Dear Label_Name,

Greetings! I hope you are well.

I am writing on behalf of an international publishing house, Science and Education Publishing, USA (http://www.sciepub.com).

Science and Education Publishing (SciEP) is a multidisciplinary open access publisher of Journals covering the fields of Science, Technology and Medicine. All SciEP publications are subject to high-quality peer review, editorial and production processes and are freely available online.

Welcome to the April, 2013 edition of SciEP newsletter, providing monthly summaries of articles on science & education related topics of interest to scientist and professionals. The mission of our journals is to provide an open access forum for publishing new findings on issues pertinent to scientific and academic field. We also invite you to submit original research papers, review articles, short reports, or case studies are considered for publication in our Multidisciplinary Journals.

American Journal of Public Health Research
DOI: 10.12691/ajphr-1-1-3

The Implementation of a Tele-Homecare System with Service Oriented Architecture and HL7 Message Transmission Standard
Ching-Sung Wang

American Journal of Medical and Biological Research
DOI: 10.12691/ajmbr-1-1-2

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico
Lelevich Sergey Vladimirovich, Khrustalev Vladislav Victorovich, Barkovsky Eugene Victorovich, Shedogubova Tatyana Aleksandrovna

American Journal of Medical Sciences and Medicine
DOI: 10.12691/ajmsm-1-1-1

Clinical and Histological Features in Wegener Granulomatosis
Li Cavoli Gioacchino, Passantino Rita, Bono Luisa, Tortorici Calogera, Ferrantelli Angelo, Giammarresi Carlo, Rotolo Ugo

American Journal of Infectious Diseases and Microbiology
DOI: 10.12691/ajidm-1-1-2

The Curse of Lymphatic Filariasis: Would the Continual Use of Diethylcarbamazine Eliminate this Scourge in Papua New Guinea?
Anne Lanham, Lillian Mwanri

We have released issues of some journals on February 2013.
American Journal of Public Health Research
American Journal of Medical Sciences and Medicine
American Journal of Medical and Biological Research
American Journal of Pharmacological Sciences
American Journal of Clinical Medicine Research
American Journal of Nursing Research
American Journal of Cancer Prevention
American Journal of Medicine Studies
American Journal of Infectious Diseases and Microbiology
American Journal of Cardiovascular Disease Research
American Journal of Biomedical Research
American Journal of Mechanical Engineering
American Journal of Microbiological Research
Journal of Preventive Medicine
American Journal of Food and Nutrition
American Journal of Hypertension Research
American Journal of Sports Science and Medicine
Journal of Cancer Research and Treatment
American Journal of Zoological Research
Journal of Biomedical Engineering and Technology
American Journal of Microbiological Research
Biomedical Science and Engineering

We are pleased to announce that submissions are now being accepted for peer review for all the journals across all our subject areas in SciEP.

Please submit your manuscript via our online submission system:
http://www.sciepub.com/author/signin

To unsubscribe from our mailing list, please click on the following link: unsubscribe

I am looking forward to hearing from you.

Kind regards,

David Rain
Email:join@sciepub.com
Science and Education Publishing (http://www.sciepub.com)

Cutaneous Manifestations in COVID-19 “Long Haulers”: Is This A Part of the Multisystem Inflammatory Syndrome?

Cameron Y. S. Lee

Private Practice, Oral, Maxillofacial and Reconstructive Surgery, Aiea, Hawaii, 96701

Abstract: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multisystem inflammatory syndrome that affects many different organs of the body. Extrapulmonary cutaneous manifestations are now being reported in greater frequency as occurring before or after onset of clinical symptoms. To the authors knowledge, there are few, if any published study that has documented the persistent cutaneous manifestations in patients who have recovered from COVID-19. In this report, we describe some of the cutaneous manifestations in patients known as COVID-19 “long haulers”.

Keywords: COVID-19, long haulers, persistent symptoms, Cutaneous manifestations

Received April 21, 2021; Revised May 27, 2021; Accepted June 06, 2021

Citation: Cameron Y. S. Lee, Cutaneous Manifestations in COVID-19 “Long Haulers”: Is This A Part of the Multisystem Inflammatory Syndrome?. American Journal of Infectious Diseases and Microbiology, 9 (2). 48-50. January 2021. doi:10.12691/ajidm-9-2-3

1. Introduction

“Long Haulers” has been coined to describe patients that continue to experience persistent symptoms weeks to months after they have recovered from Covid-19. [1] The prevalence of persistent symptoms remains unclear. [2] It is estimated that even after 12 weeks, patients continue to experience symptoms related to the coronavirus. [3,4] The most reported post-COVID-19 symptoms include dyspnea and fatigue. Extrapulmonary symptoms reported include myalgia, arthralgia, chest pain, cognitive deficits, neurological symptoms, fever, diarrhea, and skin rashes. [5,6,7,8,9] Reports of decreased oxygen saturations as low as 88% have also been reported. [10]

2. Cutaneous Manifestations

Whether cutaneous manifestations are part of the clinical spectrum of COVID-19 remains unclear as they are observed in other viral infections. But, as the number of COVID-19 cases increase reporting cutaneous symptoms, our understanding will continue in terms of how the coronavirus affects the skin. Six morphologic cutaneous findings have been described: urticarial rash, confluent erythematous/maculo-papular/morbilliform rash, papulovesicular eruptions, purpuric vasculitic rash; livedo reticularis and chilblain-like acral rash. [11,12]

The incidence of cutaneous manifestations in patients infected with the coronavirus is estimated between 0.2 to 20%. [13,14] Although most skin lesions occurred simultaneously or after other COVID-19 symptoms, reports of skin lesions occurring before other COVID-19 symptoms have been reported. [9,15,16]

Persistent dermatological manifestations have been reported with increasing frequency in patients that have recovered from COVID-19. Persistent cutaneous manifestations in long haulers can be defined as lasting more than 60 days. [5] Morbilliform, urticarial and macular-erythema type lesions were frequently observed with laboratory confirmed polymerase chain reaction (PCR) testing. Further, polymorphic skin lesions have been reported. [9,17,18]

As COVID-19 is a multisystem disorder that can affect many different organ systems, we hypothesize that the cutaneous manifestations are part of the newly identified multisystem inflammatory syndrome. Although the pathogenesis for development of rashes in patients infected with the coronavirus is yet to be elucidated, one hypothesis is a direct effect of the virus on the skin due to high concentrations of lymphocytes, lymphohistiocytic infiltrates and papillary dermal edema. [19,20] A second theory is activation of the complement system resulting in a diffuse microvascular vasculitis. [21] Vascular injury leads to increased circulating angiotensin 2 levels that result in vasoconstriction, thrombosis and endothelial dysfunction. [22]

In one of our patients, edematous pruritic plaques occur at various times on the palmar surface of the hands and fingers (Figure 5). To the authors knowledge, there is only one case report documenting cutaneous manifestations on the surface of the hand. [23] However, in a study by Estebanez et al [24] they reported confluent erythematous plaques on the heels of their patient. Such clinical findings of extremity involvement may be due to increased bradykinin production that results in increased vasodilation and vascular permeability. Increased bradykinin levels may result in the observed edematous urticarial plaques due to its host exuberant inflammatory response. [25,26,27]

Figure 1. Confluent erythematous maculopapular rash on right lower extremity

Figure 2. Erythematous pruritic maculopapular rash on right lower extremity. Note the cutaneous wheals

Figure 3. Pseudovesicular rash on right preauricular region of face

Polymorphic cutaneous lesions (Figure 4A and 4B) in the same host are being reported in greater frequency and may be due to infection from multiple variants because of viral mutation. [11,28] However, such polymorphous manifestations could also represent the entire effect of the coronavirus on the immune system. One of our patients experienced three different skin variants-urticarial, maculopapular and pseudovesicular over a period of 120 days (Figure 1, Figure 2, and Figure 3). Angioedema of the lips have also been reported (Figure 6). Angiotensin-converting enzyme 2 (ACE2) is the primary functional host receptor for SARS-CoV-2 and plays a key role in the pathogenesis of Covid-19 infections. It is expressed in many different organs, including the mucosa of the oral and nasal cavities. [29] ACE2 cleaves bradykinin and down-regulation leads to increased bradykinin production and angioedema.

Figure 4A. Polymorphic rash. Scarlatiniform eruptions on the upper half of the trunk and the confluent erythematous rash on the lower half of the patient

Figure 4B. Close up view of patient in Figure 4A. Note the scarlatiniform eruptions

Figure 5. Palmar erythema. Note the erythematous edematous plaques on the palm and fingers

Figure 6. Angioedema of lips

3. Conclusion

Such post-viral cutaneous manifestations are present with other COVID-19 symptoms and may be correlated with immune or inflammatory mechanisms in the pathogenesis of coronavirus infection. The presence of cutaneous manifestations after COVID-19 recovery needs to more fully understood and may suggest that viral infection may not be completely resolved and is part of the multisystem inflammatory syndrome.

References

[1]   | Rubin R. As their number grow, Covid-19. “Long Haulers” stump experts. JAMA. 2020; 324(14): 1381-1383.
[2]   | Alwan NA. Surveillance is underestimating the burden of the Covid-19 pandemic. Lancet. 2020; 396 (10252):e24.
[3]   | Tenforde M, Kim S, Lindsell C, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network- United States, March-June 2020. MMWR Morb Mortal Wkly Rep. 2020, ePub. 24 July 2020.
[4]   | Ladds E, Rushforth A, Wieringa S, et al. Persistent symptoms after Covid-19: qualitative study of 114 “long Covid” patients and draft quality principles for services. BMC Health Services Research. 2020; 20: 1144.
[5]   | Carfi A, Bernabei R, Landi F. Persistent symptoms in patients after acute Covid-19. JAMA. 2020; 324(6): 603-605.
[6]   | Greenhalgh, T, Knight M, Burton M, et al. Management of post-acute covid-19 in primary care. BMJ. 2020; 370m3026.
[7]   | Arnold DT, Hamilton FW, Milne A, et al. Patient outcomes after hospitalization with COVID-19 and implications for follow-up; results from a prospective UK cohort. medRxiv. 2020.
[8]   | Goertz YMJ, Van Herck M, Delbressine JM, et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post COVID-19 syndrome? ERJ Open Res. 2020; Oct 26; 6(4): 00542-2020.
[9]   | Freeman EE, McMahon DE, Lipoff JB, et al. The spectrum of COVID-19-associated dermatologic manifestations: An international registry of 716 patients from 31 countries. J Am Acad Dermatol. 83: 1118-1129. 2020.
[10]   | Dhont S, Derom E, Van Braeckel E, et al. The pathophysiology of ‘happy’ hypoxemia in Covid-19. Respir Res. 21, 198 (2020).
[11]   | Galvan Casas C, Catala A, Carretero Hernandez 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.
[12]   | Marzano AV, Cassano N, Genovese G, et al. Cutaneous manifestations in patients with COVID-19: a preliminary review of an emerging issue. Br J Dermatol. 2020; 183: 431-442.
[13]   | Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020.
[14]   | De Giorgi V, Recalcati S, Jia Z, et al. Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): a prospective study from China and Italy. J Am Acad Dermatol. 83: 674-675. 2020.
[15]   | Lee CYS. Cutaneous rash: A clinical manifestation prior to respiratory symptoms of Covid-19 infection. J Fam Med Dis Prev. 7: 137. 2021.
[16]   | Daneshgaran G, Dubin DP, Gould DJ. Cutaneous manifestations of COVID-19: An evidenced based review. Am J Clin Dermatol. 2020.
[17]   | Fernandez-Nieto D, Ortega-Quijano D, Jimenez-Cauhe J, et al. Clinical and histological characterization of vesicular COVID-19 rashes: a prospective study in a tertiary care hospital. Clin Exp Dermatol. 2020.
[18]   | Tan SW, Tam YC, Oh CC. Skin manifestations of COVID-19: A worldwide review. JAAD Int. 2021. 2: 119-133.
[19]   | Sanchez A, Sohier P, Benghane S, et al. Digitate papulosquamous eruption associated with severe acute respiratory syndrome Coronavirus-2 infection. JAMA Dermatol. April 30, 2020.
[20]   | Gianotti R, Veraldi S, Recalcati S, et al. Cutaneous clinico-pathological findings in three COVID-19-positive patients observed in the metropolitan area of Milan, Italy. Acta Derm Venereol. 2020. [published online ahead of print, 2020 Apr 21].
[21]   | 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. [S1931-5244(20)30070- 0.
[22]   | Vaduganathan M, Vardeny O, Michel T, et al. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020; 382: 1653-1659.
[23]   | Kroumpouzos G. Cutaneous manifestations of COVID-19: An unusual presentation with edematous plaques and pruritic, erythematous papules, and comment on the role of bradykinin storm and its therapeutic implications. Dermatol Ther. 2021, e14753.
[24]   | Estebanez A, Perez-Santiago L, Silva E, et al. Cutaneous manifestations in COVID-19: new contribution. J Eur Acad Dermatol Venereol. 2020; 34: e250-e251.
[25]   | Liang J, He Y, Ji W. Bradykinin-evoked scratching responses in complete Freund’s adjuvant-inflamed skin through activation of B1 receptor (Maywood). 2012; 37: 318-326.
[26]   | Ghahestani SM, Mahmoudi J, Hajebrahimi S, et al. Bradykinin as a probable aspect in SARS-CoV-2 scenarios: is bradykinin sneaking out of our sight? Iran J Allergy Asthma Immunol. 2020; 19(S1): 13-17.
[27]   | Kaushik A, Parsad, D, Kumaran MS. Urticaria in the times of COVID-19. Dermatol Ther. 2020; e13817.
[28]   | Matar S, Oules B, Sohier P, et al. Cutaneous manifestations in SARS-CoV-2 infections (COVID-19): a French experience and a systematic review of the literature. J Eur Acad Dermatol Venereol. 2020. Jun: jdv. 16775.
[29]   | Hamming I, Timens W, Bulthius MLC, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203: 631-637.