Lessons from dermatology about inflammatory responses in Covid‐19

Abstract

Summary The SARS‐Cov‐2 is a single‐stranded RNA virus composed of 16 non‐structural proteins (NSP 1‐16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid‐19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid‐19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a ‘cytokine storm’. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D‐dimer, lactic dehydrogenase, reactive‐C‐protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug‐related intertriginous and flexural exanthema. This review describes the complexity of Covid‐19, its pathophysiological and clinical aspects.

Clinicopathologic correlations of COVID-19–related cutaneous manifestations with special emphasis on histopathologic patterns

“…SARS-CoV-2 might directly and/or indirectly induce mast cell and basophil activation, although not yet showed. 65 Late-onset persistent lesions are probably related to the general immune system activation, confirmed by the association with vasculitis and absence of eosinophils in the infiltrate, with spongiotic or lichenoid interface dermatitis. 63 , 64 …”

“…Of the 84 contributions accepted for our analysis, 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14. , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , ...…”

“…Age appears as a limiting factor, as severe coagulopathy is unlikely to develop in young otherwise healthy patients, and the host response against the viral spread is more effective. 11 Advanced age, together with comorbidities, unleashes an exaggerate innate immune response, named “macrophage activation syndrome associated with a more severe prognosis.” 1 , 2 , 3 , 11 , 65 …”

Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies

“…A hypergeometric test returned a p-value of 3.59e-03, demonstrating the reliability and validity of our computational approaches. 30 further drugs that we identified have also been reported as being potential candidates against COVID-19 (Courtney J. Mycroft-West, Dunhao Su , Yong Li , Scott E. Guimond, Timothy R. Rudd and Elli, Gavin Miller, Quentin M. Nunes, Patricia Procter, Antonella Bisio, Nicholas R. Forsyth, Jeremy E. Turnbull, Marco Guerrini, David G. Fernig, Edwin A. Yates, 2020;Criado et al, 2020;Kuleshov et al, 2020;kumar, arun;C.S, Sharanya;J, Abhithaj;MirIbrahim Sajid, Javeria Tariq, SheharBano Awais, ZehraNaseem, SamiraShabbir Balouch, 2020;Shin et al, 2020). Thus, drug efficacy simulation has revealed 70 drugs in total that are either in COVID-19 clinical trials or being considered as potential drug candidates in pre-clinical studies, supporting the strength of our approach.…”

Projected supportive effects of PycnogenolⓇ in patients suffering from multi-dimensional health impairments after a SARS-CoV2 infection

“…In addition, recent studies depict an association of kidney diseases, like nephritis, resulting in capillary leak syndrome in severe cases of COVID-19 [ 20 , 21 ]. Furthermore, the dermatological symptoms that come with a SARS-CoV2 infection can be very diverse and severe, as erythematous and urticarial rashes, blue toe syndrome, vesicles lesions, retiform purpura, livedo racemose and other conditions are described in patients [22] .The progression of the disease varies considerably between individuals, regarding the onset and severity of the different symptoms and of the outcome [23] . Advanced age, obesity and comorbidities, such as chronic heart disease, diabetes, chronic obstructive pulmonary disease and asthma increase the susceptibility of patients to the corona virus [ 23 , 24 ].…”