Reply: Potential role of Janus with severe infection with extensive lung disease and

kinase inhibitors in COVID-19 with elevated IL-6 levels detected by the laboratory.
All of these preclinical data seem to suggest that
To the Editor: We read with interest the letter of
treatment with both baricitinib and upatacitinib should
Peterson et al1 about the use of Janus kinase (JAK)
not be stopped during the COVID-19 pandemic.
inhibitors in the time of severe acute respiratory
Obviously, a careful assessment is mandatory for
syndrome coronavirus 2 (SARS-CoV-2). The authors
each individual patient reporting any adverse effect.
reported that discontinuation of JAK inhibitors in the
setting of the initial infection, such as with SARS-
Maddalena Napolitano, MD,a Gabriella Fabbro-
CoV-2, may be beneficial given the role of JAK-signal
cini, MD,b and Cataldo Patruno, MD, PhDc
transducer and activator of transcription (STAT)e
dependent type I (/) and type II (
) interferons in From the Department of Health Sciences Vincenzo
antiviral immunity. However, data in the literature
regarding the possible use of JAK inhibitors in
COVID 19 patients is growing.
Recently, Richardson et al2 proposed baricitinib as
potential treatment for pneumonia during COVID-
19, because it would be able to reduce the ability of
the virus to infect lung cells.2 The lung is particularly
prone to SARS-CoV-2 infection probably because of
the presence of the alveolar type II cell. This cell
expresses on its surface the protein angiotensin-
converting enzyme 2, a receptor used by the virus to
invade the host.2 One of the known regulators of
endocytosis is the AP2-associated protein kinase 1
(AAK1).2 Disruption of AAK1 might, in turn, inter-
rupt the passage of the virus into cells and also the
intracellular assembly of virus particles.3 Baricitinib
on therapeutic dosing is reported to be able to inhibit
AAK1 functions and to bind the cyclin G-associated
kinase, another regulator of endocytosis of virus.3
In both phase II and phase III trials on atopic
dermatitis, baricitinib had a good safety profile.
Headache, nasopharyngitis, and an increase in cre-
atine phosphokinase levels were the most common
adverse events.4 The increased incidence of infective
diseases, such as reactivation of varicella zoster,
herpes simplex, and Epstein-Barr virus strains, re-
ported in trials for rheumatoid arthritis was not
observed in patients with atopic dermatitis.4
Upadacitinib is a selective JAK1 inhibitor and is
currently being investigated for atopic dermatitis
treatment.5 Preclinical research showed that disrup-
tion of JAK1 signaling induced by upatacitinib
reduced not only the expression of T-helper 2 and
22 cytokines but also the levels of interleukin (IL) 6,
through inhibition phosphorylation of STAT3.6 IL-6
also plays a central role in the ‘‘cytokine storm’’
damaging lung in COVID-19 patients.1 Recently,
tocilizumab, a monoclonal antibody that competi-
tively inhibits the binding of IL-6 to its receptor, has
been used to treat complications of COVID-19ein-
duced pneumonia. In addition, China’s National
Health Commission and the Italian Medicines
Agency approved the tocilizumab use in patients
J AM ACAD DERMATOL
Tiberio, University of Molise, Campobassoa; the
Section of Dermatology, Department of Clinical
Medicine and Surgery, University of Naples
Federico II, Naplesb; and the Department of
Health Sciences, University Magna Graecia of
Catanzaro, Catanzaro, Italy.c
Funding sources: None.
Conflicts of interest: Dr Napolitano has acted as a
speaker for Sanofi. Dr Fabbrocini has acted as a
speaker and consultant for AbbVie and LEO
Pharma. Dr Patruno has acted as a speaker
and consultant for AbbVie, Novartis, Pfizer, and
Sanofi.
IRB approval status: Not applicable.
Reprints not available from the authors.
Correspondence to: Dr Maddalena Napolitano, Via
Pansini 5, Naples 80131, Italy
E-mail: maddy.napolitano@gmail.com
REFERENCES
1. Peterson D, Damsky W, King B. The use of Janus kinase inhibitors
in the time of SARS-CoV-2. J Am Acad Dermatol. 2020;82(6):
e223-e226.
2. Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential
treatment for 2019-nCoV acute respiratory disease. Lancet.
2020;395(10223):e30-e31.
3. Pu SY, Xiao F, Schor S. Feasibility and biological rationale of
repurposing sunitinib and erlotinib for dengue treatment.
Antiviral Res. 2018;155:67-75.
4. Napolitano M, Fabbrocini G, Cinelli E, Stingeni L, Patruno C.
Profile of baricitinib and its potential in the treatment of
moderate to severe atopic dermatitis: a short review on the
emerging clinical evidence. J Asthma Allergy. 2020;13:89-94.
5. Guttman-Yassky E, Thaçi D, Pangan AL, et al. Upadacitinib in
adults with moderate to severe atopic dermatitis: 16-week
results from a randomized, placebo-controlled trial. J Allergy
Clin Immunol. 2020;145(3):877-884.
6. Parmentier JM, Voss J, Graff C, et al. In vitro and in vivo
characterization of the JAK1 selectivity of upadacitinib
(ABT-494). BMC Rheumatol. 2018;2:23.
https://doi.org/10.1016/j.jaad.2020.04.098
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