Microvascular Skin Manifestations Caused by COVID-19

Abstract

Hypercoagulability and vascular injury, which characterize morbidity in COVID-19 disease, are frequently observed in the skin. Several pathomechanisms, such as inflammation caused by angiotensin-converting enzyme 2–mediated uptake into endothelial cells or SARS-CoV-2-initiated host immune responses, contribute to microthrombus formation and the appearance of vascular skin lesions. Besides pathophysiologic mechanisms observed in the skin, this review describes the clinical appearance of cutaneous vascular lesions and their association with COVID-19 disease, including acro-ischemia, reticular lesions, and cutaneous small vessel vasculitis. Clinicians need to be aware that skin manifestations may be the only symptom in SARS-CoV-2 infection, and that inflammatory and thrombotic SARS-CoV-2-driven processes observed in multiple organs and tissues appear identically in the skin as well.

Keywords

COVID-19 - skin manifestation - microvascular

Publikationsverlauf

Eingereicht: 31. März 2021

Angenommen: 09. August 2021

Artikel online veröffentlicht:
25. Oktober 2021

• References

• 1 Suhail S, Zajac J, Fossum C. et al. Role of oxidative stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) infection: a review. Protein J 2020; 39 (06) 644-656
• 2 Accessed September 26, 2021 at: https://covid19.who.int
• 3 Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health 2020; 25 (03) 278-280
• 4 Conforti C, Dianzani C, Agozzino M. et al. Cutaneous manifestations in confirmed COVID-19 patients: a systematic review. Biology (Basel) 2020; 9 (12) 449
• 5 Unterluggauer L, Pospischil I, Krall C. et al. Cutaneous manifestations of SARS-CoV-2 - a two-center, prospective, case-controlled study. J Am Acad Dermatol 2021; :S0190-9622(21)00619-8
• 6 Ou X, Liu Y, Lei X. et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020; 11 (01) 1620
• 7 Satarker S, Nampoothiri M. Structural proteins in severe acute respiratory syndrome coronavirus-2. Arch Med Res 2020; 51 (06) 482-491
• 8 Thomas C. Reply to: “A dermatologic manifestation of COVID-19: transient livedo reticularis”. J Am Acad Dermatol 2020; 83 (02) e155-e156
• 9 Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 2020; 9 (01) 45
• 10 Magro C, Mulvey JJ, Berlin D. 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
• 11 Santos RA. Angiotensin-(1-7). Hypertension 2014; 63 (06) 1138-1147
• 12 Rotman JA, Dean KE, Magro C, Nuovo G, Bartolotta RJ. Concomitant calciphylaxis and COVID-19 associated thrombotic retiform purpura. Skeletal Radiol 2020; 49 (11) 1879-1884
• 13 Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203 (02) 631-637
• 14 Magro CM, Mulvey JJ, Laurence J. et al. Docked severe acute respiratory syndrome coronavirus 2 proteins within the cutaneous and subcutaneous microvasculature and their role in the pathogenesis of severe coronavirus disease 2019. Hum Pathol 2020; 106: 106-116
• 15 Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: their roles in pathogenesis. J Microbiol Immunol Infect 2020; :S1684-1182(20)30082-7
• 16 Shang J, Wan Y, Luo C. et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A 2020; 117 (21) 11727-11734
• 17 Khadke S, Ahmed N, Ahmed N. et al. Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents. Virol J 2020; 17 (01) 154
• 18 Colantuoni A, Martini R, Caprari P. et al. COVID-19 sepsis and microcirculation dysfunction. Front Physiol 2020; 11: 747
• 19 Gencer S, Lacy M, Atzler D, van der Vorst EPC, Döring Y, Weber C. Immunoinflammatory, thrombohaemostatic, and cardiovascular mechanisms in COVID-19. Thromb Haemost 2020; 120 (12) 1629-1641
• 20 Ferrario CM, Jessup J, Chappell MC. et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005; 111 (20) 2605-2610
• 21 Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. [published correction appears in Nat Rev Immunol. 2020 Jun 4] Nat Rev Immunol 2020; 20 (07) 389-391
• 22 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395 (10234): 1417-1418
• 23 Mawhirt SL, Frankel D, Diaz AM. Cutaneous manifestations in adult patients with COVID-19 and dermatologic conditions related to the COVID-19 pandemic in health care workers. Curr Allergy Asthma Rep 2020; 20 (12) 75
• 24 Magro CM, Mulvey J, Kubiak J. et al. Severe COVID-19: a multifaceted viral vasculopathy syndrome. Ann Diagn Pathol 2021; 50: 151645
• 25 Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol 2020; 11: 1446
• 26 Conti P, Caraffa A, Tetè G. et al. Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19. J Biol Regul Homeost Agents 2020; 34 (05) 1629-1632
• 27 West NR. Coordination of immune-stroma crosstalk by IL-6 family cytokines. Front Immunol 2019; 10: 1093
• 28 Libby P, Lüscher T. COVID-19 is, in the end, an endothelial disease. Eur Heart J 2020; 41 (32) 3038-3044
• 29 Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemost 2020; 18 (07) 1559-1561
• 30 Kaya G, Kaya A, Saurat JH. Clinical and histopathological features and potential pathological mechanisms of skin lesions in COVID-19: review of the literature. Dermatopathology (Basel) 2020; 7 (01) 3-16
• 31 Park A, Iwasaki A. Type I and Type III interferons - induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe 2020; 27 (06) 870-878
• 32 Lee JS, Shin EC. The type I interferon response in COVID-19: implications for treatment. Nat Rev Immunol 2020; 20 (10) 585-586
• 33 Hadjadj J, Yatim N, Barnabei L. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 2020; 369 (6504): 718-724
• 34 Chua RL, Lukassen S, Trump S. et al. COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nat Biotechnol 2020; 38 (08) 970-979
• 35 Cameron MJ, Ran L, Xu L. et al; Canadian SARS Research Network. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol 2007; 81 (16) 8692-8706
• 36 Stoermer KA, Morrison TE. Complement and viral pathogenesis. Virology 2011; 411 (02) 362-373
• 37 Ram Kumar Pandian S, Arunachalam S, Deepak V, Kunjiappan S, Sundar K. Targeting complement cascade: an alternative strategy for COVID-19. . 3 Biotech 2020; 10 (11) 479
• 38 Campbell CM, Kahwash R. Will complement inhibition be the new target in treating COVID-19 related systemic thrombosis?. Circulation 2020; 141 (22) 1739-1741
• 39 Chua JS, Baelde HJ, Zandbergen M. et al. Complement factor C4d is a common denominator in thrombotic microangiopathy. J Am Soc Nephrol 2015; 26 (09) 2239-2247
• 40 Xiao M, Zhang Y, Zhang S. et al. Antiphospholipid antibodies in critically ill patients with COVID-19. Arthritis Rheumatol 2020; 72 (12) 1998-2004
• 41 Zuo Y, Estes SK, Ali RA. et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med 2020; 12 (570) eabd3876
• 42 Showers CR, Nuovo GJ, Lakhanpal A. et al. A COVID-19 patient with complement-mediated coagulopathy and severe thrombosis. Pathobiology 2021; 88 (01) 28-36
• 43 Zhang Y, Xiao M, Zhang S. et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020; 382 (17) e38
• 44 Bowles L, Platton S, Yartey N. et al. Lupus anticoagulant and abnormal coagulation tests in patients with Covid-19. N Engl J Med 2020; 383 (03) 288-290
• 45 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513
• 46 Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease 2019. Crit Care Med 2020; 48 (09) 1358-1364
• 47 Zhang Y, Zeng X, Jiao Y. et al. Mechanisms involved in the development of thrombocytopenia in patients with COVID-19. Thromb Res 2020; 193: 110-115
• 48 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
• 49 Zhang L, Yan X, Fan Q. et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020; 18 (06) 1324-1329
• 50 Zhang X, Yang X, Jiao H, Liu X. Coagulopathy in patients with COVID-19: a systematic review and meta-analysis. Aging (Albany NY) 2020; 12 (24) 24535-24551
• 51 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
• 52 Carlson JA. The histological assessment of cutaneous vasculitis. Histopathology 2010; 56 (01) 3-23
• 53 Camprodon Gómez M, González-Cruz C, Ferrer B, Barberá MJ. Leucocytoclastic vasculitis in a patient with COVID-19 with positive SARS-CoV-2 PCR in skin biopsy. BMJ Case Rep 2020; 13 (10) e238039
• 54 Jennette JC, Falk RJ, Bacon PA. et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65 (01) 1-11
• 55 Tan SW, Tam YC, Oh CC. Skin manifestations of COVID-19: a worldwide review. JAAD Int 2021; 2: 119-133
• 56 Alonso MN, Mata-Forte T, García-León N. et al. Incidence, characteristics, laboratory findings and outcomes in acro-ischemia in COVID-19 patients. Vasc Health Risk Manag 2020; 16: 467-478
• 57 Marzano AV, Cassano N, Genovese G, Moltrasio C, Vena GA. Cutaneous manifestations in patients with COVID-19: a preliminary review of an emerging issue. Br J Dermatol 2020; 183 (03) 431-442
• 58 Andina D, Belloni-Fortina A, Bodemer C. et al. Skin manifestations of COVID-19 in children: Part 2. Clin Exp Dermatol 2021; 46 (03) 451-461
• 59 Almeida G, Arruda S, Marques E, Michalany N, Sadick N. Presentation and management of cutaneous manifestations of COVID-19. J Drugs Dermatol 2021; 20 (01) 76-83
• 60 Fernandez-Nieto D, Jimenez-Cauhe J, Suarez-Valle A. et al. Characterization of acute acral skin lesions in nonhospitalized patients: a case series of 132 patients during the COVID-19 outbreak. J Am Acad Dermatol 2020; 83 (01) e61-e63
• 61 Freeman EE, McMahon DE, Lipoff JB. et al; American Academy of Dermatology Ad Hoc Task Force on COVID-19. Pernio-like skin lesions associated with COVID-19: a case series of 318 patients from 8 countries. J Am Acad Dermatol 2020; 83 (02) 486-492
• 62 Galván Casas C, Català A, Carretero Hernández G. et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol 2020; 183 (01) 71-77
• 63 Kolivras A, Dehavay F, Delplace D. et al. Coronavirus (COVID-19) infection-induced chilblains: a case report with histopathologic findings. JAAD Case Rep 2020; 6 (06) 489-492
• 64 Novak N, Peng W, Naegeli MC. et al. SARS-CoV-2, COVID-19, skin and immunology - What do we know so far?. Allergy 2021; 76 (03) 698-713
• 65 Rosés-Gibert P, Gimeno Castillo J, Saenz Aguirre A. et al. Acral lesions in a pediatric population during the COVID-19 pandemic: a case series of 36 patients from a single hospital in Spain. World J Pediatr 2020; 16 (06) 629-632
• 66 Piccolo V, Neri I, Filippeschi C. et al. Chilblain-like lesions during COVID-19 epidemic: a preliminary study on 63 patients. J Eur Acad Dermatol Venereol 2020; 34 (07) e291-e293
• 67 Cordoro KM, Reynolds SD, Wattier R, McCalmont TH. Clustered cases of acral perniosis: clinical features, histopathology, and relationship to COVID-19. Pediatr Dermatol 2020; 37 (03) 419-423
• 68 Colmenero I, Santonja C, Alonso-Riaño M. et al. SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases. Br J Dermatol 2020; 183 (04) 729-737
• 69 Gambichler T, Reuther J, Stücker M. et al. SARS-CoV-2 spike protein is present in both endothelial and eccrine cells of a chilblain-like skin lesion. J Eur Acad Dermatol Venereol 2021; 35 (03) e187-e189
• 70 Magro CM, Mulvey JJ, Laurence J. et al. The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series. Br J Dermatol 2021; 184 (01) 141-150
• 71 Roca-Ginés J, Torres-Navarro I, Sánchez-Arráez J. et al. Assessment of acute acral lesions in a case series of children and adolescents during the COVID-19 pandemic. JAMA Dermatol 2020; 156 (09) 992-997
• 72 Damsky W, Peterson D, King B. When interferon tiptoes through COVID-19: Pernio-like lesions and their prognostic implications during SARS-CoV-2 infection. J Am Acad Dermatol 2020; 83 (03) e269-e270
• 73 Novara E, Molinaro E, Benedetti I, Bonometti R, Lauritano EC, Boverio R. Severe acute dried gangrene in COVID-19 infection: a case report. Eur Rev Med Pharmacol Sci 2020; 24 (10) 5769-5771
• 74 Manalo IF, Smith MK, Cheeley J, Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis. J Am Acad Dermatol 2020; 83 (02) 700
• 75 Ramachandran R, Vasudevan Pillai A, Raja S, Sailesh S. Axillary artery thrombosis resulting in upper limb amputation as a COVID-19 sequela. BMJ Case Rep 2021; 14 (01) e240981
• 76 Galanis N, Stavraka C, Agathangelidis F, Petsatodis E, Giankoulof C, Givissis P. Coagulopathy in COVID-19 infection: a case of acute upper limb ischemia. J Surg Case Rep 2020(6):rjaa204
• 77 Bellosta R, Luzzani L, Natalini G. et al. Acute limb ischemia in patients with COVID-19 pneumonia. J Vasc Surg 2020; 72 (06) 1864-1872
• 78 Bikdeli B, Madhavan MV, Jimenez D. et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) 2950-2973
• 79 Bamgboje A, Hong J, Mushiyev S, Pekler G. A 61-year-old man with SARS-CoV-2 infection and venous thrombosis presenting with painful swelling and gangrene of the lower limb consistent with phlegmasia cerulea dolens. Am J Case Rep 2020; 21: e928342
• 80 Adekiigbe R, Ugbode F, Seoparson S, Katriyar N, Fetterman A. A 47-year-old Hispanic man who developed cutaneous vasculitic lesions and gangrene of the toes following admission to hospital with COVID-19 pneumonia. Am J Case Rep 2020; 21: e926886
• 81 Visveswaran GK, Morparia K, Narang S. et al. SARS-CoV-2 infection and thrombosis: phlegmasia cerulea dolens presenting with venous gangrene in a child. J Pediatr 2020; 226: 281-284
• 82 Balestri R, Termine S, Rech G, Girardelli CR. Late onset of acral necrosis after SARS-CoV-2 infection resolution. J Eur Acad Dermatol Venereol 2020; 34 (09) e448-e449
• 83 Sajjan VV, Lunge S, Swamy MB, Pandit AM. Livedo reticularis: a review of the literature. Indian Dermatol Online J 2015; 6 (05) 315-321
• 84 Sachdeva M, Gianotti R, Shah M. et al. Cutaneous manifestations of COVID-19: report of three cases and a review of literature. J Dermatol Sci 2020; 98 (02) 75-81
• 85 Jindal R, Chauhan P. Cutaneous manifestations of coronavirus disease 2019 in 458 confirmed cases: a systematic review. J Family Med Prim Care 2020; 9 (09) 4563-4569
• 86 Giavedoni P, Podlipnik S, Pericàs JM. et al. Skin manifestations in COVID-19: prevalence and relationship with disease severity. J Clin Med 2020; 9 (10) 3261
• 87 Genovese G, Moltrasio C, Berti E, Marzano AV. Skin manifestations associated with COVID-19: current knowledge and future perspectives. Dermatology 2021; 237 (01) 1-12
• 88 Wysong A, Venkatesan P. An approach to the patient with retiform purpura. Dermatol Ther (Heidelb) 2011; 24 (02) 151-172
• 89 Verheyden M, Grosber M, Gutermuth J, Velkeniers B. Relapsing symmetric livedo reticularis in a patient with COVID-19 infection. J Eur Acad Dermatol Venereol 2020; 34 (11) e684-e686
• 90 Cappel JA, Wetter DA. Clinical characteristics, etiologic associations, laboratory findings, treatment, and proposal of diagnostic criteria of pernio (chilblains) in a series of 104 patients at Mayo Clinic, 2000 to 2011. Mayo Clin Proc 2014; 89 (02) 207-215
• 91 Khalil S, Hinds BR, Manalo IF, Vargas IM, Mallela S, Jacobs R. Livedo reticularis as a presenting sign of severe acute respiratory syndrome coronavirus 2 infection. JAAD Case Rep 2020; 6 (09) 871-874
• 92 Becker RC. COVID-19-associated vasculitis and vasculopathy. J Thromb Thrombolysis 2020; 50 (03) 499-511
• 93 Occidental M, Flaifel A, Lin LH, Guzzetta M, Thomas K, Jour G. Investigating the spectrum of dermatologic manifestations in COVID-19 infection in severely ill patients: a series of four cases. J Cutan Pathol 2021; 48 (01) 110-115
• 94 García-Gil MF, García García M, Monte Serrano J, Prieto-Torres L, Ara-Martín M. Acral purpuric lesions (erythema multiforme type) associated with thrombotic vasculopathy in a child during the COVID-19 pandemic. J Eur Acad Dermatol Venereol 2020; 34 (09) e443-e445
• 95 Bosch-Amate X, Giavedoni P, Podlipnik S. et al. Retiform purpura as a dermatological sign of coronavirus disease 2019 (COVID-19) coagulopathy. J Eur Acad Dermatol Venereol 2020; 34 (10) e548-e549
• 96 Zhang Y, Cao W, Xiao M. et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia [in Chinese]. Zhonghua Xue Ye Xue Za Zhi 2020; 41 (0): E006
• 97 Tehrani HA, Darnahal M, Vaezi M, Haghighi S. COVID-19 associated thrombotic thrombocytopenic purpura (TTP): a case series and mini-review. Int Immunopharmacol 2021; 93: 107397
• 98 Mayor-Ibarguren A, Feito-Rodriguez M, Quintana Castanedo L, Ruiz-Bravo E, Montero Vega D, Herranz-Pinto P. Cutaneous small vessel vasculitis secondary to COVID-19 infection: a case report. J Eur Acad Dermatol Venereol 2020; 34 (10) e541-e542
• 99 Gouveia PADC, Cipriano IC, de Melo MAZ. et al. Exuberant bullous vasculitis associated with SARS-CoV-2 infection. IDCases 2021; 23: e01047
• 100 Jamiolkowski D, Mühleisen B, Müller S, Navarini AA, Tzankov A, Roider E. SARS-CoV-2 PCR testing of skin for COVID-19 diagnostics: a case report. Lancet 2020; 396 (10251): 598-599
• 101 AlGhoozi DA, AlKhayyat HM. A child with Henoch-Schonlein purpura secondary to a COVID-19 infection. BMJ Case Rep 2021; 14 (01) e239910
• 102 Sandhu S, Chand S, Bhatnagar A. et al. Possible association between IgA vasculitis and COVID-19. Dermatol Ther (Heidelb) 2021; 34 (01) e14551
• 103 Suso AS, Mon C, Oñate Alonso I. et al. IgA vasculitis with nephritis (Henoch-Schönlein purpura) in a COVID-19 patient. Kidney Int Rep 2020; 5 (11) 2074-2078
• 104 Allez M, Denis B, Bouaziz JD. et al. COVID-19-related IgA vasculitis. Arthritis Rheumatol 2020; 72 (11) 1952-1953
• 105 Nasiri S, Dadkhahfar S, Abasifar H, Mortazavi N, Gheisari M. Urticarial vasculitis in a COVID-19 recovered patient. Int J Dermatol 2020; 59 (10) 1285-1286
• 106 de Perosanz-Lobo D, Fernandez-Nieto D, Burgos-Blasco P. et al. Urticarial vasculitis in COVID-19 infection: a vasculopathy-related symptom?. J Eur Acad Dermatol Venereol 2020; 34 (10) e566-e568
• 107 Jindal AK, Pilania RK, Prithvi A, Guleria S, Singh S. Kawasaki disease: characteristics, diagnosis, and unusual presentations. Expert Rev Clin Immunol 2019; 15 (10) 1089-1104
• 108 Ebina-Shibuya R, Namkoong H, Shibuya Y, Horita N. Multisystem inflammatory syndrome in children (MIS-C) with COVID-19: insights from simultaneous familial Kawasaki disease cases. Int J Infect Dis 2020; 97: 371-373
• 109 Burgi Vieira C, Ferreira AT, Botelho Cardoso F, Pelicano Paulos J, Germano N. Kawasaki-like syndrome as an emerging complication of SARS-CoV-2 infection in young adults. Eur J Case Rep Intern Med 2020; 7 (10) 001886
• 110 Verdoni L, Mazza A, Gervasoni A. 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 (10239): 1771-1778
• 111 Sokolovsky S, Soni P, Hoffman T, Kahn P, Scheers-Masters J. COVID-19 associated Kawasaki-like multisystem inflammatory disease in an adult. Am J Emerg Med 2021; 39: 253.e1-253.e2
• 112 Shaigany S, Gnirke M, Guttmann A. et al. An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. Lancet 2020; 396 (10246): e8-e10
• 113 Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int 2021; 41 (01) 19-32
• 114 CDC Health Alert Network. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019. Accessed September 26, 2021 at: https://emergency.cdc.gov/han/2020/han00432.asp
• 115 Wen W, Su W, Tang H. et al. Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing [published correction appears in Cell Discov. 2020 Jun 20;6:41]. Cell Discov 2020; 6: 31 . Published 2020 May 4.