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The SARS-CoV-2 virus was first noted in December 2019 with an outbreak in China. The disease caused by the virus, COVID-19, quickly went from being a Public Health Emergency of International Concern to a pandemic, as declared by the World Health Organization on March 11, 2020 (Lango, 2020). With more than 20 million cases in the United States and about 85 million cases worldwide as of this writing (Centers for Disease Control and Prevention, 2021), nurses across specialties play a key role in the response to the crisis, providing care for infected patients.

Various interventions are being evaluated as potential treatment regimens for COVID-19, and numerous clinical trials are underway. These include studies of antiviral drugs such as remdesivir, the antimalarial agent hydroxychloroquine in combination with azithromycin, and monoclonal antibodies such as tocilizumab (Psaltopoulou et al., 2020). In addition to drug therapy, convalescent plasma has emerged as a possible treatment. This article will provide education for nurses directed at understanding the historical evidence for the use of convalescent plasma, as well as its mechanism of action, safety profile, and administration guidelines.

Background

Passive immunization, the transfer of antibodies to an unprotected individual, has been successfully used to treat infectious diseases (Slifka & Amanna, 2017). High specific antibody titers and early timing of antibody transfer in relation to disease onset are two important factors in the efficacy of the treatment. Convalescent plasma has long been investigated as a means of providing passive immunity and has been used in viral outbreaks for more than 100 years. The Spanish influenza pandemic of 1918–1919 is often reported as the first use of convalescent plasma (Marson et al., 2020). The outbreaks of influenza A (H1N1) in 2009, Ebola virus in 2014, Middle East Respiratory Syndrome (MERS) in 2015, and avian influenza A (H5N1) in 2019 led to further use of convalescent plasma as treatment for some infected individuals (Hassan et al., 2020).

Previous studies of convalescent plasma have shown a positive impact on patient outcomes, including shortened hospital stay and decreased mortality (Wooding & Bach, 2020; Zeng et al., 2020). Despite promising results of past studies and early data on the use of convalescent plasma for COVID-19 treatment, there are limitations, including the lack of large randomized clinical trials with control groups. In addition, in some studies, convalescent plasma was administered concurrently with antiviral drugs or corticosteroids (Roback & Guarner, 2020). The transfusion of convalescent plasma remains an empiric treatment based on observation and experience. It is not routinely available or licensed as an approved product by the U.S. Food and Drug Administration (FDA).

The number of confirmed cases of COVID-19 and the disease fatality rates in the United States exceed those of any other country (Joyner et al., 2020). In response, the FDA in collaboration with the Mayo Clinic and blood banking centers across the United States developed a national expanded access program (EAP) in April 2020. Expanded access, sometimes called compassionate use, allows providers and patients access to an investigational drug or device without participating in a clinical trial (Rizk et al., 2020). The purpose of this EAP was to collect and distribute convalescent plasma. In less than six months, more than 100,000 patients were enrolled in the program, with more than 85,000 of these patients receiving a convalescent plasma transfusion (Bloch, 2020). Considering the analysis of the first 20,000 patients enrolled in the EAP, historical data on convalescent plasma use, and published results from additional studies conducted during the COVID-19 pandemic, the FDA issued an Emergency Use Authorization (EUA) for convalescent plasma in the treatment of COVID-19 (FDA, 2020a). An EUA authorizes the FDA to facilitate availability of a drug or device during a public health crisis or state of emergency. Table 1 compares EAPs and EUAs. With the EUA announcement on August 23, 2020, enrollment in the EAP ended. Data from the EAP continue to be analyzed through the Mayo Clinic, which serves as the data coordinating center.

Source

Convalescent plasma is obtained from individuals who have recovered from an infection and generated an immune response. Donors are selected based on the presence and titer of neutralizing antibodies, which are antibodies that bind to the pathogen and keep it from infecting a cell (Rajendran et al., 2020). Ideally, the plasma should contain antibodies at a sufficient titer to provide passive immunity to the recipient. The titer is determined through serial dilutions that evaluate the number of dilutions after which activity is maintained. At the time of this writing, the sufficient titer of neutralizing antibody for COVID-19 is not yet known (Bloch, 2020). The FDA recommends that donors be at least 28 days removed from symptoms associated with COVID-19 and 28 days removed from close contact with anyone with an active infection. Alternatively, individuals who are 14 days removed from active symptoms and are willing to undergo diagnostic testing can be eligible to donate if test results are negative for active COVID-19 (Psaltopoulou et al., 2020).

Antibodies are found in plasma and can be obtained via apheresis or separated from a whole blood donation in a certified blood collection facility (Focosi et al., 2020). Apheresis is the preferred method because larger volumes of plasma can be collected, compared to smaller volumes from whole blood separation. An apheresis machine is used to separate the blood into different components. The plasma is removed, and the remaining red blood cells are returned to the donor. The return of red blood cells to the donor prevents unnecessary anemia and allows the individual to donate at more frequent intervals (every two weeks) compared to whole blood donation (every eight weeks). Once collected and prepared, convalescent plasma can be transfused as a fresh product or frozen for later use.

Eligibility Criteria

Convalescent plasma has been limited to COVID-19–positive patients requiring hospitalization for severe or life-threatening disease (Psaltopoulou et al., 2020). Severe disease is characterized by dyspnea, respiratory rate of more than 30 breaths per minute, oxygen saturation of less than 93%, or a greater than 50% increase in lung infiltrates in a 24- to 48-hour window. Life-threatening disease includes respiratory failure, sepsis, or multiorgan failure. Healthcare providers prescribing or administering COVID-19 convalescent plasma must provide recipients with the Fact Sheet for Patients and Parents/Caregivers (FDA, 2020c). Specific information must be communicated to the patient or their legally authorized representative (see Figure 1).

Administration

Administration of convalescent plasma is consistent with standard blood product administration (Bloch, 2020). Hospital procedures and institutional guidelines for transfusions should be followed. The blood type of the patient must be known to ensure ABO compatibility between the donor and recipient (FDA, 2020a). Some institutions routinely premedicate with antihistamines with or without acetaminophen to prevent a transfusion reaction. Overall, there is little evidence to support the use of premedication (Bloch, 2020). The transfusion can be given through a peripheral or central venous catheter. The typical convalescent plasma volume is 200–250 ml and is transfused at a rate of 100–200 ml per hour. Patients should be monitored during and post-transfusion per institutional policy. An additional convalescent plasma transfusion may be ordered if the treating physician feels that the patient may benefit.

Safety Profile and Efficacy

Convalescent plasma transfusion carries risks like standard plasma administration. Known risks include the potential for transfusion-associated acute lung injury, allergic reactions, and transfusion-associated circulatory overload (TACO) (Focosi et al., 2020). The risk of transfusion-transmitted infection, such as hepatitis and HIV, has been dramatically reduced through meticulous donor screening and nucleic acid testing for all blood products. The most recent EAP update included review of 22,000 recipients and provided the following report of patient complications: transfusion reactions in 89 (less than 1%), thromboembolic complications in 87 (less than 1%), and cardiac events in 680 (3%). Transfusion is generally regarded as a safe procedure, with the incidence of serious adverse events being less than 1% and most events considered to be unrelated to the transfusion (Joyner et al., 2020).

Early randomized trials and observational studies suggest improved survival or a trend toward improved survival with convalescent plasma transfusion (Bloch, 2020). However, limited conclusions can be drawn from the few randomized trials reported because of small sample size and early discontinuation. The reports of multiple observational studies in patients hospitalized with COVID-19 are affected by various sources of bias related to study size, patient eligibility criteria, variable dosing and timing of convalescent plasma administration, and concomitant use of additional antiviral therapies (Bloch, 2020). Regardless, these studies have shown modest to high reductions in mortality, severity of disease, and viral shedding. In addition, there are multiple anecdotal and small series reports describing a dramatic recovery for many critically ill patients treated with convalescent plasma. Reports of patients weaned from mechanical ventilation and discharged from the hospital can be found throughout the growing body of COVID-19 literature.

Implications for Practice

As of December 2020, more than 100,000 units of convalescent plasma have been transfused in the United States, and the number increases daily (Bloch, 2020). To provide evidence-based quality care to patients, an understanding of the administration guidelines and safety profile of convalescent plasma remains crucial for nursing practice.

Standard plasma, commonly called fresh frozen plasma, is not convalescent plasma. Convalescent plasma is obtained from individuals who have recovered from the illness and have developed antibodies. Nurses need to ensure that the product they are transfusing is labeled as convalescent plasma. As with other blood products, ABO compatibility is important with convalescent plasma to help prevent transfusion reactions. Patient monitoring is consistent with standard blood transfusion guidelines, and institutional policies should be followed. Remaining in visual contact with the patient for the first 15 minutes of the infusion to monitor for a transfusion reaction is considered best practice (Miller-Hoover, 2018). In addition, recommendations include ensuring patient identification; recording temperature, pulse, respiratory rate, and blood pressure before the transfusion, 15 minutes after starting, and at the end of the transfusion; and monitoring the patient for chills, flushing, pain, and shortness of breath.

Nurses play a key role in patient education and should support the healthcare team by ensuring that patients and caregivers receive and verbalize an understanding of the fact sheet mandated by the FDA. Nurses also help to ease patient anxiety by answering questions and reinforcing teaching.

Conclusion

While awaiting a vaccine for the prevention of COVID-19, convalescent plasma has emerged as a reasonable treatment option. Based on the clinical data that have been gathered, this treatment may improve symptoms and reduce mortality. However, convalescent plasma remains an investigation product and is available via an FDA-issued EUA. Large randomized clinical trials are needed to definitively evaluate the efficacy and safety of convalescent plasma and to determine the most effective timing and dosing schedule. Healthcare providers are encouraged to enroll patients in clinical trials.

About the Author(s)

Julie C. Martin, DNP, AOCN^®, FNP-BC, is the director of cancer research at Prisma Health in Greenville, SC. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. Martin can be reached at julie.martin@prismahealth.org, with copy to CJONEditor@ons.org.