oronavirus disease 2019 (COVID-19) is a complex clinical syndrome caused by SARS-CoV-2. Despite extensive research into severe disease of hospitalized patients 1 and many large studies leading to approval of vaccines and antivirals 2-4 , the global spread of SARS-CoV-2 continues and is, indeed, accelerating in many regions. Infections are typically mild or asymptomatic in younger people, but these likely drive community transmission 5 , and the detailed time course of infection and infectivity in this context has not been fully elucidated 6,7 . Deliberate human infection of low-risk volunteers enables the exact longitudinal measurement of viral kinetics, immunological responses, transmission dynamics and duration of infectious shedding after a fixed dose of

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.

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Abstract. Severe papillomatosis developed in the oral cavity and spread throughout the haired skin of the trunk and limbs of an 8-month-old female Chinese Shar Pei dog. The dog had received corticosteroids prior to referral, which was associated with the onset of demodecosis and papillomatosis. Papillomavirus structural antigens were detected in biopsies by immunohistochemistry using a panel of monoclonal and polyclonal antibodies. An 8.2-kilobase papillomavirus-specific DNA molecule was detected in the cutaneous lesions by high stringency Southern blot hybridization using a cloned canine oral papillomavirus DNA probe. Restriction enzyme analysis revealed that the virus in the cutaneous lesions was identical to the canine oral papillomavirus. Discontinuation of the steroids combined with the use of a mitocide, antibiotics, and an autogenous vaccine resolved the demodecosis and papillomatosis. This case report suggests that corticosteroid-induced immunosuppression can expand the tissue tropism of papillomaviruses.Key words: Papillomavirus; skin; immunosuppression; steroids; oral cavity.The papillomaviruses are a large group of speciesspecific, double-stranded DNA viruses that infect a wide variety of vertebrate hosts, including man.33 In dogs, papillomaviruses are known to cause benign papillomas of the skin as well as the oral, ocular, and genital mucous membranes.27 To date, only the genome of the canine oral papillomavirus (COPV) has been cloned and chara~terized.~~ Based on transmission, immunohistochemistry, and in situ hybridization studies, it is believed that more than one papillomavirus infects the dog and that each virus has a tropism for a specific anatomic site.27Florid oral papillomas in Beagle dogs has been associated with an IgA deficiency (Sundberg, unpublished data).29.3n Rare case-studies document that dogs with florid oral papillomas developed small, solitary papillomas on the planum nasale, but not widespread lesions on the haired kin.^", ^^ We report extensive papillomatosis of the haired skin as well as the oral mucosa in an iatrogenically immunosuppressed Chinese Shar Pei dog. The COPV was identified by restriction fragment analysis as the virus present in the cutaneous lesions. The presence of an oral papillomavirus in cutaneous lesions in an immunosuppressed host raises the possibility that the tissue specificity of papillomaviruses is influenced by the immune system. Materials and Methods Clinical historyAn 8-month-old, 20-kg female Chinese Shar Pei dog was referred (to EKS) with alopecia, erythematous suppurative dermatitis, and generalized exophytic papillomatosis of the oral mucosa as well as the truncal and appendicular haired skin. The papillomas had been present for 4 months. A littermate had died with severe oral papillomatosis. In the same littermate, oral papillomas had been removed surgically by the attending veterinarian but the lesions had recurred rapidly. In the dog described here, skin scrapings demonstrated the presence of mites (Demodex canis), which were responsible f...