virology of the Chinese Academy of Sciences and colleagues reported February 4 in Cell Research. Remdesivir also stopped the virus from growing in human cells. Chloroquine can block infections by interfering with the ability of some viruses — including coronaviruses — to enter cells. Wang and colleagues found that the drug could also limit growth of the new coronavirus if given after entry. Chloroquine also may help the immune system fight the virus without the kind of over­reaction that can lead to organ failure, the researchers propose.

In China, Remdesivir is already being tested in patients. And NIAID announced February 25 that it had launched a clinical trial of Remdesivir at the University of Nebraska Medical Center in Omaha. The first enrolled patient was an American evacuated from the Diamond Princess cruise ship in Japan that had been quarantined in February because of a COVID-19 outbreak.

Ultimately, nearly 400 sick people at 50 centers around the world will participate in the NIAID trial, which will compare "Remdesivir" with a placebo. The trial may be stopped or altered to add other drugs depending on results from the first 100 or so patients, says Andre Kalil, an infectious disease physician at the University of Nebraska Medical Center.

Researchers considered many potential therapies, but based on results from the animal and lab studies, “remdesivir seemed to be the one that was more promising,” Kalil says.

man donating plasma
This man in Wuhan, China, recovered from COVID-19 and is donating plasma for critically ill patients. The plasma contains antibodies that may fight the virus.
BARCROFT MEDIA/GETTY IMAGES
In the early patient studies, figuring out when to give Remdesivir to patients might not be easy, Sheahan says. Often drugs are tested on the sickest patients. For example, those in the NIAID trial must have pneumonia to participate. By the time someone lands in the intensive care unit with COVID-19, it may be too late for Remdesivir to combat the virus, Sheahan says. It may turn out that the drug works best earlier in the disease, before viral replication peaks.

“We don’t know because it hasn’t really been evaluated in people how Remdesivir will work, or if it will work at all,” Sheahan cautions.

The drug seems to have helped a 35-year-old man in Snohomish County, Wash., researchers reported January 31 in the New England Journal of Medicine. The man had the first confirmed case of COVID-19 in the United States. He developed pneumonia, and doctors treated him with intravenous Remdesivir. By the next day, he was feeling better and was taken off supplemental oxygen.

That’s just one case, and the company that makes Remdesivir has urged caution. “Remdesivir is not yet licensed or approved anywhere globally and has not been demonstrated to be safe or effective for any use,” the drug’s maker, biopharmaceutical company Gilead Sciences, headquartered in Foster City, Calif., said in a statement on January 31.

Too many trials of less-promising candidates are being offered. “We have got to start prioritizing enrollment into those things that may save lives and save them faster.”

Bruce Aylward, WHO assistant director-general
But global health officials are eager to see the drug tested in people. “There’s only one drug right now that we think may have real efficacy, and that’s remdesivir,” WHO’s assistant director-general Bruce Aylward said during a news briefing on February 24. But researchers in China are having trouble recruiting patients into remdesivir studies, partly because the number of cases has been waning and partly because too many trials of less-promising candidates are being offered. “We have got to start prioritizing enrollment into those things that may save lives and save them faster,” Aylward said.

Decoy defense
Another strategy for combating COVID-19 involves distracting the virus with decoys. Like the SARS virus, the new virus enters human cells by latching on to a protein called ACE2. The protein studs the surface of cells in the lungs and many other organs. A protein on the surface of the new virus binds to ACE2 10 to 20 times as tightly as the SARS protein does.

Researchers at Vienna-based Apeiron Biologics announced February 26 that they would use human ACE2 protein in a clinical trial against the new coronavirus. When released into the body, the extra ACE2 acts as a decoy, glomming on to the virus, preventing it from getting into cells.

ACE2 isn’t just a virus’s doorway to infection. Normally, it helps protect the lungs against damage, says Josef Penninger, an immunologist at the University of British Columbia in Vancouver and a cofounder of Apeiron. Penninger and colleagues reported the protein’s protective qualities, based on studies with mice, in Nature in 2005.

During a viral infection, the protein is drawn away from the cell surface and can’t offer protection. Penninger thinks that adding in extra ACE2 may help shield the lungs from damage caused by the virus and by immune system overreactions. The protein is also made in many other organs. Penninger and colleagues are testing whether the new virus can enter other tissues, which might be how the virus leads to multiple organ failures in severely ill people.

The decoy protein drug, called APN01, has already been through Phase I and Phase II clinical testing. “We know it’s safe,” Penninger says. Now researchers just need to determine whether it works.

Persistent problem solving
No one knows whether any of these approaches can help stem the spread of COVID-19.

“Right now, we need lots of people working with lots of ideas.”

Karla Satchell
“Right now, we need lots of people working with lots of ideas,” Satchell says. Similarities between the viruses that cause SARS and COVID-19 may mean that some drugs could work against both. “There is a hope that several small molecules that were identified as inhibitors of the SARS protease would represent reasonable starting points for trying to make a drug for the 2019 coronavirus,” Burley says.

“The open question is, can you produce a drug that is both safe and effective quickly enough to have an impact?” SARS was stopped by traditional infection-control measures in 2004, before any virus-fighting drugs made it through the development pipeline.

But had a decision been made then to spend $1 billion to make a safe and effective drug against SARS, Burley says, such a drug might be working now against the new coronavirus, eliminating the need to spend hundreds of billions of dollars to contain this new infection.

An investment in SARS would not have paid off for people with MERS, which is still a danger in the Middle East. The MERS virus is too different from SARS at the RNA level for SARS drugs to work against it.

But a future coronavirus might emerge that is similar enough to SARS and SARS-CoV-2 to be worth the cost, Burley says. Even if the current outbreak dwindles and disappears, he says, governments and companies should keep investing in drugs that can stop coronaviruses.

“I’m quite certain that the economic impact of the epidemic is going to run into the hundreds of billions,” he says. “So you would only need a 1 percent chance of something that was treatable with the drug to show up in the future to have made a good investment.”


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CITATIONS
AbbVie Inc. AbbVie Statement on Coronavirus and lopinavir/ritonavir. January 27, 2020.

World Health Organization. Global research on coronavirus disease (COVID-19).

Y. Li et al. Therapeutic drugs targeting 2019-nCoV main protease by high-throughput screening. bioRxiv.org. January 29, 2020. doi:10.1101/2020.01.28.922922.

X. Liu and X.-J. Wang. Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines. bioRxiv.org. January 29, 2020. doi:10.1101/2020.01.29.924100

A. Wu et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host & Microbe. Published online February 7, 2020. doi:10.1016/j.chom.2020.02.001

S. Mulangu et al. A randomized, controlled trial of Ebola virus disease therapeutics. New England Journal of Medicine. Published on November 27, 2019. doi: 10.1056/NEJMoa1910993

T.P. Sheahan et al. Comparative therapeutic efficacy of Remdesivir and combination lopinavir, ritonavir, and Interferon-beta against MERS-CoV. Nature Communications. Published online January 10, 2020. doi:10.1038/s41467-019-13940-6.

M. Wang et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Reports. Published online February 4, 2020. doi:10.1038/s41422-020-0282-0.

E. de Wit et al. Prophylactic and therapeutic Remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proceedings of the National Academy of Sciences. Published online February 13, 2020. doi:10.1073/pnas.1922083117.

Gilead Sciences. Gilead Sciences' statement on the company’s ongoing response to the 2019 novel coronavirus (2019-nCoV). January 31, 2020.

M.L. Holshue et al. First case of 2019 novel coronavirus in the United States. New England Journal of Medicine. Published online January 31, 2020. doi:10.1056/NEJMoa2001191.

D. Wang et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. Published online February 7, 2020. doi:10.1001/jama.2020.1585.

G. Li and E. de Clercq. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature Reviews Drug Discovery. Published online February 10, 2020. doi:10.1038/d41573-020-00016-0.

Y. Imai et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. Vol. 436, July 7, 2005, p. 112. doi: 10.1038/nature03712

Tina Hesman Saey
About Tina Hesman Saey
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Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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Pilot clinical trial in China to test UBC researcher’s findings as a targeted therapy for COVID-19
February 25, 2020
APN01 — a drug made by Apeiron Biologics and developed based on the work of UBC’s Josef Penninger — already shown to block viral spread in SARS
A UBC Faculty of Medicine researcher is part of an international team working with a biotechnology company on a pilot clinical trial of a potential new treatment for patients with severe coronavirus infections in China.

Dr. Josef Penninger, director of UBC’s Life Sciences Institute and Canada 150 Chair in Functional Genetics, is working closely with Vienna-based APEIRON Biologics AG on a randomized, dual-arm trial that will treat 24 patients for seven days to determine whether APN01 treatment improves outcomes in patients with severe SARS-CoV-2 infection, the virus that causes COVID-19 disease.

APN01, a drug candidate of APEIRON, is based on previous work in the early 2000s, when Penninger, together with Drs. Arthur Slutsky (University of Toronto) and Chengyu Jiang (Peking Medical Union College), discovered that a protein called ACE2 was the critical receptor for the SARS virus and also protected the lung.


Dr. Josef Penninger

“As a result of SARS revealing its secrets of how it damages the lung, it has also shown us how to develop new medicines to treat other diseases,” says Penninger, a professor in the department of medical genetics. “Now, it turns out that the SARS-CoV-2 virus also uses ACE2 to infect cells. So ACE2 is the rational and targeted therapy for the new epidemic. First, APN01 keeps the virus from infecting cells, and second, it should prevent lung failure and multiple organ complications, the source of most of the mortality we are seeing with COVID-19.”

During the trial, which will begin shortly in China, researchers will assess participants to determine if APN01 reduces the viral load of SARS-CoV-2 virus, as well as the number of days patients endure fever. Data from the trial will be evaluated to determine if there is a need for an additional clinical trial in a larger number of patients.

An international team of Canadian, Chinese, and European experts, including Penninger, co-founder of APEIRON and the APEIRON team, Dr. Liqun Zhang and team of Angalpharma Co., Ltd (Suzhou, China), are coordinating the Chinese clinical trial with the support of dMed Pharmaceutical Co., a CRO team based in China. Drs. Haibo Zhang and Arthur Slutsky at St. Michaels Hospital in Toronto will determine if APN01 improves severe disease of the new coronavirus outbreak.

The trial in China is being led by Dr. Yimin Li, the ICU director who fought the 2003 SARS outbreak Guangdong Province, and Dr. Nanshan Zhong, the Chair of the National COVID-19 Commission in China.

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