Awareness of COVID-19 Skin and Mucosal Manifestations

As wound clinicians have discovered over the past year, COVID-19 can target various organs such as the skin and mucosa, and many of the resulting manifestations are only beginning to be understood. This author takes a look at the current findings on skin and mucosa manifestations, how COVID manifestations can mimic other conditions, and what you need to be aware of to assist in the differential diagnosis.

An awareness of COVID-19 skin manifestations caused by the SARS-CoV-2 virus is needed across the continuum of care settings.

In November 2020, a 25-year-old man went to the emergency center at his local hospital with a rash from his chest to his feet. He asked for a COVID-19 test because he’d heard that this virus can cause skin rashes. The emergency room physician explained to this young man that “there’s no such thing as COVID skin manifestations.” The young man left the hospital with instructions to take Benadryl, apply topical cortisone cream to his skin if it itched, and that he could go back to work.

The point related to this story is the provider was not aware of COVID-19 skin manifestations. This story is playing out in many care settings where neither the health care workers nor the general public are aware of and alert to skin and mucosal manifestations from COVID-19 disease.  

This article emphasizes awareness that these skin manifestations may be related to COVID-19. This disease is creating skin issues that we are just beginning to understand, at least from the perspective of the damage seen through autopsies and scanning electron microscope technology, and differential diagnosis by providers who have an awareness of these skin manifestations related to COVID-19. However, the definitive “why” of these dermatologic changes is still under investigation.    

The Cytokine Storm

We’ve all heard of or read about the cytokine storm associated with COVID-19. Cytokines are part of our immune system and have an effect on other cells. For instance, in wound healing cytokines are a normal component of the inflammatory response to skin and tissue damage and are necessary to facilitate wound closure.^1,2

However, with COVID-19 the immune activity becomes overactive, creating a situation in which the immune cells are not able to stop themselves. The overactive cytokines spread beyond the infected body parts and start attacking healthy tissues.³

This virus damages multiple organs, systems and tissues of the body and has been assigned to the ranks of other “great imitators”—diseases that can mimic many other conditions (Figure 1).^4–6  Recently, the Centers for Disease Control and Prevention (CDC) included dermatologic manifestations as a symptom of COVID-19.⁶ In addition, there are several studies that have documented COVID-19 in patients who are asymptomatic or pre-symptomatic for this disease.^7–10 Pre-symptomatic skin issues have been documented 2–5 days before the more widely recognized symptoms of COVID-19 appeared.^7,11

One of the complications of the cytokine storm appears to be blood clots that develop throughout the body. This inflammatory response and overreaction of the cytokines creates blood clots, which can cause decreased vascularity to the organs. This causes a person to go into shock, risking permanent organ damage and/or death due to multiorgan failure.³

As we all know the skin is the largest organ of the body with abundant blood flow to the skin’s surface. This disease, COVID-19, is disrupting skin vascularity.

As mentioned it appears this cytokine storm, creating skin and organ coagulopathy issues, is responsible for some of the skin changes, such as COVID digits (toes and fingers) and skin necrosis—with viral exanthema, a term for general rashes, which occurs with other types of viruses—being another cause of dermatologic changes. Both conditions, coagulopathy and viral exanthema, are seen with people who have COVID-19 (Figure 2).^11–13

Listed below are the main symptoms of COVID-19, which most of us recognize as we’ve been watching health care–related news, seeing patients, residents, friends—and in many cases ourselves or our family members—become infected with this virus.

These symptoms include fever, which can be low or high grade, or no fever; coughing; breathing issues; fatigue; and chills. Headache, sore throat, loss of smell or taste, nausea, and diarrhea are other frequent symptoms mentioned in the literature.⁶

Consider that skin symptoms may be silent symptoms of COVID-19 and should be considered when found on the body as potential signs of this disease. These dermatoses should be assessed and differentiated from other dermatological symptoms as long as COVID-19 disease exists.  

What the Research Says About COVID-19 Skin and Mucosa Manifestations

We now have multiple observational studies that are helping to create an awareness of the COVID-19 skin and mucosa manifestations. In a community-based study from the United Kingdom, 8.8% of the study group—336,847 UK users of the COVID Symptom app who had a positive SARS-CoV-2 viral swab or recognized symptoms of the disease—reported skin eruptions.¹⁴ Both acral manifestations and body rashes were reported. The timing of these skin manifestations is important to note:

In up to 17% of patients, a skin eruption was the first clinical feature of the disease. Forty-seven percent reported skin symptoms during the illness and up to 39% of patients reported skin symptoms after their illness. In addition, 21% of participants reported only skin symptoms with no other clinical manifestations. The takeaway is that these skin symptoms may be of diagnostic value for COVID-19 disease.¹⁴

Our skin teams, including our CNAs, need to be on the lookout for any new skin rash, eye redness, or oral manifestations and report these to the appropriate person for escalating the findings to the provider for differential diagnosis. All facilities in the United States, regardless of the care setting, have protocols in place to start the assessment process to determine the need for COVID-19 testing, cohorting, and implementing treatment options. Having an awareness of skin and mucosal symptoms is critical knowledge for all health care associates to help slow the spread of COVID-19, particularly in care settings where communal living takes place, such as long-term/skilled nursing facilities. The general public needs this information to help monitor their health and that of their families in relation to the COVID-19 skin manifestations that may be early signs of this disease. It is important to have an awareness of and recognize rashes as an opportunity to identify new and earlier COVID-19 cases.^14,15

COVID-19 Skin Manifestations Mimic Other Etiologies

These skin changes imitate known dermatologic manifestations, and, in some cases, mimic wound etiologies such as pressure injuries and peripheral arterial disease. However, at this time the number of COVID-19 related skin manifestations is unknown. Research regarding these skin issues is now getting attention due to the number of skin disruptions appearing in all ages, from the young to the elderly. Although there are several hypotheses on the pathophysiological mechanisms causing these skin and mucosal membrane eruptions, more evidence is needed to support what is being seen clinically.  

Many studies have discussed the polymorphic nature of the skin disruptions associated with COVID-19. Clinical patterns include: urticarial rashes, erythematous/maculopapular/morbilliform rashes, papulovesicular exanthem, chilblain-like acral patterns, livedo reticularis and necrotic lesions, pityriasis rosea-like patterns, and mucosal (enanthema) symptoms of the mouth and conjunctiva of the eye.^14–17

One of the issues for every care setting is differentiating these skin eruptions from wound etiologies.

Differentiating skin manifestations from COVID-19 becomes even more confusing when compared to other skin disruptions that appear similar. In this set of photos these 3 different etiologies have comparable appearances. This becomes a quality issue in all care settings, requiring savvy clinicians to determine the difference between these skin issues. Two of these conditions, the Kennedy terminal ulcer/skin failure and COVID-19 necrotic skin, are unavoidable tissue injuries. The deep tissue pressure injury (DTPI) is considered an avoidable condition in most circumstances.

It is worth noting that there is a high risk for the surveyors in long-term care to give F-tags for COVID-19 skin damage. Surveys are performed to ensure that the long-term care facility is meeting state and federal standards, which are spelled out very specifically as to how care must be provided for facility residents.²⁰ Acquiring an F-tag related to COVID-19 skin damage may happen because neither the clinical staff nor the surveyors know exactly what they are seeing and are basing their decisions on what it looks like—a DTPI—and not what it is—a COVID-19 skin manifestations. Recently an article from LeadingAge²¹ stated that prevention and healing of pressure ulcer/injuries, (F-Tag 686) ²⁰ were in the top 10 F-Tags of 204 possible deficiencies given during the survey process in January and February of 2021. The question is how many of these F-tags were from pressure injuries and how many due to skin failure or necrotic skin from coagulopathy issues due to COVID-19?

Summary: Awareness of Skin and Mucosal Manifestations

•    COVID-19 has varied clinical manifestations that targets multiple organs, including the skin and mucosa.
•    These cutaneous changes present in many forms and manifest at different stages of the disease—before, during, after.
•    Sometimes these skin changes appear as the first symptom of the COVID-19 or may be the only symptom.
•    Providers need to be aware of these skin changes to assist with the differential diagnosis process.
•    Differentiating DTPI from Kennedy terminal ulcers from a COVID-19 skin manifestation is important and can be confusing as these skin changes can have similar presentations.
•    The lay and health care communities need an awareness of the potential for these skin manifestations to be a symptom of this disease.
•    Although skin rashes and mucosal symptoms can be associated with many other causes, in the era of COVID-19 an awareness of these symptoms may make a difference in the diagnostic, cohorting and treatment sequala of an event.
•    Perhaps catching the SARS-CoV-2 virus earlier in its disease progression may create an opportunity to intervene earlier and create better outcomes for our patients and residents.

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Pamela Scarborough, PT, DPT, MS, CWS, FAAWC, is the Vice President of Clinical Affairs for Restorix/American Medical Technologies in Irvine, CA.

References
1.    Nosenko MA, Ambaryan SG, Drutskaya MS. Proinflammatory cytokines and skin wound healing in mice. Mol Biol. 2019; 53(5):653–664.
2.    Agyare C, Osafo N, Boakye YD. Biomarkers of wound healing. IntechOpen, DOI: 10.5772/intechopen.80222. Published December 17, 2018.  
3.    Dance A. What is a cytokine storm? Knowable Magazine. Published April 10, 2020. Accessed 3/2/21
4.    Pathak N. The great invader: How COVID attacks every organ. WebMD. Published Oct. 16, 2020.
5.    Columbia University. Coronaviruses are masters of mimicry, new study finds. Published Oct. 27, 2020. Accessed 3/26/21
6.    Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19).
7.    Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility—King County, Washington, March 2020. MMWR. 2020 Mar 27;69(13):377–81 doi:10.15585/mmwr.mm6913e1external icon.
8.    Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020 Mar 4;63(5):706–11. doi:10.1007/s11427-020-1661-4
9.    Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406–1407.doi:10.1001/jama.2020.2565 doi:10.1001/jama.2020.2565
10.    Wang Y, Liu Y, Liu L, Wang X, Luo N, Ling L. Clinical outcomes in 55 patients with severe acute respiratory syndrome coronavirus 2 who were asymptomatic at hospital admission in Shenzhen, China. J Infect Dis. 2020; 221(11):1770–74. doi:10.1093/infdis/jiaa119
11.    Kaya G, Kaya A, Saurat J-H. Clinical and histopathological features and potential pathological mechanisms of skin lesions in COVID-19: Review of the literature. Dermatopathology. 2020; 7(1):3–16.
12.    Young S, Fernandez AP. Skin manifestations of COVID-19. In COVID-19 Curbside Consultants. Cleveland Clinic. Posted May 7, 2020. Accessed 1/25/21
13.    Marzano AV, Genovese G, Fabbrocini G, et al. Varicella-like exanthema as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients. J Am Acad Dermatol. 2020 Apr 16; 831(1):280–85. .doi:10.1016/j.jaad.2020.04.044
14.    Visconti A, Bataille V, Rossi N, et al. Diagnostic value of cutaneous manifestation of SARS-CoV-2 infection. Br J Dermatol. 2021;  epub Jan. 14.
15.    Young S, Fernandez AP. Skin manifestations of COVID-19.  In COVID-19 Curbside Consultants. Cleveland Clinic.
16.    Wollina U, Karadag AS, Rowland-Payne C, Chiriac A, Lotti T. Cutaneous signs in COVID-19 patients: A review. Dermatologic Therapy. 2020;e13549. https://doi.org/10.1111/dth.13549
17.    Galván Casas C, Catala ACHG, 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(1):71–77.
18.    Amorim dos Santos J, Costa Normando AG, Carvalho da Silva RL, et al. Oral mucosal lesions in a COVID-19 patient: New signs or secondary manifestations? Int J Infect Dis. 2020; 97:326–28.  
19.    Genovese G, Moltrasio C, Berti E, Marzano A, V. Skin manifestations associated with COVID-19: current knowledge and future perspectives. Dermatology. 2021;237:1-12. doi: 10.1159/000512932
20.    State Operations Manual Appendix PP-Guidance to Surveyors for Long Term Care Facilities (Rev. 11-22-17). Section F686.
21.    Finck-Boyle. Top 10 Survey Citations-March 2021. LeadingAge.