Series on COVID Therapy Studies – Considering COVID Convalescent Plasma
Unless you just returned from a deep jungle safari, you know about COVID 19. This little virus, supposedly arising from some animal in a China wet market, changed the face of reality for the entire world. Lethal for some, easily spread, and absent any confirmed successful therapy, COVID has the research world hopping especially for any effective therapy. The pharmaceutical world, the natural medicine world, and the public health world are all working at a feverish pace to turn the tide against this virus.
Convalescent plasma and hyperimmune globulin therapy have not yet gained as much attention as various pharmaceuticals but deserve our attention for today’s edition. As some other therapies have fallen off the radar with unsuccessful studies, this method from earlier years of medicine arises as a possible weapon against this pandemic.
Medicine recognizes that most infections results in antibodies against a repeat invasion of the same virus or bacteria. While not always true, for those cases in which it works, the individual goes not get sick from that microbe again. Convalescent plasma and hyperimmune globulin builds on the concept that we can take those antibodies out of the recovered person’s blood and share them with another. The goal is that the recipient now has antibodies which fight the infection they are facing. It does not given them protection forever, but gives a big helping hand in the thick of the battle.
For this to work, several factors must align for success. First, the initial person must get the disease, recover from it, and eradicate it. Infusing blood that still carries viruses goes against the whole goal of therapy. Besides the first person surviving the disease, they must produce antibodies which neutralize the intended target. In the case of COVID, the antibodies must somehow prevent the entrance of the virus into cells or its replication. From there, those antibodies must be extracted from the first person by drawing out blood. At this point, the antibodies intersperse with the other elements of blood.
To create the convalescent plasma, the cells are filtered out. The cells can even be returned to the first donor. Infusing the cells into the recipient would also increase the risk of a negative reaction. At this point we have the liquid portion of blood carrying a variety of antibodies, including antibodies against COVID. Doctors can either infuse this product into the ill patient or further concentrate the antibodies into the hyperimmune globulin before infusion.
The idea arises from decades past and has been tested with other more recent infections. In the 1918 Spanish Flu pandemic two Naval physicians attempted therapy for influenza pneumonia with plasma (1). Their results were successful enough that it warranted more investigation (2). With the recent Ebola, SARS, and MERS outbreaks researchers tested and developed protocols to treat these otherwise untreatable infections (3-16)
Early research offers some hopeful results with COVID 19 as well (17). In real time, the FDA announced on April 3, 2020 that it will begin accepting requests for clinical trial using convalescent plasma in COVID therapy (18). The also opened the opportunity for expanded access. This means that COVID infected patients who do not have access to trials of this therapy may receive it through their healthcare facility applying for expanded access. Even with expanded access, some may still not have access to this therapy and their doctors may apply for a single patient exception to receive the therapy.
In summary, we still don’t have enough information to say if this is an answer. From a logistical standpoint, the need for convalescent donors limits the number of doses available. So I would say that while it may help, it does not solve the entire problem. We need a lot more donors that we probably will ever have. Ultimately, if experiencing a severe COVID infection, I would probably choose hydroxychloroquine and azithromycin as my first option, but why not add the plasma on top of that? Well, while the two antibiotics might help alone, we don’t know if the plasma would help or hinder the overall attempt at cure. That will need further studies to decide the best option.
For more information on FDA studies or special access to convalescent plasma therapy, go to the FDA site link on reference #18.
Appendix and Disclaimer
With the onslaught by COVID and its coinciding onslaught of self-proclaimed experts with every opinion under the sun, I choose to respond with a series of research study reports so you can choose for yourself. Each edition will bring a few studies describing possible therapies for COVID under investigation or reported in past research. As my recent Facebook Live video noted, we do not know enough about this virus to be definite at this time. I am not claiming any of these are the preventive or curative answer for you or your family’s safety. I just want you to be aware of these studies and have knowledge so that you can grow in wisdom rather than stumble about in panic.
One huge challenge in identifying effective therapies for COVID lies in the novelty of it all. Research requires time, something of which we have little in an emerging pandemic. We don’t have the luxury of studying 100 years of research or 10,000 past experiments. This battle requires a great deal of extrapolation. Extrapolation means that we take the little information we do have and attempt to use it in predicting what we don’t know. This process takes place every time an experiment proceeds in science, but the urgency in this case makes it more frustrating than usual. As we walk through a different possible therapy each post, keep this paragraph in mind.
References
- McGuire, L. W. and W. R. Redden (1918). “THE USE OF CONVALESCENT HUMAN SERUM IN INFLUENZA PNEUMONIA—A PRELIMINARY REPORT.” American Journal of Public Health 8(10): 741-744.
- Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006; 145: 599–609.
- Chen, Long et al. “Convalescent plasma as a potential therapy for COVID-19.” The Lancet. Infectious diseases vol. 20,4 (2020): 398-400. doi:10.1016/S1473-3099(20)30141-9
- Kraft, Colleen S et al. “The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 61,4 (2015): 496-502. doi:10.1093/cid/civ334
- van Griensven, Johan et al. “Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea.” The New England journal of medicine vol. 374,1 (2016): 33-42. doi:10.1056/NEJMoa1511812
- Florescu, Diana F et al. “Administration of Brincidofovir and Convalescent Plasma in a Patient With Ebola Virus Disease.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 61,6 (2015): 969-73. doi:10.1093/cid/civ395
- Zhou, Boping et al. “Treatment with convalescent plasma for influenza A (H5N1) infection.” The New England journal of medicine vol. 357,14 (2007): 1450-1. doi:10.1056/NEJMc070359
- Hung, Ivan Fn et al. “Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 52,4 (2011): 447-56. doi:10.1093/cid/ciq106
- Burnouf, T, and M Radosevich. “Treatment of severe acute respiratory syndrome with convalescent plasma.” Hong Kong medical journal = Xianggang yi xue za zhi vol. 9,4 (2003): 309; author reply 310.
- Lai ST. Treatment of severe acute respiratory syndrome. Eur J Clin Microbiol Infect Dis 2005; 24: 583–91.
- Soo YO, Cheng Y, Wong R, et al. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect 2004; 10: 676–78.
- Cheng Y, Wong R, Soo YO, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005; 24: 44–46.
- Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks. 2014. http://apps.who.int/iris/rest/bitstreams/604045/retrieve (accessed Feb 20, 2020).
- Arabi Y, Balkhy H, Hajeer AH. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus 2015; 4: 709.
- Hung IFN, To KKW, Lee CK, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest 2013; 144: 464–73.
- Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis 2015; 211: 80–90.
- Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783
- FDA https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.