Omalizumab and COVID‐19 treatment: Could it help?

Dear Editor,

Therapeutics that may assist to control current pandemic of coronavirus disease 2019 (COVID‐19) rapid spread and reduce its high mortality rates are urgently needed. It might be prudent to look into existing therapies used in dermatology that could be effective against this virus. Omalizumab (OMZ), a recombinant humanized monoclonal immunoglobulin G1 (IgG1) antibody, blocks IgE binding to its high‐affinity FcεRI receptor. By this mechanism, it secondarily reduces free IgE and IgE‐mediated reactions. The reduction of free IgE also results in downregulation of the FcεRI expression. The drug is Food and Drug Administration‐approved for treatment of moderate‐to‐severe allergic asthma and H1‐antihistamine refractory chronic spontaneous urticaria (CSU). ¹

The current threat of COVID‐19 pandemic may cause close to half a billion deaths, that is, 6% of the global population—and potentially more. ² The nasal epithelium is one of the first sites of infection with SARS‐CoV‐2. Angiotensin‐converting enzyme 2 (ACE2) is a cellular receptor which has been proven to bind to SARS‐CoV‐2 spike protein and promote internalization of the virus into human cells, thus inhabitating and replicating in the nasal and pharyngeal mucosa. SARS‐CoV‐2, like other coronavirus species, is primarily attacked by immune cells, such as mast cells (MCs) that are located in the submucosa of the respiratory tract and in the nasal cavity and involved in prevention of microinvasion. Activation of MCs results in release inflammatory agents, such as histamine and protease, in addition to pro‐inflammatory cytokines including interleukin (IL)‐1, IL‐6, and IL‐33. ³

OMZ has showed reduction of local nasal mucosal inflammation and improving nasal respiration, in addition to improvement of sinonasal function in patients with chronic rhinosinusitis, ⁴ a mechanism that could be essential for the initial combating of COVID‐19. OMZ can be used in treatment of patients with different types of MCs disorders, even in low‐dose, ⁵ mitigating viral‐triggered release of the pro‐inflammatory mediators and risk of subsequent serious complications in COVID‐19 patients. Researchers noted OMZ treatment in vivo restored interferon alpha responses to both rhinovirus and influenza via OMZ‐reduced expression of FcεRIα on the cell surface secondary to OMZ‐reduction of free serum IgE levels, denoting an antiviral potential of OMZ. ⁶

Furthermore, excessive synthesis of pro‐inflammatory cytokines such as IL‐6, IL‐1β, and tumor necrosis factor alpha (TNF‐α) is induced by activated neutrophils and alveolar macrophages, which attracts more neutrophils and results in further release of chemokines and cytokines. Pro‐inflammatory mediators and upstream nuclear factor kappa β (NF‐kβ) signaling pathways might have a key role in COVID‐19‐related acute lung injury (ALI) pathogenesis. Interestingly, these cytokines are significantly elevated when lung tissue is exposed to SARS‐CoV. ⁷ Infiltration of inflammatory cells into lung parenchyma is a crucial process in acute lung injury with subsequent acute respiratory distress syndrome (ARDS). OMZ has not only anti‐IgE effect, but also have inhibitory effects on inflammatory cells, such as neutrophil, and coagulation in patients with CSU. ⁸

In addition to clinical manifestations of COVID‐19, such as fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to ARDS and death, it may manifest with cutaneous signs. Among the cutaneous manifestations of COVID‐19 in hospitalized patients, urticaria has been reported, which may be widespread, according to reports from Wuhan, China, and Lombardy. ⁹ , ¹⁰ Infected COVID‐19 patients have a hypercoagulable state presented with vascular skin symptoms, such as acroischemia and chilblain‐like lesions. ¹¹ OMZ may be tried for COVID‐19 patients manifested with urticaria or vascular lesions.

In an experimental study, Wang et al noted that intramuscular injection of OMZ‐small peptide segment (SPT) could inhibit the synthesis of IL‐6, IL‐1β, and TNF‐α in bronchoalveolar lavage fluid (BALF), and thereby attenuate acute inflammation in female C57BL/6 mice suffering from lipopolysaccharide‐induced ALI. Also, OMZ‐SPT could inhibit the synthesis of periostin (which modulates pulmonary inflammation) in BALF. Furthermore, OMZ‐SPT could inhibit activation of the NF‐kβ signaling induced by lipopolysaccharide in mouse lungs. Also, OMZ‐SPT has a suppressive effect on total expression of NF‐kB in RAW264.7 cells. ¹²

On the basis of current evidence at this time, and according to the experts, the use of ACE inhibitor should be maintained for the control of blood pressure and not to be discontinued. ¹³ In only one report, ACE inhibitors have shown to sustain CSU exacerbations and to annul the therapeutic effect of OMZ in two patients who had been previously responding to the drug. ¹⁴ Whether that therapeutic resistance was dose dependent or patient specific remains to be studied in accumulating similar cases.

OMZ may be worth to try in the treatment of COVID‐19 by international research groups. With possible home administration of OMZ, the patients would refrain from usual clinic visits and keep on the recommended social distancing. ¹⁵

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

AUTHOR CONTRIBUTIONS

The authors worked equally in preparing this manuscript for submission to Dermatologic therapy. All the authors collected the scientific data and shared in writing the initial draft. All the authors reviewed and approved the final draft. First author submitted the final draft.

Abdelmaksoud A, Goldust M, Vestita M. Omalizumab and COVID‐19 treatment: Could it help? Dermatologic Therapy. 2020;33:e13792. 10.1111/dth.13792