What is the target effect of utilization of plasma of cured people from COVID-19 to critically ill patient, has their any studies confirm it?
There are several studies that confirm the utilization of plasma cured people from COVID-19 to critically ill patients.
Yes Plasma is a part of treatment in covd 19 and at which stage it should be given depend upon clinician to reduces the load of virus . so many studies are there and AABB also confirming it
Yes, it is quite contributory although there are few case-selective complications. You may please go through this very recent review article: Article Convalescent Plasma Therapy for COVID-19: State of the Art
Please see the link below
https://www.mayoclinic.org/tests-procedures/convalescent-plasma-therapy/about/pac-20486440
Potential caveats limiting use of convalescent plasma therapy for COVID-19.
Convalescent plasma therapy is not being used as much as are the potential donors recovered from COVID-19 because of the following reasons:
1. Cross matching for ABO blood is needed and only matched recipients can get it.
2. Donors may not like to donate the plasma (and sometimes sell it, and there have been scandals about this in third world countries).
3. Donors may be too sick or have other comorbidities that reject them as a donor (HBV, HCV, HIV, cancer, drug addiction).
4. The donor's plasma has to be checked for SARS-CoV-2 antibodies titers. Donors with absent or low antibody titers are not very suitable.
As viremia occurs before the commencement of host immune response, the body is almost defenseless. Therefore using the plasma from recovered patients can helps blocking the infection.
The studies are very interesting. In the near future, however, since only cases of re-infection have been described, the effectiveness of the therapy will have to be carefully evaluated ...
It is certainly an important therapeutic approach. However, patients should be strictly selected and the compatibility between donor and host should carefully evaluated.
There are certain limitations that CP may generate Syphilis , Hep B virus , Hep C virus , HIV like immuno-tranfusion diseases - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146649/#
As the experience of work in this direction in our country has shown.
This method is effective. However, it is necessary that the plasma donor has a high titer of antibodies to covid-19. Otherwise, these procedures will be meaningless.
Regards, Sergey Viktorovich Pushkin
The recent study showing the benefit of plasm advocated it in the initial 2 days of admission. Thus clinical criteria and timing are probably both important to derive a benefit.
There have been several studies showing efficacy, most are relatively small. See for example doi:10.1001/jama.2020.4783, doi:10.1001/jama.2020.10044, doi:10.1073/pnas.2004168117, doi:10.1002/jmv.25882, doi: 10.1016/j.ajpath.2020.08.001.
Generally speaking antibody therapies to treat infectious disease need to be administered before a (disease-specific) critical time point. After that it is difficult to rescue the patient.
Safety of blood products is very tightly controlled, at least in North America and Europe. Convalescent plasma will go through the same kinds of pathogen reduction procedures and testing before use as any other plasma (an overview on plasma products is at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997294/). So the risk of getting a disease from convalescent plasma is of the same degree as getting a disease as the result of blood transfusion during major surgery.
EDIT - FDA has made available the decision memo for the Emergency Use Authorization to give convalescent plasma therapeutically at https://www.fda.gov/media/141480/download. This provides a summary of the evidence in animals and humans for the efficacy of convalescent plasma, the risk analysis etc that supported the decision to approve the EUA.
Currently, obtained evidences are not insufficient. So, more study needed.
Also, with low protection of COVID-19 and risk of reinfection and also risk of the mentioned side effects should be considered.
Dear Prof. Deleme!
You raised a crucial issue as this kind of treatment could be a firm tool to fight this virus. So I did my best to find resources:
1) Kai Kupferschmidt, John Cohen (2020)." In FDA’s green light for treating COVID-19 with plasma, critics see thin evidence—and politics" August 24, 2020, © 2020 American Association for the Advancement of Science Available at:
https://www.sciencemag.org/news/2020/08/fda-s-green-light-treating-covid-19-plasma-critics-see-thin-evidence-and-politics
2) Eric, Salazaar et al. (20200. "Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma" The American Journal of Pathology
Volume 190, Issue 8, August 2020, Open Access © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. Available at:
Article Treatment of COVID-19 Patients with Convalescent Plasma
3) Miao Liu et al. (2020). "Lessons learned from early compassionate use of convalescent plasma on critically ill patients with Covid‐19" Journal of AABB Transfusion 08 August 2020, Open Access, © 2020 AABB Available at:
Article Lessons learned from early compassionate use of convalescent...
Yours sincerely, Bulcsu Szekely
Bulcsu Szekely ، Jalil Zorriehzahra، Alshaymaa Ali، Doug Barker، Yuanfeng Shi، Pranav Ish، Pushkin Sergey Viktorovich، Wisam Thamer Al-Mayah، Jaydip Datta، Pietro Emanuele Napoli, Md Rabiul Alam,
Thanks alot dear colleges for your percious informations.
Please see this link-
Article Use of different Drugs and Plasma Therapy against Treatment ...
Based on the largest trial to date by the Mayo Clinic (https://www.mayoclinic.org/tests-procedures/convalescent-plasma-therapy/about/pac-20486440), there is no evidence of reduced mortality as this and no trials have been conducted with a placebo control. Instead the data indicate that the 7-day mortality rate ranged from 8.9% to 13.7% for high to low doses of plasma, respectively. The misquoted 35% figure for reduction in mortality is a relative number and comes from the difference between these percentages [(13.7-8.9)/13.7 = 35%], which is a meaningless comparison without a placebo control and barely showed statistical significance (p=0.048). The 30-day mortality data were even less significant. The best estimates for absolute reduction of mortality by plasma infusion are about 3.5%. Worth doing in certain sub-populations, but hardly a breakthrough.
no benefit was seen in the latest study from India. It is in of label recommendation in our national guidelines
It was hyped as a miracle cure. The results in our country were not encouraging in the evidence published till now
More evidence needed. Clinical trials have to enter phase 3 to be considered reliable
even the large placid trial in India has found no benefit. the trial had limitations but it is the largest evidence from my country.
Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P, et al. Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial). 2020. doi: https://doi.org/10.1101/2020.09.03.20187252
Not much benefit was reported yet. I didn't find full evidence and 100 % success reported in the literature.
Some Doctors and technicians are getting benefit interms of commission from rich patients. Some patients are purchasing plasma by paying huge amount..The major beneficiaries are...Brokers, Some Doctors, Plasma donating people, Plasma collecting technician etc.....
I think that we need to consider that T cell immunity is particularly important as an immune response to the virus. HCV and Ebola had similar properties where cytotoxic T cell differentiation gave a strong immune response for the resolution of viral infection.
Taking an entirely different direction in perspective, we know that some individuals are asymptomatic or with mild symptoms and that the cytokine storm causing hyper-inflammatory immunology is associated with mast cell activation and expression of inflammatory factors such as histamine. Dengue fever has similar aspects in immunology that can me reduced with antihistamines. Also, the use of dexamethasone for patients with severe symptoms indicates that some early therapy would be advantageous.
Surely advising patients, who test positive for COVID 19, should be advised to take H1 antihistamines that are readily and tolerated as ‘off the shelf’ drugs.
There is theoretical evidence to this concept but no trial data, apart from a small French trial that proved highly effective.
As most patients who have symptoms or test positive do not see a GP but are encouraged to phone 111 or ask for an ambulance with breathing difficulties, how can patients be advised to trial this? Like the public information about vitamin D, should everyone be advised to try this?
As did dexamethasone, in the third of severely affected patients, the concept of prescribing antihistamines to stem the effect of histamine at an early stage, possibly inhibiting the alveolar inflammation and hypoxia, may be highly simplistic but may also reduce some severe symptoms and reduce hospital intake.
How can we test this?
No benefit in mortality in large studies- Even a large trial in our country did not find any benefit- Thus should be used early, as a part of a trial and with continuous monitoring. It is no magic drug as claimed by many.
Pranev, are you referring to the plasma therapy? In the Ebola epidemic, convalescent whole blood was beneficial, as activated cytotoxic T cells specific for the virus were present as a much better response than antibody alone.
I still think that combatting the chemotaxis and inflammatory symptoms, caused by activated resident masts cell-expressed histamine, could be reduced in some patients, if antihistamine drugs are taken when early symptoms are experienced.
Theoretically justified and past experiences being encouraging, I agree plasma therapy should be beneficial.
But till we have evidence for the same, it should be used under strict conditions, supervision and monitoring
Thanks Alexander,
Very interesting but really not my field and does not sit easily with my current understanding of virology and escape mutant variants caused by evolutionary immune pressure.
I am more concerned about recombination and rearrangement of RNA viruses and the ability of the human immune system to evolve virus specific antibodies and T cell receptors.
Could the vaccination clinical trial in UK, Brazil and South africa have provided sufficient immune mutation pressure to evolve the recent worrying SARSCoV-2 variants?
Dear Annwyne,
The point is that current view on Virology shoud be completely modified taken into account the previous and latest findings of Astrobiology.
As I'm not clinical researcher can't provide correct answer to your question, please check the papers in his profile: Edward J Steele
Lack of standardization patient to patient antibody concentration in plasma of convalescent COVID-19 individuals is the reason for variable results.
Please have a look at these articles:
1. Article Early High-Titer Plasma Therapy to Prevent Severe Covid-19 i...
2.Article The Three Pillars of COVID-19 Convalescent Plasma Therapy
Current NIH treatment guidelines do not recommend for or against use of CCP.
These are a few thoughts about blood-based therapies for COVID 19 patients based on findings from the Ebola epidemic.
Although the virions of SARSCoV-2 and EBOV are clearly very different indeed, SARSCoV-2 being single positive stranded RNA virus and EBOV having single negative stranded RNA. Serum antibody therapies were not found to be as successful as expected during the Ebola epidemic as suggested with COVID 19.
Patients who survive viral infections often have antibodies at the end of the infection that are particularly beneficial in viral resolution in early stages of viral infection. However, there has been a mixed success in the use of post exposure serum treatment for Ebola virus infection and the activity of antibodies against filoviruses is not well understood. It is thought that neutralizing antibodies are produced but at a relatively low frequency. The immune response is weak from serum provided by convalescent patients due to low titres of antibody after recovering from Ebola infection and this possibly explains why the serum therapy or antibody alone is not very successful. Some researchers surmise that the virus takes up the antibodies and few are left after recovery from infection. Borisevich IV, et al. (1995) [Development and study of the properties of immunoglobulin against Ebola fever] Vopr Virusol 40:270–273.
Perhaps this emphasizes the importance of whole blood therapy assuming that there are other active immune elements other than antibody in the blood? There is some evidence from research that survivors mount a large, broad epitope spectrum of cytotoxic T cells, which require a supportive cytokine environment to accentuate the immune response to such RNA viruses. A late adaptive response has been suggested as being important which will be apparent in convalescent patients. Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection, Steven B. Bradfute. The Journal of Immunology March 15, 2008 vol. 180 no. 6 4058-4066.
Can this cytotoxic response be transferred to recipients and mount a new immune response by transfusion of whole blood products, such as T cells in COVID 19 patients?
On the subject of cytokine balance, the Journal of Infectious Diseases reports elevated levels of IL-10 are associated with Ebola fatalities, which suggests a that a humoral response is less favourable for resolution of the virus (driven by IL-10), as apposed to a cytotoxic response. Ebola Hemorrhagic Fever: Novel Biomarker Correlates of Clinical Outcome, J Infect Dis. (2014) 210 (4): 558-566.
Treatment of Ebola Hemorrhagic Fever with Blood Transfusions from Convalescent Patients, K. Mupapa,
An American cameraman with Ebola was reported to be successfully treated with convalescent whole blood.
Back to SARSCoV-2, meta-analysis and systematic reviews of studies that investigated the lymphocyte count, on admission to intensive care units, showed that lymphopenia was significantly associated with poor patient outcomes in COVID-19 patients. This could be used as a marker, especially in younger patients, as an indication of severity of disease. Lymphopenia was defined as less that 1100/μ L associated with a threefold risk of poor outcome. One hypothesis to explain this phenomenon is that lymphocytes express ACE2 and that they themselves may be the targets for SARSCoV-2, and that an increase in proinflammatory cytokines, such as, IL-6, in COVID-19 may reduce lymphocytes further. This level of T cell exhaustion and reduced functional diversity in peripheral blood may be an indication of severe progression in COVID-19 patients.
Should we be considering blood collection and blood transfusions for severely affected COVID 19 patients?
Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, Dong XQ, Zheng YT. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):541-543. doi: 10.1038/s41423-020-0401-3. Epub 2020 Mar 17. PMID: 32203186; PMCID: PMC7091621.
Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;: PMID: 31986264; PMCID: PMC7159299.
Huang I, Pranata R. Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis. J Intensive Care. 2020 May 24;8:36. doi: 10.1186/s40560-020-00453-4. PMID: 32483488; PMCID: PMC7245646.
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec;9(1):727-732. doi: 10.1080/22221751.2020.1746199. PMID: 32196410; PMCID: PMC7170333.
www.bmj.com/content/349/bmj.g4997/rr778286
A systemic review and meta-analysis published in January 2021 did not show any effectiveness of convalescent plasma in COVID-19 patients admitted in ICU and ventilated due to ARDS
For details have a look at this RG link:
Preprint Clinical effectiveness of convalescent plasma in hospitalize...
Dear Pranav Ish
Convalescent plasma therapy: Practically justified but nullified by evidence for COVID-19 treatment
The plasma therapy may be practically justified but nullified by evidence in a systematic review and meta-analysis (1).
Preprint Clinical effectiveness of convalescent plasma in hospitalize...
Plasma also does not contain T cells, like serum, and both come from a liquid portion of blood once the cells are removed. Plasma comes from unclotted blood and serum from clotted blood. Serum is plasma minus the clotting factors. The white cells are in the white buffy coat above the red cells layer and below the plasma after centrifugation.
https://i.ytimg.com/vi/RQLbSxvVej4/maxresdefault.jpg
My previous discussion about convalescent blood refers to whole blood, including T cells (white blood cells), that have already adapted to recognise SARSCoV-2 in a convalescent patient. This therapy was found to have some successful in treating Ebola infected patients, where convalescent antibody and serum therapy was less successful.
Passive immunisation using whole blood is an old therapy to prevent and treat infectious diseases but this approach has not been widely reported for use in COVID 19 patients.
Marano G, Vaglio S, Pupella S, Facco G, Catalano L, Liumbruno GM, Grazzini G. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 2016 Mar;14(2):152-7. doi: 10.2450/2015.0131-15. Epub 2015 Nov 6. PMID: 26674811; PMCID: PMC4781783.