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Convalescent Plasma and Immune Globulins

Last Updated: May 12, 2020

Recommendation:

  • There are insufficient data to recommend either for or against the use of COVID-19 convalescent plasma or SARS-CoV-2 immune globulins for the treatment of COVID-19 (AIII).

Rationale for Recommendation

Although convalescent plasma and virus-specific immune globulin have been used for other viral infections, sufficient clinical data are lacking for COVID-19, and potential risks include transfusion reactions. Theoretical risks include antibody-dependent enhancement of infection.

Rationale for Use in Patients with COVID-19

Plasma donated from individuals who have recovered from COVID-19 includes antibodies to SARS-CoV-2,1 and SARS-CoV-2 immune globulin is a concentrated antibody preparation derived from the plasma of people who have recovered from COVID-19. Both products may help suppress the virus and modify the inflammatory response.

Clinical Data for COVID-19

Data supporting the use of convalescent plasma for COVID-19 are limited to a small retrospective cohort study, small case series, and case reports.1-6 There are no clinical data on the use of SARS-CoV-2 immune globulin or hyperimmune globulin in patients with COVID-19.

Clinical Data for Other Viral Infections

The use of convalescent plasma has been evaluated for other viral diseases, such as severe acute respiratory syndrome (SARS), with some suggestion of potential benefit.7-9 However, no convalescent blood products are currently licensed by the Food and Drug Administration (FDA).

There are no clinical data on the use of specific immune globulin or hyperimmune globulin products in patients with SARS or Middle East respiratory syndrome (MERS).

Several virus-specific immune globulin products are licensed for preventing post-transplant cytomegalovirus (CMV) disease (CytoGam) and post-exposure prophylaxis of varicella in high-risk individuals (VariZig).

Clinical Trials and Access

Randomized clinical trials to evaluate convalescent plasma for the treatment of COVID-19 are underway; a list is available at ClinicalTrials.gov. Trials evaluating SARS-CoV-2 immune globulins are in development.

The FDA has provided guidance for the use of COVID-19 convalescent plasma under an Emergency Investigational New Drug Application. The FDA has also approved a national expanded access program for the use of convalescent plasma for the treatment of patients with COVID-19. Clinicians can refer to the National COVID-19 Convalescent Plasma Project website for more information. People who have been fully recovered from COVID-19 for at least two weeks and who are interested in donating plasma can contact their local blood donor or plasma collection center or refer to the American Red Cross website.

Adverse Effects

The risks associated with plasma transfusion include antibody-mediated enhancement of infection, transfusion-associated acute lung injury, transfusion-associated circulatory overload, and allergic transfusion reactions.3,10 Rare complications include the transmission of infectious pathogens and red cell alloimmunization.

Considerations in Pregnancy

Pathogen-specific immune globulins are used clinically during pregnancy to prevent varicella zoster virus (VZV) and rabies and have also been used in clinical trials of therapies for congenital CMV infection.

Considerations in Children

Hyperimmune globulin has been used to treat several viral infections in children, including VZV, respiratory syncytial virus, and CMV; efficacy data for other respiratory viruses is limited. The efficacy and adverse effects associated with administration of convalescent plasma have not been well established.

Non-SARS-CoV-2-Specific Intravenous Immune Globulin

Recommendation:

  • The COVID-19 Treatment Guidelines Panel recommends against the use of non-SARS-CoV-2-specific intravenous immune globulin (IVIG) for the treatment of COVID-19, except in the context of a clinical trial (AIII). This should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19.

Rationale for Recommendation

Currently, only a small proportion of the U.S. population has been infected with SARS-CoV-2. Therefore, products derived from the plasma of donors who were not confirmed to have had SARS-CoV-2 infection are not likely to contain SARS-CoV-2 antibodies.

Clinical Data for COVID-19

These data have not been peer reviewed.

In a retrospective, non-randomized cohort study of IVIG in eight treatment centers in China between December 2019 and March 2020, the authors found no difference in 28-day or 60-day mortality between the 174 patients who were treated with IVIG and the 151 patients who were not treated with IVIG.1 Patients who received IVIG were hospitalized for a longer period (median of 24 days vs. 16 days) and experienced longer duration of disease (median of 31 days vs. 23 days). It should be noted that a higher proportion of IVIG-treated patients had severe disease at study entry (71 patients [41%] with critical status in the IVIG group vs. 32 [21%] in the non-IVIG group). A subgroup analysis that was limited to the critical patients suggested a mortality benefit at 28 days, which was no longer significant at 60 days.

The results of this study are difficult to interpret because of important limitations in the study design. In particular, patients were not randomized to receive IVIG or no IVIG, and the IVIG group was older, was more likely to have coronary heart disease, and had a higher proportion of patients with severe COVID-19 disease at study entry. Patients also received numerous other concomitant therapies for COVID-19.

References

  1. Wang X, Guo X, Xin Q, et al. Neutralizing antibodies responses to SARS-CoV-2 in COVID-19 inpatients and convalescent patients. medRxiv. 2020. [Preprint]. Available at: https://www.medrxiv.org/content/10.1101/2020.04.15.20065623v3.
  2. Ahn JY, Sohn Y, Lee SH, et al. Use of convalescent plasma therapy in two COVID-19 patients with acute respiratory distress syndrome in Korea. J Korean Med Sci. 2020;35(14):e149. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32281317.
  3. Pei S, Yuan X, Zhang Z, et al. Convalescent plasma to treat COVID-19: Chinese strategy and experiences. medRxiv. 2020. [Preprint]. Available at: https://www.medrxiv.org/content/10.1101/2020.04.07.20056440v1.
  4. Ye M, Fu D, Ren Y, et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32293713.
  5. Zeng Q, Yu Z, Gou J, et al. Effect of convalescent plasma therapy on viral shedding and survival in COVID-19 patients. The Journal of Infectious Diseases. 2020. [Accepted Manuscript]. Available at: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa228/5826985.
  6. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32253318.
  7. Burnouf T, Radosevich M. Treatment of severe acute respiratory syndrome with convalescent plasma. Hong Kong Med J. 2003;9(4):309; author reply 310. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12904626.
  8. 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(1):44-46. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15616839.
  9. 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(1):80-90. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25030060.
  10. Narick C, Triulzi DJ, Yazer MH. Transfusion-associated circulatory overload after plasma transfusion. Transfusion. 2012;52(1):160-165. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21762464.