Cutaneous Manifestations of COVID-19: A Systematic Review and Analysis of Individual Patient-Level Data

Background: Distinctive cutaneous manifestations of COVID-19 have been recently reported. It is unclear whether such skin manifestations are associated with the severity of COVID-19 infection. Methods: We conducted a systematic review and analysis of patient-level data to identify case reports and case series characterizing cutaneous manifestations of confirmed COVID-19. PubMed, Embase, Cochrane databases, Google Scholar, Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry, Elsevier website, Wiley website, Research Square, and medRxiv were searched for eligible articles published from October 1, 2019 to May 21, 2020. Key demographic and clinical data from each case were extracted and analyzed. The primary outcome measure was risk factor analysis of skin related outcomes for severe COVID-19 disease. Findings: Seventy-one case reports and case series comprising 144 cases of cutaneous involvement in COVID-19 were included. The most frequently occurring morphologies were: morbilliform (30·6%), varicelliform (18·8%), urticarial (13·2%), chilblains-like (12·5%), and acro-ischemia (9%). The median age of patients was 51 years (mean: 45·9, range: 0 to 91). Five out of 18 patients with chilblains-like eruptions had no extracutaneous COVID-19 symptoms (27·8%, p=0·0003) and were less likely to have severe COVID-19 disease (2/18, 11%, 95% CI 1·4% to 34·7%, p=0·02), and patients with livedo and acro-ischemic morphologies had severe COVID-19 more frequently than those with other morphologies (17/21, 81%, 95% CI 58·0% to 94·5%, p<0·0001). Interpretation: The most frequently reported cutaneous manifestations of COVID-19 (morbilliform, varicelliform, and urticarial) are well described patterns of viral exanthems. However, chilblains-like, livedo, and acro-ischemic morphologies are not traditionally associated with viral infections and were significantly associated with severity of COVID-19 disease.Funding Statement: None.Declaration of Interests: None.