{"id":5920,"date":"2024-01-24T06:00:00","date_gmt":"2024-01-24T11:00:00","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=5920"},"modified":"2024-01-16T11:23:45","modified_gmt":"2024-01-16T16:23:45","slug":"maculopapular-skin-eruptions-associated-with-covid%e2%80%9019-a-systematic-review","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=5920","title":{"rendered":"Maculopapular skin eruptions associated with Covid\u201019: A systematic review"},"content":{"rendered":"\n

Authors: Saad Shams,\u00a0 <\/sup>Sawai Singh Rathore,\u00a0 <\/sup>et. al. Dermatol Ther.<\/a>\u00a02021 Mar-Apr; 34(2)e14788. 202Feb2.\u00a0doi:\u00a010.1111\/dth.14788<\/a>PMCID:\u00a0PMC7995033PMID:\u00a033481314<\/a><\/p>\n\n\n\n

Abstract<\/h2>\n\n\n\n

In this systematic review, we anticipated in summarizing clinical features, histopathological hallmarks, and possible pathology behind the maculopapular skin eruptions occurring in Covid\u201019 patients. A literature search was executed using MEDLINE\/PubMed and Embase databases for articles published till 20 November 2020. All eligible articles including observational studies, case reports, and case series reporting the maculopapular skin lesion in Covid\u201019 patients were included. Data were obtained for 354 Covid\u201019 patients presenting with maculopapular lesions from 40 studies. The mean age of these patients was 53\u2009years, and with 42% of them being male. These maculopapular lesions differed considerably in terms of distribution and appearance, ranging from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques. The mean duration of the lesion was 8\u2009days. These lesions were frequently localized on trunks and extremities. Superficial perivascular dermatitis with lymphocytic infiltrate was a histopathological hallmark of these lesions. As these skin lesions may have a possible association with diagnosis, management, prognosis, and severity of the disease, all health practitioners need to be well acquainted with these Covid\u201019 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may help manage this infection’s further spread.<\/p>\n\n\n\n

1.\u2003INTRODUCTION<\/h2>\n\n\n\n

A new infectious pathogen called severe acute respiratory syndrome (SARS\u2010CoV\u20102) came into view in Wuhan, China, in December 2019 1 <\/a>. It was associated with an unconventional cause of pneumonia. The disease was later entitled Coronavirus disease 2019 (Covid\u201019). Following then it has quickly disseminated across the globe. Due to its asymptomatic transmission, high infectivity rate, and high mortality rate among the elderly and immunocompromised, it was declared a pandemic by the world health organization on March 11. By through end of November, 63 million cases of Covid\u201019 have been documented worldwide, accompanied by 1.34 million deaths. 2<\/a><\/p>\n\n\n\n

SARS\u2010CoV\u20102 is a \u03b2\u2010Coronavirus, which is an enveloped, positive\u2010sense, single\u2010stranded RNA virus. 3 <\/a>SARS\u2010CoV\u20102 enters the human cell via protein receptor angiotensin\u2010converting enzyme 2 (ACE2) and causes infection. Despite the fact that this virus predominantly targets the respiratory tract, several human tissues, including gastrointestinal and skin tissue have been discovered to have ACE2 expression, this may contribute to dermatologic finding present in Covid\u201019. 4<\/a><\/p>\n\n\n\n

The clinical manifestation of Covid\u201019 is pretty diverse, extending from mild symptoms to critical lethal respiratory failure, septic shock, ultimately to multiorgan failure. The most common clinical symptoms of SARS\u2010CoV\u20102 infection include fever, dry cough, fatigue, sore throat, and dyspnea, and headache; less commonly, vomiting, diarrhea, and anosmia or ageusia. 1 <\/a>Besides these typical symptoms, new symptoms including a range of cutaneous manifestations have been recorded globally. The first record of cutaneous signs was documented in a study from China, in this study out of 1099 Covid\u201019 patients only, 2(0.2%) presented with cutaneous manifestation. 5 <\/a>Later another report from Italy reported a higher prevalence of about 21% of the patient out of 88 presenting with cutaneous manifestation. 6 <\/a>Subsequently, many case reports and case series have been published reporting this manifestation in Covid\u201019 patients. These cutaneous lesions vary greatly in terms of clinical features of which maculopapular eruptions seem to be one of the most common lesions occurring in about 22% to 47% of Covid\u201019 cases presenting with cutaneous manifestation. 7 <\/a>, 8 <\/a>, 9<\/a><\/p>\n\n\n\n

As these lesions may provide a sooner and more reliable diagnosis and management of the infection, It is important for all health practitioners to be well acquainted with these Covid\u201019 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may also help in managing the further spread of this infection. In this systematic review, we aim to summarize clinical features, histopathological hallmarks, and possible pathology behind the maculopapular skin lesion occurring in Covid\u201019 patients.<\/p>\n\n\n\n

2.\u2003METHODS<\/h2>\n\n\n\n

The existing systematic review is accomplished and reported in conjunction with preferred reporting items for systematic reviews and meta\u2010analyses (PRISMA) guidelines. 10<\/a><\/p>\n\n\n\n

2.1. Search strategy<\/h3>\n\n\n\n

A literature search was executed using MEDLINE\/PubMed and Embase databases for articles published from December 2020 till 20 November 2020. Following search terms were used, ([Coronavirus] or [Covid\u201019] or [SARS\u2010CoV\u20102] and [skin] or [cutaneous] or [rash] or [maculopapular]OR [exanthem]). Studies from all over the world without any language constraints were included. On the basis of the title and abstract, eligibility for the article was determined. Reference lists of the incorporated studies and associated literature were manually inspected for additional qualifying studies. PRISMA flow diagram is illustrated in Figure \u200bFigure11<\/a>.<\/p>\n\n\n\n

<\/a><\/p>\n\n\n\n

\"An<\/a><\/figure>\n\n\n\n

FIGURE 1<\/a><\/p>\n\n\n\n

Preferred reporting items for systematic reviews and meta\u2010analyses (PRISMA) flow diagram<\/p>\n\n\n\n

2.2. Eligibility criteria<\/h3>\n\n\n\n

All eligible articles including observational studies, case reports, and case series reporting the maculopapular skin lesion in Covid\u201019 patients were included. Articles like review articles, hypothesis articles, and commentaries were discarded.<\/p>\n\n\n\n

2.3. Study selection and data extraction<\/h3>\n\n\n\n

The title and abstract of studies from formerly investigated databases were evaluated by three authors (S. T., N. K.). These authors ascertained studies, on the basis of predetermined eligibility criteria. From these selected studies, three authors (S. S. R., P. A., M. S.) retrieved data manually. For every report, subsequent details were extracted, author, country of origin, study design, sample size, mean age, clinical features of skin lesions, mean duration, location of skin lesion, sign, and symptoms, laboratory findings, histopathological findings, treatment of Covid\u201019, and outcome of the lesion.<\/p>\n\n\n\n

3.\u2003RESULT<\/h2>\n\n\n\n

A total of 354 patients with Maculopapular eruption were included from 40 studies. The average age of these patients was 53\u2009years(which ranged from 6 months to 84\u2009years) with 42% of them being male. Most of the published cases were from Spain (224 patients,63%) followed by France (33 patients, 9.3%), Italy (31 patients, 8.7%), Turkey (14 patients, 3.9%), United States (5 patients, 1.4%), India (3 patients, 0.8%), Thailand (2 patients, 0.5%).There was one case each from the UK, Portugal, Russia, Poland, Japan. 38(10.7%) patients were from the multinational registry. Considering many cutaneous manifestation cases might not have been documented in the literature for numerous reasons, these data are not consistent with the actual cutaneous lesion occurrence in Covid\u201019 patients from different countries. Table \u200bTable11<\/a> compiles the study characteristics and patient demographics information.<\/p>\n\n\n\n

TABLE 1<\/h3>\n\n\n\n

Study characteristics and patients demographics<\/p>\n\n\n\n

First author<\/th>Location<\/th>Study type<\/th>Covid\u201019 status (diagnostic technique)<\/th>Sample size(n) a<\/sup><\/th>Mean age (years) and gender (male or female)<\/th>Cases having maculopapular eruptions<\/th><\/tr><\/thead>
Ahouach et al 17<\/a><\/td>France<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>57\/F<\/td>1<\/td><\/tr>
Diaz\u2010Guimaraens et al 13<\/a><\/td>Spain<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>48\/M<\/td>1<\/td><\/tr>
Galvan Casas et al 8<\/a><\/td>Spain<\/td>Retrospective study<\/td>Positive (n\/m): 122\/176 (69.3%), suspected: 54\/176 (30.6%)<\/td>375<\/td>55\u00b73\/44% Male<\/td>176<\/td><\/tr>
Gianotti et al 25<\/a><\/td>Italy<\/td>Case series<\/td>Positive (PCR)<\/td>3<\/td>68\/33% Male<\/td>3<\/td><\/tr>
Hunt et al 39<\/a><\/td>United States<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>20\/M<\/td>1<\/td><\/tr>
Najarian et al 40<\/a><\/td>United States<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>58\/M<\/td>1<\/td><\/tr>
Sachdeva et al 30<\/a><\/td>Italy<\/td>Case series<\/td>Positive (PCR)<\/td>3<\/td>74\/100% Female<\/td>2<\/td><\/tr>
Askin et al 29<\/a><\/td>Turkey<\/td>Cohort<\/td>Positive (PCR): 34\/52 (65.4%) negative: 18\/52 (34.6%)<\/td>52<\/td>N\/M<\/td>12<\/td><\/tr>
Dalal et al 20<\/a><\/td>India<\/td>Cohort<\/td>Positive (PCR)<\/td>102<\/td>49\/66% Male<\/td>3<\/td><\/tr>
Herrero\u2010Moyano et al 21<\/a><\/td>Spain<\/td>Case series<\/td>Positive (n\/m)<\/td>8<\/td>72.2\/50% Male<\/td>8<\/td><\/tr>
Reymundo et al 38<\/a><\/td>Spain<\/td>Case series<\/td>Positive (PCR)<\/td>7<\/td>66.57\/28.6% Male<\/td>7<\/td><\/tr>
Rubio\u2010Muniz et al 28<\/a><\/td>Spain<\/td>Case series<\/td>Positive PCR: 6\/10 (60%) positive radiology: 3\/10 (30%) negative PCR: 1\/10 (10%)<\/td>34<\/td>53\/40% Male<\/td>10<\/td><\/tr>
Bouaziz et al 41<\/a><\/td>France<\/td>Case series<\/td>Positive (PCR)<\/td>14<\/td>N\/M<\/td>4<\/td><\/tr>
Recalcati et al 6<\/a><\/td>Italy<\/td>Case series<\/td>Positive (n\/m)<\/td>18<\/td>N\/M<\/td>14<\/td><\/tr>
Mahe et al 22<\/a><\/td>France<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>64\/F<\/td>1<\/td><\/tr>
Hedou et al 42<\/a><\/td>France<\/td>Prospective study<\/td>Positive (PCR)<\/td>103<\/td>N\/M<\/td>2<\/td><\/tr>
Morey\u2010Oliv\u00e9 et al 43<\/a><\/td>Spain<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>6\/Male<\/td>1<\/td><\/tr>
Rivera\u2010Oyola et al 14<\/a><\/td>United States<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>60\/Male<\/td>1<\/td><\/tr>
Avellana Moreno et al 15<\/a><\/td>Spain<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>32\/Female<\/td>1<\/td><\/tr>
Jimenez\u2010Cauhe et al 16<\/a><\/td>Spain<\/td>Case report<\/td>Positive (n\/m)<\/td>1<\/td>84\/Female<\/td>1<\/td><\/tr>
Gaspari et al 23<\/a><\/td>Italy<\/td>Case series<\/td>Positive (n\/m)<\/td>20<\/td>N\/M<\/td>9<\/td><\/tr>
Rosell\u2010Diaz et al 27<\/a><\/td>Spain<\/td>Case series<\/td>Positive (PCR)<\/td>12<\/td>66.3\/50% Male<\/td>12<\/td><\/tr>
Olisova et al 44<\/a><\/td>Russia<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>12\/Female<\/td>1<\/td><\/tr>
Klimach et al 18<\/a><\/td>UK<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>1\/Male<\/td>1<\/td><\/tr>
Jones et al 31<\/a><\/td>United States<\/td>Case report<\/td>Positive (n\/m)<\/td>1<\/td>6\u2009mo\/Female<\/td>1<\/td><\/tr>
De Masson et al 24<\/a><\/td>France<\/td>Retrospective study<\/td><\/td>277<\/td>29\/48% Male<\/td>25<\/td><\/tr>
Freeman et al 9<\/a><\/td>Multinational<\/td>Case series from an international registry<\/td>Positive (PCR):135(78.9%), positive (serology);19(11.1%), positive (unspecified testing):17(10%)<\/td>171<\/td>N\/M<\/td>38<\/td><\/tr>
Carbrera\u2013Hernandez et al 45<\/a><\/td>Spain<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>58\/Female<\/td>1<\/td><\/tr>
Paolino et al 19<\/a><\/td>Italy<\/td>Case report<\/td>Positive (n\/m)<\/td>1<\/td>37\/Female<\/td>1<\/td><\/tr>
Zengarini et al 46<\/a><\/td>Italy<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>67\/Female<\/td>1<\/td><\/tr>
Mendez\u2010Maestro et al 47<\/a><\/td>Spain<\/td>Cohort<\/td>Positive (PCR or serology)<\/td>75<\/td>N\/M<\/td>4<\/td><\/tr>
\u00d6ks\u00fcm Solak et al 48<\/a><\/td>Turkey<\/td>Case report<\/td>Positive (radiological)<\/td>1<\/td>24\/Female<\/td>1<\/td><\/tr>
Farabi et al 49<\/a><\/td>Turkey<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>55\/Female<\/td>1<\/td><\/tr>
Rossi et al 50<\/a><\/td>Italy<\/td>Case report<\/td>Positive(PCR)<\/td>1<\/td>34\/Male<\/td>1<\/td><\/tr>
Mazan et al 51<\/a><\/td>Poland<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>35\/Male<\/td>1<\/td><\/tr>
Goncalves et al 37<\/a><\/td>Portugal<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>57\/Male<\/td>1<\/td><\/tr>
Motahashi et al 52<\/a><\/td>Japan<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>52\/Male<\/td>1<\/td><\/tr>
Punyaratabandhu et al 53<\/a><\/td>Thailand<\/td>Case series<\/td>Positive(PCR)<\/td>2<\/td>51\/100 %Female<\/td>2<\/td><\/tr>
Lopez et al 26<\/a><\/td>Spain<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>31\/Female<\/td>1<\/td><\/tr>
Beaupre et al 54<\/a><\/td>United States<\/td>Case report<\/td>Positive (PCR)<\/td>1<\/td>42\/Female<\/td>1<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Open in a separate window<\/a><\/p>\n\n\n\n

Abbreviations: Covid\u201019, Coronavirus disease 2019; PCR, polymerase chain reaction; N\/M, not mentioned.<\/p>\n\n\n\n

a <\/sup>Sample size denotes total COVID\u201019 infected patients in a each study.<\/p>\n\n\n\n

3.1. Clinical characteristics of maculopapular lesion<\/h3>\n\n\n\n

Maculopapular lesions are one of the most frequent skin manifestations observed during the Covid\u201019 pandemic. Adverse drug reactions or viral infections(eg, HHV\u20106, HIV\u20101, HHV\u20104) are important triggers for this type of lesion. 11 <\/a>When caused by viral or bacterial infections they are often linked with fever, myalgia, headache, and fatigue. Ebstein Barr virus infection, Herpes, scarlet fever, Measles, Ebola, Zika, and HIV are common viral infections associated with maculopapular rash. 12 <\/a>The maculopapular eruption is prominent on the chest, back, abdomen, and extremities and can range from confluent lesions to erythematous, scattered blanching rash.<\/p>\n\n\n\n

Article stating the association of maculopapular rash with Covid\u201019 infection has diverse clinical depiction. Distribution and appearance of maculopapular eruption ranged from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques to erythematous macules and plaques with a violaceous targetoid appearance. Some maculopapular lesions associated with Covid\u201019 were marked by a petechial portion. 13 <\/a>, 14 <\/a>, 15 <\/a>, 16 <\/a>Detailed clinical characteristics features of the lesion from each study are compiled in Table \u200bTable22<\/a>.<\/p>\n\n\n\n

TABLE 2<\/h3>\n\n\n\n

The clinical characteristic feature of the maculopapular lesions<\/p>\n\n\n\n

Author<\/th>Clinical features of maculopapular lesions<\/th>Mean duration of the lesion<\/th>Location of lesions<\/th>Relation to the onset of other Covid\u201019 symptoms<\/th>Outcome of lesion<\/th>Treatments for Covid\u201019<\/th>Signs, symptoms, laboratory, and radiological findings<\/th><\/tr><\/thead>
Ahouach et al 17<\/a><\/td>Diffuse erythematous blanching maculopapular lesions, with the burning sensation only on the palm<\/td>9\u2009d<\/td>Trunk and limbs<\/td>After<\/td>Slowly resolved<\/td>Paracetamol<\/td>Fever (39\u00b0C) and dry cough<\/td><\/tr>
Diaz\u2010Guimaraens et al 13<\/a><\/td>Mildly pruritic, confluent erythematous macules, papules, and petechiae in symmetric periflexural distribution<\/td>5\u2009d<\/td>Buttocks and legs<\/td>3\u2009d after<\/td>Slowly resolved<\/td>Hydroxychloroquine, lopinavir\/ritonavir, and azithromycin<\/td>Fever (up to 39\u00b0C), pleuritic chest pain, and shortness of breath. Increased C\u2010reactive protein and D\u2010dimer level, ground\u2010glass opacities on chest radiograph<\/td><\/tr>
Galvan Casas et al 8<\/a><\/td>Maculopapular eruptions with itching (99 patients), pain (4 patients), and burning (9 patients). Few maculopapular lesions were interpreted as resembling pityriasis rosea.<\/td>8.6\u2009d<\/td>Generalized<\/td>Before\u20103 patients, At onset\u2010108, After \u221260 patients<\/td>Slowly resolved<\/td>Paracetamol, NSAIDS, Chloroquine, Hydroxychloroquine Lopinavir\/ritonavir, Tocilizumab, systemic corticosteroid, Azithromycin<\/td>Fever, Cough, dyspnea, asthenia, headache, nausea, vomiting, diarrhea, anosmia, Pneumonia<\/td><\/tr>
Gianotti et al 25<\/a><\/td>Widespread erythematous macules with the presence of pruritis in one patient<\/td>7.7\u2009d<\/td>Trunk\u20103 patients, Arms\u20102 patients, Legs\u20101 patient<\/td>Before (1 patient), After (2 patients)<\/td>Slowly resolved<\/td>Lopinavir\/ritonavir, heparin and levofloxacin, Ceftriaxone and azithromycin, Hydroxychloroquine<\/td>Fever, headache, cough and arthralgias, elevated transaminase and fibrinogen level in one patient<\/td><\/tr>
Hunt et al 39<\/a><\/td>Non\u2010pruritic, Diffuse morbilliform maculopapular rash sparing the face<\/td>N\/M<\/td>Trunk and limbs<\/td>At onset<\/td>N\/M<\/td>N\/M<\/td>Fever, pneumonia, elevated C\u2010reactive proteins<\/td><\/tr>
Najarian et al 40<\/a><\/td>A pruritic diffuse morbilliform rash<\/td>2\u2009d<\/td>Limbs, shoulders, trunk, chest, and abdomen<\/td>After<\/td>Slowly resolved<\/td>Azithromycin and benzonatate<\/td>Cough, pain in legs and hands, no fever<\/td><\/tr>
Sachdeva et al 30<\/a><\/td>A maculopapular pruritic rash appearing like that of Grover disease in one patient while Morbilliform rash and hemorrhagic macular rash on legs in another<\/td>N\/M<\/td>Trunk and limbs<\/td>After in one patient while at onset in another<\/td>Slowly resolved<\/td>Lopinavir\/ritonavir and hydroxychloroquine and subcutaneous low molecular weight heparin<\/td>Cough, fever, lymphadenopathy, arthralgia, headache, and myalgia<\/td><\/tr>
Askin et al 29<\/a><\/td>Diffused Maculopapular rash, with one of the lesions on the trunk resembling pityriasis rosea<\/td>N\/M<\/td>Trunk (most of the patients), on the extremities in one patient<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td><\/tr>
Dalal et al 20<\/a><\/td>Maculopapular rash with centripetal distribution<\/td>N\/M<\/td>Trunk and limbs<\/td>After<\/td>Slowly resolved<\/td>Hydroxychloroquine, Azithromycin<\/td>Sore throat, cough, fatigue, headache, fever, cough and, dyspnoea<\/td><\/tr>
Herrero\u2010Moyano et al 21<\/a><\/td>Indistinct erythematous patches to coalescent maculopapules, some with a violaceous center, in one patient progressed into pustules and desquamation<\/td>12\u2009d<\/td>Trunk\u20107 patients,Flexures\u20104 patients,Proximal extremities\u20102 patients,Face\u20102 patients<\/td>N\/M<\/td>N\/M<\/td>Hydroxychloroquine, lopinavir\/ritonavir, ceftriaxone, metamizole, linezolid, piperacillin\u2010tazobactam, amiodarone, furosemide<\/td>N\/M<\/td><\/tr>
Reymundo et al 38<\/a><\/td>Diffused maculopapular rash<\/td>11\u2009d<\/td>Trunk\u20107 patients,Proximal upper limbinvolvement\u20106 patients,Lower limb involvement\u20101 patient<\/td>After<\/td>Slowly resolved<\/td>Systemic corticosteroid<\/td>Pneumonia<\/td><\/tr>
Rubio\u2010Muniz et al 28<\/a><\/td>Erythematic Maculopapular exanthems<\/td>N\/M<\/td>N\/M<\/td>After<\/td>N\/M<\/td>N\/M<\/td>Pneumonia in 8 patients<\/td><\/tr>
Bouaziz et al 41<\/a><\/td>Maculopapular exanthema<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td><\/tr>
Recalcati et al 6<\/a><\/td>Mild itching or asymptomatic rash<\/td>N\/M<\/td>Mainly trunk<\/td>N\/M<\/td>Resolved a few days later<\/td>N\/M<\/td>N\/M<\/td><\/tr>
Mahe et al 22<\/a><\/td>An erythematous rash resembling as reminiscent of symmetrical drug\u2010related intertriginous and flexural exanthema (SDRIFE)<\/td>5\u2009d<\/td>Trunk and Flexors<\/td>N\/M<\/td>Resolved a few days later<\/td>Paracetamol<\/td>Fever (up to 40\u00b0C) and asthenia<\/td><\/tr>
Hedou et al 42<\/a><\/td>Maculopapular rash with Itching<\/td>N\/M<\/td>Trunk and neck that gradually spanning to the cheeks and upper and lower extremities<\/td>N\/M<\/td>Resolved a few days later<\/td>N\/M<\/td>N\/M<\/td><\/tr>
Morey\u2010Oliv\u00e9 et al 43<\/a><\/td>Erythematous, confluent, non\u2010pruritic maculopapular rash<\/td>5\u2009d<\/td>Generalized<\/td>After<\/td>Resolved a few days later<\/td>N\/M<\/td>The fever increased bilirubin and transaminases<\/td><\/tr>
Rivera\u2010Oyola et al 14<\/a><\/td>Scattered erythematous macules coalescing into papules, 1\u2009wk later purpuric round macules developed in the areas of the previous eruption.<\/td>N\/M<\/td>Back, bilateral aspect of the flanks, groin, and proximal lower limb<\/td>After<\/td>Resolved a few days later<\/td>None<\/td>Low\u2010grade fever (38\u00b0C), myalgias, fatigue, mild cough<\/td><\/tr>
Avellana Moreno et al 15<\/a><\/td>Generalized, itching morbilliform lesions with cephalocaudal growth, characterized as a petechial and erythematous maculopapular lesion. A scaly reaction observed on the fourth day<\/td>4\u2009d<\/td>Face, neck, thorax, abdomen, buttocks, extremities, including folds and scalp<\/td>After<\/td>N\/M<\/td>N\/M<\/td>Fever, myalgia, asthenia, cough, and diarrhea<\/td><\/tr>
Jimenez\u2010Cauhe et al 16<\/a><\/td>Erythematous purpuric, coalescing macules<\/td>N\/M<\/td>Periaxillary regions<\/td>After<\/td>N\/M<\/td>Hydroxychloroquine and lopinavir\/ritonavir<\/td>N\/M<\/td><\/tr>
Gaspari et al 23<\/a><\/td>Erythematous exanthema<\/td>N\/M<\/td>Trunk and face<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td><\/tr>
Rosell\u2010Diaz et al 27<\/a><\/td>Generalized maculopapular confluent exanthema with itching<\/td>N\/M<\/td>Generalized<\/td>After<\/td>Slowly resolved<\/td>Hydroxychloroquine, Lopinavir\/Ritonavir, ceftriaxone, azithromycin<\/td>Fever, pneumonia<\/td><\/tr>
Olisova et al 44<\/a><\/td>Purpuric eruptions and erythematous macula rash and swollen tongue with lingual papillae<\/td>3\u2009d<\/td>Upper eyelids, above the eyebrows, and in the temporal region<\/td>After<\/td>Slowly resolved<\/td>Paracetamol<\/td>Fever, fatigue, and headache<\/td><\/tr>
Klimach et al 18<\/a><\/td>Erythematous papular rash in the axillae. Multiple painful, erythematous papules on plantar surface of lower limb<\/td>14\u2009d<\/td>Axillae and lower extremities<\/td>After<\/td>N\/M<\/td>Paracetamol<\/td>Fever, myalgia, and headache<\/td><\/tr>
Jones et al 31<\/a><\/td>Blanching, polymorphous maculopapular rash<\/td>N\/M<\/td>Generalized<\/td>N\/M<\/td>N\/MN\/M<\/td>N\/M<\/td>Fever, limbic sparing conjunctivitis, hand, and feet swelling<\/td><\/tr>
De Masson et al 24<\/a><\/td>Maculopapular rash<\/td>N\/M<\/td>Trunk and limbs 25, face (in 2 patients)<\/td>N\/M<\/td>N\/M<\/td>N\/M<\/td>Fever, Respiratory symptoms, Anosmia\/ageusia, Digestive symptoms<\/td><\/tr>
Freeman et al 9<\/a><\/td>Pruritic to burning Morbilliform rash<\/td>7 fays<\/td>Head and Face\u2010 10 patients, Trunk\u2010 76 patients, Upper limb\u201028, Lower limb\u201031 patients and generalized in 4 patients<\/td>Before\u20103 patients, after\u201029, at onset\u20105<\/td>N\/M<\/td>Antimalarial agents, antibiotics, bevacizumab, remdesivir, serpin inhibitors, IL\u20106 inhibitors, lopinavir\/ritonavir<\/td>Fever, cough, shortness of breath, sore throat, headache, myalgia, diarrhea, vomiting. ARDS in 4 patients, thrombotic event in 3 patients<\/td><\/tr>
Carbrera\u2013Hernandez et al 45<\/a><\/td>Confluent, erythematous macules and plaques with a violaceous targetoid appearance<\/td>N\/M<\/td>Trunk and proximal limbs<\/td>After<\/td>Resolved<\/td>Hydroxychloroquine, Azithromycin, Lopinavir\/Ritonavir<\/td>Fever, cough, dyspnea, myalgia, pneumonia<\/td><\/tr>
Paolino et al 19<\/a><\/td>Erythematous maculopapular lesions without itching<\/td>8\u2009d<\/td>Trunk, neck, and face<\/td>After<\/td>Resolved<\/td><\/td>Fever (up to 39\u00b0C), dry cough, myalgia, and arthralgia<\/td><\/tr>
Zengarini et al 46<\/a><\/td>Itching erythematous confluent lesion, with ill\u2010defined border<\/td>7\u2009d<\/td>Neck, trunk, and proximal portions of upper and lower extremities<\/td>After<\/td>Resolved<\/td>Hydroxychloroquine, omeprazole, piperacillin\/tazobactam, and remdesivi<\/td>Dyspnoea and fever<\/td><\/tr>
Mendez\u2010Maestro et al 47<\/a><\/td>Maculopapular exanthemas<\/td>N\/M<\/td>Trunk and proximal extremities, one case of flexural involvement<\/td>After<\/td>N\/M<\/td>Hydroxychloroquine, omeprazole, piperacillin\/tazobactam, and remdesivir<\/td>N\/M<\/td><\/tr>
\u00d6ks\u00fcm Solak et al 48<\/a><\/td>Erythematous maculopapular, eruptions 1\u20132\u2009mm in caliber, scattered on the body and separated from each other, while some advanced into patches and plaques<\/td>N\/M<\/td>Generalized, more prominent on extremities<\/td>After<\/td>N\/M<\/td>Hydroxychloroquine, oseltamivir, and azithromycin<\/td>Cough and fever, Pneumonia, Peripheral ground\u2010glass appearance in both lungs on CT<\/td><\/tr>
Farabi et al 49<\/a><\/td>Erythematous, maculopapular lesions, 2 to 5\u2009mm diameter lesions<\/td>3\u2009d<\/td>Bilateral jawline and periauricular area<\/td>After<\/td>N\/M<\/td>Favirapir and hydroxychloroquine<\/td>Malaise and fatigue<\/td><\/tr>
Rossi et al 50<\/a><\/td>Non\u2010pruritic erythematous maculopapular rash<\/td>5\u2009d<\/td>Generalized<\/td>After<\/td>Resolved<\/td>Acetaminophen, Hydroxychloroquine, and Tocilizumab<\/td>Fever, Dyspnoea<\/td><\/tr>
Mazan et al 51<\/a><\/td>Itchy, maculopapular rash with non\u2010tender erythematous macules and papules<\/td>10\u2009d<\/td>Trunk and arms<\/td>After<\/td>Resolved<\/td>Lopinavir\/ritonavir<\/td>Optic neuritis<\/td><\/tr>
Goncalves et al 37<\/a><\/td>An erythematous papular rash with irregular borders<\/td>N\/M<\/td>Elbows and Abdomen<\/td>After<\/td>N\/M<\/td>None<\/td>Fever, cough, diarrhea, and, malaise. Bilateral pulmonary opacities on CT<\/td><\/tr>
Motahashi et al 52<\/a><\/td>Non\u2010pruritic, miliary\u2010sized, maculopapular exanthem and erythematous confluent rash<\/td>10\u2009d<\/td>Trunk and on the flexor surfaces of limbs<\/td>After<\/td>resolved<\/td>N\/M<\/td>Fever<\/td><\/tr>
Punyaratabandhu et al 53<\/a><\/td>Itchy maculopapular rash without mucosal involvement<\/td>5 and 7\u2009d<\/td>Trunk and extremities<\/td>After<\/td>resolved<\/td>Favipiravir, lopinavir\/ritonavir, hydroxychloroquine (HCQ), azithromycin, meropenem and tocilizumab, ertapenem<\/td>Fever, cough, and muscle pain<\/td><\/tr>
Lopez et al 26<\/a><\/td>Non\u2010pruritic erythematous maculopapular lesions in plaques, discretely palpable<\/td>7\u2009d<\/td>Abdomen, neckline, the inner side of the arm<\/td>Before<\/td>N\/M<\/td>N\/M<\/td>Fever, cough, and parenchymal consolidation in the right middle lobe on X\u2010ray<\/td><\/tr>
Beaupre et al 54<\/a><\/td>Non\u2010blanching maculopapular rash with a concomitant non\u2010blanching purpuric rash<\/td>N\/M<\/td>Abdomen<\/td>After<\/td>N\/M<\/td>N\/M<\/td>Abdominal pain, nausea, vomiting, dyspnoea. diabetic ketoacidosis<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Open in a separate window<\/a><\/p>\n\n\n\n

Abbreviations: Covid\u201019, Coronavirus disease 2019; N\/M, not mentioned.<\/p>\n\n\n\n

Many lesions presented with itching while in few cases manifested with a burning sensation. 9 <\/a>, 17 <\/a>Two reports described the painful character of maculopapular lesion. 8 <\/a>, 18 <\/a>Some reports have identified a substantial craniocaudal development of a rash, involving the folds without the engagement of the palmar\u2010plantar area and the mucous membranes. 15 <\/a>, 19 <\/a>Dalal et al reported the centripetal distribution of maculopapular lesions. 20<\/a><\/p>\n\n\n\n

These maculopapular eruptions vary based on the location of the lesion and are most commonly localized in trunks and extremities. However, these lesions have been reported from on the head and face, on the neck, and in periaxillary areas. 9 <\/a>, 15 <\/a>, 19 <\/a>, 21 <\/a>, 22 <\/a>, 23 <\/a>, 24 <\/a>These eruptions are diverse in the duration for which they remain on the skin. While not all studies commented on the mean length of these cutaneous manifestations, with available data for 249 patients, the lesion’s mean duration was 8\u2009days with a range of 2 to 14\u2009days.<\/p>\n\n\n\n

In most of the studies, lesions appeared either at onset or after the onset of other symptoms of Covid\u201019 however, few studies reported the appearance of rash 2 to 3\u2009days before the onset of symptoms. 8 <\/a>, 9 <\/a>, 25 <\/a>, 26 <\/a>One observational study suggested an increased severity of Covid\u201019 illness in patients with maculopapular lesions, which was established by a 2% mortality rate recorded in those patients. 8<\/a><\/p>\n\n\n\n

The most frequent medication used in these patients with maculopapular lesions were hydroxychloroquine\/chloroquine (46.5% patients), paracetamol (31.8% patients), lopinavir\/ritonavir (28.8% patients), and azithromycin (20.7%). No medication was used in about 16.3% of patients. The summary of medications used across all patients is consolidated in Table \u200bTable33<\/a>.<\/p>\n\n\n\n

TABLE 3<\/h3>\n\n\n\n

Summary of medications used in patients with maculopapular lesion<\/p>\n\n\n\n

Medication<\/th>Total patients with available data \u2010 271(%)<\/th><\/tr><\/thead>
No medication<\/td>44 (16.3)<\/td><\/tr>
Paracetamol<\/td>86 (31.8)<\/td><\/tr>
Hydroxychloroquine\/chloroquine<\/td>126 (46.5)<\/td><\/tr>
Azithromycin<\/td>56 (20.7)<\/td><\/tr>
Lopinavir\/ritonavir<\/td>78 (28.8)<\/td><\/tr>
Tocilizumab<\/td>15 (5.5)<\/td><\/tr>
NSAIDS<\/td>16 (5.9)<\/td><\/tr>
Corticosteroids<\/td>27 (10)<\/td><\/tr>
Ceftriaxone<\/td>14 (5.1)<\/td><\/tr>
Piperacillin\/tazobactam<\/td>7 (2.6)<\/td><\/tr>
Antibiotics (other than AZ and CFT)<\/td>13 (4.8)<\/td><\/tr>
Heparin<\/td>5 (1.8)<\/td><\/tr>
Interferon\u2010beta<\/td>9 (3.4)<\/td><\/tr>
Remdesivir<\/td>7 (2.6)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Open in a separate window<\/a><\/p>\n\n\n\n

3.2. Histopathological hallmarks<\/h3>\n\n\n\n

From the histological perspective, several features of the maculopapular lesion have been recognized. Maculopapular lesions exhibit superficial perivascular dermatitis with lymphocytic infiltrate and dilated vessels in the papillary and mid dermis with neutrophils, eosinophils, and nuclear debris. Epidermis revealed dispersed foci of hydropic changes, accompanied by minimum acanthosis, subcorneal pustules, slight spongiosis, Basal cell vacuolation, and foci of parakeratosis. One study by Rosell\u2010Diaz et al showed a lichenoid pattern with eosinophils’ presence on biopsy of skin lesions. 27 <\/a>Table \u200bTable44<\/a> summarizes histopathological features reported from different studies.<\/p>\n\n\n\n

TABLE 4<\/h3>\n\n\n\n

Histopathological features of the maculopapular lesion<\/p>\n\n\n\n

Author<\/th>Histopathological hallmarks<\/th><\/tr><\/thead>
Ahouach et al 17<\/a><\/td>Slight spongiosis and basal cell vacuolation and moderate perivascular lymphocytic infiltrate<\/td><\/tr>
Diaz\u2010Guimaraens et al 13<\/a><\/td>Superficial perivascular lymphocytic infiltrate with a surplus of red cell extravasation and focal dermal papillary edema, accompanying by focal parakeratosis and isolated dyskeratotic cells<\/td><\/tr>
Gianotti et al 25<\/a><\/td>Superficial perivascular dermatitis with slight lymphocytic exocytosis, patchy, swollen thrombosed vessels in the mid dermis with neutrophils, eosinophils, and nuclear debris<\/td><\/tr>
Herrero\u2010Moyano et al 21<\/a><\/td>Subcorneal pustules, spongiosis, papillary edema, dense perivascular and neutrophilic interstitial infiltrate with the decent presence of eosinophils<\/td><\/tr>
Reymundo et al 38<\/a><\/td>Mild superficial perivascular lymphocytic infiltrate and spongiosis<\/td><\/tr>
Rubio\u2010Muniz et al 28<\/a><\/td>In early\u2010onset cases\u2010moderate epidermal spongiosis and perivascular lymphocytic infiltrate with eosinophils in the dermis. In late\u2010onset, cases\u2010perivascular lymphocytic infiltrate and histiocytes within collagen fibers devoid of mucin deposits<\/td><\/tr>
Rivera\u2010Oyola et al 14<\/a><\/td>Mild perivascular infiltrate with paramount of mononuclear cells around the superficial blood vessels, epidermis exhibited dispersed foci of hydropic changes, accompanying with minimal acanthosis, minor spongiosis, and foci of parakeratosis<\/td><\/tr>
Gaspari et al 23<\/a><\/td>Superficial perivascular dermatitis with lymphocytic infiltrate, a dilated vessel in the papillary and mid dermis<\/td><\/tr>
Rosell\u2010Diaz et al 27<\/a><\/td>Superficial perivascular inflammation with eosinophils in one patient and the other displayed a lichenoid pattern with eosinophils<\/td><\/tr>
Freeman et al 9<\/a><\/td>Interface dermatitis in one patient<\/td><\/tr>
Carbrera\u2013Hernandez et al 45<\/a><\/td>Mixed interface pattern with dilated vessels filled with neutrophils, recurrent blood extravasation, and dispersed necrotic keratinocytes<\/td><\/tr>
Zengarini et al 46<\/a><\/td>Superficial perivascular lymphocytic infiltrate, a remarkably dilated vessel in the papillary and mid dermis<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

Open in a separate window<\/a><\/p>\n\n\n\n

Rubio\u2010Muniz et al described the histology of rashes according to the onset of lesion. Early\u2010onset lesions exhibited perivascular lymphocytic infiltrate with eosinophils in the dermis with moderate epidermal spongiosis. In comparison, perivascular lymphocytic infiltrate and histiocytes contained in collagen fibers were seen in the histology of late\u2010onset cases. These late\u2010appearing lesions lack mucin deposits. 28<\/a><\/p>\n\n\n\n

Go to:<\/a><\/p>\n\n\n\n

4.\u2003DISCUSSION<\/h2>\n\n\n\n

The consequences of the SARS\u2010CoV\u20102 pandemic are severe, as it had health\u2010related, economic, and social impacts on millions of peoples around the globe. Owing to asymptomatic transmission, high infectivity rate, and droplet infection of SARS\u2010COV\u20102, it has become horribly challenging to control this virus. Dermatological interpretation of Covid\u201019 originally thought not to be very important has proved to be diverse and sophisticated. Regardless of rapidly evolving research, the number of skin manifestations of Covid\u201019 remains largely unexplained. Owing to the absence of large\u2010scale prospective studies, the true prevalence of skin manifestations in Covid\u201019 is hard to interpret. Incidents of dermatological lesions in Covid\u201019 highly vary according to published literature and extent from 0.6% to 20.4%. 5 <\/a>, 6<\/a><\/p>\n\n\n\n

Maculopapular eruptions seem to be one of the most common cutaneous manifestations occurring in Covid\u201019 patients. 8 <\/a>Although there are reports of maculopapular lesions associated with Covid\u201019 patients in published literature, they remain to be appraised systematically. This systematic review aims to fill that gap, by compiling the characteristics of 354 patients from 40 studies originating from 12 different countries. Investigators have variedly characterized macular\u2010papular lesions in Covid\u201019 patients as erythematic, purpuric rash, and morbilliform. This lesion appears after the onset of other symptoms of Covid\u201019 in most cases, however, few studies reported the appearance of eruptions before any other symptoms. Since Covid\u201019 infection has the propensity to remain asymptomatic for 10 to 14\u2009days, these signs can assist in early detection of Covid\u201019 and prevent the spread of this highly contagious illness.<\/p>\n\n\n\n

As stated in the result, these lesions vary in distribution and appearance. Other than that, a few peculiar patterns of the maculopapular lesion have been reported. Few studies reported perifollicular lesions coupled with scaling and confluence, which may lead to an appearance similar to pityriasis rosea. 8 <\/a>, 29 <\/a>Similarly, In a study by Galvan Casas et al few patients exhibited infiltrated papules on the extremities, principally the dorsum of the hands, that resemble pseudovesicular just like erythema elevatum diutinum or erythema multiforme. 8 <\/a>Sachdeva et al reported a Maculopapular pruritic rash resembling that of Grover disease in one patient. 30 <\/a>One of the studies on Covid\u201019 patient\u2010reported polymorphous maculopapular rash linked with fever, conjunctivitis, raised tongue papillae, dry cracked lips, swelling of the hands, and lower limbs satisfying the criteria for Kawasaki disease. 31 <\/a>Mahe et al described an erythematous rash involving flexors as similar to symmetrical drug\u2010related intertriginous and flexural exanthema (SDRIFE). 22 <\/a>Further studies are needed to undertake to explain these lesions as, considering the diverse morphological representations, they are potentially a variegated collection of manifestations.<\/p>\n\n\n\n

In Covid\u201019 patients, pathological pathways behind the skin lesions are poorly recognized. According to published literature, the Pathological mechanism behind Skin manifestation in SARS\u2010COV\u20102 may be categorized into:<\/p>\n\n\n\n

    \n
  1. An immune response to viral nucleotides, clinical characteristics like viral exanthem.<\/li>\n\n\n\n
  2. Secondary cutaneous lesions expedited by the systemic effect of Covid\u201019, in particular, vasculitis and thrombotic vasculopathy.<\/li>\n\n\n\n
  3. Due to adverse drug reactions.<\/li>\n<\/ol>\n\n\n\n

    SARS\u2010CoV\u20102 is a single\u2010stranded RNA virus consisting of 16 nonstructural proteins designated as NSP1 to NSP1 with unique functions in the replication of Coronaviruses (CoVs). For instance, NSP3 can block the innate immune reaction of the host and facilitate cytokine expression. Similarly, interferon (IFN) signaling is inhibited by NSP5 and NSP16 prevents MAD5 (melanoma differentiation\u2010associated gene 5) recognition, damping innate immunity. 32 <\/a>Some investigations have recognized SARS\u2010like viral particles and SARS\u2010CoV RNA in T lymphocytes indicating direct T cell viral infection. 33 <\/a>This direct T cell infection may lead to a strong immune response and may be responsible for skin lesions occurring Covid\u201019 illness.<\/p>\n\n\n\n

    Hyperactive immune responses in Covid\u201019 patients can contribute to the induction \u201ccytokine storm\u201d (in particular, IL\u20106); these cytokines could enter the skin and trigger dermal dendritic cells, lymphocytes, macrophages, mast cells, and neutrophils, and can assist in the development of lesions such as maculopapular rash. 34 <\/a>This representation of cutaneous lesion has been described earlier in diseases having an overactive immune response and excessive cytokine release (example, systemic lupus erythematosus, adult Still’s a disease, antiphospholipid syndrome). 35<\/a><\/p>\n\n\n\n

    Several drug therapies have been used to manage Covid\u201019 patients. A couple of these drugs may be involved in maculopapular eruptions. A sub\u2010analysis done on the study by Galvan Casas et al reported that 78% of maculopapular lesions had concurrent drug consumption. 36 <\/a>The most common drug taken by these patients was chloroquine\/hydroxychloroquine, followed by lopinavir\/ritonavir, tocilizumab, and azithromycin. 36 <\/a>A case report by Mazan et al described the development of Itchy, maculopapular rash with non\u2010tender erythematous macules and papules following 10\u2009days of lopinavir\/ritonavir administration. 37 <\/a>In spite of this, in case series with the patients taking no new medications, the maculopapular rash has been recognized, hinting that these lesions may not just be associated with drugs. 38<\/a><\/p>\n\n\n\n

    As can be observed, Covid\u201019 related maculopapular rash can occur in various appearances, affect patients of all ages and genders, and affect any part of the body. For maculopapular lesions, topical corticosteroid and moisturization of skin remain the primary mode of treatment. Systemic corticosteroid therapy may be needed in extensive involvement of the body surface.<\/p>\n\n\n\n

    In this literature review, one of the limitations that must be taken into account is that since research related to Covid\u201019 and skin manifestation is rapidly evolving, these reports are small\u2010scale studies based on early restricted understanding, rather than large\u2010size clinical trials, hence these data may not be decisive and relevant for the entire population. Further large\u2010scale studies, addressing maculopapular eruptions and their clinical characteristics and pathology behind them are warranted.<\/p>\n\n\n\n

    5.\u2003CONCLUSION<\/h2>\n\n\n\n

    In this article, a systematic review of the cutaneous maculopapular eruptions associated with SARS\u2010COV\u20102 is provided. Covid\u201019 patients most typically have respiratory symptoms, but multiple organ involvement with various cutaneous signs like maculopapular rash may occur. These maculopapular lesions differ considerably in terms of distribution and appearance, ranging from diffuse erythematous maculopapular lesions to scattered erythematous macules coalescing into papules to maculopapular lesions in plaques and may resemble other well\u2010known dermatological disorders. Even though these results do not suggest that Covid\u201019 is the absolute cause of these maculopapular eruptions, they indicate these lesions should be regarded in the context of possible presentations associated with this illness. As these lesions may have a possible association with diagnosis, management, prognosis, and severity of the disease, all health practitioners need to be well acquainted with these Covid\u201019 skin lesions. Also, in the middle of this worldwide pandemic, early identification of this eruption may help manage this infection’s further spread.<\/p>\n\n\n\n

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    Authors: Saad Shams,\u00a0 Sawai Singh Rathore,\u00a0 et. al. Dermatol Ther.\u00a02021 Mar-Apr; 34(2)e14788. 202Feb2.\u00a0doi:\u00a010.1111\/dth.14788PMCID:\u00a0PMC7995033PMID:\u00a033481314 Abstract In this systematic review, we anticipated in summarizing clinical features, histopathological hallmarks, and possible pathology behind […]<\/p>\n","protected":false},"author":2,"featured_media":9084,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[924,925,533,592],"tags":[],"class_list":["post-5920","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-rash","category-rash-erythematous","category-skin-dermatology","category-treatments"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/5920","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=5920"}],"version-history":[{"count":1,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/5920\/revisions"}],"predecessor-version":[{"id":9083,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/5920\/revisions\/9083"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/9084"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=5920"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=5920"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=5920"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}