Background Coronavirus disease 2019 (COVID-19) is a systemic multi-organ viral illness. Previous studies have found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the damage to vascular tissues are not well-elucidated yet. Histological data in COVID-19 patients are still limited and are mainly focused on post-mortem analysis. Given that the skin is affected by COVID-19 and the relative ease of its histological examination, we aimed to examine the histology of skin lesions in COVID-19 patients to better understand the disease's pathology. Methods Five skin lesions from COVID-19 adult patients were selected for a deep histological tissue examination. Results A strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cell growth was identified. Endothelial cell distortion generated vascular lumen obliteration and striking erythrocyte and serum extravasation. Significant deposition of C4d and C3 throughout the vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also observed. Conclusions COVID-19 could comprise an obliterative microangiopathy consisting on endothelial and myointimal growth with complement activation. This mechanism, together with the increased vascular permeability identified, could contribute to obliteration of the vascular lumen and hemorrhage in COVID-19. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent increased risk of hemorrhage. Findings of this study could contribute to a better understanding of physiopathological mechanisms underlying COVID-19 on living patients and could help further studies find potential targets for specific therapeutic interventions in severe cases.

Background: Severe coronavirus disease 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet. Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to assess the pathophysiologic mechanisms in depth in living skin tissue related to Covid-19.Methods: Five skin lesions from caucasian Covid-19 adult patients were selected for cutaneous tissue histological examination including immunohistochemistry (IHC) and direct immunofluorescent (DIF) vast amount of data. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage in Covid-19 disease. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying Covid-19 infection on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients.

<b><i>Introduction:</i></b> Refractory cases of alopecia areata (AA) may be considered a therapeutic challenge. Intralesional methotrexate (IL-MTX) has been used in other dermatological diseases rather than AA. Likewise, its topical use as an immunosuppressant drug may be of interest for the control of the lymphoid infiltrate in AA. On the other hand, the use of fractional ablative laser is supported in literature as an alternative or complementary treatment in AA, whilst the generation of columns of thermal damage may favour the migration of cells and cytokines that are beneficial. <b><i>Case Presentation:</i></b> In this paper, we present 2 cases in which IL-MTX and ablative fractional CO₂ laser were combined with excellent outcomes. <b><i>Conclusion:</i></b> Previous research encompasses a total of 23 patients. Most patients presented with patchy AA. The doses administered ranged from 2.5 to 50 mg with an average frequency of 3 weeks. On average, most patients required a minimum of 3 sessions. One case employed 1% topical methotrexate ointment. Adverse local events were mild and transient. In conclusion, the concomitant application of these treatments has not been reported previously. Specific recommendations relating to the appropriate dosing of the drug, frequency of administration, and requirements for analytical control studies should be determined in further studies.

Background: Severe coronavirus disease 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet. Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to examine in depth skin lesions related to Covid-19 in order to understand better how the disease might affect living tissue.Methods: Five skin lesions from Covid-19 adult patients were selected for histological tissue examination. Vast amount of data of immunohistochemistry (IHC) and direct immunofluorescent (DIF) were part of the assessment. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage in Covid-19. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying SARS-CoV-2 infection on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients.