George Sakoulas, MD Sharp Memorial Hospital and Sharp Rees-Stealy Medical Group Associate Adjunct Professor UC San Diego School of Medicine San Diego

COVID-19: IVIG Reduced Progression to Ventilator and Shortened Hospital Stays in Sicker Patients

MedicalResearch.com Interview with:

George Sakoulas, MD Sharp Memorial Hospital and Sharp Rees-Stealy Medical Group Associate Adjunct Professor UC San Diego School of Medicine San Diego

Dr. Sakoulas

George Sakoulas, MD
Sharp Memorial Hospital and
Sharp Rees-Stealy Medical Group Associate Adjunct Professor
UC San Diego School of Medicine
San Diego

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by IVIG?  

Response: IVIG stands for intravenous immunoglobulin. It is a preparation from pooled blood donors isolating antibodies in their blood and highly concentrated for use. It’s uses are to either replace immunoglobulins in patients who do not produce enough of them because of some underlying immunodeficiency or, as in the case of COVID, they take advantage of the immune signaling properties of the non-variable part of the antibodies. Many immune cells have receptors that bind the non-variable (also called the Fc-gamma region), and when bound, the activity of these activated immune cells is modulated. IVIG is used in many immunologic complications of infections like Guillan-Barre, Kawasaki’s disease, immune mediated encephalitis from mycoplasma, just to name a few. We decided to study IVIG because:

  1. Our anecdotal yet successful use of IVIG in treating ARDS due to influenza and other viruses.
  2. Our very definitive successful use of IVIG in a very sick patient with COVID early in the pandemic.
  3. The weak yet positive retrospective data from China of IVIG in COVID.
  4. The mechanism of IVIG inhibiting neutrophil extracellular trap (or NETS) thought to play an important role in COVID severe disease.
  5. IVIG has been around to 4 decades and many physicians have a level of prescribing comfort.

It is worth clarifying that the benefit here is NOT from neutralizing antibodies against SARS-CoV-2 virus but rather the immunomodulatory effect. It will be very interesting to see if the effect/benefit changes over time as pooled blood donors feeding the IVIG supply do develop more antibodies against SARS-CoV-2, but this is not yet known. 

MedicalResearch.com: What are the main findings?

Response: Overall, in the small study, we saw a very strong trend in reducing rates of progression to needing a ventilator to breath, shorter hospital stays in patients receiving IVIG vs the control patients that did not receive IVIG. However, in a post-hoc analysis where we decided to look at the sicker patients with A-a gradients > 200 mm HG, these differences became statistically significant. In other words, the less sick patients in this study improved regardless of whether they received IVIG or not. Once we removed that less sick group in the post-hoc analysis, the benefit of IVIG became clear. Note that this difference was irrespective of the steroids given to the IVIG group as a premedication to prevent possible allergic reaction and headache and the vast majority of the sicker control group with A-a gradient > 200 (10/12) received IVIG. We also saw a significantly improved oxygenation at day 7 after enrollment in the IVIG group compared to the control group.

MedicalResearch.com: What should readers take away from your report?

Response: IVIG is a readily available medication that many physicians feel comfortable in using that helps many (but not all) patients with moderate to severe COVID-19.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: A Phase 3 FDA registrational trial is well under way. It is larger, randomized, blinded, and multi-center including hospitals in and outside the USA. We hope to have results as early as January. I anticipate that the results will not only validate these findings, but they may also show benefits in other ways, including patients’ improvement and sense of well-being 5 weeks out from their illness. This important information was not captured in the initial pilot study but will be captured in the larger trial.

Citation: ASH 2020 Poster Presentation

1746Use of Intravenous Immunoglobulin Therapy Reduces Progression to Mechanical Ventilation in COVID‑19 Patients with Moderate to Severe Hypoxia

Sunday, December 6, 2020, 7:00 AM-3:30 PM

George Sakoulas, MD1*, Matthew Geriak, PharmD2*, Ravina Kullar, PharmD2*, Kris Greenwood, PhD2*, MacKenzie Habib2*, Anuja Vyas, MD2*, Mitra Ghafourian, MD2*, Venkata Naga Kiran Dintyala, MD2*, Fadi Haddad, MD2* and Syed Rizvi, PharmD3*

https://ash.confex.com/ash/2020/webprogram/Paper141003.html

 

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