SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.
Background: Telephones, internet-connected devices (phablets, personal computers), chat platforms, and mobile apps (eg, Skype, Facebook Messenger, WhatsApp) can be exploited for telemedicine applications. WhatsApp and similar apps are also widely used to facilitate clinical communication between physicians. Moreover, WhatsApp is used by emergency department (ED) physicians and consulting physicians to exchange medical information during ED consultations. This platform is regarded as a useful app in the consultation of dermatological and orthopedic cases. Preventing overcrowding in the ED is key to reducing the risk of disease transmission, and teleconsulting practice is thought to be effective in the diagnosis, treatment, and reduction of transmission risk of disease, most notably during the COVID-19 pandemic. Video consultation is highly recommended in some countries on the grounds that it is likely to reduce the risk of transmission. WhatsApp-like apps are among the video consultation platforms that are assumed to reduce the risk of contamination by minimizing patient-physician contact. Objective: The aim of this study was to investigate the effects of WhatsApp video consultation on patient admission and discharge times in comparison to bedside consultation in the evaluation of potential patients with COVID-19 visiting a COVID-19 outpatient clinic during the pandemic. Methods: Patients who presented to the ED COVID-19 outpatient clinic between March 11 and May 31, 2020, and for whom an infectious disease specialist was consulted (via WhatsApp or at bedside) were included in the study in accordance with the inclusion and exclusion criteria. Eventually, 54 patients whose consultations were performed via WhatsApp and 90 patients whose consultations were performed at bedside were included in our study. Results: The median length of stay in the ED of discharged patients amounted to 103 minutes (IQR 85-147.75) in the WhatsApp group and 196 minutes (IQR 141-215) in the bedside group. In this regard, the length of stay in the ED was found to be significantly shorter in the WhatsApp group than in the bedside group (P<.001). Among the consulted and discharged patients, 1 patient in each group tested positive for SARS-CoV-2 by polymerase chain reaction test and thus was readmitted and hospitalized (P=.62). The median length of stay of the inpatients in the ED was found to be 116.5 minutes (IQR 85.5-145.5) in the WhatsApp group and 132 minutes (IQR 102-168) in the bedside group. The statistical analysis of this time difference revealed that the length of stay in the ED was significantly shorter for patients in the WhatsApp group than in the bedside group (P=.04). Conclusions: Consultation via WhatsApp reduces both contact time with patients with COVID-19 and the number of medical staff contacting the patients, which contributes greatly to reducing the risk of COVID-19 transmission. WhatsApp consultation may prove useful in clinical decision making as well as in shortening process times. Moreover, it does not result in a decreased accuracy rate. The shortened discharge and hospitalization timespans also decreased the length of stay in the ED, which can have an impact on minimizing ED crowding. Trial Registration: ClinicalTrials.gov NCT04645563; https://clinicaltrials.gov/ct2/show/NCT04645563.
Immune cell-type composition changes with age, potentially weakening the response to infectious diseases. Profiling epigenetics marks of immune cells can help us understand the relationship with disease severity. We therefore leveraged a targeted DNA methylation method to study the differences in a cohort of pneumonia patients (both COVID-19 positive and negative) and unaffected individuals from peripheral blood. This approach allowed us to predict the pneumonia diagnosis with high accuracy (AUC = 0.92), and the PCR positivity to the SARS-CoV-2 viral genome with moderate, albeit lower, accuracy (AUC = 0.77). We were also able to predict the severity of pneumonia (PORT score) with an R2 = 0.69. By estimating immune cellular frequency from DNA methylation data, patients under the age of 65 positive to the SARS-CoV-2 genome (as revealed by PCR) showed an increase in T cells, and specifically in CD8+ cells, compared to the negative control group. Conversely, we observed a decreased frequency of neutrophils in the positive compared to the negative group. No significant difference was found in patients over the age of 65. The results suggest that this DNA methylation-based approach can be used as a cost-effective and clinically useful biomarker platform for predicting pneumonias and their severity.
Background/Aim: Endoplasmic reticulum (ER) stress plays a critical role in the development of cardiac hypertrophy and heart failure. Heart failure is a crucial health problem that affects 23 million people worldwide, causes approximately 2.4 million people to be hospitalized every year in the USA, and leads to the death of more than 300,000 people. In this study, we aimed to investigate the clinical significance of ER stress markers and the predictive value of acute decompensated heart failure in patients with low ejection fraction heart failure (ADHF). Patients and Methods: This is a prospective case control study. The data included laboratory parameters pertaining to patients with ADHF in the emergency service and lipid parameters obtained during their admission to the hospital. In addition, the same parameters obtained from the control group patients with chronic heart failure (CHF) during their routine polyclinic control were recorded in the data set. Admission time to the hospital and length of hospital stay were included in the data. The levels of glucose regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) in peripheral blood serum obtained from the patients and the control group were measured using the ELISA method. Results: Serum GRP78 concentration was lower in the HF group (p=0.003) compared to the control. The median value of serum PERK concentration in the HF group was higher than that of the control group (573 pg/ml, IQR=477.5-650 vs. 495.5 pg/ml, IQR=294-648, respectively) (p=0.001). However, there were no statistically significant differences in GRP78 and PERK serum concentrations between ADHF and CHF subgroups. Receiver operating characteristic (ROC) curve analysis showed greater area under the curve (AUC) for the serum GRP78 levels of the healthy individuals (AUC=0.748, 95% CI=0.681-0.814, p=0.0003). The serum GRP78 level was found to be 80% sensitive and 70% specific at 147.5 pg/ml (p=0.0003) for distinguishing healthy individuals from HF patients. In the ADHF subgroup, there was a moderate correlation between hospitalization time and serum CHOP concentrations (Spearman rho=0.586 and p=0.001). Conclusion: High GRP78 serum concentration may protect the patient from ER stress. In addition, the serum PERK level is high in patients with HF, whereas it is insufficient in predicting acute decompensation. CHOP may be useful in predicting the length of hospital stay in patients with ADHF.
1 May 2019 in The American Journal of Emergency Medicine
Recent studies have investigated the importance of Galetin-3 in inflammation, fibrosis, cell proliferation, cardiac disease, diabetes, and tumor formation. This study aims to investigate the role of the Galectin-3 level in the diagnosis of COVID-19 pneumonia and the value of the Galectin-3 level in predicting the clinical course of the patient. This study employed a prospective, case-control study design and was conducted at Bakircay University Ciğli Training and Research Hospital. A total of 100 patients (40 had moderate and 60 had severe/critical COVID-19 disease according to World Health Organisation guidelines) and 50 non-symptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, Galectin-3 levels were evaluated using the enzyme-linked immunosorbent assay (ELISA) method. The serum Galectin-3 level was measured as 13.57 (10.9-16.4) ng/mL in the control group, 13.52 (10.69-16.6) ng/mL in the moderate disease group, and 11.65 (6.09-14.33) ng/mL in the severe/critical disease group. Serum Galectin-3 levels were significantly lower in the severe/critical disease group compared to the control and moderate disease groups (p=0.001 and p=0.019, respectively). Using ROC analysis, a larger area under the curve (AUC) for the serum Galectin-3 levels of the control group (AUC=0.622, 95% CI =0.529-0.714; p=0.015) was calculated compared to the COVID-19 patient group for the diagnosis of COVID-19 disease. The Galectin-3 level was found to be 75% sensitive and 50% specific at a cut-off level of 11.3 ng/mL in predicting the need for ICU treatment. Galectin-3 levels may be a beneficial biomarker in predicting the clinical severity of COVID-19 disease when used in conjunction with other known biomarkers, at the time of admission to the emergency department (ED).