Does IVIG Use Reduce the Risk of Contracting Sars-Cov-2 in Patients with Immune Thrombocytopenia: Data from the Platelet Disorder Support Association (PDSA) Patient Registry

BACKGROUND AND AIMS Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder causing low platelet counts (PC) and increased risk of bleeding. Intravenous immunoglobulin (IVIG) is used to rapidly increase the PC. It is unknown if there is a reduced risk for SARS-CoV2 infection in patients receiving chronic IVIG use due to neutralizing antibodies against the virus or not well characterized immunomodulatory effects. This study explored patient-entered registry data to see if ITP patients using IVIG within the last 6 months were less likely to test positive for COVID-19.

METHODS Data was collected using the COVID-19 & ITP web-based survey from Platelet Disorder Support Association's ITP Natural History Study Registry from February 12, 2021, to June 23, 2022. Only participants who answered if they tested positive for COVID-19 and reported what treatments (if any) they had in the last six months were included. The 602 total survey participants were divided based on their age: 33 children were under 21 years (22 were under 18 years); 473 adults were ages 21-64 years; and 96 were over 65 years (seniors). Data were analyzed with descriptive statistics, Fisher exact tests, and chi-squared analysis.

RESULTSPediatric group: 18 (56%) participants reported having been treated for ITP with at least one medication. Eleven (11/33; 33%) participants tested positive for COVID-19; or 11/30 (37%) if excluding the three de novo cases identified following COVID-19 vaccination. Two (18%) used an immunosuppressant; four (36%) a thrombopoietin receptor agonist (TPO-RA); and 5 (46%) indicated no treatment in the last six months. None of 11 individuals who tested positive reported using IVIG in the last six months. Of 22 who tested negative, 2 (9%) received IVIG recently; 61% (20/33) reported being fully vaccinated.

Adult group: In the last six months, 217 (46%) participants received at least one treatment for their ITP. Ninety-five (20%) tested positive for COVID-19: 11 (12%) received IVIG alone or in combination with other therapies, 8 (8%) a TPO-RA, and 30 (32%) an immunosuppressant as monotherapy or combined with other treatments. Forty-six (48%) were not treated in the last 6 months. Of 378 participants who tested negative, 36 (9.5%) used IVIG in the last six months. In total, 53% (249/473) were fully vaccinated.

Senior group: In the last six months, 56 (58%) of participants reported receiving treatment for their ITP; 7/96 (7%) participants tested positive for COVID-19. Of these seven, in the last six months, 1 (14%) received IVIG alone, 1 (14%) an immunosuppressant, 1 (14%) a TPO-RA alone; and 58% (4 of the 7) reported not receiving treatment for their ITP in the last six months. Among the 89 participants who tested negative for COVID-19, 9 (10%) used IVIG recently; 69% (66/69) reported they were fully vaccinated.

Positive Rate: When comparing the proportion who screened positive for SARS-CoV-2 in each of the three groups (33%; 11/33 pediatric, 20%; 95/473 adult, and 7%; 7/96 senior), a higher proportion of ITP patients under 21 years of age contracted SARS-CoV-2 compared to older participants (X² = 13.42, p = 0.0012).

IVIG use: None of the 11 positive COVID-19 cases among the pediatric group reported recent IVIG exposure, while 12/113 (11%) adult and senior participants who tested positive reported recent IVIG exposure. When comparing positive COVID-19 cases with recent vs no recent exposure to IVIG combining the 3 groups, there was no difference regarding IVIG use (p = 0.6034). This suggests that IVIG use did not reduce the likelihood of contracting the virus if used in the last 6 months.

Limitations: IVIG lots were not tested for anti-SARS-CoV-2 antibody, or neutralization. IVIG lots were also not controlled for year of plasma collection; even if there was anti-SARS-CoV-2 antibody in the lots, it might react with a currently non-prevalent strain of virus and thus not prevent infection.

CONCLUSION A larger or more focused study may be needed to determine if ITP patients using IVIG have an added level of protection against the SARS-CoV-2 virus in addition to vaccination. As SARS-CoV-2 infection becomes more commonplace, it may be that there are more currently active antibodies indirectly transferred to ITP patients receiving IVIG. With fears that acquiring SARS-CoV-2 by patients with ITP could lead to a decreased platelet count, IVIG efficacy against SARS-CoV-2 would be reassuring as IVIG is a commonly used, front-line therapy for ITP.

MacWhirter - DiRaimo:Novartis: Consultancy. Kruse:Novartis: Consultancy. Bussel:AstraZeneca: Other: Data and Safety Monitoring Board; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; UCB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Data and Safety Monitoring Board; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rallybio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees.