Development of a novel angiotensin converting enzyme 2 stimulator with broad implications in SARS-CoV2 and type 1 diabetes.

Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory syndrome coronavirus 2 (SARs-CoV2), thus decrease infection, would be of high relevance to cardiovascular disease, diabetes and SARs-CoV2 infection. While the need for such a drug lead was highlighted over a decade ago receiving over 600 citations, 1 to date, no such drugs are available. 2 Here, we report the development of a novel ACE2 stimulator, designated '2A'(international PCT filed), which is a 10 amino acid peptide derived from a snake venom, and demonstrate its in vitro and in vivo efficacy against SARs-CoV2 infection and associated lung inflammation. Peptide 2A also provides remarkable protection against glycaemic dysregulation, weight loss and disease severity in a mouse model of type 1 diabetes. No untoward effects of 2A were observed in these pre-clinical models suggesting its strong clinical translation potential.

Utility of RT-PCR versus electronic track and trace system for pre-procedural COVID-19 screening- a retrospective cohort study.

Background and aims: COVID-19 has disrupted the patient workflow in all healthcare settings. Procedures such as bronchoscopy and spirometry require additional pre-procedure screening for SARS-CoV-2. However, there is uncertainty regarding the utility of this universal pre-procedure screening. The State of Qatar has a robust contact tracing system in place in the form of the mobile application 'Ehteraz.' This study assesses the utility of various pre-procedural screening measures in asymptomatic patients and generate recommendations for any potential improvement in the workflow. Methods: This is a cross-sectional study of asymptomatic patients who had SARS-CoV-2 RT-PCR screening performed before bronchoscopy or lung function testing scheduled on an elective basis. Descriptive statistics were used to summarize and determine the sample characteristics. The rate of the positive PCR test result was subsequently calculated. Results: Two patients (0.34%) tested positive for COVID-19 on their pre-procedural screen. Four patients (0.68%) had an inconclusive result. Conclusion: The positivity rate of SARS-CoV-2 RT-PCR is extremely low in asymptomatic individuals screened before bronchoscopy and spirometry. The authors recommend pre-procedural symptom and electronic application-based contact screening instead of universal pre-procedural SARS-CoV-2 RT-PCR for screening asymptomatic individuals.

Pulmonary embolism in COVID-19, risk factors and association with inflammatory biomarkers.

The coronavirus disease 2019 (COVID-19) pandemic affected millions of people worldwide resulting in a substantial number of hospitalizations. Venous thromboembolism including pulmonary embolism is a known complication of COVID-19 pneumonia although its incidence in such patients is unclear. In this multicenter retrospective cohort study, we looked at the incidence of pulmonary embolism in COVID-19 patients and its associations with various risk factors including demographics, comorbidities, inflammatory markers and coagulation profiles. We analyzed data from 193 patients of mixed ethnicity with a mean age of 51, mostly South Asians (62%) and Arabs (29%). Diabetes and hypertension were the most prevalent comorbidities accounting for 46% (N = 88) and 36% (N = 71) respectively. Critical COVID-19 illness was diagnosed in 67% of patients. The frequency of COVID-19 related pulmonary embolism was 21.8% (N = 42). We found no association of pulmonary embolism with demographic, comorbid or inflammatory variables. Only a raised D-Dimer was found to be associated with pulmonary embolism. Having a pulmonary embolism had no impact on the length of stay, critical illness, or mortality. Receiving steroids or being on standard thromboprophylaxis or weight/D-Dimer adjusted thromboprophylaxis also had no impact on the frequency of pulmonary embolism. Nine incidents of major bleeding were recorded independent of therapeutic anticoagulation. Patients admitted to the hospital for COVID-19 pneumonia had a relatively high incidence of pulmonary embolism. D-dimer was the only associated laboratory parameter associated with pulmonary embolism. However, further research is needed to evaluate its predictive and prognostic utility, particularly in an older population.

Pre-procedural SARS-CoV-2 PCR testing in the pulmonary function laboratory at a tertiary government hospital in Qatar: A clinical audit.

BACKGROUND: Prior to pulmonary function testing (PFT), local and international recommendations advise pre-procedural screening. Pulmonary function tests generate aerosol droplets containing millions of viruses, significantly increasing the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission not only to the individuals in and around the PFT office, but also to subsequent patients who undergo the test later in the same room. METHODS: This clinical audit was carried out to establish the rate of positive pre-procedural SARS-CoV-2 PCR testing before a PFT. The data were obtained over a 6-week period from our ATS accredited pulmonary function laboratory at the Hamad General Hospital, Qatar (December 01, 2021, to January 10, 2022). The PFT laboratory was closed from January 10, 2022, till the date of this report (January 27, 2022) owing to an increase in COVID cases in the community in Qatar during the fourth wave. RESULTS: All the patients scheduled for PFT were asymptomatic of COVID-19. A total of 331 individuals were scheduled for PFT, and 221 PFTs were performed. There were 109 no-shows for both the PCR and the PFT. Between weeks 1 and 4, all the pre-procedural SARS-CoV-2 PCR tests were negative. The weekly average number of COVID-19 cases in Qatar increased from 157 per 100,000 population in week 1 to 2,918 in week 6.2 There was a similar trend in the pre-procedural SARS-CoV-2 PCR tests that increased and resulted in identifying 9 cases with positive SARS-CoV-2 PCR test over weeks 5 and 6 (Figure 1). CONCLUSION: As the number of documented positive SARS-CoV-2 PCR tests in the community grew, so did the pre-procedural COVID-19 PCR positivity and the number of no-shows. The large number of no-shows may indicate greater worry or concern about contracting COVID-19 when visiting the hospital amid peak community cases. Our findings further call into question the utility of routinely performing pre-procedural PCR screening in asymptomatic cases when the prevalence of COVID-19 is low in the local population. Perhaps, it is time to consider replacing this with on-the-spot quick antigen testing for more effective use of resources.

In vitro Interleukin-7 treatment partially rescues MAIT cell dysfunction caused by SARS-CoV-2 infection.

MAIT cells have been shown to be activated upon several viral infections in a TCR-independent manner by responding to inflammatory cytokines secreted by antigen-presenting cells. Recently, a few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. In this study, we investigate the effect of SARS-CoV-2 infection on the frequency and phenotype of MAIT cells by flow cytometry, and we test in vitro stimulation conditions on the capacity to enhance or rescue the antiviral function of MAIT cells from patients with coronavirus disease 2019 (COVID-19). Our study, in agreement with recently published studies, confirmed the decline in MAIT cell frequency of hospitalized donors in comparison to healthy donors. MAIT cells of COVID-19 patients also had lower expression levels of TNF-alpha, perforin and granzyme B upon stimulation with IL-12 + IL-18. 24 h' incubation with IL-7 successfully restored perforin expression levels in COVID-19 patients. Combined, our findings support the growing evidence that SARS-CoV-2 is dysregulating MAIT cells and that IL-7 treatment might improve their function, rendering them more effective in protecting the body against the virus.

Severe acute respiratory syndrome coronavirus 2 as a potential cause of type 1 diabetes facilitated by spike protein receptor binding domain attachment to human islet cells: An illustrative case study and experimental data.

AIMS: Aim of this study is to report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, responsible for coronavirus disease 2019 (COVID-19), as a possible cause for type 1 diabetes by providing an illustrative clinical case of a man aged 45 years presenting with antibody-negative diabetic ketoacidosis post-recovery from COVID-19 pneumonia and to explore the potential for SARS-CoV-2 to adhere to human islet cells. METHODS: Explanted human islet cells from three independent solid organ donors were incubated with the SARS-CoV-2 spike protein receptor biding domain (RBD) fused to a green fluorescent protein (GFP) or a control-GFP, with differential adherence established by flow cytometry. RESULTS: Flow cytometry revealed dose-dependent specific binding of RBD-GFP to islet cells when compared to control-GFP. CONCLUSIONS: Although a causal basis remains to be established, our case and in vitro data highlight a potential mechanism by which SARS-CoV-2 infection may result in antibody-negative type 1 diabetes.

Pleural effusion as an isolated finding in COVID-19 infection.

Common radiological findings of COVID -19 infection include bilateral ground-glass opacities in lower lobes with a peripheral distribution. Pleural effusion is considered a rare manifestation of COVID -19 infection. We present a 52 years old patient with a three-week history of right-sided pleuritic chest pain, fever, and dyspnea. Laboratory investigations revealed high C-reactive protein and ferritin levels and a positive COVID-polymerase chain reaction (PCR) from a nasopharyngeal swab. Chest X-ray and Computed tomography (CT) identified a moderate right-sided pleural effusion, which was exudative with mixed cellularity and high Lactate dehydrogenase (LDH). Histopathology of thoracoscopic pleural biopsy didn't reveal granulomas, malignancy, or any microbiological growth. We postulate that having ruled out any other cause the effusion was likely related to the Covid-19 infection. Our case highlights that COVID-19 can present with isolated pleural effusions, therefore it should be kept as an etiology of effusions especially if other possible causes have been ruled out.

Pneumothorax In Covid-19 Pneumonia: A case series.

BACKGROUND: Coronavirus disease 2019 (Covid-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It mainly affects the lungs and common symptoms are fever, cough and shortness of breath. Pneumothorax has been noted to complicate Covid-19 cases requiring hospital admission, however the exact incidence and risk factors are still unknown. DISCUSSION: We present a series of 3 cases of primary spontaneous pneumothorax with Covid-19 pneumonia. All cases in our series did not require positive pressure ventilation and none had any pre-existing lung disease. All were never smokers and had favourable outcomes despite having severe Covid-19 with a pneumothorax during the course of the disease. In our literature review we discuss several plausible mechanisms and risk factors resulting in a pneumothorax with Covid-19. CONCLUSION: Our cases are a reminder that an acute deterioration with hypoxia in a Covid-19 patient could indicate a pneumothorax. Pneumothorax is one of the reported complications in Covid-19 and clinician vigilance is required during assessment of patients, as both share the common symptom of breathlessness and therefore can mimic each other.