Can Tofacitinib Offer Protection against COVID-19 Infection? Open Access

Dear Editor,

We would like to share our experience with a 10-year-old patient with long-standing alopecia areata universalis that was treated with tofacitinib 5 mg BID for 8 months, with excellent clinical response (Fig. 1). Following a large family gathering, attended by the patient, with no proper social distancing measures, the patient’s father and additional 25 family members were infected with SARS-CoV-2. Therefore, the entire family had entered a 14-day quarantine period. During this time, the patient and his 3 siblings were repeatedly exposed, and in close contact with ∼100 SARS-CoV-2-positive patients, in the same quarantine location, and without proper protection. All of the patients’ siblings who were quarantined with him had been diagnosed with symptomatic COVID-19 based on PCR results. Strikingly, the patient had no clinical disease and 2 consecutive PCR tests for SARS-CoV-2 were negative, despite continuing the immunosuppressive treatment without dosage modifications. This surprising finding raises the possibility of a potential protective effect of tofacitinib against SARS-CoV-2 infection and further strengthens the assumption that JAK inhibitors might be used for the prevention or treatment of CO-VID-19 as suggested by a recent correspondence by Richardson et al. [1] who postulated that the JAK inhibitor baricitinib can reduce SARS-CoV-2’s ability to infect cells by disrupting AP2-associated protein kinase 1. SARS-CoV-2 spike protein’s interaction with angiotensin-converting enzyme II was shown to facilitate the activation of metalloprotease 17 which consequently results in angiotensin-converting enzyme II shedding from host cells. This results in increased angiotensin II (Ang II) and hyaluronan (HA) concentrations. Ang II then interacts with its receptor Ang II receptor-1, resulting in JAK-STAT pathway activation, mediating a pro-fibrotic and pro-inflammatory state, as well as chronic tissue injury. The increased HA concentration, on the other hand, may promote the formation of jelly-like fluid in the lungs during the disease, resulting in respiratory distress and severe inflammation. The concentration of HA is also dependent on the induction of HA-synthase-2 in lung cells by pro-inflammatory cytokines interleukin-1 and tumor necrosis factor-α. Local production of these 2 important cytokines increases due to infiltration of immune cells mediated through the Ang II-JAK-STAT axis [2]. These 2 pathologic processes, and probably several other non-discovered ones, may be counteracted by tofacitinib. The -results of emerging clinical trials (NCT04415151, NCT04390061, and NCT04332042) on the use of tofacitinib in COVID-19 patients will shed more light on this important issue.