Potential advantages of biologics in preventing SARS-CoV-2 infected psoriasis patients from icu admission and death: the Italian and French experience

As suggested by the observational studies from Italy and France presented at the Virtual Annual Congress of the European Academy of Dermatology and Venereology, biologic therapy for psoriasis may be protective to infected patients against severe and fatal COVID-19 although such protective benefit does not prevent the infection of COVID-19.1

The biologics and small molecules involved in the systemic treatment of moderate to severe psoriasis are known to be associated with a higher risk of airway infections.1 Concerns about this in psoriasis patients during the COVID-19 outbreak led to a case-control study involving 1,193 adult psoriasis patients on biologic therapies, including apremilast, in the San Donato Hospital in Milan, Italy.1 The conditions of the psoriasis patients were assessed and compared with the 10,060,574 Lombardia population from February 21, 2020 (first case of COVID-19 identified in Italy) to April 9, 2020.1 Notably, Lombardia is an Italian region with higher numbers of confirmed, hospitalized and deceased COVID-19 patients.1

The study results demonstrated that psoriasis patients on biologics were at a higher risk of testing positive for COVID-19 (unadjusted OR=3.43; 95% CI: 2.25-5.73; p<0.0001), being self-quarantined at home (OR=9.05; 95% CI: 5.61-14.61; p<0.0001), and being hospitalized (unadjusted OR=3.59; 95% CI: 1.49-8.63; p=0.0044) when compared with the general Lombardia population.1 On the contrary, the risks of being admitted to the intensive care unit (ICU) (unadjusted OR=3.41; 95% CI: 0.21-54.55; p=0.3861) and death (unadjusted OR=0.41; 95% CI: 0.03-6.59; p=0.5306) were not statistically significantly different from the control population.1

Among the 22 psoriasis patients infected with COVID-19, 17 displayed stage I disease (viral infection phase), 2 displayed stage IIA (pulmonary phase without hypoxia) and 3 displayed stage IIB (pulmonary phase with hypoxia [PaO2/FiO2 of <300mmHg]).1 Remarkably, none displayed a progression on stage III (hyperinflammation phase).1 Of note, 7 of the COVID-19 confirmed psoriasis patients received interleukin (IL)-17 inhibitors, including secukinumab, and none received apremilast.1

A similar result was also demonstrated by a nationwide French study that evaluated the frequency of severe COVID-19 infections (hospitalization or death) in psoriasis patients receiving systemic or biologic treatment, especially during the first 4 months following treatment initiation.2 From April 27 to May 7 2020, which was the time period near the peak of the first COVID-19 wave in France, 1,418 adult psoriasis patients were recruited with 54 patients presented with a possible COVID-19 infection and no deaths were reported.2

Among the 0.35% (n=5) of patients who were presented with a severe form of COVID-19 that required hospitalization, only 40% (n=2) of them required intensive care.2 60% (n=3) of whom were also presented with other risk factors for severe infection including obesity and Crohn’s disease.2 These observations again suggested that systemic or biologic treatment did not worsen the prognosis of COVID-19.

These findings may be explained by the immunosuppressive mechanism related to the biologics. In real-life registries and trials, biologics have been shown to increase the risk of viral infections, which in turn increase the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in psoriasis patients.1 However, the situation is twisted in the final stage of COVID-19 where the disease (severe form with systemic hyperinflammation) is characterized by extrapulmonary manifestations driven by cytokines storm.3 By inhibiting the pro-inflammatory cytokines, biologics then appear to be beneficial in the hyperinflammatory phase despite their immunosuppressive mechanism being detrimental in the viral infection phase.1

Recently, angiotensin-converting enzyme 2 (ACE2) has also been suggested to be the main receptor responsible for the entry of SARS-CoV-2.4 Data from a phase 4, double-blind, randomized ObePso-S study investigating the effects of secukinumab on systemic inflammatory markers and gene expression in psoriasis patients found that inhibiting IL-17A-mediated inflammation with secukinumab led to a significant downregulation of ACE2 expression (fold change=-2.17; p<0.001) when compared to placebo.4 Given that IL-17 exerts its proinflammatory effect systemically and that ACE2 has a crucial role in SARS-CoV-2 infection, secukinumab could be beneficial for psoriasis patients at risk of SARS-CoV-2 infection.4

Overall, while the biologic therapy for psoriasis patients could not reduce the risk of SARS-CoV-2 infection, biologics have surprisingly protected patients from progression to the severe stage of the COVID-19.1-2 The inhibition of pro-inflammatory IL-17 and downregulation of ACE2 expression by the immunosuppressants may explain this observation, though further studies are necessary to make clearer conclusions.4

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