Background The multi-morbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse COVID-19 outcomes but data are limited. Objective Characterize the course of COVID-19 in psoriasis and identify factors associated with hospitalization. Methods Clinicians reported psoriasis patients with confirmed/suspected COVID-19 via an international registry, PsoProtect. Multiple logistic regression assessed the association between clinical/demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviours. Results Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% a non-biologic and 10% no systemic treatment for psoriasis. 348 (93%) fully recovered from COVID-19, 77 (21%) were hospitalized and nine (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted OR 1.59 per 10 years, 95% CI 1.19-2.13), male sex (OR 2.51, 95% CI 1.23-5.12), non-white ethnicity (OR 3.15, 95% CI 1.24-8.03) and comorbid chronic lung disease (OR 3.87, 95% CI 1.52-9.83). Hospitalization was more frequent in patients using non-biologic systemic therapy than biologics (OR 2.84, 95% CI 1.31-6.18). No significant differences were found between biologic classes. Independent patient-reported data (n=1,626 across 48 countries) suggested lower levels of social isolation in individuals receiving non-biologic systemic therapy compared to biologics (OR 0.68, 95% CI 0.50-0.94). Conclusion In this international moderate-severe psoriasis case series, biologics use was associated with lower risk of COVID-19-related hospitalization than non-biologic systemic therapies, however further investigation is warranted due to potential selection bias and unmeasured confounding. Established risk factors (being older, male, non-white ethnicity, comorbidities) were associated with higher hospitalization rates. Clinical Implications We identify risk factors for COVID-19-related hospitalization in psoriasis patients, including older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic therapies.

Cystinosis is a rare genetic disease characterized by defective lysosomal cystine transport and increased lysosomal cystine. How lysosomal cystine causes the lethal nephropathic phenotype is unknown. It was shown recently that cultured fibroblasts and renal proximal tubule epithelial cells whose lysosomes are cystine-loaded display a two-fold or greater increase in apoptosis after both intrinsic and extrinsic stimuli. The mechanism for the increased apoptosis is unknown. Protein kinase C␦ (PKC␦) is a proapoptotic protein kinase that has been shown in vitro to be activated via cysteinylation. This report now shows that PKC␦ forms disulfide bonds specifically with cystine that is released from lysosomes in cultured fibroblasts and renal proximal tubule epithelial cells during apoptosis. PKC␦ in cystinotic fibroblasts and renal proximal tubule epithelial cells have a four-to six-fold greater association with its substrate, lamin B, and a 2.5-fold increase in specific activity after TNF-␣ exposure. Both RNA inhibition and chemical inhibition of PKC␦ resulted in a significant decrease in apoptosis in cystinotic cells but not in normal cells. It is proposed that abnormally increased apoptosis plays a role in evolution of the cystinotic phenotype.

The B7 family of molecules on antigen presenting cells (APCs) regulate T cell activation. They deliver stimulatory signals through CD28 and inhibitory signals through CD152, or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). CTLA4Ig (abatacept) is a soluble chimeric protein consisting of the extracellular domain of human CD152 linked to the modified Fc portion of human IgG1. By binding to B7-1 (CD80) and B7-2 (CD86) molecules on APCs, CTLA4Ig blocks the CD28-mediated costimulatory signal for T cell activation. Success with abatacept has been noted in psoriasis. Abatacept was administered to two patients with refractory psoriasis and psoriatic arthritis after the patients had failed all conventional treatment methods. Both patients experienced very brief improvement in disease. The improvement, however, was not continued, and both patients were taken off the medication. The small patient population limits the extrapolation of the present authors' results to the larger population. Furthermore, the present authors' patients have very severe, refractory disease and do not adequately represent the majority of psoriasis patients. Although the present authors' patients demonstrated brief response to drug, this response was not sustained. No adverse events were reported in the present authors' patients.

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