Thomas Jefferson University Jefferson Digital Commons Department of Dermatology and Cutaneous Department of Dermatology and Cutaneous Biology Faculty Papers Biology 2-16-2021 Skin Manifestations in COVID-19 Patients: Are They Indicators for Disease Severity? A Systematic Review Parnian Jamshidi Bahareh Hajikhani Mehdi Mirsaeidi Hassan Vahidnezhad Masoud Dadashi See next page for additional authors Follow this and additional works at: https://jdc.jefferson.edu/dcbfp Part of the Dermatology Commons Let us know how access to this document benefits ouy This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Department of Dermatology and Cutaneous Biology Faculty Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Authors Parnian Jamshidi, Bahareh Hajikhani, Mehdi Mirsaeidi, Hassan Vahidnezhad, Masoud Dadashi, and Mohammad Javad Nasiri SYSTEMATIC REVIEW published: 16 February 2021 doi: 10.3389/fmed.2021.634208 Skin Manifestations in COVID-19 Patients: Are They Indicators for Disease Severity? A Systematic Review Parnian Jamshidi 1, Bahareh Hajikhani 2, Mehdi Mirsaeidi 3*, Hassan Vahidnezhad 4, Masoud Dadashi 5 and Mohammad Javad Nasiri 2* 1 Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 2 Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 3 Division of Pulmonary and Critical Care, University of Miami, Miami, FL, United States, 4 Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States, 5 Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran Introduction: Until now, there are several reports on cutaneous manifestations in COVID-19 patients. However, the link between skin manifestations and the severity of the disease remains debatable. We conducted a systematic review to evaluate the temporal relationship between different types of skin lesions and the severity of COVID-19. Edited by: Zisis Kozlakidis, Methods: A systematic search was conducted for relevant studies published between International Agency for Research on Cancer (IARC), France January and July 2020 using Pubmed/Medline, Embase, and Web of knowledge. The Reviewed by: following keywords were used: “SARS-CoV-2” or “COVID-19” or “new coronavirus” Dayi Zhang, or “Wuhan Coronavirus” or “coronavirus disease 2019” and “skin disease” or “skin Tsinghua University, China manifestation” or “cutaneous manifestation.” Sunny Oteikwu Ochigbo, University of Calabar, Nigeria Results: Out of 381 articles, 47 meet the inclusion criteria and a total of 1,847 *Correspondence: patients with confirmed COVID-19 were examined. The overall frequency of cutaneous Mohammad Javad Nasiri manifestations in COVID-19 patients was 5.95%. The maculopapular rash was the [email protected] Mehdi Mirsaeidi main reported skin involvement (37.3%) commonly occurred in middle-aged females [email protected] with intermediate severity of the disease. Forty-eight percentage of the patients had a mild, 32% a moderate, and 20% a severe COVID-19 disease. The mild disease was Specialty section: This article was submitted to mainly correlated with chilblain-like and urticaria-like lesions and patients with vascular Infectious Diseases - Surveillance, lesions experienced a more severe disease. Seventy-two percentage of patients with Prevention and Treatment, a section of the journal chilblain-like lesions improved without any medication. The overall mortality rate was Frontiers in Medicine 4.5%. Patients with vascular lesions had the highest mortality rate (18.2%) and patients Received: 27 November 2020 with urticaria-like lesions had the lowest mortality rate (2.2%). Accepted: 04 January 2021 Published: 16 February 2021 Conclusion: The mere occurrence of skin manifestations in COVID-19 patients is not Citation: an indicator for the disease severity, and it highly depends on the type of skin lesions. Jamshidi P, Hajikhani B, Mirsaeidi M, Chilblain-like and vascular lesions are the ends of a spectrum in which from chilblain-like Vahidnezhad H, Dadashi M and to vascular lesions, the severity of the disease increases, and the patient’s prognosis Nasiri MJ (2021) Skin Manifestations in COVID-19 Patients: Are They worsens. Those with vascular lesions should also be considered as high-priority patients Indicators for Disease Severity? A for further medical care. Systematic Review. Front. Med. 8:634208. Keywords: COVID-19, coronavirus – COVID-19, skin manifestations, skin - pathology, systematic literature search, doi: 10.3389/fmed.2021.634208 disease severity, mortality, prognosis Frontiers in Medicine | www.frontiersin.org 1 February 2021 | Volume 8 | Article 634208 Jamshidi et al. Skin Manifestations in COVID-19 Patients INTRODUCTION Data Extraction Data about the first author’s name, date of publication, A viral outbreak caused by severe acute respiratory syndrome country, number of COVID-19 patients, number of cases with coronavirus 2 (SARS-CoV-2) emerged from Wuhan, China in skin manifestations, age, gender, location and type of skin late December 2019 (1). The disease was named coronavirus manifestations, associated cutaneous symptoms, the onset of disease 2019 (COVID-19) by World Health Organization skin lesions with systemic symptoms, the median duration of (WHO) and was declared as a pandemic on 11 March 2020 the lesions, treatment strategies and main histological findings (2). After 1 year from the beginning of the pandemic, the of the lesions as well as comorbidities, associated symptoms, full spectrum of COVID-19 presentations and its relationship drug history, laboratory findings, severity and outcome of with disease severity is still unknown. Fever, cough, chills, the patients were selected for further analysis. All cutaneous dyspnea, myalgia, and sore throat are the most common clinical presentations related to COVID-19 were categorized into six presentations of COVID-19 and as time goes on, different other groups: chilblain-like, vesicular, urticaria-like, maculopapular, manifestations have been reported (3). Recently, skin lesions vascular, and miscellaneous (lesions that we couldn’t subscribe have been described as potential manifestations of COVID- to any of the groups). Petechiae, purpura, livedo, and necrosis 19 (4–6). The cutaneous changes reported to date include were classified into vascular lesions. Two authors (PJ, BH) maculopapular rash, vesicular lesions, urticaria-like lesions, and independently extracted the data from the selected studies. The chilblain-like lesions (4–8). Some of these skin manifestations data was jointly reconciled, and disagreements were discussed arise before the signs and symptoms more commonly associated and resolved between review authors (PJ, BH, MJN). with COVID-19, suggesting that they could be presenting signs of COVID-19 (9). However, the link between skin manifestations Quality Assessment and the severity of the disease remains debatable. Due to the The critical appraisal checklist for case reports provided by the great variety of reported dermatologic presentations as well Joanna Briggs Institute (JBI) was used to perform a quality as the inconsistency of data on the association between skin assessment of the studies (11). presentations of COVID-19 with poor outcome, we aimed to conduct a comprehensive systematic review on the clinical and histopathological characteristics of skin manifestations in RESULTS relation to other features of confirmed COVID-19 patients and to evaluate the temporal relationship between different types of At the first round of review, 381 articles were selected. After skin lesions and the severity of COVID-19. removing the duplicates and studies that did not meet the entry criteria, 88 full texts were finally selected for further assessment. Of these, only 47 articles had the characteristics appropriated for systematic review and were entered into the METHODS data extraction (Figure 1). Most of the studies were case reports (47%, N: 22) followed by case series (42.4%, N: 20), retrospective This review conforms to the “Preferred Reporting Items hospital/private section-based study (6.4%, N: 3), and cross- for Systematic Reviews and Meta-Analyses” (PRISMA) sectional (4.2%, N: 2). Thirteen articles were originated from statement (10). Registration: PROSPERO (pending registration Italy, 11 from Spain, 10 from France, 5 from the USA, and others ID: 215422). from Belgium, China, Thailand, Kuwait, Indonesia, Russia, Turkey, and Singapore. Information of the 47 analyzed articles Search Strategy and Selection Criteria can be found in Table 1. A total of 1,847 patients with confirmed COVID-19 (based on To investigate the prevalence and characteristics of cutaneous positive RT-PCR or positive antibody tests) were examined in 47 manifestations in COVID-19 patients, a systematic search