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Antibody Treatment Being Developed from the Blood Plasma of Patients Who Have Recovered From COVID-19

Wally

Senior Member
Messages
1,167
When looking at potential treatments for the COVID-19 coronavirus could the antibody treatment already tested in China, and similar treatments being developed in other countries, be a viable solution to protect those who are the most vulnerable (immune compromised and frontline health workers) from catching this illness?

https://www.theverge.com/2020/3/19/21186569/blood-coronavirus-patients-treatments-infection-covid-19
Blood from recovered COVID-19 patients is a key resource for scientists

When a new virus like the novel coronavirus appears and starts infecting people, one critical asset in the fight against it is blood from people who were sick and then recovered. These blood samples can help scientists understand how the immune system responds to it, and can help in the search for therapies to treat the disease.
That’s why, this week, the Vaccine Research Center at the National Institutes of Health put out a call looking for blood donations from people who had COVID-19 and are now healthy. . .

Preliminary research (that hasn’t yet been published) on COVID-19 patients shows that they do produce high levels of antibodies, which virologists say is a sign people wouldn’t get sick from the virus a second time. Another still unpublished study on monkeys found that they developed antibodies after they were infected with the novel coronavirus, and they didn’t get sick a second time if they were exposed to the virus again. “It indicates that infection results in protective immunity against SARS-CoV, at least in the short term,” Angela Rasmussen, a research scientist at the Center for Infection and Immunity at the Columbia University Mailman School of Public Health, wrote in an email to The Scientist.

Scientists also turn to the blood of patients who have recovered from COVID-19 as a possible stopgap treatment for the most at-risk people. Because their blood plasma is presumably full of protective substances like antibodies, if it’s injected into sick people, it may help them fight off disease. It’s an old strategy and dates back as far as the 1918 Spanish flu outbreak in the United States, when doctors reported that it helped reduce the number of deaths in seriously ill patients. Recently, it’s been used on an experimental basis to treat people with MERS, H1N1, and Ebola. . . .

The treatment is risky, though, and there are always concerns that the use of plasma could make any subsequent infection with the virus in question worse. It would likely only be a temporary measure until more refined treatments became available. But the benefits may outweigh the risks for health care workers or older people who are more likely to become seriously ill if they were infected with the virus. . . .


https://www.jci.org/articles/view/138003 - “The convalescent sera option for containing COVID-19

This article gives a detailed explanation of how antibodies taken from the blood of patients who became infected with a viral pathogen and subsequently recover has been used to protect and treat other patients. This type of treatment is not new and there our reports that it has already been successfully tried in China on patients with COVID-19.
 
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Wally

Senior Member
Messages
1,167
I heard that a U.S. patient (female - I believe she is a young adult) was very ill with COVID-19 and she was treated with SARS antibody serum - S230. She recovered and is doing fine.
See this paper with reference to S230. https://www.pnas.org/content/104/29/12123
Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies

. . . Here we report that two hmAbs, m396 and S230.15, potently neutralized GD03 and representative isolates from the first SARS outbreak (Urbani, Tor2) and from palm civets (SZ3, SZ16). These antibodies also protected mice challenged with the Urbani or recombinant viruses bearing the GD03 and SZ16 spike (S) glycoproteins. Both antibodies competed with the SARS-CoV receptor, ACE2, for binding to the receptor-binding domain (RBD), suggesting a mechanism of neutralization that involves interference with the SARS-CoV–ACE2 interaction. Two putative hot-spot residues in the RBD (Ile-489 and Tyr-491) were identified within the SARS-CoV spike that likely contribute to most of the m396-binding energy. Residues Ile-489 and Tyr-491 are highly conserved within the SARS-CoV spike, indicating a possible mechanism of the m396 cross-reactivity. Sequence analysis and mutagenesis data show that m396 might neutralize all zoonotic and epidemic SARS-CoV isolates with known sequences, except strains derived from bats. These antibodies exhibit cross-reactivity against isolates from the two SARS outbreaks and palm civets and could have potential applications for diagnosis, prophylaxis, and treatment of SARS-CoV infections.
 

Wally

Senior Member
Messages
1,167
https://www.dailymail.co.uk/health/...od-coronavirus-survivors-treat-newly-ill.html
FDA approves first US coronavirus treatment: Doctors across the US can now treat the sickest Americans with plasma from recovered patients


The US Food and Drug Administration on Tuesday approved the first treatment in the US for the coronavirus that has infected more than 50,000 Americans: blood plasma from people who have cleared the infection.

Blood plasma from recovered COVID-19 patients is rich in antibodies their immune system has developed to fight the infection.

China began using the century-old method to treat its patients last month, and New York Governor Andrew Cuomo announced Monday that plasma would be tested there to treat the sickest of the state's more than 25,000 coronavirus patients.


The treatment may be the best hope for critically ill COVID-19 patients while scientists work to develop new, specific treatments for the disease and test experimental drugs like chloroquine and remdesivir.
 

Gingergrrl

Senior Member
Messages
16,171
Is this sort of like IVIG (when it is used for immune deficiency) except more targeted?

I apologize for quoting myself but am hoping someone will see my question and reply. I am still trying to figure out if this new blood plasma treatment from recovered COVID-19 patients is similar to IVIG (in the concept and mechanism, etc) except more targeted against COVID-19 vs. as a general immune modulator?
 

Wally

Senior Member
Messages
1,167
I apologize for quoting myself but am hoping someone will see my question and reply. I am still trying to figure out if this new blood plasma treatment from recovered COVID-19 patients is similar to IVIG (in the concept and mechanism, etc) except more targeted against COVID-19 vs. as a general immune modulator?


@Gingergrrl - I did not respond to your question when it was first posted because I did not have an answer, sorry I probably should have at least acknowledged your question since I started this thread. Hope someone with more science knowledge than me sees your post and can provide an answer to your good question.👍
 

andyguitar

Moderator
Messages
6,595
Location
South east England
Its a method of treatment that was used to treat Ebola and SARS. Basic idea is that those who have had Covid 19 will have produced antibodies to it. Those antibodies are extracted and infused into the seriously ill who have not produced their own antibodies to Covid, provoking an immune response. So yes it is just targeted at Covid and is not an immune modulator. Good chance it will work for some.
 

Wally

Senior Member
Messages
1,167
@Gingergrrl - Not sure if this info. will help answer your question, but I thought I would pass it on for you to review.
https://www.statnews.com/2020/03/05...overed-patients-could-help-treat-coronavirus/
. . .[T]he Japanese drugmaker Takeda Pharmaceutical Co. said it was developing a new coronavirus drug derived from the blood plasma of people who have recovered from Covid-19. Its approach is based on the idea that antibodies developed by recovered patients might strengthen the immune system of new patients. . . .

Patients who have recovered from a disease have permanent antibodies generated by the immune system floating in their blood plasma, the liquid component of blood. To turn that into a drug, the plasma is harvested, tested for safety, and purified to isolate those protective antibodies. When injected into a new patient, the “plasma-derived therapy” — also known as convalescent plasma — provides “passive immunity” until the patient’s immune system can generate its own antibodies. . . .

Takeda already makes a medicine called intravenous immunoglobin, or IVIG, for treating patients who have immune disorders. It consists of antibodies of all types purified from the blood plasma of healthy people. Giving antibodies in this purified form is easier, because it requires a much lower volume of treatment; it’s safer, because there is no chance of transmitting other viruses; and it’s more efficient.

With its new treatment, TAK-888, Takeda hopes to create an IVIG from the blood of people who have been infected with the coronavirus and who have recovered. That could create a treatment or prophylactic relatively quickly. It might not need to go through phase I studies to demonstrate basic safety, or larger phase III studies to demonstrate efficacy. That means the treatment could be available sooner.

The other advantage of this approach is that researchers don’t need to figure out which antibodies work best at fighting off the novel coronavirus. They basically import the entire disease-fighting army of antibodies from patients whose bodies have already won. The antibodies in TAK-888 will be more narrowly selected to target coronavirus than those in garden variety IVIG.
Edit added to bold for emphasis.
 
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Gingergrrl

Senior Member
Messages
16,171
@Gingergrrl - I did not respond to your question when it was first posted because I did not have an answer, sorry I probably should have at least acknowledged your question since I started this thread. Hope someone with more science knowledge than me sees your post and can provide an answer to your good question.👍

No worries and I wasn't sure if you (or anyone) saw my question among the longer posts so I wanted to ask it again and am very glad I did. Thank you so much for finding that latest article.

@Gingergrrl - Not sure that if this info. will help answer your question, but I thought I would pass it on for you to review.
https://www.statnews.com/2020/03/05...overed-patients-could-help-treat-coronavirus/

This article is EXACTLY what I was trying to figure out and answered my question. It looks like this antibody treatment would be like IVIG except targeted to just COVID-19. I am going to quote a few things from the article starting from where you ended:

The antibodies in TAK-888 will be more narrowly selected to target coronavirus than those in garden variety IVIG.

This is what I had wondered and it seems to match what I was envisioning in my head... so it would be the same concept and mechanism as IVIG except targeted at COVID-19 (vs. every antibody and autoantibody under the sun like the two years of IVIG that I did called Gamunex).

“We are not looking at this as a therapy that everyone should go on,” Julie Kim, the president of Takeda’s blood plasma unit, told STAT. “This will be targeted to patients who have severe disease.”

This was my next thought, "Who would get the treatment?" since standard IVIG is so hard to get it is called "Liquid Gold". I cannot even imagine the value of this treatment and doctors trying to argue with insurance companies re: which patients should be eligible to receive it. I suspected it would only be for patients with severe disease (which totally makes sense). I just wonder if WAY later down the line when patients have a "post-COVID syndrome" if this TAK-888 specialized IVIG could bring about improvement or remission for them, too?

Kim said the hope is that a single donor might provide enough IVIG for a single patient. But it’s also possible that IVIG derived from several people would be needed to treat each patient.

That is fascinating b/c regular IVIG can literally have hundreds of thousands of different donors to make up one bag of IVIG (to have the greatest variety of antibodies possible to modulate the immune system -- either in immune deficiency or autoimmunity depending on the dose).

The IVIG approach Takeda is using is known as “polyclonal antibodies,” which means, simply, that there are a lot of different types of antibodies in the mix. But many biotech drugs are what are known as monoclonal antibodies, single antibodies that can be originally generated in mice and then manufactured in huge tanks of cells.

This is also something I had wondered about (vs. drugs like Rituximab or other MAB drugs which are monoclonal antibodies that can be generated in mice/hamsters in a lab).

So which of these approaches is better?
That’s not the right question. Convalescent plasma, and then IVIG, could provide our first-line defense for people with Covid-19, especially those who are older and at much higher risk for complications. A monoclonal antibody drug could reach a greater number of patients. We also need antiviral drugs, such as remdesivir, being tested by Gilead Sciences. And a vaccine could do the most to slow or stop transmission. “We need them all,” said Poland of the Mayo Clinic.

This all gives me hope although it is all going to take a lot of time and money and not a quick fix like we so desperately need now.
 

Wally

Senior Member
Messages
1,167
https://globalbiodefense.com/2020/0...book-penn-medicine-and-uchicago-start-trials/
]
Convalescent Plasma Therapy: Johns Hopkins Releases Guidebook, Penn Medicine and UChicago Start Trials

by Global Biodefense

20 Apr 2020

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A team of Johns Hopkins experts has created a clinical guidebook to help hospitals and medical centers rapidly scale up their ability to deliver so-called convalescent plasma therapy, which leverages immune system components found in the plasma portion of blood from people who have recovered from COVID-19 illness.

The guidebook was published online April 7 in the Journal of Clinical Investigation.


In recent weeks, infectious disease expert Arturo Casadevall, M.D., Ph.D., has led a team of physicians and scientists from around the United States to establish a network of hospitals and blood banks that can begin collecting, isolating and processing blood plasma from COVID-19 survivors.


“This paper details the nuts and bolts of how to deploy convalescent plasma, and this information should be very helpful to colleagues worldwide who are preparing to use this therapy against COVID-19,” says Casadevall . . .

The guidebook outlines a range of clinical trials underway or planned at hospitals taking part in the Johns Hopkins-led network for convalescent plasma therapy.“We’ve received many inquiries from health care providers looking to ramp up their ability to deliver this therapy,” says Evan M Bloch, M.D., M.S.. . . , “There is historical precedent for its use to prevent and treat viral illness. However, during the chaos of an epidemic, the therapy is often deployed without rigorously studying its effects. Carefully conducted studies are critically needed to understand which people are most likely to benefit from this therapy and how best to apply it to optimize that benefit.”


Bloch, also an expert on global health, says convalescent blood plasma therapy can be deployed in low-resource communities. There is a difference, however, in how blood plasma may be collected in communities with low versus high resources. . . .



Penn Medicine to Study Impact of Convalescent Plasma in Severely Ill COVID-19 Patients


pA new two-part research initiative at Penn Medicine was announced on Apr. 19 in which plasma will be collected from recovered COVID-19 patients and then administered to moderately and severely ill hospitalized patients.

The first trial will include 50 patients and take up to four months to complete. Up to two units, or 500 milliliters, of plasma will be given to each patient enrolled in the trial.

Two recent papers have shown positive results among critically-ill COVID-19 patients treated with convalescent plasma therapy. One study of ten severely-ill COVID-19 patients in Wuhan, China determined that one unit –200 milliliters–of convalescent plasma led to the improvement of clinical symptoms within three days and the disappearance of the virus from the blood in seven days. The study authors said results indicate the therapy is a promising rescue option for severely ill patients. Another study from China similarly showed clinical improvement among five critically-ill patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). However, both were uncontrolled, observational studies describing small groups of participants. . .



UChicago Medicine Recruiting Plasma Donors for Clinical Study


The University of Chicago Medicine announced on Apr. 13 a clinical trial to study whether blood plasma from people who have recovered from COVID-19 can be used to treat patients who are still in the hospital with severe disease symptoms.

The trial will recruit plasma donors from existing UChicago Medicine patients and from other people in Chicago who have tested positive and recovered from COVID-19. . . .

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