The differing pathophysiologies that underlie COVID-19 associated perniosis and thrombotic retiform purpura: a case series.

ABSTRACT: BACKGROUND:There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes: one is perniosis occurring in mildly symptomatic patients, typically children; the second is the thrombotic retiform purpura of critically ill COVID19 adults. MATERIALS AND METHODS:We compare light-microscopic, phenotypic, cytokine, and SARS-CoV-2 protein and RNA profiles in COVID-19-associated perniosis of mildly symptomatic or asymptomatic patients with the thrombotic retiform purpura of critical patients with COVID-19. RESULTS:The COVID-19-associated perniosis exhibited vasocentric and eccrinotropic T-cell and monocyte-derived CD11c, CD14, and CD123+ dendritic cell infiltrates. Both COVID associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein-A (MXA), an established marker for type I interferon signaling in tissue. SARS-CoV-2 RNA, IL- 6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, IL6, and caspase 3; SARS CoV-2 RNA was not seen. CONCLUSION:The COVID-19-associated perniosis represents an exaggerated immune reaction to a virus with significant type-I interferon signaling important to SARS-CoV-2 eradication and has implications in regards to a more generalized highly-inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID-19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response allowing excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation.

SUBMITTER: Magro C 

PROVIDER: S-EPMC7405151 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature