There are promising signs that the COVID-19 curve is beginning to flatten, however the pandemic is far from over. Scientists are working diligently to find a preventative vaccine and to prove the efficacy of many currently available drugs including antivirals, antimalarials, interleukin inhibitors, and protease inhibitors. Convalescent plasma (CP) is another therapeutic strategy that is under investigation to treat patients with severe COVID-19.
The use of convalescent blood products (CBP) to treat infectious diseases dates back to the late 1800’s when it was first used to treat diphtheria. Since that time, CBPs have been employed in the management of bacterial infections such as scarlet fever and pertussis (Marano et al., 2016). The therapeutic regimen was studied during the Spanish influenza pandemic of 1918-1920 and later explored as a remedy for the measles, Argentine hemorrhagic fever, influenza, chicken pox, cytomegalovirus, parvovirus B19, Ebola virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), H1N1 and H5N1 avian flus and severe acute respiratory infections (SARI) viruses (Marano et al., 2016). In 2009, H1N1 influenza A studies showed a reduction in mortality in those treated with convalescent plasma as well as a decrease in viral load within five days of symptom onset, without severe adverse events (Chen et al., 2020). CP is currently being studied to treat Ebola in several countries, however conclusive results are pending complete data collection. The majority of research in CP lack randomization, control subjects and large sample sizes, therefore efficacy has not been proven but instead considered empirical or anecdotal.
How does it work?
CP therapy is based on the concept of acquired passive immunity which is developed after a person receives immune system constituents, such as antibodies, from another person. This type of immunity provides immediate protection against the antigen, but is not long lasting. CP that is obtained from a patient who has survived a previous infection and developed humoral immunity against the pathogen contains a large amount of neutralizing antibodies which are able to remove the virus from the blood and tissues.
How is CP collected from the donor?
CP is obtained from the donor through apheresis, a process in which whole blood is removed from the donor via the veins and passed through a machine where the blood is separated by filtration or centrifuge into components such as platelets, plasma, leukocytes, lymphocytes and red blood cells. After separation, the desired blood component, in this case plasma, is removed and the remainder of the blood is reinfused back to the patient. The process takes a couple of hours, similar to a blood donation.
Who can donate?
Individuals who have been infected with SARS-CoV-2, the virus that causes COVID-19, and have recovered now have antibodies to the virus in their blood. Levels of antibodies will decrease over time after the initial illness, within three to four months, thus plasma from recently recovered patients may be most effective. The U.S. Food and Drug Administration (FDA)
has issued guidelines on the administration and study of investigational convalescent plasma (FDA, 2020).
CP may be collected from individuals who meet the following criteria (FDA, 2020):
- A diagnostic test (i.e. nasopharyngeal swab) at the time of illness OR a positive serological test for SARS-CoV-2 antibodies after recovery, if prior diagnostic testing was not performed
- Either one of the following:
- Complete resolution of symptoms at least 28 days prior to donation OR
- Complete resolution of symptoms at least 14 days prior to donation AND negative results for COVID-19 from one or more nasopharyngeal swab specimens or by diagnostic blood test
- Negative for human leukocyte antigen (HLA) antibodies
- SARS-CoV-2 neutralizing antibody titers, if available
- Recommended neutralizing antibody titers of at least 1:160; a titer of 1:80 may be considered if an alternative matched unit is not available
Donated CP should undergo routine laboratory testing:
- Blood type: ABO and Rhesus D (RhD) grouping
- Blood screening tests for HIV, HBV, HCV, syphilis and other locally transmitted infections
Who can receive CP?
Under the FDA (2020) guidelines, CP can only be administered: 1. Within the context of an FDA-approved clinical trial; 2. Under an expanded access protocol for patients with serious or immediately life-threatening COVID-19 disease who are not eligible or unable to participate in a clinical trial; and 3. As requested by a licensed physician for a single patient emergency.
In order to receive CP, patients must meet the following criteria (FDA, 2020):
- Laboratory confirmed COVID-19
- Severe or immediately life-threatening COVID-19:
- Severe disease is defined as one or more of the following:
- Shortness of breath (dyspnea)
- Respiratory frequency ≥ 30/min
- Oxygen saturation ≤ 93%
- Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
- Lung infiltrates > 50% within 24 to 48 hours
- Life-threatening disease defined as one or more of the following:
- Respiratory failure
- Septic shock
- Multiple organ dysfunction or failure
Nurses administering convalescent plasma should follow standard blood administration precautions outlined by their specific hospital protocols and monitor their patients closely for potential blood transfusion reactions.
Finding eligible donors and implementing testing to confirm adequate antibody levels in plasma are both logistical challenges. In addition to blood transfusion reactions, another potential complication of CP therapy is transmission of unknown pathogens. There is also an infection risk to laboratory personnel who process the plasma.
Will convalescent plasma play a key role in the treatment and recovery of severely ill COVID-19 patients? We don’t know and we will have to wait until researchers have enough data to properly analyze the efficacy. Do you have experience with convalescent plasma therapy? What have you seen in your clinical practice? Please share in the comments below.