Generalized Rash in Severe Hospitalized COVID Patients: Correlation between Histological Examination, Drug Intake, Blood Interleukins Profileand Long-Term Follow-Up

Background: There have been few reports of cutaneous skin lesions in severe COVID-19 hospitalized patients which exhibit different behavior compared to outpatients. Furthermore, a notable lack of rigorous studies exits. In this study we included patients with generalized rash during the first wave of the pandemic for characterization. Methods: Hospitalized patients with severe confirmed pulmonary COVID-19 infection and a generalized cutaneous rash during the first wave in March-May 2020 were included. The study received approval from the ethics committee. Clinical presentation, histo-logical examination, blood test, and complete blood interleukin profile were assessed. Special immunohistochemical investigations were conducted. Long term follow-up of the patient was performed throuhg a phone call 24 months later. Results: A total 28 patients were studied and classified by histological examination into three groups: G1: perivascular dermatitis (18/28, 64%); G2: Drug reaction (7/28, 25%); and G3: Generalized exanthema and chilblain (3/28, 11%). The virus was not detected in the skin, by PCR and by immunohistochemical analysis, and the interleukin expression in the skin were undetectable results. Vascular cell adhesion molecule 1 (VCAM1), E-selectine, and IT Galpha 5 were unspecific. G1 exhibited the least inflammation, G2 the most in-flammatory, and G3 had previous inflammation. Discussion: Our data suggest that generalized exanthemas during severe SARS-Cov-2 infection exhibit unspecific finding and are similar to other rashes caused by inflammation. Drug reaction should be considered, as they accounted for 25% of the rashes. Further studies including higher number of patients are necessary.