INTRODUCTION
As of July, 2021, there have been more than 182 million cases of
COVID-19 caused by the novel SARS-CoV-2 reported worldwide, leading to
nearly 4 million deaths.1-3 Recently, due to
extraordinary vaccine development efforts, the American Food and Drug
Administration issued Emergency Use Authorizations (EUA) for three
vaccines.4-6 Despite the advent of these vaccines,
effective treatments are still a target for research and development
efforts, with several therapies having been granted
EUA.7 Furthermore, the risk of patients with
inflammatory skin diseases to develop more symptomatic COVID-19
infection is unknown, particularly in context of immunomodulatory
medications.
Previous research has shown that abnormally elevated Th2 cytokines may
inhibit appropriate Th1 immune responses in the setting of viral
exposure, impeding the reliance on Th1 signaling in initial responses to
viral infections.8-11 This is especially relevant for
atopic dermatitis (AD), a disease characterized primarily by Th2
skewing,12 with an increased susceptibility to viral
infections.10 Moreover, elevated expression of Th2
cytokines in serum (e.g., IL-4, IL-10, and IL-13) was reported in
patients with COVID-19, especially during the cytokine
storm.2,13-15
Despite the greater risk for viral infections and the baseline Th2
polarization in AD, the risk for COVID-19 incidence and symptom severity
in this common disease (~7% of the adult US
population),16 is still unknown. Determining COVID-19
risk profiles is particularly important in patients with
moderate-to-severe AD on immunomodulatory medications. While some
society guidelines recommend continuing these medications, there remains
a dearth of evidence.17,18 Recent case series and
studies on some inflammatory conditions suggest that immunomodulatory
medications may not change the risk of infection or
symptomatology.19-21 However, most of these reports
were small-scale-studies or did not include AD. Furthermore, direct
comparisons of COVID-19 outcomes between specific immunomodulatory drugs
are lacking, making it difficult to draw conclusions about the
comparative effects of different immunomodulatory medications.
Dupilumab, which inhibits the key Th2 cytokines IL-4 and IL-13, is the
first FDA-approved treatment for moderate-to-severe AD, and is also
approved for asthma and chronic rhinosinusitis with nasal
polyps.22-24 While dupilumab has been shown to
robustly modulate the Th2 pathway, it does not affect Th1
signaling.23,25 Preliminary reports have not shown
increased SARS-CoV-2 infection rates among patients treated with
dupilumab.26-31 However, these limited studies did not
compare dupilumab-treated patients with those on other treatments or not
receiving systemic treatments. To date, no study has evaluated the
effects of SARS-CoV-2 exposure and infection in AD patients on dupilumab
compared to other therapeutics.
The present study is the first large-scale, prospective evaluation of
1,237 patients with moderate-to-severe AD treated with dupilumab, broad
immunosuppressants, or those not receiving systemic treatments. This
registry study aims to investigate whether targeting type 2 inflammation
with dupilumab may protect against symptomatic SARS-CoV-2 infections in
patients with AD. Our data show that patients on dupilumab were less
likely to develop symptomatic COVID-19 infection compared to patients on
other systemic treatments for AD.