A team of researchers in the United States have conducted an extensive literature review looking at the usage of convalescent plasma from recovered COVID-19 patients to treat those with an impaired immune system. Their study, titled “Therapeutic use of convalescent plasma in COVID-19 patients with immunodeficiency: A systematic review,” has been released on medRxiv*, the preprint server.
Convalescent plasma therapy involves using plasma from patients who have recovered from coronavirus disease 2019 (COVID-19) – which contain antibodies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – to treat those with compromised immune systems. It is a form of passive antibody therapy that is used to prevent or treat infectious diseases.
In the US, the use of convalescent plasma has been approved for therapy in adults and children who have been hospitalized with suspected or confirmed COVID-19, caused by the SARS-CoV-2 pathogen. As scientists race to research and develop effective treatments, there are, as yet, no safe and specific therapies against COVID-19.
Immunodeficiency and COVID-19
Those with a suppressed or deficient immune system struggle to produce antibodies against SARS-CoV-2 and so may benefit from the antibodies provided by convalescent plasma. However, the researchers have found that the association between COVID-19-related mortality among those with immunodeficiency, and the use of convalescent plasma as therapy among them, is unclear.
The researchers looked at the available scientific evidence of the use and efficacy of convalescent plasma therapy in those with primary and secondary immunosuppression during their clinical course.
The team searched medical journal databases such as PubMed, Google Scholar and medRxiv for articles in English that were published between 1st January and 1st November 2020. Their search terms included, “COVID-19, convalescent plasma, convalescent serum, immunosuppression, cancer, transplant, agammaglobulinemia, malignancy etc.”
A total of 40 reports, including 104 COVID-19 patients with immunosuppression, were found. Some patients had primary immunosuppression caused by Agammaglobulinemia, a genetically inherited condition (X-linked or autosomal). Some also had Common Variable Immunodeficiency. Some also had secondary immunodeficiencies or immunosuppression caused by other diseases or treatments such as blood cancers or solid organ transplants. All the participants included in the meta-analysis had been transfused with convalescent plasma.
Results from the literature review were as follows:
Patients with Primary Immunodeficiency
- Patients with Agammaglobulinemia:
- Among those studied, there were 6 patients with X-linked Agammaglobulinemia and 1 with Autosomal Agammaglobulinemia
- Among these 7 patients, there was a prolonged course of COVID-19 with no antibodies to COVID-19 produced
- All of them, however, improved with symptom resolution following convalescent plasma transfusion
- Some also received the remdesivir and hydroxychloroquine antivirals
- Patients with Common Variable Immunodeficiency:
- A total of 4 patients had Common Variable Immunodeficiency who were transfused with convalescent plasma
- They have intrinsic B-cell defects and thus experience suppressed antibody production
- All four had severe or life-threatening COVID-19. Two patients needed mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
- Three of the four survived following convalescent plasma transfusion
Patients with Secondary Immunodeficiency
- Patients with Hematological or blood Malignancies or cancers :
- 54 patients had blood-related cancers
- 17 patients had B-cell depletion due to the treatment they received for lymphomas or leukemias
- All 17 patients developed severe COVID-19.
- After being transfused with convalescent plasma, a majority of patients improved clinically and viral clearance.
- 14 patients with blood cancers that caused immunosuppression showed improvement on convalescent plasma transfusion.
- One patient had a long course of the infection with three separate COVID-19-related hospitalizations over 100 days; there was an improvement in symptoms after two separate convalescent plasma transfusions around 90 days apart.
- Patients who had had solid organ transplants:
- A total of 29 COVID-19 patients transfused with convalescent plasma were undergoing immunosuppressive treatments following a solid organ transplant
- 13 transplant recipients who were COVID-19 positive received convalescent plasma along with hydroxychloroquine, steroids and anticoagulant therapies; of these, 8 improved with oxygen therapy and were discharged.
- A majority of the 17 patients with COVID-19 improved on convalescent plasma therapy
- Improvement followed by discharge was seen in a liver transplant patient who had been in a 17-day coma due to COVID-19 complications
Conclusions and implications
This study shows that COVID-19 patients with immunodeficiency show beneficial outcomes with convalescent plasma therapy. However, these are few reports and mostly anecdotal. The authors call for detailed studies to look at the efficacy of convalescent plasma in patients with primary or secondary immunodeficiency.
The team writes, “from the viewpoint of establishing the efficacy of convalescent plasma administration in COVID-19 therapy, the experience with this patient set provides the important criterion that addition of a specific antibody to a host with no antibodies resulted in a favorable therapeutic effect.”
They call for the development of a clear treatment protocol for COVID-19 patients with immunodeficiency and call for support of treatment with convalescent plasma in patients with primary or secondary immunodeficiency.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Senefeld, Jonathon and Stephen A Klassen, Shane K Ford, Chad C Wiggins, Bruce C Bostrom, Michael A Thompson, Sarah E Baker, Wayne T Nicholson, Patrick W Johnson, Rickey E Carter, Jeffrey P Henderson, William R Hartman, Liise-anne Pirofski, R. Scott Wright, DeLisa Fairweather, Katelyn A Bruno, Nigel S Paneth, Arturo Casadevall, Michael J Joyner. (2020) ‘Therapeutic use of convalescent plasma in COVID-19 patients with immunodeficiency: A systematic review’. medRxiv; doi: https://doi.org/10.1101/2020.11.08.20224790, https://www.medrxiv.org/content/10.1101/2020.11.08.20224790v1