Methods
Since it is quite difficult to verify, in which context the skin lesions occur in terms of SARS-CoV-2 infections, we would like to summarize in the next few sections current knowledge about the pathophysiologic background of virus-induced and drug-induced lesions of the skin and the vascular system.
Data for this Review were identified by searches of MEDLINE, Current Contents, PubMed, and references from relevant articles using the search terms “SARS-CoV-2”, “COVID-19”, “skin”, ”vascular system“, ”virus (infection)“ and ”drug hypersensitivity reaction“. Only articles published in English between 1995 and 2020 were included.
Possible pathogenic mechanisms involved for skin manifestations
Viral rashes
Viral exanthema is defined as a skin rash, which is sometimes associated with an enanthem and goes along with fever and other systemic symptoms (51, 52 ). In this context, it is important to notice that also the ACE2 receptor has been described to be expressed in the oral cavity (11 ), lesions of the mucous membranes have not been reported so far to occur very frequently together with skin lesions in SARS-CoV-2 positive cases,
In principle, skin manifestation of viral infections can derive by
  1. direct inoculation of the virus,
  2. dissemination or reactivation of the virus from another site or
  3. interaction of the virus with the immune system in general and related cellular and humoral immune responses including virus-specific lymphocytes and antibodies (51 ).
The onset of the skin lesions in relation to viremia and general symptoms can help to understand the pathophysiologic mechanisms behind the lesions in COVID-19 patients. In the case of skin lesions precede general symptoms or might even be the only sign for a putative infection, they might serve as important early indicators of the disease or indicator for asymptomatic virus carriers. On the other hand-side, skin symptoms, which occur quite late during infection or even after resolution of main symptoms might indicate a lack of viral clearance and cascades of immune responses induced by the virus .
Viremia often predates the typical COVID-19 symptoms and virus-specific virology might be both, false negative or false positive due to cross-reactivity to other members of the coronavirus family, but could provide important information about acute or previous infection by the analysis of virus-specific IgM and IgG. Nucleotide testing of tissue specimens is highly sensitive and specific, but stability of samples and RNA, contamination, and other issues may occur and limit information gained, so that even part of smear taken from the mouth remain false negative (52 ).