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Introduction COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients.Methods and analysis COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle.Ethics and dissemination Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.Trial registration Clinical Trials.gov (NCT05271929), EudraCT (2021-006621-22)

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin. [ABSTRACT FROM AUTHOR]

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