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      Dermatological Manifestations of COVID-19 in Patients Reporting to a Tertiary Care Hospital in Rawalpindi, Pakistan

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          Abstract

          Introduction

          The clinicopathological description of dermatological manifestations of COVID-19 leaves much to be desired. There is a need to determine their association with disease severity, outcome, and other clinical variables.

          Objectives

          The objectives of this study are to record and histopathologically examine the cutaneous manifestations of COVID-19 and correlate these to age, disease severity, and mortality.

          Methods

          All confirmed COVID-19 patients admitted to a single tertiary healthcare hospital in Rawalpindi, Pakistan, were included. Their diseases were classified as mild, moderate, severe, and critical. The recent onset skin eruptions in these patients were recorded via photographs along with relevant clinical data. The photographs were independently reviewed by a group of three dermatologists without knowledge of the clinical information. The skin manifestations were divided into disease-specific and nonspecific categories using an already defined algorithm. Histopathological examination of skin manifestations was conducted.

          Results

          A total of 23% (n=47) had “new” skin manifestations. Specific skin findings were seen in 21.6% (n=44), which consisted of ecchymosis/purpura in 50% (n=22), maculopapular exanthem in 18% (n=8), livedo reticularis in 16.2% (n=7), ischemia/gangrene in 16.2% (n=7), perniosis in 15.9 % (n=7), vesiculo-bullous rash in 9% (n=4) and urticaria in 4% (n=1). Non-specific findings were seen in 6% (n=13) and included bedsores, dermatitis passivata, dryness, herpes labialis, oral ulcerations, and nasogastric tube-induced ulcerations. There was a significant association (p=0.03) between disease severity and specific skin lesions. Ischemia/gangrene was significantly associated with COVID-19 disease severity and mortality. Vesiculobullous lesions were associated with higher mortality, though not with disease severity. Livedo reticularis had a higher-than-expected count in critical disease, albeit statistically insignificant. The association of maculopapular exanthem and ecchymosis/purpura with severe/critical disease was statistically insignificant. Urticaria was significantly associated with low disease severity. Mean age with specific manifestations was 56.86 ± 15.81 and with nonspecific/without any manifestations was 42.58 ± 16.96, a highly significant difference, with p-value < 0.001. Old age (>60 years) was significantly associated with ecchymosis (p=0.038), maculopapular exanthem (p=0.021), and vesiculo-bullous rash (p=0.029). Histopathology varied according to the type of skin lesion.

          Conclusions

          Dermatological manifestations coexist in many patients and tend to appear more in severe cases of COVID-19 among the older age group and only minimally in mild/moderate cases. Their presence could help set prognostic criteria of COVID-19 disease in the future.

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          Most cited references30

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. 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. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases

              Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19). We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n=5) and purpuric skin rash (n=3). The pattern of COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the inter-alveolar septa by neutrophils. No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic ARDS, were not prominent. These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the alternative and lectin-based complement pathways. The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin. In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the inter-alveolar septa and the cutaneous microvasculature of two cases examined. In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state. It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                22 October 2021
                October 2021
                : 13
                : 10
                : e18973
                Affiliations
                [1 ] Dermatology, Pak-Emirates Military Hospital, Rawalpindi, PAK
                [2 ] Dermatology, Academy of Aesthetic Medicine, Sheffield, GBR
                [3 ] Histopathology, Armed Forces Institute of Pathology, Rawalpindi, PAK
                [4 ] Basic Sciences, Army Medical College, Rawalpindi, PAK
                [5 ] Endocrinology and Diabetes, Pak-Emirates Military Hospital, Rawalpindi, PAK
                Author notes
                Article
                10.7759/cureus.18973
                8606119
                1db76dc8-dcfa-4362-8b49-26f47c9229e8
                Copyright © 2021, Muhammad et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 October 2021
                Categories
                Dermatology
                Pathology
                Infectious Disease

                covid 19,dermatological manifestaion,limb ischemia,covid and skin,histological features

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