Skin necrosis in COVID-19 patients: complication of therapy or one of clinical and pathological mechanisms of viral infection?

Walaa Fadhil Abbas, Tamrazova Olga Borisovna, Molochkov Anton Vladimirovich, Stadnikova Antonina Sergeevna


The coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV). Dermatological disorders are among the numerous observations in COVID-19 patients that are consistently reported from various clinical sites throughout the world, although their relationship with illness severity is unknown. Urticarial rash, maculopapular or morbilliform rash, papulovesicular lesions, chilblain, livedo reticularis, vasculitis-like picture, and skin necrosis have all been reported with different frequencies and associated circumstances. In this review article, we will highlight reports of skin necrosis, one of the rare skin findings that are associated with COVID, and their clinical and pathophysiological aspects, in addition to attempting to determine whether they are one of the possible outcomes of this virus infection or a complication of various treatment programs. and to discuss the overlap between skin necrosis due to COVID-19-associated coagulopathies and disseminated intravascular coagulation. Cutaneous necrosis in COVID-19 patients during the pandemic period, according to this review, is not rare. possibly It is simple to diagnose and recognize this dermatological condition, but determining the causal variables and their function in pathogenesis is a complex and difficult task. It's also tough to categorize because it affects people of all ages, regardless of gender, ethnicity, or health status. All hypotheses discuss the direct viral role, the immune system's hyperinflammatory state with cytokine storm, the hypercoagulable state with vasculitis, anticoagulant therapy complications, and deep secondary necrotizing infections as possible interactions that lead to necrosis, which can result in serious outcomes such as disseminated intravascular coagulation if not properly treated.


COVID-19, Skin necrosis, Coagulopathy, Vasculitis, DIC

Full Text:



Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, et al. A pathological report of three COVID-19 cases by minimal invasive autopsies. Zhonghua Bing Li Xue Za Zhi. 2020;49:411-7.

Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18:1094-9.

Liao D, Zhou F, Luo L, Xu M, Wang H, Xia J, et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol. 2020;7:e671-8.

Zhou X, Cheng Z, Luo L, Zhu Y, Lin W, Ming Z, et al. Incidence and impact of disseminated intravascular coagulation in COVID-19 a systematic review and meta-analysis. Thromb Res. 2021;201:23-9.

Bouaziz JD, Duong TA, Jachiet M, Velter C, Lestang P, Cassius C, et al. Vascular skin symptoms in COVID-19: a French observational study. J Eur Acad Dermatol Venereol. 2020;34:e451-52.

Zhang Y, Cao W, Xiao M, Li YJ, Yang Y, Zhao J, et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020;41:E006.

Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with COVID-19. N Engl J Med. 2020;382:e38.

Riker RR, May TL, Fraser GL, Gagnon DJ, Bandara M, Zemrak WR, et al. Heparin-induced thrombocytopenia with thrombosis in COVID-19 adult respiratory distress syndrome. Res Pract Thromb Haemost. 2020;4:936-41.

East JM, Cserti-Gazdewich CM, Granton JT. Heparin-Induced Thrombocytopenia in the Critically Ill Patient. Chest. 2018;154:678-90.

Rosell-Díaz AM, Mateos-Mayo A, Nieto-Benito LM, Balaguer-Franch I, Hernández de la Torre-Ruiz E, Lainez-Nuez A, et al. Exanthema and eosinophilia in COVID-19 patients: has viral infection a role in drug induced exanthemas? J Eur Acad Dermatol Venereol. 2020;34:e561-63.

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033-4.

Herrero-Moyano M, Capusan TM, Andreu-Barasoain M, Alcántara-González J, Ruano-Del Salado M, Sánchez-Largo Uceda ME, et al. A clinicopathological study of eight patients with COVID-19 pneumonia and a late-onset exanthema. J Eur Acad Dermatol Venereol. 2020;34:e460-4.

Mungmunpuntipantip R, Wiwanitkit V. COVID-19 and Cutaneous manifestations. J Eur Acad Dermatol Venereol. 2020;34:e246.

Liu J, Li Y, Liu L, Hu X, Wang X, Hu H, et al. Infection of human sweat glands by SARS-CoV-2. Cell Discov. 2020;6:84.

Tatu AL, Baroiu L, Fotea S, Anghel L, Drima Polea E, Nadasdy T, et al. A Working Hypothesis on Vesicular Lesions Related to COVID-19 Infection, Koebner Phenomena Type V, and a Short Review of Related Data. Clin Cosmet Investig Dermatol. 2021;14:419-23.

De Masson A, Bouaziz JD, Sulimovic L, Cassius C, Jachiet M, Ionescu MA, et al. Chilblains is a common cutaneous finding during the COVID-19 pandemic: A retrospective nationwide study from France. J Am Acad Dermatol. 2020;83:667-70.

El Hachem M, Diociaiuti A, Concato C, Carsetti R, Carnevale C, Ciofi Degli Atti M, et al. A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection. J Eur Acad Dermatol Venereol. 2020;34:2620-9.

Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Takeshita J, et al. Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries. J Am Acad Dermatol. 2020;83:486-92.

Battesti G, El Khalifa J, Abdelhedi N, Ferre V, Bouscarat F, Picard-Dahan C, et al. New insights in COVID-19-associated chilblains: A comparative study with chilblain lupus erythematosus. J Am Acad Dermatol. 2020;83:1219-22.

Zervou FN, Louie P, Stachel A, Zacharioudakis IM, Ortiz-Mendez Y, Thomas K, et al. SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection. J Med Virol. 2021;93:5409-15.

Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med. 2008;359:938-49.

Emmi G, Silvestri E, Squatrito D, Amedei A, Niccolai E, D'Elios MM, et al. Thrombosis in vasculitis: from pathogenesis to treatment. Thromb J. 2015;13:15.

Henn V, Slupsky JR, Gräfe M, Anagnostopoulos I, Förster R, Müller-Berghaus G, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998;391:591-4.

Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res. 2020;220:1-13.

Chaturvedi S, Braunstein EM, Yuan X, Yu J, Alexander A, Chen H, et al. Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS. Blood. 2020;135:239-51.

Droesch C, Do MH, DeSancho M, Lee EJ, Magro C, Harp J. Livedoid and Purpuric Skin Eruptions Associated with Coagulopathy in Severe COVID-19. JAMA Dermatol. 2020;156:1-3.

Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020;383:334-46.

Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020;324:259-69.

Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood. 2014;123:2768-76.

Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395:1771-8.

Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, et al. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. N Engl J Med. 2020;383:288-90.

Harzallah I, Debliquis A, Drénou B. Lupus anticoagulant is frequent in patients with COVID-19. J Thromb Haemost. 2020;18:2064-5.

Tung ML, Tan B, Cherian R, Chandra B. Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots. Rheumatol Adv Pract. 2021;5:rkaa081.

Iba T, Warkentin TE, Thachil J, Levi M, Levy JH. Proposal of the Definition for COVID-19 Associated Coagulopathy. J Clin Med. 2021;10:191.

Nakahara K, Okuse C, Adachi S, Suetani K, Kitagawa S, Okano M, et al. Use of antithrombin and thrombomodulin in the management of disseminated intravascular coagulation in patients with acute cholangitis. Gut Liver. 2013;7:363-70.

Delrue M, Siguret V, Neuwirth M, Brumpt C, Voicu S, Burlacu R, et al. Contrast between Prevalence of HIT Antibodies and Confirmed HIT in Hospitalized COVID-19 Patients: A Prospective Study with Clinical Implications. Thromb Haemost. 2021;121:971-5.

Madala S, Krzyzak M, Dehghani S. Is COVID-19 an Independent Risk Factor for Heparin-Induced Thrombocytopenia?. Cureus. 2021;13:e13425.

Uaprasert N, Tangcheewinsirikul N, Rojnuckarin P, Patell R, Zwicker JI, Chiasakul T. Heparin-induced thrombocytopenia in patients with COVID-19: a systematic review and meta-analysis. Blood Adv. 2021;5:4521-34.

Comer SP, Cullivan S, Szklanna PB, Weiss L, Cullen S, Kelliher S, et al. COVID-19 induces a hyperactive phenotype in circulating platelets. PLoS Biol. 2021;19:e3001109.

Rotman JA, Dean KE, Magro C, Nuovo G, Bartolotta RJ. Concomitant calciphylaxis and COVID-19 associated thrombotic retiform purpura. Skeletal Radiol. 2020;49:1879-84.

Abutaki FH, Alfaraj D, Alshahrani A, Elsharkawy T. Warfarin-Induced Calciphylaxis in a COVID-19 Patient. Cureus. 2020;12:e12249.

Xin C, Hu D, Li M. Late onset warfarin-induced skin necrosis. G Ital Dermatol Venereol. 2019;154:205-8.

Gheisari M, Baghani M, Ganji R, Forouzanfar MM. Huge carbuncle leading to necrotizing fasciitis in the COVID-19 pandemic era. Clin Case Rep. 2021;9:1583-6.

Elashry MM, Alagha M, Salama M. Pre and retroperitoneal necrotizing fasciitis after COVID-19 infection: A case report. Radiol Case Rep. 2021;16:2949-52.