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Investigating Immune Responses in AD and COVID-19: Q&A With Dr Emma Guttman

Investigating Immune Responses in AD and COVID-19: Q&A With Dr Emma Guttman

Fri, 07/31/2020 - 15:53

Dr Guttman

A new study being conducted in the department of dermatology at Icahn School of Medicine at Mount Sinai (New York City, NY) will investigate the impact of systemic medications and biologic therapies on COVID-19 immune responses among patients with atopic dermatitis (AD) and psoriasis. The research team at Mount Sinai will investigate whether systemic therapies, such as dupilumab, are associated with protective effects against COVID-19, as well as ethnic differences in mounting immune responses. This research is funded by a grant from the National Institutes of Health (NIH) on behalf of the National Institute of Allergy and Infectious Disease.

“Overall, I think this study will inform the community about how to treat patients with inflammatory skin diseases in this era,” said principal investigator, Emma Guttman, MD, PhD, Sol and Clara Kest Professor of Dermatology and current vice chair and the system chair of the department of dermatology (starting in January) at Icahn School of Medicine.

In an interview with The Dermatologist, Dr Guttman discussed the goals of the study and how it could help shape COVID-19 treatment among patients with inflammatory skin diseases.

The Dermatologist: What is the importance of this study as the COVID-19 pandemic progresses?

Dr Guttman: This study is exciting to us. We think it will inform general treatment of patients with inflammatory skin diseases, and maybe it will also provide some agents that may be protective during this time.

Patients with moderate to severe AD are treated with systemic medications, some of which are broad immune antagonists, such as cyclosporine, methotrexate, and azathioprine. Others, such as phototherapy, monoclonal antibodies, or specific Janus kinase inhibitors, modulate immune responses, but we do not exactly understand how these agents affect immune responses against COVID19. Similar, for agents used to treat patients with psoriasis.

At this time, no one really knows how these systemic agents affect immune responses to COVID-19, whether good or bad. We are doing a broad registry at the department at Mount Sinai that will include our AD and psoriasis patients treated with systemics (several thousands). Through an NIH grant we will assess immune responses in the blood and also nasal swabs in a subset of patients who tested positive with COVID-19. This will help us understand how their immune response to this virus is affected by systemic medications.

Our hypothesis is that there might be some specific immune antagonists that may be protective (such as anti Th2 modulators) whereas some agents may actually exacerbate the responses of patients. Also, we may find that one of the therapies used to treat AD may be protective against COVID-19 and can be considered even beyond inflammatory skin diseases.

While we do not have results yet, we are seeing some more broad-based agents, such as cyclosporine, are potentially exacerbating responses. However, this is very preliminary, which is exactly why we need to study it.

The Dermatologist: Could you elaborate more on the patient population in this registry?

Dr Guttman: At Mount Sinai, we have the largest patient population in the United States that is treated with systemic medications, and we are well known for treating inflammatory skin diseases. Also, because we are located in New York City, we have a diverse patient population and will be able to study ethnic differences in immune responses.

In this registry, we will have 2400 patients, of whom 1200 are being treated for AD and 1200 are being treated for psoriasis. We will assess abnormalities in the blood using samples from 200 patients who were infected with COVID-19. In this way, we will learn how treatment with therapies for AD or psoriasis affects COVID-19 immune responses.

The Dermatologist: How does ethnicity play a role in your research?

Dr Guttman: We believe we will be able to identify differences in responses to COVID-19 among different ethnic groups, including ones that are now suggested to be potentially more prone to having deleterious effects of COVID-19, such as African Americans.1

Also, African Americans have a higher incidence and severity of AD and are also more prone to asthma.2,3 Thus, it is very important to understand how these skin diseases impact patients’ responses to COVID-19, as well as whether systemic medications are protective in this population.

So far, it seems that treatment with certain monoclonal antibodies for AD and for psoriasis may be protective. However, these results are still preliminary.

The Dermatologist: Does dupilumab appear to have protective effects?

Dr Guttman: We hypothesize that dupilumab may have some protective effects here, and we are currently investigating this in a large sample size.

In general, it is not just dupilumab itself that is beneficial. Targeting the TH2 axis may actually affect COVID-19 responses because some immune molecules involved in the cytokine storm associated with COVID-19 are TH2 immune products. Thus, in this study, we are investigating whether targeting the TH2 axis may actually have protective effects against COVID-19 response.

References

1. Abedi V, Olulana O, Avula V, et al. Racial, economic and health inequality and COVID-19 infection in the United States. medRxiv. Preprint posted online May 1, 2020. doi:10.1101/2020.04.26.20079756

2. Brunner PM, Guttman-Yassky E. Racial differences in atopic dermatitis. Ann Allergy Asthma Immunol. 2019;122(5):449-455. doi:10.1016/j.anai.2018.11.015

3. Tam-Williams JB, Jones BL. Closing the gap: understanding African American asthma knowledge and beliefs. Ann Allergy Asthma Immunol. 2018;121(4):458-463. doi:10.1016/j.anai.2018.07.015

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