Single-cell RNA sequencing analysis of a COVID-19-associated maculopapular rash in a patient with psoriasis treated with ustekinumab.

Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but extrapulmonary manifestations, including the skin, have been well documented. However, transcriptomic profiles of skin lesions have not been performed thus far. Here, we present a single-cell RNA sequencing analysis in a patient with COVID-19 infection with a maculopapular skin rash while on treatment with the interleukin (IL)-12/IL-23 blocker ustekinumab for his underlying psoriasis. Results were compared with healthy controls and untreated psoriasis lesions. We found the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry receptors ACE2 and TMPRSS2 in keratinocytes of the patient with COVID-19, while ACE2 expression was low to undetectable in psoriasis lesions and healthy skin. Among all cell types, ACE2+ keratinocyte clusters showed the highest levels of transcriptomic dysregulation in COVID-19, expressing type 1-associated immune markers such as CXCL9 and CXCL10. In line with a generally type 1-skewed immune microenvironment, cytotoxic lymphocytes showed increased expression of the IFNG gene and other T-cell effector genes, while type 2, type 17, or type 22 T-cell activation was largely absent. Conversely, downregulation of several anti-inflammatory mediators was observed. This first transcriptomic description of a COVID-19-associated rash identifies ACE2+ keratinocytes displaying profound transcriptional changes, and inflammatory immune cells that might help to improve the understanding of SARS-CoV-2-associated skin conditions.

Viral exanthems Unravelling viral rashes

Common causes of viral exanthems in Australia include herpesviruses, enteroviruses, parvovirus B19, varicella, measles and rubella viruses and mosquito-borne alphaviruses. The cause can often be diagnosed clinically from the rash distribution and morphology, confirmed only when necessary with serological or PCR tests. Most viral exanthems are self-limiting, requiring supportive care alone.

Dermatological Manifestations in Patients with COVID-19 Pneumonia in Veracruz, Mexico

Background. A large number of viral infections are characterized by the presence of cutaneous manifestations. Multiple dermatological manifestations have been observed in patients with COVID-19. Dermatological lesions in patients infected by SARS-CoV-2 such as livedo reticularis, rash and vascular lesions may represent manifestations of secondary phenomena such as paraviral rashes or by participation of the innate or adaptive immune system that cause vasodilation, vascular leakage or procoagulant effects Methods. Descriptive and observational study, adult patients with COVID-19 pneumonia were selected, confirmed by RT-PCR and chest CT. General symptoms, hematic cytometry results, pneumonia severity, prognosis as well as dermatological manifestations are characterized. Results. 100 patients were entered into the study, with an average age of 49.4 years, 54% male. The general symptoms with the highest incidence were: fever, cough and dyspnea characteristic of SARS-CoV-2 infection, followed by chest pain, headache, anosmia and dysgeusia. The main alteration of the hemogram was lymphopenia, no leukopenia or plaquetopenia was demonstrated. 54% of those affected had mild pneumonia, the rest severe pneumonia. 75% progressed towards improvement and 25% died. Among the dermatological manifestations identified, all occurred in cases with severe pneumonia, the one with the highest incidence was the morbilliform viral exanthema in 18%, the presence of diffuse partial alopecia in 7% as well as manifestations of lividity and maceration in 1%. Regarding alopecia, in 6% it was reversible androgenetic alopecia, having manifested during the acute stage of pneumonia (all men), in 1% it presented alopecia areata (male) that has been persistent beyond the acute phase and in frank recovery Demographic and clinical variables Conclusion. The incidence of dermatological manifestations is low in this study population, the most frequent being the morbilliform viral exanthema expected in a virus, however they present manifestations of low incidence such as reversible androgenetic alopecia associated with severity of the disease, a finding that has been documented recently as a manifestation associated with COVID-19.

Maculopapular rash and fever: A diagnostic challenge to the paediatrician in the COVID-19 pandemic

Introduction: Several clinical conditions can manifest with fever and a maculopapular rash in paediatric age. Although some presentations are benign, others may be medical emergencies, which demand a prompt diagnosis and treatment. Some of the more common causes of fever and maculopapular rash include infectious diseases (Sars-CoV-2, Parvovirus B19;Coxsackie;Epstein-Barr virus infection, Mycoplasma Pneumoniae, etc), hypersensitivity reactions, Autoinflammatory syndromes, vasculitis, Kawasaki disease (KD), autoimmune diseases. Objectives: In the COVID-19 pandemic era these symptoms need a well-organized hospital strategy to rapidly exclude Sars-CoV-2 infection and to distinguish severe and rapidly developing patients. Methods: We evaluated the medical records of children admitted to a paediatric tertiary centre in the years 2020-202, excluding children with suspected or documented COVID-19 infection. Results: We retrospectively identified 21 patients (13M;9F), age: 0.7- 12 years, admitted with the diagnosis of fever and rash and with a definite diagnosis. 10 children had a documented infection (2 Mycoplasma;2 Parvovirus;5 EBV;1 Adenovirus);3 patients had a KD;4 had an autoimmune disease;3 had an Autoinflammatory syndrome, 1 a vasculitis;1 had a Macrophage Activation Syndrome (MAS). Distribution of the rash, a persistent/vanishing rash, the associated lymphadenopathy did not contribute to the differential diagnosis. Haemoglobin levels were significantly lower in KD (8.3- 11.2). CRP was significantly higher in KD (3.23-34) vs autoimmune diseases and Autoinflammatory syndromes. The other laboratory parameters did not contribute to the differential diagnosis, otherwise reached by specific IgM and PCR. In children with clinical signs of suspicion of Autoinflammatory syndromes, the genetic approach permitted to reach the treat-to-target. Conclusion: The numerous viral skin diseases that affect children present a diagnostic challenge to the clinicianIn some situations, viral rash may be difficult to clinically differentiate from nonviral diseases;extensive laboratory evaluation isolates the virus. Otherwise, autoimmune diseases must be excluded and, in this suspicion, the alert must be high to promptly diagnose a MAS. A most severe presentation can hide the first attack of an Autoinflammatory syndrome: hence, the genetic study of these condition is a milestone in the differential diagnosis and avoid a diagnostic delay.