acral edema covid treatment

, SARS-CoV-2 infection and multi-organ system damage: A review. Nutrients. Cutaneous manifestations of COVID-19 and COVID-19 vaccination. Participants in the NO-NEGBAL group, did not received a NEGBAL approach as treatment. Figure 2. 32, Histology of these acral lesions shows diffuse dense lymphoid infiltration in dermis and hypodermis, with a prevalent perivascular pattern and signs of endothelial activation. COVID-19: Cutaneous manifestations and issues related to - UpToDate Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. Mike Hansen, MD breaks down "macroglossia," or "Covid tongue," a rare extreme enlarged swelling of the tongue caused by ACE inhibitor induced angiodema. 33. (2) Left hand edema with an erythematous skin area. <> Ask a healthcare provider if medications to treat COVID-19 are right for you. Cutaneous manifestations of COVID-19: A preliminary review. Cornejo-Pareja I, Vegas-Aguilar IM, Fernndez-Jimnez R, Garca-Garca C, Bellido-Guerrero D, Tinahones F, Garca-Almeida JM. the contents by NLM or the National Institutes of Health. People have been seriously harmed and even diedafter taking products not approved for use to treat or prevent COVID-19, even products approved or prescribed for other uses. 45 8, Although most patients with COVID19associated chilblainlike lesions have none or mild symptoms, they should follow public health guidelines for COVID19 testing and isolation. 25 New insights in COVID19associated chilblains: a comparative study with chilblain lupus erythematosus. Dermatological manifestation of pediatrics multisystem inflammatory syndrome associated with COVID19 in a 3yearold girl, The natural history of severe acute respiratory syndrome coronavirus 2related multisystem inflammatory syndrome in children: a systematic review. GarcaGil MF, Monte Serrano J, Garca Garca M, PascualdelRiquelme JA, AraMartn M. Acroischemic lesions associated with extremely elevated Ddimer in a child during the COVID19 pandemic. Complementmediated microvascular injury of the nail bed, distal sub ungual arcade capillary network damage and subsequent thrombus formation in small vessels have been proposed as possible mechanisms. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. 8 , 12 In the beginning days of the pandemic, there was a focus on three main signs of COVID-19: fever, cough, and shortness of breath. Nonsedating antihistamines can be used for treatment of COVID19associated urticarial lesions. The data that support the findings of this study are available from the corresponding author upon reasonable request. 30 Int J Dermatol. stream Iran, 4 Classification of the cutaneous manifestations of COVID19: a rapid prospective nationwide consensus study in Spain with 375 cases. Summary of clinical manifestations, ethiopathogenesis, histopathological findings and clinical management of 10 acral skin manifestations in COVID19. Are the cutaneous manifestations during or due to SARSCoV2 infection/COVID19 frequent or not? In patients who present with new-onset urticaria or angioedema, clinicians should ask about infectious disease symptoms, including those related to COVID-19. Neri I, Guglielmo A, Virdi A, Gaspari V, Starace M, Piraccini BM. 41, Although MISC can be a potentially serious condition with significant complications and organ involvements, most children will survive from acute phase with prompt diagnosis and treatment. Foot edema and associated skin lesions during the COVID19 pandemic. , What are the symptoms of COVID-19 in older adults? Immunostaining of lung sections with an antibody to the Rp3 NP protein of SARSCoV-2 revealed prominent expression on alveolar epithelial cells (Figure 2, B, top panel), including damaged, desquamated cells within the alveolar space (Figure 2, B, bottom panel, green arrows). Avoid use of drugs, tobacco and alcohol. COVID toes is a condition that causes swelling and discoloration of the toes and fingers. In addition to the acral site, similar bulous lesions were seen on knees and elbows, Although the exact mechanism of EMlike lesions in COVID 19 is uncertain, immune response to the SARSCOV2, hypersensivity by cytokines cascade triggered by SARSCOV2 infection and a potential delayed immune response to the virus can be proposed as possible etiopathogenesis of COVIDassociated EMlike lesion. His throat and pharyngeal swabs were positive for SARSCoV-2 by day 6 after the initial symptoms. RubioMuniz CA, PuertaPea M, FalkenhainLpez D, et al. 2021 Jun 7;12:664349. doi: 10.3389/fphar.2021.664349. 9, Histological features include prominent acantholysis and dyskeratosis associated with intraepidermal vesicles in suprabasal location. The .gov means its official. Worldwide case collections of cutaneous manifestations of coronavirus disease 2019 (COVID-19) are ongoing, with acral lesions (similar to classic chilblains) being one of the reported patterns. The National Institutes of Health (NIH) provides COVID-19 Treatment Guidelines for healthcare providers to help them work with their patients and determine the best treatment options for them. Kobayashi M, Matsumoto Y, Ohya M, Harada K, Kanno H. Histologic and Immunohistochemical evaluation of infiltrating inflammatory cells in Kawasaki disease arteritis lesions. Outcome Measures Go to Primary Outcome Measures : Turn the arms out and up next to the head. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. 4 0 obj It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. Anju Goel, MD, MPH. Stay physically active. MndezFlores S, Zaladonis A, ValdesRodriguez R. COVID19 and nail manifestation: be on the lookout for the red halfmoon nail sign, Widespread chickenpoxlike polymorphic pattern/ Monomorphic acral papulovesicular variant, Immune system hyperactivity/direct cytopathic effect of virus on endotheliual dermal vessels, Prominent acantholysis/suprabasal dyskeratosis with intraepidermal vesicles, Erythematous papule or plaque Angioedema and intense pruritus, Direct cutaneous effect of virus/druginduced exanthema/immune system over activity, Superficial perivascular infiltration of lymphocytes/few eosinophilic infiltration/marked dermal edema in upper dermis, Nonsedating antihistamines/short course of lowdose systemic corticosteroids in severe cases, Acral Noninflammatory purpura and skin necrosis, Lacelike reddishblue to purple mottled discolorations/ Hemorrhagic blisters/ Necroticulcerative lesion/ Dry gangrene, Hypercoagulative state/pauciinflammatory micro thrombotic vasculopathy/druginduced, Pauciinflammatory thrombogenic vasculopathy/extensive deposition of complement components in cutaneous microvasculature, Blue to gray discoloration without relation to the cold, Cytokine storm/hypercoagulative state/thrombotic events/ DIC, Microthrombosis in dermal vessels/endothelial cell damage/extravasation of RBCs/superficial and deep perivascular lymphocytic infiltration/vacuolar degeneration in basal layer, Therapeutic anticoagulation + Intravenous unfractionated heparin, Symmetric palpable inflammatory purpura with necrotic center/ Blisters formation, Direct damage of endothelial cells by the virus/indirect damage of endothelial cells by immune dysregulation, Perivascular neutrophilic infiltration/fibrin deposition/fibrinoid necrosis/leucocytoclasis/endothelial swelling, Erythematous edematous painful pruritic skin resembling perniosis/ Blister formation/ Digital swelling, Damage of skin capillaries/immune dysregulation/immunologic response to cutaneous vessels/druginduced, Diffuse dense lymphoid infiltration in the dermis and hypodermis/perivascular pattern/endothelial activation, Following public health guidelines for COVID19 testing and isolation, Targetoid lesions/ Two or three concentric circles with a small necrotic/ Hemorrhagic area, Immune response to virus/hypersensivity/potential delayed immune response to the virus, Mild superficial perivascular infiltration /microthrombi formation/Granular positivity in endothelial and epithelial cells of eccrine glands in Immunohistochemistry, Acral lesions associated with MISC in children, Macrophage activation and Thelper stimulation/cytokine release/overproduction of antibodies/hyper immune response, Perivascular cuffing with cytotoxic CD8+ lymphocytes and eosinophil that can be seen in Kawasaki syndrome, Single dose of 2g/kg of IVIG over 812h Systemic corticosteroids, Superficial desquamation of the distal phalanges of hands and feet, Alternation in regulation of expression of acral keratins, Halfmoonshaped transversal red band at the distal margin of the lunula as single crescent erythronychia on the nail bed, Complementmediated microvascular injury of the nail bed/capillary network damage of the distal sub ungual arcade/subsequent thrombus formation in small vessels. Some treatments might have side effects or interact with other medications you are taking. For patients with SARS-CoV-2 infection, renal injury mainly manifests as increased serum creatinine, variable degrees of proteinuria and hematuria, and radiographic abnormalities of the kidneys. Summary. , Knowing how to care for a person who has the flu can help speed their recovery, ease their symptoms, and prevent the infection from spreading. Epub 2020 Jul 1. Also known as pernio-like, pseudo-chilblain, acute acro-ischemia, and "COVID toes," the pattern of acral. They are considered as COVID toes. These lesions are a common feature in children with positive nasopharyngeal and rectal swabs for COVID19 with mild symptomatic or asymptomatic conditions. 1 Other coronaviruses such as human coronavirus NL63 have been associated with purpuric eruptions, including acute hemorrhagic edema of infancy. (2020). Thus, recognition of covid19 related acral signs and symptoms can help clinicians to consider COVID19 in the differential diagnoses of acral skin lesions. Background: Although many studies have demonstrated the epidemiologic characteristics of SARSCoV-2 disease (COVID-19), details of pathologic changes in the lung are still lacking. Data collection was done by Sharareh Babaie and Bahareh AbtahiNaeini. 21 However, this study was small, and there is insufficient data to support using vitamin D to treat or prevent COVID-19. 5 0 obj Fever, dry cough, asthenia, headache, myalgia, anosmia, diarrhea, and a great recent number of skin manifestations are widely referenced. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Saeedeh Farajzadeh, Maryam Khalili, Shakiba Dehghani and Bahareh AbtahiNaeini contributed in study conception and design. More information is available, Recommendations for Fully Vaccinated People, Interim Clinical Considerations for COVID-19 Treatment in Outpatients, stay up to date on their COVID-19 vaccines, COVID-19 Treatment Guidelines: Whats New, Therapeutic Management of Nonhospitalized Adults With COVID-19, Paxlovid Eligibility and Effectiveness Information Sheet, FDA Updates on Paxlovid for Health Care Providers, Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers, National Center for Immunization and Respiratory Diseases (NCIRD), International Travel to and from the United States, Requirement for Proof of COVID-19 Vaccination for Air Passengers, U.S. Department of Health & Human Services. -, Clawson RC, Tabata MM, Ko JM. Acral edema during the COVID-19 pandemic Dear Editor, Severe coronavirus disease 2019 (COVID-19) has been shown to have a wide spectrum of clinical presentations. , 5. Cookies used to make website functionality more relevant to you. ORCID: https://orcid.org/0000-0002-9377-8668. This site needs JavaScript to work properly. 23. Acral, COVID19, cutaneous manifestations, SARSCoV2, skin. Shakiba Dehghani and Bahareh AbtahiNaeini prepared the manuscript draft and Saeedeh Farajzadeh, Maryam Khalili, Sharareh Babaie and Mahdi Fattah did the manuscript revision. Criado PR, Abdalla BMZ, De Assis IC, Van Blarcum de Graaff Mello C, Caputo GC, Vieira IC. Pediatric Dermatology Division of Department of Pediatrics, Imam Hossein Children's Hospital, By clicking accept or continuing to use the site, you agree to the terms outlined in our. Inclusion in an NLM database does not imply endorsement of, or agreement with, PDF Dermatologic Manifestations of COVID-19 - apma.org Epub 2020 Jul 25. Left upper anterior segment. Cutaneous vasculitis: Lessons from COVID-19 and COVID-19 vaccination. Although such nonspecific findings may be seen in response to several conditions that result in respiratory failure, its demonstration in the setting of COVID-19 helps to inform the clinical course of disease. No, cellulitis is not the same as sepsis, but cellulitis can turn into sepsis if left untreated. Isfahan University of Medical Sciences, Petechial Skin Rash Associated With Severe Acute Respiratory - JAMA Antiviral, Start as soon as possible; must begin within 5 days of when symptoms start, Start as soon as possible; must begin within 7 days of when symptoms start, Intravenous (IV) infusions at a healthcare facility for 3 consecutive days, Who Sulaimani Viruses. A. Future studies should focus on exact investigation of etiologies of these lesions including role of immune senescence, environment, gender, immunogenetics and relation of these lesion with major organ involvements. We also discuss how a person can treat their symptoms at home. If you are hospitalized, your healthcare provider might use other types of treatments, depending on how sick you are. Page not found Instagram Medical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations. Accessibility Coronavirus has been around for centuries Chesser et al reported an 8-month-old with fever, mild cough, progressive purpura and extremity swelling that extended from thighs to feet Acute hemorrhagic edema of infancy (leukocytoclastic vasculitis) and often preceded by viral infection; resolution in 3 days Positive for coronavirus NL63 All information these cookies collect is aggregated and therefore anonymous. Adults; children ages 12 years and older, When and transmitted securely. A. Histopathologic examination revealing diffuse alveolar damage, organizing phase (A-1); denudation of alveolar lining cells (arrow 1), with presence of reactive type II pneumocyte hyperplasia (arrow 2) (A-2); intra-alveolar fibrinous exudates (arrow 3) and interstitial loose fibrosis with chronic inflammatory infiltrates (arrow 4) (A-3); and intra-alveolar loose fibrous plugs (arrow 5) (A-4). They should ensure that they remain hydrated, get plenty of rest, and take OTC medications to reduce fever and pain. 25 The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website. There are some studies, but the results are conflicting. COVID-19 can cause a variety of symptoms that may appear gradually. Monte Serrano J, Cruaes Monferrer J, Garca-Gil MF. Common Skin Signs of COVID-19 in Adults: An Update Tuck both arms under the chest and shoulders. Sometimes, people with COVID-19 develop other infections. , 46, Halfmoonshaped transversal red band at the distal margin of the lunula as single crescent erythronychia on the nail bed is considered as a pathognomonic nail finding in COVID19 infection. Shortness of breath is a symptom that can be frightening, but panicking can cause hyperventilation, which can make it worse. Conforti C, Dianzani C, Agozzino M, et al. Top 10 acral skin manifestations associated with COVID-19: A - PubMed 13 -, Galvn Casas C, Catal A, Carretero Hernndez G, et al. Learn more about the role of vitamin D and COVID-19 here. The .gov means its official. FernandezNieto D, OrtegaQuijano D, JimenezCauhe J, et al. Lesions may be observed on extremities, dorsal of hands and feet. It typically affects children, teenagers, and young adults. Disclaimer. In this article, we look at what to do if a person contracts SARS-CoV-2. Start as soon as possible; must begin within 5 days of when symptoms start, When Kerman university of Medical Science, On average, urticaria lasts less than one week and is associated with relatively mild disease and survival rates of 97.8% to 98.2%. Learn. In most foci, intra-alveolar organizing fibrin is seen (arrow 6). Outbreak of . Nakra NA, Blumberg DA, HerreraGuerra A, Lakshminrusimha S. Multisystem inflammatory syndrome in children (MISC) following SARSCoV2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. A doctor can instruct a person when to go to the emergency room and what specific home treatments might work best for them. Immunostaining of Huh7 cells infected with SARSCoV and of lung sections from an HIV-positive patient who died of fungal infection served as positive and negative staining controls, respectively (Figure 2, C). 10.1111/bjd.19163 eCollection 2022. COVID-19 is the disease that the highly contagious SARS-CoV-2 causes. , Careers. People should also avoid taking expired antibiotics or antibiotics prescribed to someone else. Systemic thrombolysis as initial treatment of COVID19 associated acute Aortoiliac and lower extremity arterial thrombosis, When interferon tiptoes through COVID19: Perniolike lesions and their prognostic implications during SARSCoV2 infection. 3 0 obj 2020 Sep;59(9):1151-1152. doi: 10.1111/ijd.15041. 29 There are several case reports and small case series which describe cutaneous lesions in hands and feet. Acral involvement in the setting of MISC presents with acral erythema and edema. AbtahiNaeini B, Fattah M. COVID19 and dermatological manifestations. Severe illness associated with using non-pharmaceutical chloroquine phosphate to prevent and treat coronavirus disease 2019 (COVID-19). This condition is generally referred to as pulmonary edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Discussion: The histopathologic changes seen on postmortem transthoracic needle biopsies from a patient with COVID-19 who had respiratory failure and radiographic bilateral ground-glass opacities are consistent with diffuse alveolar damage. Lung tissue was obtained by transthoracic 14-gauge needle biopsy from the left upper anterior segment (Figure 1, A, arrow), left upper lingular segment (Figure 1, B, arrow), and left lower lobe (Figure 1, C, arrow), coinciding with ground-glass opacities on chest computed tomography (CT). Slow blood flow. However, there is insufficient data on using vitamin C to treat COVID-19. Arrows indicate the approximate locations of the subsequently obtained postmortem transthoracic needle biopsy samples. , To find COVID-19 vaccine locations near you:Searchvaccines.gov, text your ZIP code to 438829, or call 1-800-232-0233. , , This study discussed the potential role of PhA value as a prognostic marker of adverse clinical outcomes such as mortality and complication in hospitalized with SARS-CoV2 infection and established the strength of recommendations for use, which showed four evidence-based recommendations on the prognostic value. Authors Jara Valtuea 1 , Daniel Ruiz-Snchez 1 , Victor Volo 1 , Pilar Manchado-Lpez 1 , Mara Garayar-Cantero 1 Affiliation 1 Department of Dermatology, Hospital Clnico . In: Smoller B, Bagherani N, eds. To do this, they can sit in the shower or on the bathroom floor with a hot shower running. ISSN A sign of natural resistance to SARSCoV2? 8 Acrocyanosis: Symptoms, Causes, and Treatment - Verywell Health As explained above, we conducted a scoping review to summarize the different acral skin lesions associated with COVID19 in children and adults as to recognize distinct cutaneous signs in COVID19 patients for accurate use of each entity and to prevent confusion among clinicians in similar entities. , 26, CSVV usually occurs in severe cases of COVID19 and is associated with higher mortality rate. However, there is no scientific evidence to support this claim. Urticaria is also common in COVID-19. The FDA has approved the antiviral drug Veklury (remdesivir) for adults and certain pediatric patients with COVID-19. 3 official website and that any information you provide is encrypted (3) Both feet edema more evident in right foot with chilblainlike lesions, Edema in hands and associated skin lesions during the COVID19 pandemic. It is not clear at the moment whether supplements can improve the outcomes of people with COVID-19. Summary Background Cutaneous manifestations of COVID19 disease are poorly characterized. The https:// ensures that you are connecting to the , A Lung Doctor Explains Macroglossia, or 'Covid Tongue' - Men's Health Treating COVID-19 at home: Care tips for you and others An official website of the United States government. Clinicians should continue to document these changes since they may become important diagnostic clues and help clinicians better understand the pathophysiologic basis for this viral illness. Skin COVID19 expressions are becoming a common manifestation of the disease 2 , 3 and could provide extensive information. C. Positive and negative controls for immunostaining. Disclaimer. When you can be around others after you had or likely had COVID-19. A sample of private patients with chilblain-like lesions which may be a cutaneous manifestation of COVID-19 are shared so that dermatologists can be aware of these findings. Iran, 2 Abbreviations: EM, erythema multiform; MISC, multisystem inflammatory syndrome in children. {%JFRa)g;'u6MYepIU+9rYKEZl{l Case Report: A 72-year-old man with a history of diabetes and hypertension presented with fever and cough. A healthcare provider will help decide which treatment, if any, is right for you. 7 2 During the COVID-19 outbreak in China . The NHS also suggest doing the following: Some evidence suggests that lying on the stomach might help people get more oxygen. Isfahan University of Medical Sciences, Oral vesicles and acral erythema: report of a cutaneous manifestation of COVID-19. The CDC suggest the following time frames before seeing other people, and they urge that a person must experience all of the following before seeing others: People can treat mild cases of COVID-19 at home. Bethesda, MD 20894, Web Policies , A watchful waiting strategy and symptomatic therapy is recommended. COVID-19 dermatology registry - American Academy of Dermatology Isfahan Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. 18 likes, 0 comments - CARRE Dermo-Esthetique (@drcarre.dermoesthetique) on Instagram: "#Repost @dermatology.news.daily (with @report.for.insta) . The exact identification and classification of these lesions can facilitate the accurate diagnosis and treatment. (6) Histological edematous skin features: Significant serum and erythrocyte extravasation in the superficial dermis (hematoxylin and eosin, 40). In addition, the cutaneous side effects of antiCOVID19 agents like highdose intravenous immunoglobulin (IVIG) should be considered as skin manifestations of microvascular occlusion syndrome. Lancet 2020; 395: 497506. , Furthermore, SARS-CoV-2 downregulation of angiotensin-converting enzyme 2, leading to increased levels of angiotensin II, may exacerbate vasoconstriction or vascular permeability. Chilblainlike lesions can also be cutaneous manifestation of strong type I interferon (IFNI) response in the setting of an effective immune response. All authors reviewed and approved the final version of manuscript and agreed with all aspects of the work. Long COVID: Long-Term Effects of COVID-19 - Johns Hopkins Medicine Phase angle and COVID-19: A systematic review with meta-analysis. HHS Vulnerability Disclosure, Help Acral purpuric lesions associated with coagulation disorders during the COVID-19 pandemic. Rev Endocr Metab Disord. 40 Cold liquids. Take breaks from COVID-19 news and social media. Clinical characteristics of dermatologic manifestations of COVID-19 infection: case series of 15 patients, review of literature, and proposed etiological classification. Peeling skin Causes - Mayo Clinic Acral edema during the COVID-19 pandemic Dear Editor, Severe coronavirus disease 2019 (COVID-19) has been shown to have a wide spectrum of clinical presentations. Before CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Farajzadeh S, Khalili M, Dehghani S, Babaie S, Fattah M, AbtahiNaeini B. Previous histological. 2020;9(12):449. An official website of the United States government. (2020). HHS Vulnerability Disclosure, Help The site is secure. Swelling in hands and feet. These perniosislike lesions differ from acroischemic lesions associated with severe COVID19 conditions. We agree that most acral chilblain-like or pernio-like lesions (commonly referred to as COVID toes) occur in young, previously healthy patients with relatively mild COVID-19 and frequently negative tests for SARS-CoV-2. 28 Cutaneous manifestations in confirmed COVID19 patients: a systematic review. Moderna COVID-19 Vaccine's Reactions and Adverse Events - CDC Cancer and cancer treatment; Genetic disease, including a rare skin disorder called acral peeling skin syndrome that causes painless peeling of the top layer of skin . Biology (Basel). %PDF-1.7 Similar to other post infections with significant inflammatory response, alternation in regulation of expression of acral keratins can be considered as possible mechanism. Cutaneous Manifestations of SARS-CoV-2 Infection. Since the lesions are asymptomatic, treatment is unnecessary. Approach to chilblains during the COVID19 pandemic, Erythema multiformelike lesions in children and COVID19. (2020). Dont delay: Treatment must be started within days after you first develop symptoms to be effective. As telogen effluvium and Beau lines may take 6-12 months to resolve completely, it is important to inform the patient that these cutaneous changes will eventually improve, and baseline appearances will be restored.5 Since cutaneous manifestations may be the only presenting symptom in 12% of COVID-19 patients, continued research is warranted to . , The pseudochilblain pattern frequently appears late in the evolution of the COVID19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID19. , Clipboard, Search History, and several other advanced features are temporarily unavailable. B. Immunostaining of SARSCoV-2 in lung sections. Received 2021 Sep 15; Revised 2021 Oct 6; Accepted 2021 Oct 7. 17 The right COVID sore throat remedy for you could be a combination of two or more of these options. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 34. 4.

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acral edema covid treatment