Are H1 and H3 haplotypes of endothelial protein C receptor (PROCR) an important factor in contracting COVID-19?

The development of cardiovascular disease shows increase after contracting coronavirus 2019 (COVID-19) disease and myocardial damage is observed in patients who have had the disease severely. The relationship between genetic cardiovascular risk factors with COVID-19 infection was investigated in our study. One hundred thirty-five patients, 27 of whom were COVID-19 (-) and 108 were COVID-19 (+) patients, were included in the study. Patients were divided into three groups ([COVID-19 [-], COVID-19 [+] asymptomatic, and COVID-19 [+] symptomatic + patients with pulmonary involvement]). Genetic cardiovascular risk factors were examined in blood samples taken from the patients with new generation sequencing analysis. In the clinical classification, there were no significant differences between the three groups in fibrinogen beta chain-455G>A, human platelet antigen 1 (HPA1b)/platelet receptor GPIIIa/(ITGB3) (HPA1a/b; GpIIIa; integrin beta 3 L33P), ACE I/D, AGT (M268T), AGTR1 (1166A>C), Apo E (E2/E3/E4) (rs7412, rs429358), eNOS (786T>C), eNOS (894G>T) genes (p > 0.05). However, significant differences were observed in PROCR H3 haplotype/G (endothelial protein C receptor gene [EPCR] 4600A>G [A3 haplotype]), PROCR H1 haplotype/C (EPCR 4678G>C [A1 haplotype]) genes (p < 0.05). When COVID-19 (+) and COVID-19 (-) groups were compared, it was observed that the infection was more common in people with PROCR H1 haplotype/C and PROCR H3 haplotype/G genotypes (p < 0.05). PROCR H1 and PROCR H3 haplotypes may be an important factor in contracting COVID-19 disease. In people with COVID-19 disease, revealing PROCR genetic differences and measuring sEPCR levels will be beneficial in the follow-up of the disease.

Relationship between serum soluble endothelial protein C receptor level and COVID-19 findings.

Coronavirus-related disease-2019 (COVID-19)-associated coagulopathy presents predominantly with thrombosis and leads to complications in close association with inflammatory process. Soluble endothelial protein C receptor (sEPCR), which is the soluble form of EPCR, reduces the anticoagulant and anti-inflammatory activity of activated protein C. The purpose of this study is to investigate the relationship between sEPCR and the laboratory parameters and thorax computed tomography (CT) findings in the course of COVID-19. Twenty-five laboratory-confirmed [reverse transcription-quantitative polimerase chain reaction (RT-qPCR) positive] and 24 clinically diagnosed (RT-qPCR negative) COVID-19 patients were enrolled in the study. Blood specimens were collected for sEPCR and haematological and biochemical parameter measurement. Thorax CT was performed to detect COVID-19 findings. These parameters from RT-qPCR positive and negative patients were then compared. Although there was no difference between the groups in terms of symptoms, the time between the onset of symptoms and the admission time was shorter in RT-qPCR positive group (P = 0.000). sEPCR levels were significantly higher in the RT-qPCR positive group (P = 0.011). Patients with ground-glass opacity and bilateral involvement on thorax CT have higher serum sEPCR levels (P = 0.012 and 0.043, respectively). This study has shown for the first time that serum sEPCR levels, which is a member of coagulation cascade and has also been reported to be associated with inflammation, is higher in patients with positive RT-qPCR test and patients with GGO or bilateral involvement on thorax CT regardless of the PCR result.

Could Soluble Endothelial Protein C Receptor Levels Recognize SARS-CoV2-Positive Patients Requiring Hospitalization?

INTRODUCTION: The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in COVID-19 has not been explored. In this study, we investigated whether sEPCR levels were related to COVID-19 patients' requirement for hospitalization. METHODS: Plasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients, and in 11 non-hospitalized SARS-CoV2-positive patients approximately 6 days after reported manifestation of their symptoms. Multiple logistic regression analysis was performed to identify potential risk factors for hospitalization and receiver operating characteristic (ROC) curves were generated to assess their value. RESULTS: In our cohort, hospitalized patients had considerably higher sEPCR levels upon admission compared with outpatients [107.5 (76.7-156.3) vs. 44.6 (12.1-84.4) ng/mL; P < 0.0001)]. The ROC curve using hospitalization as the classification variable and sEPCR levels as the prognostic variable generated an area under the curve at 0.845 (95% CI = 0.710-0.981, P < 0.001). Additionally, we investigated the predictive value of sEPCR combined with BMI, age, or D-dimers. CONCLUSIONS: In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared with outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2-positive patients.

SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung.

Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins in COVID-19 patients imply local derangement of pathways that limit fibrin formation and/or promote its clearance. We examined transcriptional profiles of bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these coagulopathies. mRNA levels for regulators of the kallikrein-kinin (C1-inhibitor), coagulation (thrombomodulin, endothelial protein C receptor), and fibrinolytic (urokinase and urokinase receptor) pathways were significantly reduced in COVID-19 patients. While transcripts for several coagulation proteins were increased, those encoding tissue factor, the protein that initiates coagulation and whose expression is frequently increased in inflammatory disorders, were not increased in BALF from COVID-19 patients. Our analysis implicates enhanced propagation of coagulation and decreased fibrinolysis as drivers of the coagulopathy in the lungs of COVID-19 patients.