Immunoglobulins: Non-SARS-CoV-2 Specific
Last Updated: July 17, 2020
- The COVID-19 Treatment Guidelines Panel recommends against the use of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific intravenous immunoglobulin (IVIG) for the treatment of COVID-19, except in a clinical trial (AIII). This recommendation should not preclude the use of IVIG when 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, it is unknown whether products derived from the plasma of donors without confirmed SARS-CoV-2 infection contain high titer of SARS-CoV-2 neutralizing antibodies. Furthermore, although other blood components in IVIG may have general immunomodulatory effects, it is unclear whether these theoretical effects will benefit patients with COVID-19.
Clinical Data for COVID-19
This study has not been peer reviewed.
A retrospective, non-randomized cohort study of IVIG for the treatment of COVID-19 was conducted across eight treatment centers in China between December 2019 and March 2020. The study showed no difference in 28-day or 60-day mortality between 174 patients who received IVIG and 151 patients who did not receive IVIG.1 More patients in the IVIG group had severe disease at study entry (71 patients [41%] with critical status in the IVIG group vs. 32 patients [21%] in the non-IVIG group). The median hospital stay was longer in the IVIG group (24 days) than in the non-IVIG group (16 days), and the median duration of disease was also longer (31 days in the IVIG group vs. 23 days in the non-IVIG group). A subgroup analysis that was limited to the critically ill 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 either IVIG or no IVIG, and the patients in the IVIG group were older and more likely to have coronary heart disease than those in the non-IVG group. In addition, the IVIG group had a higher proportion of patients with severe COVID-19 disease at study entry. Patients in both groups also received many concomitant therapies for COVID-19.
Considerations in Pregnancy
IVIG is commonly used in pregnancy for other indications such as immune thrombocytopenia with an acceptable safety profile.2,3
Considerations in Children
IVIG has been widely used in children for the treatment of a number of conditions. including Kawasaki disease, and is generally safe.4 IVIG has been used in pediatric patients with COVID-19 and multiorgan inflammatory syndrome in children (MIS-C), especially those with a Kawasaki disease-like presentation, but the efficacy of IVIG in the management of MIS-C is still under investigation.
- Shao Z, Feng Y, Zhong L, et al. Clinical efficacy of intravenous immunoglobulin therapy in critical patients with COVID-19: A multicenter retrospective cohort study. medRxiv. 2020;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2020.04.11.20061739v2.
- Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 207: thrombocytopenia in pregnancy. Obstet Gynecol. 2019;133(3):e181-e193. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30801473.
- Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21325604.
- Agarwal S, Agrawal DK. Kawasaki disease: etiopathogenesis and novel treatment strategies. Expert Rev Clin Immunol. 2017;13(3):247-258. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27590181.