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We have read with great interest the case of a recovery from COVID-19 in a man with spondyloarthritis treated with etanercept and methotrexate, described by Duret et al.1
We describe the case of a 53-year-old man suffering from psoriatic arthritis and psoriasis since he was 22, with no other medical conditions. He was previously treated with phototherapy, cyclosporine, methotrexate, acitretin, efalizumab and etanercept.
Since 2010, he was treated with ustekinumab (90 mg) with complete remission of both psoriatic arthritis and psoriasis. On 10 February 2020, he administered an injection of 90 mg ustekinumab. On 28 February, the patient developed low-grade fever, cough and general malaise. On 2 March, he was tested positive for Severe Acute Respiratory Syndrome (SARS) - Coronavirus (CoV)-2, after his office manager was discovered to be affected by COVID-19.
On 5 March, the body temperature rose to 39.5°C, cough and fatigue worsened and he was hospitalised in the infectious disease unit.
On the day of hospitalisation his blood tests revealed leucopenia, anaemia, thrombocytopenia, increased C reactive protein (28 mg/L), ferritin (508 ug/L) and lactate dehydrogenase (228 U/L) while fibrinogen and D-dimer were normal. Chest X-rays were suggestive for SARS-CoV-2 infection. He was treated with chloroquine, lopinavir and ritonavir, methylprednisolone, paracetamol and azithromycin. He initially received high-flow oxygen; however, since dyspnoea was worsening and inflammatory markers were rising, he was transferred to the subintensive pulmonary unit, where he received non-invasive ventilation.
From 13 March, the patient showed a progressive improvement of chest X-rays and respiratory symptoms and, on 19 March, he was discharged. After being tested negative twice, on 2 April, he was considered healed.
To date, only few reports have described the outcome of COVID-19 in rheumatological patients treated with biological agents.1 2 Notably, an isolated case of COVID-19 in a patient with psoriatic arthritis treated with guselkumab has been reported to occur with only mild symptoms.2
To our knowledge, this is the first description of SARS-CoV-2 infection in a patient with psoriatic arthritis and psoriasis treated with ustekinumab.
Ustekinumab targets both interleukin (IL)-23 and IL-12 by binding to their common subunit p40.3
Available data currently suggest that targeting the IL-23/IL-17 axis may be beneficial in COVID-19, dampening the systemic inflammation known as ‘cytokine storm’ which can lead to multiorgan failure and death.2
Confirming this hypothesis, a real-life database collecting patients with inflammatory bowel disease affected by COVID-19 reported a lower incidence of adverse outcomes in patients treated with ustekinumab.4 Likewise, tumour necrosis factor inhibitors seem to be associated with lower admission to intensive care units and lower fatality rates, in agreement with the case described by Duret.1 4
Since IL-12 leads Th1 polarisation, which is needed for efficient viral clearance, its inhibition may be deleterious in COVID-19. In fact, polymorphisms of IL-12 receptor less responsive to IL-12 signalling have been associated with increased susceptibility to SARS infection.5 On the other hand, IL-12 seems to contribute to the inflammatory manifestations of the disease, thus exerting also a detrimental role.5
Overall, despite the potential increased risk of infection, ustekinumab may exert a protective action in COVID-19, due to the anti-inflammatory effect of the double neutralisation of IL-12 and IL-23. Further data are warranted to clarify this issue.
Contributors FM performed the researches, wrote the paper and contributed to its revision. FP performed the researches and wrote the paper. SP conceived, wrote the paper and performed the revision.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; internally peer reviewed.