MacInTouch Amazon link...

transfusion of plasma sourced from resistant individuals

I try to provide tech support and informed analysis of science and political news, as well as computer technology for family and friends. Although not a medical professional, my background from experience and family (18 months low-level work in two hospitals, and father, great grandfather and grandfather’s brother were all physicians), plus formal training (biology and chemistry through a doctorate) help in understanding the current pandemic. Recently reviewing available information, I believe I see a reasonable way out rapidly coming together. Rather than simply listing the articles, an informed discussion linking their contributions and significance might help others better understand.

A relatively simple, inexpensive and broadly available technology, using traditional semi-abandoned “antiquated” methods, may stop the pandemic. Prominent researchers at medical institutions including the Mayo Clinic, Johns Hopkins and others have been promoting this approach, with increasing vigor, since January. Independent testing against COVID-19 began in China in January, with positive, though limited, results published last week. The National COVID-19 Convalescent Plasma Project is now calling for plasma donation from COVID-19 convalescents to support this treatment method. More details are added below from earlier discussions with family and friends, including local politicians, with whom I routinely communicate.

My comments are not authoritative, but rather informed commentary intended to help others make sense of the pandemic.
 


(April 2)

I am out of touch with the medical establishment. A benefit is that I have more free time to investigate news. Yesterday I discovered that a long-used historical practice for treating acute viral infections, among other medical maladies, is being developed for Covid-19. To me this seems potentially very significant, yet it is not much discussed in the popular media. If you think this information might be useful, I hope you will forward it to those who can make use of it....

Transfusion of serum sourced from resistant individuals is a well known traditional alternate antiviral therapy, which seems broadly neglected in modern times. Current efforts at the Mayo Clinic seek to update procedures for its use against Covid-19. When revalidated, its use could entail greatly increased use of transfusion technologies, as well as requiring a list of recovered Covid-19 infectees willing to give plasma. Preparation now might enable this alternate technology to alleviate the predicted shortfall in capacity to treat acute victims of Covid-19.

Current information states that roughly 20% of infections lead to serious medical issues. Conversely, 80% of infected individuals are resistant, and may experience mild or even unnoticed symptoms. Thus, the rate of increase of sources of anti-Covid-19 plasma, resistant individuals, is four times the increase of serious cases. The extent of persistence of resistance in previously infected individuals is unknown, maybe months but more likely years. Thus, this potential source of a cure is expected to grow much more rapidly than Covid-19 spreads, and endure much longer.

Possible use of this method might entail stockpiling plasma from resistant individuals now. Then for newly infected individuals who appear very susceptible, supplement their resistance by infusion of the resistant plasma. The consequent temporary reduction in pathogenicity could provide additional time for development of the patient’s intrinsic immune response. Hopefully, this would allow many of the 20% of cases now considered severe to join the 80% for whom the disease is less serious. As well as possibly saving the lives of the treated patients, lessening the severity of their symptoms could reduce the need for facilities and equipment, alleviating the anticipated shortfall.

I believe this procedure has the benefit of using existing well-known technology and skills which are in place throughout the medical establishment, primarily that of blood transfusions, making the procedure broadly available and scalable. An important component, currently missing, is the ability to positively identify individuals resistant to Covid-19 due to previous infection. While this capability is under development, resistant individuals can be identified as having recovered after previously testing positive, or after having shown characteristic diagnostic signs such as loss of taste or smell.

As reported in the Washington Post (linked below), this treatment regime is being investigated by the Mayo Clinic. I did not find any information on this research available to the general public when last night I searched the Internet and the Mayo Clinic web site. I suspect an inquiry from medical professionals would yield more information.

Current acutely ill patients might benefit if clinical staff were more aware of this possible treatment regime. No doubt the method can be improved by current research, and further analysis in light of modern knowledge. Even so, patients may die while waiting for research results and modern methods. It could be much better to use this method as it is now, with its use record extending over 100 years, rather than nothing.
 


(April 4)

Reading for myself, I found more information, which suggests to me this method could resolve much of the current health crisis. Probably we will hear much more about this on news reports. These links provide more details, including what we can do to help make this work: donate blood (serum) if you become infected and recover.

The history of the method dates to the origins of immunology in the 19th century, when serum produced in horses to cure diphtheria and tetanus in humans led to the first Nobel Prize in Medicine, awarded in 1901. The method has since been used to cure many other maladies. For example, in the 1960s I heard of severe snake bite victims being cured by serum from snake handler Ross Allen, who in surviving many bites had developed considerable immunity.

Preliminary study conducted in China from January 20, 2020, to March 25, 2020 yields encouraging results reported March 27.

A national project coordinates information for health care providers, patients, plasma donors and the general public.
National COVID-19 Convalescent Plasma Project
We are a group of physicians and scientists from 34 institutions in 17 states who have self-organized for the purpose of investigating the use of convalescent plasma in the current COVID-19 pandemic. …
... instantly recognized the promise and importance of examining whether this mode of treatment might work in COVID-19 ...
The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly.
US FDA approves convalescent plasma as broadly available Investigative New Drug.
Investigational COVID-19 Convalescent Plasma - Emergency INDs | FDA
Expanded Access: FDA has worked with multiple federal partners and academia to open an expanded access protocol to facilitate access to COVID-19 convalescent plasma. For patients with, or at risk of, severe or life-threatening COVID-19 disease who are not eligible or who are unable to participate in randomized clinical trials, access may be available through participation of acute care facilities in an investigational expanded access protocol

Single Patient Emergency IND: … given the public health emergency that the expanding COVID-19 outbreak presents, while clinical trials are being conducted and an expanded access protocol is available, FDA also is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections through the process of the patient’s physician requesting a single patient emergency Investigational New Drug Application … This process allows the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorization.

How to obtain authorization for use of COVID-19 convalescent plasma to treat patients using an emergency IND
  • • For requests that are not highly time sensitive (response from FDA provided within 4 to 8 hours), the requesting physician may contact FDA by completing form 3926
In the event of an emergency that is highly time sensitive (response required in less than 4 hours) or where the provider is unable to complete and submit form 3926 due to extenuating circumstances, the provider may contact FDA’s Office of Emergency Operations at 1-866-300-4374 to seek verbal authorization
How people can help.

Trials begin in New York.

Recent related research supporting convalescent plasma treatment method.

Summaries of Current efforts.

Political leadership by example.

Blood supply organizations provide necessary support.

Simple convalescent plasma works pretty well. Well-informed effort may make it much better.
 


This review and explanation is intended to enable readers to better appreciate convalescent plasma therapy and its significance.

Discussion with Ric led to this attempt to explicate my original posts. Work confirming the use of convalescent plasma against Covid-19, describing the rapidly developing national system for its use, and requesting support from individuals, is described by sites linked earlier.

I am not a medical professional. I am an informed observer. From reading, I believe the potential exists now to change the coronavirus pandemic from widespread intractable terminal illness, to a manageable problem. Convalescent plasma therapy is simple enough that it does not require elaborate modern hospital technology. It can probably be used many remote places, such as Africa.

Principal points are convalescent plasma therapy works, it is available now, and it depends on broad support from Covid-19 convalescent donations.

1. Convalescent plasma is a traditional method which appears to cure Covid-19 infections using cheap, immediately and universally available technology.​
2. Convalescent plasma as a possibility was recognized early by Chinese medical researchers, who in January began a preliminary clinical study of 5 patients. The conclusion of that study, reported March 27, confirmed this possibility.​
3. US medical researchers (Johns Hopkins, the Mayo Clinic and others) also recognized this possibility early on. The National Convalescent Plasma Project is their work to evaluate and implement it. Results thus far confirm convalescent plasma’s promise as a solution.​
4. Convalescent plasma has been given Investigative New Drug (IND) status by the Food and Drug Administration (FDA). Recognizing its potential, the FDA will readily grant individual doctors immediate permission for compassionate use.​
5. Blood banks are collecting and distributing Covid-19 convalescent plasma now.​

The Covid-19 problem is not an intractable. Cheap, readily available classic medical methods appear to work, and are rapidly being confirmed. Relief efforts should enlist coronavirus convalescents as serum donors, and support collection of serum by local blood banks. Those who have recovered from coronavirus should donate plasma now.

Blood transfusion technology is well established, with equipment and personnel in almost all locales, so the logistical issues in use of convalescent plasma are understood and the technical people who will implement this solution are in place. That is a large part of the beauty of this solution. Type and cross-match. Women who have given birth should be excluded as donors, because they may have developed an immune reaction against the baby’s blood. All that and more; many issues in serum collection and use have been pretty much solved in well over 100 years of practice of blood transfusions.

Basic elements of processing blood for transfusion are not complex. A convalescent coronavirus patient donates blood. Blood cells, white and red, are removed by centrifugation. The supernatant plasma, already much less likely to create issues for the recipient, is tested for agents which could transmit disease. A few drops from a specific unit of plasma are tested against a few drops of blood from a prospective recipient. If no adverse reaction is observed, the plasma is transfused onto the patient.

Back in the 1890's and earlier there was no known cure for diphtheria or tetanus, so many patients died. Then transfusion of convalescent plasma was introduced. It stopped people from dying.

Nowadays in the 2020's there is no known cure for Covid-19 infection. People are dying. Fortunately 95% of infected people develop immunity and convalesce. Modern technology will almost certainly provide a cure, in a year or two. Oh, whatever can we do, what should we do, as people die while we wait for a vaccine?

Answer: extract immunity-conferring serum from convalescents, and transfer the serum to infected individuals.


Ric asked “At what point can this therapy work? Can it be administered shortly before the point where a ventilator is required, or does it have to be much earlier - and, if so, how much earlier?”

I think the answer will be empirical, with the details varying from patient to patient. In this pandemic there will be many opportunities to experiment and perfect the method.

For example, this study confirms that the level of response to infection varies among different people. Because of the varying response, it is important to assay the level of immune factors in convalescent serum from each donor before possibly using it to treat patients. Variability is expected. Causes of variability are a topic for future study.
Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications
The variations of SARS-CoV-2 specific NAbs [neutralizing antibodies] in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment.
The world has come alive in searching for solutions to the pandemic. Information about convalescent serum may seem lost in the noise. Looking a little deeper awareness can be seen in many places, along with rapid movement towards implementation. I predict an impending major change in the tenor of news, as people realize this solution is available and in use now. The transformation will be from “COVID-19 produces mass deaths, and soon is coming to you!” to “Traditional medicine cures novel infections, ending pandemic. High-tech vaccines to follow in a year or two, insuring permanent end of threat.”

Ric’s questions continue:
I assume convalescent serum treatment takes time to ramp up, not to mention needing donors. Meanwhile, the COVID-19 explosion is outrunning everyone and everything in hotspots around the world.

So... stuff I'm still unclear about:

- Can serum ever be manufactured or must it come only from harvesting human blood?
- Are there matching issues (e.g. blood type)?
- What kind of volume/ramp is feasible (vs. the infections we're seeing)?
- At what stages can the serum be injected?
- How effective will it be vs. the next viral variant/mutation?
My answer:

The questions you ask are mostly answered already in the links and explanations posted. This is not to criticize your questions, but to point out how difficult it is for a message to be understood by those with less background. One part of the communication problem is people are desperate, frantic and panicking. Another may be people learn to use intricate modern tools, but awareness of the historic background may be neglected. It can be difficult to know when an explication is inadequate, sufficient or excessive, so please bear with me.

The basic operation takes relatively little time to ramp up. In Covid-19 infections, the number of convalescents, who are sources of convalescent plasma, increase several times faster than the initial problem spreads. The disease runs its course in an infected person in about a month. Survivors, who are probably more than 95% of those who ever become infected, are potential sources of convalescent plasma. If I read correctly, plasma from one convalescent donation may be sufficient for multiple recipients. Each convalescent can donate plasma about every four weeks, maybe for years.

Convalescent serum must come from convalescents. The convalescents are recovering from the disease because their bodies’ immune systems have overcome the infection. A considerable part of this immunity is present within the serum (other aspects of resistance to the infection are in other parts of the body). Transfer of serum from a convalescent to a currently infected person transfers the immunity. The sick person suddenly becomes immune to the disease, which is to say, the infecting agent becomes neutralized. The damaged parts of the sick person’s body are still damaged, but they can heal because no more damage is being inflicted.

One problem in getting people to understand convalescent plasma therapy is modern thought tends to be reductionist. People want to take a problem apart, find what is not working right, and fix it. Or they want to figure out what causes a malady, then create a cure which targets some specific thing known to be necessary for the malady. In contrast, convalescent plasma therapy should be understood differently, in a more whole system phenomenological way. The fact that a person is convalescent indicates that the person’s system has whatever it takes to overcome the infection. That is all we know, but that is almost all we need to know. It works. The other thing we need to know is that a large part of whatever it is that works is in the serum, which can easily be transferred. This has been validated by over a hundred years of medical practice treating many types of illness, all over the world. Refinements and details learned have made the procedure work even better, and knowing these improvements, they should be used. But these are refinements. The crude, basic operation reliably yields crude basic success.

Presumably the active ingredients in convalescent serum are antibodies created against the Covid-19 virus or some of its metabolic parts. The immune system of the convalescent person has created many different kinds of these antibodies. Thus convalescent serum is a mix of polyclonal antibodies. Contrast this with a typical reductionist approach, which for example could be to isolate a single antibody known to target some aspect of Covid-19, mass produce this single antibody in cell culture, then introduce this monoclonal antibody into the patient. That would be a manufactured serum (more or less). Such “manufactured serum” would be better known and understood, and thus cleaner and have more predictable function. The cost of “manufactured serum” is the understanding and manufacturing needed. This cost has major time (years), as well as economic ($$$$), components.

Convalescent serum is here now. The cost is not much more than finding a convalescent willing to donate blood. The blood is centrifuged to remove cells. The supernatant is serum, the pellet is “packed cells”. This is a standard operation in blood clinics all over the world. After a few checks, the serum is transfused into a COVID-19 sufferer. Preliminary results indicate that in about two days the person is no longer infected and begins to heal.

My understanding of testing blood for transfusion, which is not strong, is that most if not all of the clotting factors are removed in the packed cells. There are tests in which a few drops of the serum are paired with drops of the intended recipient’s blood (serum?), perhaps in a Petri dish, and observed for reaction. I think this technology (type and cross-match?) is well known.

As discussed, potential donors increase much more rapidly than new infections. Potential donors remain in the population for an undetermined but presumably long time. As the pandemic endures, the supply of convalescent plasma donors becomes increasingly massive.

The serum is pretty much just like what is already in your blood, except it also has antibodies against the disease vector. You can give it to people when there is no disease vector around, and nothing much will happen. You just have a little bit more blood in your body. If such a person encounters the disease vector, the person’s immune system, supplemented by the convalescent serum, will be already tuned to attack the vector, and the vector will be eliminated. “Tuned to attack” in this case means “contains a variety of types of antibodies specific for”. Such prophylactic use of convalescent serum is being tested to protect healthcare workers in New York right now. It almost certainly will work.

Convalescent serum worked in the convalescent donor. We do not need to know how. Figuring out how all this works led to the science of immunology, which in turn gave rise to large parts of modern medicine and biology.

Serum from patients convalescing from Covid-19 infection is polyclonal, meaning it has many different parts which do different things. The virus could change so one or more of these parts become less effective, but there are a lot of different ones, so presumably some will still work. Even when blood banks standardize the serum, it is still a hodge-podge mix of a large variety of antibodies produced in a lot of individuals. Suppose the virus changes in some way to become less susceptible to particular antibodies. We will know because when the serum is used, people infected with the new form of virus will not recover as rapidly. Presumably some patients infected with the new form of virus will survive, as their own immune system responds to the new challenge and creates antibodies in new forms which deal with the changed virus. But where does the convalescent serum come from? Patients who have recovered from the infection. Serum obtained from patients convalescing from the new form of virus will be modified when compared to the earlier serum, with modifications which allow it to neutralize the new form of the virus.

It seems almost like a living thing, because it is derived from a living thing. This is also why the reductionists do not like this approach. Living things have unpredictable aspects. Nevertheless they work, if you understand and work with them.
 


Confirming the use of convalescent serum, call for public support through plasma donation.

March 13. Review of historical use of convalescent plasma, and to action.

March 26. Significant institutional use of convalescent plasma.
The BMJ said:
Covid-19: FDA approves use of convalescent plasma to treat critically ill patients
Jeffrey Henderson of Washington University School of Medicine in St Louis, Missouri, told National Public Radio, “The FDA just opened the floodgates. Our institution is scrambling to be ready to use this. …”
March 27. Review of possible use.

March 28. Confirmation of effectiveness in 4 severe cases.

April 6. Confirmation of effectiveness in 10 severe cases.

April 7. Use in New York, call for more plasma donors.

April 7. Review of scale up and use of convalescent plasma.

April 7. Review of progress.

April 8. The origins of the current collaborative effort.

April 13. Update on convalescent plasma as in Investigative New Drug (IND)

Red Cross program collects plasma, provides plasma to doctors, and calls for plasma donation.
Information on convalescent plasma use, and a call for plasma donations, from a Florida blood organization.

April 13. University of Wisconsin participates.

April 13. Review of what convalescent plasma is and why it is being used.
 



Ric Ford

MacInTouch
A "plasmabot" from Microsoft plus the CoVIg-19 Plasma Alliance:
CNBC said:
Microsoft is launching a 'plasmabot' to encourage people who recovered from the virus to donate their plasma as a possible treatment
Microsoft is working with a consortium of pharmaceutical companies to recruit people who have recovered from Covid-19 to donate their plasma, which could be used in treatments for the disease.

To help get the word out, the company is launching a chatbot, which it refers to as its "plasmabot," to lead people through a series of questions to determine if they're a candidate to donate plasma. The plasmabot, which goes live this weekend, will also provide information about the procedure and direct them to a nearby site where they can safely make the donation.
CoVIg-19 said:
CoVIg-19 Plasma Alliance
Experts from the world’s leading plasma companies have come together to create a new alliance aimed at treating the new coronavirus. The CoVIg-19 Plasma Alliance is an initiative to accelerate the development of a potential treatment for COVID-19. The first phase of the Alliance is collecting plasma at licensed plasma collection centers across the U.S. from healthy individuals who have recovered from COVID-19. Known as convalescent plasma, the plasma of recovered COVID-19 patients contains critical antibodies that could be used to make an experimental treatment. The “I” and “g” in CoVIg-19 stand for immune globulin, which the CoVIg-19 Plasma Alliance will use to concentrate the antibodies into an investigational medicine
 


Ric Ford

MacInTouch
The Guardian has a story about convalescent plasma:
The Guardian said:
'Liquid gold': the rush for plasma and the Covid-19 survivors who want to help
... Once a national resource of convalescent plasma has been gathered, academic laboratories will need to work with industry partners to extract the antibodies so that they can create hyper-immune globulin, vials of purified antibodies, which are easy to ship worldwide (unlike plasma). This is already done with treatments for rabies, for example.

“If we continue to have a supply, that might buy us time to develop new vaccines or new treatments [that can defeat the virus],” he adds.

Fortunately for researchers, the supply side of the equation has been solved by Survivor Corps, a growing grassroots movement of 32,000 Covid-19 patients and survivors. The group posts regular updates of blood centres accepting donations and links to clinical trials. So far, the Columbia trial has had to waitlist 2,000 respondents because their programme facilities are oversubscribed by Survivor Corps members.
 


Amazon disclaimer:
As an Amazon Associate I earn from qualifying purchases.

Latest posts