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1.
Biol Chem ; 402(12): 1505-1518, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1562377

ABSTRACT

COVID-19 primarily affects the respiratory system and may lead to severe systemic complications, such as acute respiratory distress syndrome (ARDS), multiple organ failure, cytokine storm, and thromboembolic events. Depending on the immune status of the affected individual early disease control can be reached by a robust type-I-interferon (type-I-IFN) response restricting viral replication. If type-I-IFN upregulation is impaired, patients develop severe COVID-19 that involves profound alveolitis, endothelitis, complement activation, recruitment of immune cells, as well as immunothrombosis. In patients with proper initial disease control there can be a second flare of type-I-IFN release leading to post-COVID manifestation such as chilblain-like lesions that are characterized by thrombosis of small vessels in addition to an inflammatory infiltrate resembling lupus erythematosus (LE). Mechanistically, SARS-CoV-2 invades pneumocytes and endothelial cells by acting on angiotensin-II-converting enzyme 2 (ACE2). It is hypothesized, that viral uptake might downregulate ACE2 bioavailability and enhance angiotensin-II-derived pro-inflammatory and pro-thrombotic state. Since ACE2 is encoded on the X chromosome these conditions might also be influenced by gender-specific regulation. Taken together, SARS-CoV-2 infection affects the vascular compartment leading to variable thrombogenic or inflammatory response depending on the individual immune response status.


Subject(s)
Blood Coagulation , COVID-19 , Humans
2.
Dermatopathology (Basel) ; 7(3): 57-63, 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-965388

ABSTRACT

Contemporarily to the new SARS-CoV-2 mediated COVID-19 pandemic, a rise in patients with acral chilblain lesions has been described. They manifest late after mild disease or asymptomatic exposure to SARS-CoV-2. Their pathogenic evolution is currently unknown. In biopsies from three patients with acral partially ulcerating chilblain lesions that occurred associated to the COVID-19 pandemic, we analysed the expression of type I interferon induced proteins and signal transduction kinases. Histology demonstrated perivascular and periadnexal lymphohistiocytic infiltrates and endothelial dominated MxA-staining, as well as pJAK1 activation. Our findings demonstrate induction of the type I IFN pathway in lesional sections of COVID-19-associated chilblain-like lesions. This may indicate a local antiviral immune activation status associated with preceding exposure to SARS-CoV-2.

3.
J Dtsch Dermatol Ges ; 18(8): 810-814, 2020 Aug.
Article in German | MEDLINE | ID: covidwho-966839
5.
J Dtsch Dermatol Ges ; 18(8): 810-813, 2020 08.
Article in English | MEDLINE | ID: covidwho-693539

ABSTRACT

The current SARS-CoV-2 pandemic particularly endangers older people with pre-existing cardiopulmonary and metabolic conditions. However, it is also currently under discussion whether patients under immunosuppressive therapy also have a higher risk of suffering a severe course of the COVID-19 disease. In principle though, there is currently no data available for a general reduction or pause of immunosuppression in patients with autoimmune diseases because of the SARS-CoV-2 pandemic. However, since there is currently neither an effective therapy nor corresponding vaccination protection, the indication for a prolonged immunosuppressive therapy should be made with special care. In particular, immunotherapeutic agents that produce long-term effects (e.g., rituximab) should be used with special caution. In contrast, immunomodulating substances that do not suppress antiviral immunity (e.g. systemic immunoglobulins, doxycycline), or that have intrinsic effects on SARS-CoV-2 (calcineurin inhibitors, chloroquine, hydroxychloroquine) may be useful alternatives.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , /adverse effects , COVID-19/immunology , Chloroquine/pharmacology , Doxycycline/pharmacology , Humans , Hydroxychloroquine/pharmacology
6.
J Dtsch Dermatol Ges ; 18(8): 815-824, 2020 08.
Article in English | MEDLINE | ID: covidwho-675932

ABSTRACT

COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.


Subject(s)
COVID-19/complications , Skin Diseases/etiology , COVID-19/immunology , Humans , Skin Diseases/pathology
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