الفهرس 
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Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 is a novel virus that causes COVID-19 outbreak. It is known that the ACE2 receptor is widely spread in human tissues. Thus, there exist a plethora of clinical manifestations of COVID-19 as opposed to it being limited only to the respiratory tracts. Recently, researchers have found that the ACE2 receptor is also expressed in skin tissues. Keratinocytes show the highest expression of ACE2 among endothelial cells, fibroblasts, hair follicles, melanocytes, sweat gland cells, and immune cells in the skin. This arises a unique challenge due to the skin‟s nature as our first-line defense from the environment. As such, many cutaneous clinical manifestations have also been found in COVID-19 patients.
The aim of our study is to assess the immunohistochemical expression of ACE 2 receptor in skin of patients affected by COVID 19 with or without skin manifestations and also to correlate ACE2 expression with the clinical and pathological parameters.
This cross sectional study was carried out on forty-seven patients presented with COVID-19 disease. They were selected from COVID-19 Quarantine Department in Sirs El-Layan and El-Bagour General Hospitals, Menoufia, Egypt, during the period from October 1st, 2021, to March 31st, 2022. All patients were not complaining of any experienced chronic skin lesions before COVID-19 disease.
All studied cases were subjected to complete history taking and thorough general and dermatological examinations. Assessment of ABCD score for triage of COVID-19 patients was done. Skin biopsies were taken under local anesthesia and sent to Pathology Department, Faculty of Medicine, Menoufia University for routine tissue processing and preparation of H&E stained slides and immunohistochemical procedure for detection of ACE2 receptor.
Highly significant differences were noted between COVID-19 patients with no skin manifestations and COVID-19 patients with skin manifestations. Since patients with no skin manifestations were of older age (P-value<0.001), have more comorbidities (P-value<0.001), positive family history (P-value<0.001) and higher ABCD score (Pvalue<0.001) compared to patients with skin manifestations. On the other hand, patients presented with skin manifestations showed histopathological inflammatory changes while no significant changes were detected in patients presented with no skin manifestations (Pvalue <0.001).
Hemoglobin levels (P-value =0.007), platelets count (Pvalue=0.001) and lymphocytes count (P-value<0.001) were lower in patients with no skin manifestations than those with skin manifestations.
Patients with skin manifestations had significantly lower CRP levels (P-value <0.001), lower LDH levels (P-value <0.001) and lower D- Dimer levels (P-value <0.001) than those with no skin manifestations.
Respiratory rate of patients with skin manifestations was lower than those with no skin manifestations (P-value <0.001) and patients with skin manifestations had higher O2 saturation than those without skin manifestations (P-value<0.001).
Regarding immunohistochemical results, ACE2 was expressed in the basal layer of epidermis in 40 (85.1%) cases with mild intensity in 24 (60%) cases moderate intensity in 14 (35%) cases and strong intensity in 2 (5%) cases. ACE2 expression was negative in 7(14.9%) cases.
In all 40 patients with positive ACE2 expression, there were 24 (60%) patients with normal skin and 16 (40%) patients presented with abnormal skin. However, in all 7 patients with negative ACE2 expression, there were one patient (14.3%) presented with normal skin and 6 patients (85.7%) presented with abnormal skin (P-value=0.040).
In positive COVID-19 patients LDH and D- Dimer levels were associated with positive ACE2 expression. ACE2 expression was significantly associated with high respiratory rate (P-value=0.033) and low O2 saturation (P-value=0.030) in the studied cases.