|
 
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| REVIEW ARTICLE |
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| Year : 2020 | Volume
: 7
| Issue : 1 | Page : 5-11 |
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Novel corona virus infection: a dermatologist’s perspective
Rashmi Sarkar1, Preethi B Nayak2
1 Department of Dermatology, Lady Hardinge Medical College, New Delhi, India
2 Cutis Academy of Cutaneous Sciences, Bangalore, Karnataka, India
| Date of Submission | 24-May-2020 |
| Date of Acceptance | 24-May-2020 |
| Date of Web Publication | 10-Jul-2020 |
Correspondence Address:
Dr. Rashmi Sarkar
Department of Dermatology, Lady Hardinge Medical College, New Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/Pigmentinternational.Pigmentinternational_
Novel corona virus infection or COVID-19 saw its dawn in first fortnight of Decemberin the city of Wuhan, China, since then it is unstoppable and has spread like a wild-fire, involving most parts of the world. The causative virus is named as SARS-CoV-2. Although the reproductive number (R0) of two to three has been suggested, it is still unknown. The symptoms of COVID-19 infection have a broad spectrum of severity, which ranges from asymptomatic to mildly symptomatic to severe illness that require mechanical ventilation. The virus seldom causes any viral exanthem, but dermatologists should have good working knowledge about COVID-19 and its manifestations, which would help to explore the unexplored cutaneous manifestation of the disease in near future. Due to limited availability of testing kits, RT-PCR test is done only in patients who have a clinical diagnosis of COVID-19 based on symptoms, exposures and chest imaging. Basic public health measures like frequent efficient handwashing, social distancing, staying home, respiratory etiquette like covering nose and mouth while coughing and sneezing are to be followed to prevent the spread of disease. It is now time for our specialty to get involved actively and share the burden of COVID-19. Though not directly connected in dealing with COVID-19 patients, dermatologists should work together with other specialties as a multidisciplinary team. We carried out a PubMed, Medline search using the following terms “COVID-19, dermatology, rash, skin, health care” and have included all data and latest national guidelines related to COVID-19 in dermatology.
Keywords: COVID-19, corona virus, dermatology, skin rash
How to cite this article:
Sarkar R, Nayak PB. Novel corona virus infection: a dermatologist’s perspective. Pigment Int 2020;7:5-11 |
Key Messages
What is known about COVID-19 is just the tip of iceberg, many areas are still unexplored, and varied clinical features still unknown. Hence dermatologists should have good working knowledge about COVID-19 and its manifestations, which would help to explore unexplored cutaneous manifestation of the disease in the near future.
| Introduction | |  |
In the first fortnight of December, in the city of Wuhan, China, a novel and unusual type of pneumonia was diagnosed in a patient. By 31st December, the regional office of World Health Organization (WHO) in Beijing received a report of cluster of cases of similar symptoms, but cause unknown. The Wuhan Institute of Virology then performed metagenomic analysis on the bronchoalveolar lavage swab samples and detected a novel coronavirus 2019 or nCoV-2019. The novel coronavirus has got a varied nomenclature, it is called as 2019-nCoV by the US Centres for Disease Control and Prevention (CDC) and now the disease renamed to COVID-19 (Corona Virus Disease 2019), it is also called as SARS-CoV-2 by the International Committee on Taxonomy of Viruses.[1],[2] The infection since the dawn has seen its spread as wild-fire. As of May 24, 2020, the global confirmed cases range around 53,44,539, with around 342,695deaths. According to the present statistics, in India there are around 131,868 confirmed cases and 3867 deaths.[3] We carried out a PubMed, Medline search using the following terms “COVID-19, dermatology, rash, skin, health care” and have included all data and latest national guidelines related to COVID-19 in dermatology.
| Epidemiology | | |
The virus
The novel coronavirus is a human infecting Beta-coronavirus, with genetic proximity to two bat-derived SARS-like coronavirus, derived from the chrysanthemum bats. The virus genome was rapidly sequenced allowing the research into therapeutics and vaccine, and development of diagnostic test. The virus consists of densely glycosylated spike (S) protein, which aids in entering the host cell. Upon entry, it has high affinity and binds to the angiotensin-converting enzyme 2(ACE2) human receptor. ACE2 enzymes are expressed mainly in the nasopharynx and type 2 alveolar cells. SARS-CoV-2 affects the ACE2 receptor similar to SARS-CoV, but the monoclonal antibodies against the receptor binding domain are not the same, hence suggesting the origin of new virus. The novel virus shares genomic sequence of 79.5% with SARS-CoV and 96.2% with bat coronavirus.[1],[4]
Comparison of COVID-19 with MERS and SARS
The present COVID-19 outbreak is similar, but yet so different from the prior outbreaks. The Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) have both been a zoonotic transmission of coronavirus likely from bats via dromedary camels in Saudi Arabia and from bats via palm civets in Guangdong Province of China, respectively. All these viral infections present commonly with fever and cough, eventually leading to lower respiratory tract disease with poorer outcomes, in patients with co-morbidities and older age group. As of now it appears like the SARS-CoV-2 has greater infectivity but lower case-fatality rate compared to other two zoonotic virus outbreak seen in the last two decades.[1],[5],[6]
The host
Pangolin (scaly anteater) has been suspected as an intermediate host between humans and bats. This has to be confirmed before assessing the transmissibility and targets for therapeutics and vaccine.[4]
The epidemics
According to a large study involving 72,314 cases, most of the patients were in between the age group of 30 to 79 years (87%).[5] A male preponderance was seen, which may be due to higher ACE2 enzyme levels in Asian males or due to higher smoking history in males. The incubation period ranges from 2 to 14 (4 days) days.[1],[3],[4],[7] Genomic sequencing data have suggested that there was a single introduction into humans, which was followed by human to human spread. There is no clarity on when the transmission begins but reports suggest that majority of secondary transmissions occur from symptomatic individual than during the asymptomatic phase. Majority of transmission of COVID-19 occurs among close contacts.[1],[5],[8] Although there are many reports suggesting reproductive number (R0) (the expected number of secondary cases produced by a single infected person in a susceptible population) of 2 to 3, but it is still too soon to develop an accurate Ro used to assess the transmission dynamics. SARS-CoV-2 has been isolated from nasopharynx, saliva and lower respiratory tract samples. Virus has also been isolated from plasma and faeces. Though peri-natal transmission is unlikely but larger studies are needed.[1],[2],[4],[5]
| Clinical syndrome | | |
The features are non-specific, characterized by fever (77–98%), dry cough (46–82%), shortness of breath (3–31%), myalgia (11–52%), headache, diarrhoea and sore throat. The fever course in COVID-19 may be prolonged and intermittent, and is not much understood. Most of the cases appear to be mild but features of pneumonia can be seen on chest X-ray and chest computed tomography. Advanced stages of the disease needing intensive care unit, are seen in 20–30% of patients who develop acute respiratory distress. The older age individuals and patients with co-morbidities are more prone to severe symptoms. This may be due to, individuals with hypertension and diabetes are on ACE inhibitors or angiotensin two receptor blockers (ARB), which would lead to the increase in ACE2 expression, which is not inhibited by the ACE inhibitors or ARBs. Case fatality rates among those aged 60–69 years: 3.6%, 70–79 years: 8% and > 80 years: 14.8%. The patients with no co-morbidity had an overall case fatality of 0.9% and with co-morbidities:10.5%for cardiovascular disease, 7% for diabetes and 6% each for hypertension, chronic respiratory disease and cancer. Nasopharynx has the highest viral load as ACE2 is highly expressed in the nasopharynx. Patient presenting with above symptoms with a travel history of COVID-19 infected nations should be considered as patient under investigation (PUI) and depending on symptoms can be quarantined and treated.[1],[3],[5],[8],[9] However due to varied characteristics of the virus, generational transmission and mutation, infected patients may have diverse symptoms. There is often a mismatch between the CT chest reports and clinical symptoms, but the outcomes usually follow clinical features. There are reports of third and fourth generation transmission and even asymptomatic carriers. Asymptomatic latency denotes that unobvious respiratory symptoms in early infected patients are due to the pathogenic latency of SARS-CoV-2. The presence of asymptomatic latency also indicates that SARS-CoV-2 may gradually evolve into an influenza-like virus or it may remain latent in individuals for a long time.[3],[9] The symptoms of COVID-19 infection has a broad spectrum of severity, which ranges from asymptomatic to mildly symptomatic to severe illness that require mechanical ventilation.[10]
| Testing | | |
Confirmation of the infection is done by nucleic acid testing of nasopharynx and/or oral swabsby RT-PCR (Reverse transcriptase − Polymerase Chain Reaction). Due to reduced availability of testing kits, RT-PCR is done only in patients who have a clinical diagnosis of COVID-19 based on symptoms, exposures and chest imaging. Bronchoalveolar lavage, expectorated sputum and tracheal aspirate samples from the lower respiratory tract can also be considered. Other added tests like complete blood count and molecular testing to rule out other respiratory virus can be done. Viral cultures are not recommended. Imaging (CT chest) shows ground-glass opacification, with or without consolidation, bilateral peripheral involvement, especially in the lower lobe, these can occur without any clinical symptoms.[4],[5] Self-diagnostic kits for home/ self-quarantined individuals are being made available now.[11]
| Treatment | | |
A lot of research and clinical trials are needed with respect to treatment. Supportive care is all that is needed in most of the cases. Oxygen supplementation when needed. Anecdotal reports state that Remdesivir; a nucleoside prodrug act by inhibiting viral RNA transcription, can be used but clinical trials are underway. Lopinavir/Ritonavir has been used by few doctors across the globe, including India. Favilavir, an antiviral used in influenza has been approved in China as investigational therapy. Other anti-influenza drugs like oseltamivir and umifenovir are under investigation.[4],[5] Presently, in India, National Task force for COVID-19 constituted under ICMR (Indian Council of Medical Research) recommends the use of hydroxy-chloroquine for prophylaxis of SARS-CoV-2 infection for population at high risk. The high-risk population who can take chemoprophylaxis with hydroxy chloroquine are: asymptomatic household contacts of laboratory confirmed cases and the asymptomatic health care workers involved care of suspected or confirmed COVID-19 cases, it should be taken 400 mg twice daily on day 1 followed by weekly once for 3 weeks and 7 weeks, respectively.[12] There are reports of using combination of hydroxy-chloroquine and azithromycin, but it is highly debatable due to both drugs leading to involvement of cardiac system.[13] Passive prophylaxis or therapeutic immunotherapy with monoclonal antibody are novel future options, but have not been successful with antibodies used to treat influenza or respiratory syncytial virus. Vitamin-C and elements of Chinese medicine are other options under evaluation.[2] There are more than 100 clinical trials presently to test repurposed and novel compounds for the treatment of COVID-19. But there are no proven treatments or vaccine. Basic public health measures like frequent efficient hand-washing, social distancing, staying home, respiratory etiquette like covering nose and mouth while coughing and sneezing are to be followed to prevent the spread of disease and a future pandemic [Table 1].[1],[4]
| COVID-19 IMPACT ON DERMATOLOGY | | |
Skin rash in COVID-19 patients
It is still too early to associate any kind of skin rash to patients with coronavirus disease. Recently there are few authors from Thailand, who have reported a case who had petechial rashes and was misdiagnosed as dengue. But later due to the involvement of respiratory symptoms along with rash and fever, COVID-19 was suspected and tested, which turned to be positive.[14] Hence a possibility of COVID-19 should be kept in mind, and a proper extensive history should be taken in all cases presenting during this COVID-19 outbreak.
The COVID-19 patients are receiving several systemic drugs, including antibiotics, antivirals like remdesivir, ritonavir and immunomodulators like mycophenolic acid, chloroquine and cyclosporine. Many of these medications are known to cause drug rash which may range from generalized skin eruptions to severe drug eruptions like DRESS. Severe drug reactions may further involve other systems and may complicate COVID-19. Febrile condition and general skin eruption may even occur secondary to variety of viral infections like parvovirus, zika virus, rubella, measles, coxsackie, and dengue fever. Hence dermatologists should recognize the general skin eruptions either by drugs and viral infections and treat it.[15] There are reports on the prophylactic use of hydroxychloroquine in COVID-19, this has created a panic among the general population, who are now taking the medication without doctors’ prescription. Though, hydroxychloroquine has a safe profile, due to higher doses or without proper monitoring might lead to side effects, hence drug rash due to hydroxychloroquine to be considered as well.
Skin care in COVID-19 health care workers
Since the dawn of COVID-19 outbreak, there is increase in preventive measures, especially for the one who work in hospitals, to prevent occupational hazard. The preventive measures consist of personal protective equipment (PPE); coveralls/gowns, triple-layered/N95 masks, goggles, face shield, double-layered gloves, head covers and shoe covers. Constant use of PPE and frequent use of hand sanitizers/ soaps leads to skin damage, which would affect the enthusiasm and cause anxiety among the health care workers. Previously, hand eczema was the most prevalent problem among health care worker due to frequent hand hygiene and long periods of wearing gloves. In the COVID-19 era, due to long term wearing of PPE there is increased occurrence of occupational skin diseases such as pressure marks, eczema, acne by prolonged mask wearing, milaria rubra and milaria pustulosa by the coveralls, along with sweating and severe painful hand eczema.[15],[16],[17] In a study, during the corona virus outbreak in China, 97% of the health care workers had skin damages, with affected sites including the nasal bridge, hands, forehead and cheeks. Nasal bridge was most commonly affected. Dryness/tightness was the most common symptom and desquamation was the most common sign. As the health care worker kept the medical devices over 6 hours the risk of skin damage increased. Longer time of glove wearing increased the risk of skin damage over hands followed by that due to frequent hand hygiene (>10 times/day). Hence the working hours of the first line health workers should be arranged reasonably, and the use of prophylactic dressings/adhesive barrier films prior to donning the PPE to avoid pressure-related device injury should be encouraged. It is difficult to wear protective gears over the face with ulcers and abrasion, and may reduce the effectiveness of protective equipment.[16],[17] As already known, skin disease accounts for a large proportion of occupational injury and impacts the quality of life and work. The presence of abrasion over the face would increase the likelihood of touching the face while not using PPE and may breach the PPE protocols due to mask touching in an unconscious effort to relieve the irritation while using the PPE. Inappropriate doffing of the PPE by the health care workers is common as well. The skin-related issues can be handled by; educating the health care workers to expect mild irritation, topical agents to reduce the irritation but should be applied with great care using sterile cotton-tipped applicator and single use petroleum jelly box prior to the possible exposure, full face respirator or full face shield to be used in those with history of sensitivity, and as already mentioned prophylactic padding or dressing can be used but the potential impact of such dressings on efficacy of PPE is unexplored.[18] Pre-existing skin disease could also get accentuated in the health care worker due to physical and mental stress when providing health services to COVID-19 patients.[15] In this crisis situation it is duty of dermatologist to help the involved health care workers, by familiarizing with these skin-related issues and should treat/prevent it promptly.
Dermatological disorders during COVID-19 outbreak
As it is already known, that COVID-19 can affect patients of older age group and those with co-morbidities more severely. Many of the dermatological conditions are chronic, needing long term immune-suppressants. According to previous reports of death and increased risk of infection from viral diseases in immunosuppressed patients, it is alarming situation, we should take a call on whether to continue the medications in patients who are already on immunosuppressant or whether to stop the therapy and shift them to alternative medicines. Dermatologist should assess the risk-benefit ratio, on one hand the risk of opportunistic infection on starting immunosuppressive therapy in patients with psoriasis, and on other hand the absolute need of immunosuppression in erythrodermic psoriasis and severe psoriatic arthritis. But increased risk of COVID −19 among these patients is still uncertain. In particular, the areas with high rate of infection or outbreaks, it would become extremely important to limit and/or reduce the time and dosage of administration, and to prefer topical drugs with lower impact on immune system. All the immunosuppressive and biological therapy should be stopped in patients with confirmed COVID-19.[19] During pre-corona era; respiratory infection rate was comparable between patients on TNF-alpha-inhibitors and placebo. But it is not clearly known whether biological therapies make patients more susceptible to COVID-19. Dermatologist must also consider loss of response and production of antibodies to discontinued biological which will interrupt re-introduction of the biological at a later date.[20] According to recent BAD guidelines, the dermatology patients who are on immunosuppressive treatment are categorized, and advised either shielding or social distancing depending on the risk of infection. Patients who are in definite high-risk category are strictly advised shielding, these include those on; corticosteroids > 20mg/ml of prednisolone per day for more than 4weeks, any two agent within the following classes − immunosuppressants (cyclosporine, azathioprine) or biologicals (anti-TNF, IL17) or novel small molecule immunosuppressants (apremilast), cyclophosphamide at any dose orally or if received intravenously in the last 6 months, rituximab or infliximab prescribed for skin conditions, and corticosteroid dose of > 5mg of prednisolone per day for 4 weeks along with one of the immunosuppressive medication/ biologicals/ novel small molecule immunosuppressants. The next category advised to shield only if other concerns or high-risk circumstances (decision individualized by the clinician) are well-controlled patients with minimal disease activity and no comorbidities on single agent of standard oral immunosuppressants/biologicals/ novel small molecule immunosuppressants or on single biologic plus methotrexate at standard dose or on single dose standard oral immunosuppressants plus hydroxychloroquine/sulfasalazine. The final category to maintain social distancing like everyone else are the ones on topical skin treatments, hydroxychloroquine, acitretin, alitretinoin, isotretinoin, dapsone, chloroquine, sulfasalazine, only inhaled or rectally places immunosuppressants example steroid inhalers and 5-ASA medications (mesalazine).[21]
Pigmentary disorders and COVID-19
The authors are of the opinion that, though reports are suggesting COVID-19 infection to have involvement of immune system, and vitiligo is a well-known autoimmune condition, there may not be direct impact of either increase or decrease of vitiligo patches during this pandemic. It may be due to, autoimmunity in vitiligo is specific to melanocytes and there are no reports presently that COVID −19 has any effects on melanocytes. The role of COVID-19 on treatment of vitiligo is varied. The patients who are already on mini pulse steroids or in those where mini pulse steroids are needed to arrest the disease progress can be continued or started, as it is of short-course and there is no long term or severe immunosuppression. But for those requiring immunosuppressants like methotrexate or azathioprine, risk-benefit has to be assessed and the decision should be individualized. For those who were on narrow band UV-B or excimer light therapy, exposure of the patches to sunlight or PUVASOL can be suggested. Disorders of hyperpigmentation like melasma may be benefitted during this pandemic, as patients are staying indoors. The use of sunscreens should be stressed to the patients as even inside their houses they can be exposed to indirect sunlight or infra-red rays. Few of them may even have a habit of sitting in their balconies/ roof tops at this time of leisure which may have adverse effect due to sunlight and increase melasma.
COVID-19 and role of dermatologists
As already discussed, the virus seldom causes any viral exanthem, but dermatologists should be actively engaged in the health care and in the academics related to COVID-19.
Telemedicine in dermatology practice should be considered in the time of COVID-19 crisis. It not only allows real-time management of skin disease for the patient but also helps the treating dermatologist to maintain social distance and prevents potential physician exposure to virus with face to face consultation. Tele-dermatology will be a boon in future health care system to deal with massive contagious disease outbreak.[15]
As a social responsibility, almost all the dermatologists in COVID-19 affected area had stopped all non-emergency services, including out-patient department. The screening and cancelling appointments for those with symptoms and /or travel history. The following measures have to be followed to fight against the virus by dermatologist:- While giving appointments, to consider only those who need immediate attention and deferring others by discussion with the patient about the existing situation and safety of everyone involved
- To advice patients on cough etiquette, hand hygiene, wearing of mask in hospital/clinic premises and social distancing.
- Patient in case of emergency, related to drug/ follow up can be done, if possible, can be contacted through telephone or email, in case of extreme emergency the patients are advised to report to nearest emergency department
- The following patients should be considered to consult nearby emergency facility/admission − angioedema with respiratory distress, severe drug rash, erythroderma of any aetiology and patients of autoimmune blistering disease with body surface area involvement >5%
- Elective procedures − due to presence of virus in aerosol for many hours and over various surfaces for days, elective procedures to be avoided as and when possible.[22],[23],[24]
- Tele-consultation − Telemedicine which was previously not permitted in India, now due to the lockdown and as patients are not able to approach medical practitioners, the Medical Council of India and the Government of India has approved and formulated certain guidelines for Registered Medical Practitioner to practice telemedicine in this time of need. This has been adapted by the Indian Association of Dermatologists, Venereologists and Leprologists, and tele-dermatology guidelines have been formulated and tele-consultation for dermatological conditions is practiced now.[25],[26]
Due to the limited number of health care workers, dermatology consultants and residents may be called upon to treat COVID-19 patients similar to what is happening in Italy currently.23 But as of now, every health worker should get involved academically, and at community level to spread awareness and stop the spread of COVID-19.
| Conclusion | | |
“Dermatology… this young daughter of medicine” Paul Gerson. Dermatology is a subspecialty under medicine. It is now time for our specialty to get involved actively and share the burden of COVID-19. Though not directly connected in dealing with COVID-19 patients, dermatologists should work together with other specialties as a multidisciplinary team. What is known about COVID-19 is just the tip of iceberg, many areas are still unexplored, and varied clinical features still unknown. Hence dermatologists should have good working knowledge about COVID-19 and its manifestations, which would help to explore the unexplored cutaneous manifestation of the disease in the near future.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1]
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