Further Findings Concerning Endothelial Damage in COVID-19 Patients

Gelzo, Monica; Cacciapuoti, Sara; Pinchera, Biagio; Rosa, Annunziata De; Cernera, Gustavo; Scialò, Filippo; Comegna, Marika; Mormile, Mauro; Fabbrocini, Gabriella; Parrella, Roberto; Corso, Gaetano; Gentile, Ivan; Castaldo, Giuseppe

doi:10.3390/biom11091368

Cited by 10 publications

(12 citation statements)

References 40 publications

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“…Neutrophils transiently increased at 2 dpi, and PTPRC + B cells increased at 2 and 5 dpi and then decreased at 7 dpi (Figure 3C; Supplementary Figure 4). The neutrophil-to-lymphocyte (NTL) ratio is crucial for prognosis and mortality in patients with COVID-19 (29)(30)(31)(32)(33)(34)(35); thus, we hypothesised that the composition of peripheral blood leucocytes would also vary in the SARS-CoV-2 infection mouse models. CBC analysis showed that the NTL ratio significantly increased to 7.34%, 20.64%, 11.94%, and 25.01% at 1, 2, 5, and 7 dpi, respectively, in K18-hACE2 mice (Figure 3D).…”

Section: Sars-cov-2 Infection Is Lethal In K18-hace2 Mice But Not In ...mentioning

confidence: 99%

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits

Kim

Jang

et al. 2022

Front. Immunol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

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Section: Sars-cov-2 Infection Is Lethal In K18-hace2 Mice But Not In ...mentioning

confidence: 99%

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits

Kim

Jang

et al. 2022

Front. Immunol.

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“…The authors believe that this confirms the importance of endothelial activation in the VTE mechanism in this disease (Fenyves et al, 2021). However, other authors believe (Gelzo et al, 2021) that endothelial damage is less relevant, since the level of E-selectin did not change, in contrast to platelet P-selectin. However, as the experience of many researchers shows, in most patients, along with coagulopathy, endotheliopathy is observed, and there is a need to strictly monitor the blood coagulation parameters of patients with varying degrees of COVID-19.…”

Section: P-selectin Is An Early Biomarker Of Thrombotic Complicationsmentioning

confidence: 56%

Role of P-Selectin in the Development of Hemostasis Disorders in COVID-19

Golubeva

2022

Biol Bull Rev

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This is a review of data on the impact of COVID-19 on blood clotting. An important feature of the pathogenesis of severe acute respiratory syndrome caused by the SARS-Co-2 coronavirus is the risk of thrombotic complications including microvascular thrombosis, venous thromboembolism, and stroke. These thrombotic complications, like thrombocytopenia, are markers of the severe form of COVID-19 and are associated with multiple organ failure and increased mortality. One of the central mechanisms of this pathology is dysregulation of the adhesive protein P-selectin. The study of the mechanisms of changes in hemostasis and vascular pathology, and the role in these processes of biomarkers of thrombogenesis, and primarily of P-selectin of various origins (platelets, endothelial cells, and plasma), can bring some clarity to the understanding of the pathogenesis and therapy of COVID-19.

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“…For instance neutrophil/lymphocyte ratio was been associated with disease severity with the original SARS-COV-2 variant due to significant reduction in lymphocytes and increase of neutrophils in patients with severe COVID during this phase of the pandemic. However this has not been replicated with subsequent waves and counts of neutrophils and lymphocytes may not change significantly between different severity groups [18]. There are some limitations to our report.…”

Section: Plos Onementioning

confidence: 60%

Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients

Ritchie

Kadwani²,

Saleh³

et al. 2022

PLoS ONE

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A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p<0.05) and d-dimer lower. The 28-day mortality was not statistically significant (1st wave: 42.2% vs 2nd wave: 39.8%). However, when adjusted for key covariates, the hazard ratio for 28-day mortality in those patients with B.1.1.7 was 3.79 (CI 1.04–13.8; p = 0.043) compared to the original strain. During the second surge in the UK, where the COVID-19 variant B.1.1.7 was most prevalent, significantly more patients presented to critical care with severe ARDS. Furthermore, mortality risk was significantly greater in our ICU population during the second wave of the pandemic in those patients with B.1.1.7. As ICUs are experiencing further waves (particularly by the delta (B.1.617.2) variant), we highlight the urgent need for prospective studies describing immunological and pathophysiological differences across novel emerging variants.

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Further Findings Concerning Endothelial Damage in COVID-19 Patients

Cited by 10 publications

References 40 publications

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits

Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits

Role of P-Selectin in the Development of Hemostasis Disorders in COVID-19

Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients

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