Discordant <scp>anti‐SARS‐CoV</scp>‐2 spike protein and <scp>RNA</scp> staining in cutaneous perniotic lesions suggests endothelial deposition of cleaved spike protein

Ko, Christine J.; Harigopal, Malini; Gehlhausen, Jeff R.; Bosenberg, Marcus W.; McNiff, Jennifer M.; Damsky, William

doi:10.1111/cup.13866

Cited by 47 publications

(57 citation statements)

References 41 publications

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“…Another recent study by Ko et al. demonstrated protein spikes fragments in endothelial cells of cutaneous lesions lacking RNA evidence in ISH suggesting that endothelial incorporated spikes elements rather than the presence of virions may play the pathogenic role in COVID-19 endotheliitis [65] …”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

et al. 2021

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

et al. 2021

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“…of endothelial infection in deceased COVID-19 patients [30] and called into question the validity of identifying virally-infected cells based on the presence of the SARS-CoV-2 spike protein [31,32].…”

Section: Introductionmentioning

confidence: 99%

“…Autopsy studies on COVID-19 patients have suggested the presence of viral particles in the vascular beds of different organs [3,25,26] and others have shown SARS-CoV-2 infection of cultured endothelial cells [27,28] and human blood vessel organoids [29]. In contrast, several studies have failed to find evidence of endothelial infection in deceased COVID-19 patients [30] and called into question the validity of identifying virally-infected cells based on the presence of the SARS-CoV-2 spike protein [31,32].…”

Section: Introductionmentioning

confidence: 99%

“…Autopsy studies of deceased COVID-19 patients have also shown SARS-CoV-2 RNA to be enriched in pulmonary endothelial cells 33 . In contrast, several studies have failed to find evidence of endothelial infection in deceased COVID-19 patients and called into question the validity of identifying virally-infected cells based on the presence of the SARS-CoV-2 spike protein 25,34,35 . Animal models of SARS-CoV-2 infection have also failed to identify any obvious signs of endothelial infection 36,37 , despite clear endothelial dysfunction and thrombosis 38 .…”

Section: Introductionmentioning

confidence: 99%

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Endothelial cells elicit a pro-inflammatory response to SARS-CoV-2 without productive viral infection

Schimmel

Chew

Stocks

et al. 2021

Preprint

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Thrombotic and microvascular complications are frequently seen in deceased COVID-19 patients, suggesting that vascular pathology is a major driver of severe disease. However, whether this is caused by direct viral infection of the endothelium or inflammation-induced endothelial activation remains highly contentious. What role the endothelium plays in viral amplification and inflammation thus remains a key unresolved question in the pathogenesis of SARS-CoV-2. Here, we use patient autopsy samples, primary human endothelial cells and an in vitro model of the pulmonary epithelial-endothelial cell barrier to show that primary human endothelial cells express the SARS-CoV-2 receptor ACE2 and the protease TMPRSS2, albeit at low levels. Accordingly, when present in a sufficiently high concentration, SARS-CoV-2 can enter primary human endothelial cells from either the apical or basolateral surface. Whilst inducing an inflammatory response, this is not a productive infection. We further demonstrate that in a co-culture model of the pulmonary epithelial-endothelial barrier, endothelial cells are not infected with SARS-CoV-2. They do however, sense and respond to an infection in the adjacent epithelial cells, resulting in the induction of a pro-inflammatory response. Taken together, these data suggest that in vivo, endothelial cells are unlikely to be infected with SARSCoV-2 and that infection is only likely to occur if the adjacent pulmonary epithelium is denuded (basolateral infection) or a high viral load is present in the blood (apical infection). In such a scenario, whilst SARS-CoV-2 infection of the endothelium can occur, it does not contribute to viral amplification. However, endothelial cells are still likely to play a key role in SARS-CoV-2 pathogenesis by sensing and mounting a pro-inflammatory response to SARS-CoV-2.

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“…Despite the increasing knowledge of COVID‐19‐related skin lesions, few studies have attempted to demonstrate the presence of the virus in skin lesions by real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) 1,2 …”

Section: Case Cutaneous Manifestation Age Sex Medical History Systemic Symptoms Rt‐pcr Nasopharyngeal Sars‐cov‐2 Serology Clinical Evolumentioning

confidence: 99%

Absence of SARS‐CoV‐2 RNA detection in tissue samples of COVID‐19‐related cutaneous lesions analyzed by real‐time RT‐PCR

García‐Gil

Serrano

García

et al. 2021

Acad Dermatol Venereol

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infection has not been found. 5 This is the first description of the second wave, and cases of CLL are probably expected to increase again.The reason of this phenomenon is still unknown, but two different hypotheses could be advanced.The first and most accepted one supports a relationship with SARS-CoV-2 infection, whose contact would induce in young patients a higher innate more than cell-mediated immune response with consequent fast clearance of antibodies and appearance of CLL. [6][7][8][9][10] The second less likely hypothesis is due to immobility; indeed, in Italy the first outbreak was observed during the lockdown and the second outbreak is now occurring during the soft lockdown as well. Young guys are the most affected by these measures because they are not attending schools and spending most of their time sat down watching monitors or TV. The lack of mobility could create a decreased blood flow with consequent appearance of CLL. Although interesting, against this second hypothesis is that frostbite is not among the cutaneous signs observed in paraplegic or wheelchair-immobilized patients.We would like to share these new data about the second outbreak and need to wait what is going to happen in the next future in order to understand whether the Italian CLL will be followed by the rest of Europe.

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Discordant anti‐SARS‐CoV‐2 spike protein and RNA staining in cutaneous perniotic lesions suggests endothelial deposition of cleaved spike protein

Cited by 47 publications

References 41 publications

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

Endothelial cells elicit a pro-inflammatory response to SARS-CoV-2 without productive viral infection

Absence of SARS‐CoV‐2 RNA detection in tissue samples of COVID‐19‐related cutaneous lesions analyzed by real‐time RT‐PCR

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