Human complement Factor H and Properdin act as soluble pattern recognition receptors and differentially modulate SARS-CoV-2 Infection (preprint)

Severe cases of SARS-CoV-2 infection are characterised by an imbalanced immune response, excessive inflammation, and the development of acute respiratory distress syndrome, which can lead to multiorgan failure and death. Several studies have demonstrated dysregulated complement activity as an indicator of immunopathogenesis in the SARS-CoV-2 infection. Notably, the complement alternative pathway has been implicated in driving the excessive inflammation during severe SARS-CoV-2 infection. Reduced levels of factor H (FH), a down-regulator of the alternative pathway, and increased levels of properdin (Factor P/FP), the only known up-regulator of the alternative pathway, have been observed in individuals with severe COVID-19 infection. The present study investigated the complement activation-independent, and a more direct role of FH and FP against SARS-CoV-2 infection. Using direct ELISA, the interactions of FH and FP with the SARS-CoV-2 spike (S) and receptor binding domain (RBD) were assessed. Using S protein expressing lentiviral pseudotypes, the cell binding and luciferase-based virus entry assays were employed to assess the potential modulatory effects of FH, FP, and recombinant thrombospondin repeats 4 and 5 (TSR4+5) on SARS-CoV-2 cell entry. We also evaluated the immunomodulatory functions of FH and FP in the cytokine response triggered by SARS-CoV-2 pseudotypes via RT-qPCR. SARS-CoV-2 S and RBD proteins were found to bind both FH and FP. Treatment of A549 cells expressing human ACE2 and TMPRSS2 with FP or TSR4+5 resulted in increased cell entry and binding of SARS-CoV-2 pseudotypes. In silico studies revealed that FP increases affinity between SARS-CoV-2 and host ACE2. The impact of FP on viral cell entry and binding was reversed by anti-FP antibody treatment in A549-hACE2+TMPRSS2 cells. However, FH treatment reduced the cell entry and binding of SARS-CoV-2 lentiviral pseudotypes. Furthermore, the A549-hACE2+TMPRSS2 cells challenged with SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes pre-treated with FP or TSR4+5, exhibited upregulation of the transcripts of pro-inflammatory cytokines, such as IL-1{beta}, IL-8, IL-6, TNF-, IFN- and RANTES (as well as NF-kB). Conversely, FH pre-treatment downregulated the expression of these pro-inflammatory cytokines. Treatment of A549-hACE2+TMPRSS2 cells with FP increased S protein-mediated NF-kB activation, while FH treatment reduced it. These findings suggest that FH may act as an inhibitor of SARS-CoV-2 cell entry and binding, thereby attenuating the infection-associated inflammatory response in a complement activation-independent manner. FP may contribute to viral cell entry, binding, and exacerbating the immune response. That may result in potentially influencing the severity of the infection.

Knowledge of Antibiotic Use and Antibiotic Resistance During the COVID-19 Pandemic Among Healthcare Professionals

Infections can be treated with antibiotics, which have also saved countless lives. But whenever antibiotics are administered, they run the risk of having negative side effects and fueling antibiotic resistance that was a significant public health issue. The current study aimed to describe healthcare workers' knowledge of antibiotic use and resistance during the COVID-19 epidemic in the city of Riyadh and included an online survey that was disseminated on social media. About 78% of the healthcare providers in the present study had an average knowledge score of more than 75%, so most of them had good knowledge. Most of the healthcare professionals in the present study had good knowledge about bacterial resistance and antibiotic use, but there was still a knowledge gap on antibiotic use. Therefore, it is crucial to raise their awareness by attending conferences, lectures, and workshops.

Optic neuropathy after COVID-19 vaccination: Case report and systematic review

Purpose:: To report a case of anterior ischemic optic neuropathy (AION) following COVID-19 vaccination and provide a systematic review of all published cases of optic neuropathy following COVID-19 vaccination. Method(s):: A systematic literature search was performed using PubMed and Ovid MEDLINE for cases of optic neuropathy following COVID-19 vaccination. Terms used in the search included "COVID-19 vaccination", "optic neuropathy", "optic neuritis", and "ischemic optic neuropathy". Titles and s were initially screened then full texts of eligible studies were reviewed for data extraction. Only cases published in the English language, peer reviewed, and that included details on optic nerve involvement were included. All study types were eligible for inclusion. Result(s):: Including our patient, a total of 10 patients (8 females) were identified as developing optic neuropathy following COVID-19 vaccination. Five patients (50.0%) were diagnosed with AION, while 4 (40.0%) were diagnosed with optic neuritis. One patient was diagnosed with papillitis and neuroretinitis. Three patients (30.0%) had bilateral involvement. Mean age of patients was 48.5+/-19.7 years. Mean time from vaccination to onset of ophthalmic symptoms was 6.5+/-6.4 days. Median (IQR) presenting visual acuity was logMAR 0.3 (0-1). For the 8 eyes which had both presenting and final follow-up visual acuity, median (IQR) presenting vision was logMAR 0.2 (0-0.7) and at final follow-up was logMAR 0 (0-0.05) (P=0.184). Conclusion(s):: COVID-19 vaccination may result in optic neuropathy in the form of optic neuritis and ischemic optic neuropathy. Further studies are needed to determine the incidence, management, and prognosis of optic neuropathies associated with COVID-19 vaccination.Copyright © 2022

Online Education amid COVID-19 Crisis: Issues and Challenges at Higher Education Level in Pakistan

The objective of this study is to examine the main constraints experienced in the online mode of education during this pandemic at higher education level in Pakistan. The COVID-19 pandemic credibly transformed the method of learning and teaching from face to face to online. In unexpected sudden septicity, universities in Pakistan have started online education without proper instructional provision and relevant experience. For this purpose, the data is collected from 750 students and teachers across all over the regions in Pakistan. The study has used partial least square structural equation modeling (PLS-SEM). The findings show that technological bottlenecks, institutional preparedness, and digital divide are significant challenges. The differences in perceptions of rural and urban areas are also very important referring to several policies implications, implementing information communication technology (ICT), friendly curriculums, enhancing online accessibility and infrastructure development. This study contributes to help universities for developing effective e-learning policies for students in the situation of COVID-19.

Implementing Infection Control Unit and Antimicrobial Use Committee Policies and Guidelines to Reduce the Incidence of Healthcare-associated Infections

To prevent or reduce the incidence and prevalence of infections, infection prevention and con-trol strategies are utilized. Antibiotic stewardship programs are also utilized to avoid antimicrobial-related toxicity, lower the costs of inappropriate antimicrobial usage, and reduce health-care-associated infections. The present study aimed to describe the effect of implementing infection control unit and antimicrobial use committee policies and guidelines in reducing the incidence of healthcare-associated infections. Data for all infected cases confirmed by an infection disease specialist between 2019 and 2021 was exported. The informa-tion was gathered from the reports written by the infection control unit. Central line-associated bloodstream infection rate was decreased from 1.15 per 1000 central line days in 2019 to 0 per 1000 central line days in 2021, and catheter-associated urinary tract infections rate decreased from 1.01 per 1000 urinary catheter days in 2019 to 0 per 1000 urinary catheter days in 2021, ventilator-associated pneumonia rate decreased from 2.11 per 1000 ventilator days in 2019 to 0 per 1000 ventilator days in 2019, surgical site infection rate decreased from 0.41% un 2019 to 0.2% in 2021, the rate of MDRO was decreased from 3.95 per 1000 patient days to 2.3 per 1000 patient days in 2021. Infection control unit practices, as well as an antibiotic stewardship program, were highly effective in preventing healthcare-associated infections, with significant decreases in antibiotic resistance.

SARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent pandemic outbreak threatening human beings worldwide. This novel coronavirus disease-19 (COVID-19) infection causes severe morbidity and mortality and rapidly spreading across the countries. Therefore, there is an urgent need for basic fundamental research to understand the pathogenesis and druggable molecular targets of SARS-CoV-2. Recent sequencing data of the viral genome and X-ray crystallographic data of the viral proteins illustrate potential molecular targets that need to be investigated for structure-based drug design. Further, the SARS-CoV-2 viral pathogen isolated from clinical samples needs to be cultivated and titrated. All of these scenarios demand suitable laboratory experimental models. The experimental models should mimic the viral life cycle as it happens in the human lung epithelial cells. Recently, researchers employing primary human lung epithelial cells, intestinal epithelial cells, experimental cell lines like Vero cells, CaCo-2 cells, HEK-293, H1299, Calu-3 for understanding viral titer values. The human iPSC-derived lung organoids, small intestinal organoids, and blood vessel organoids increase interest among researchers to understand SARS-CoV-2 biology and treatment outcome. The SARS-CoV-2 enters the human lung epithelial cells using viral Spike (S1) protein and human angiotensin-converting enzyme 2 (ACE-2) receptor. The laboratory mouse show poor ACE-2 expression and thereby inefficient SARS-CoV-2 infection. Therefore, there was an urgent need to develop transgenic hACE-2 mouse models to understand antiviral agents' therapeutic outcomes. This review highlighted the viral pathogenesis, potential druggable molecular targets, and suitable experimental models for basic fundamental research.

A Macromarketing Prescription for Covid-19: Solidarity and Care Ethics

Contextualized in the current pandemic, this essay discusses social marketing and public policy efforts from a ?social solidarity and care ethics? perspective. It presents a prototypical inclusivity-based approach for managing pandemics, with adaptive and maladaptive examples to show how the ?social solidarity and care ethics nexus? can and should ?travel? within and between societal strata. It positions this perspective as a form of phronetic polysemic marketing, and thus considers the complexity of pandemic sociopsychology and stresses the need for practical wisdom.

Management of a diagnostic radiology department amid Coronavirus disease-19 (COVID-19) pandemic.

Severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is a highly contagious infectious disease and spreads through aerosols and fomites. Health care personnel who are at the forefront of the fight against coronavirus disease-19 (COVID-19) pandemic are also at greater risk of contracting the infection. Mixing of uninfected people with infected people is potentially hazardous, especially in a radiology department. Implementation of meticulous operational changes, curtailment of nonurgent radiological work, rationalization of staff, equipment disinfection, use of personal protection equipment, and psychological support are needed to combat COVID-19 or any such infectious disease outbreak. This technical note will familiarize radiology workers with infectious disease outbreak-response to be adopted to ensure the safety of staff and patients.

Spectrum of chest CT manifestations of coronavirus disease (COVID-19): A pictorial essay.

Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus belonging to the family of betacoronaviruses. Chest computed tomography (CT) has helped us in understanding this new disease. Typical CT features of COVID-19 pneumonia are ground-glass opacities (GGO), crazy paving pattern and GGO with superimposed consolidation with a basal, posterior and peripheral lung predilection. Less commonly bronchial wall thickening, bronchial dilatation and pleural thickening are seen. Presence of pleural effusion, pericardial effusion and mediastinal lymphadenopathy is seen in severe cases. Reticulations, fibrous stripes, reverse halo sign and perilobular opacities are seen late (>2 weeks) in the course of illness. We aim to present a pictorial review of CT imaging findings in COVID-19 to illustrate the typical and atypical manifestations of this disease in a bid to familiarize radiologists with the myriad imaging manifestations of this disease.

Cavitary pulmonary tuberculosis with COVID-19 coinfection.

The COVID-19 pandemic has strained the healthcare system worldwide, leading to an approach favoring judicious resource allocation. A focus on resource preservation can result in anchoring bias and missed concurrent diagnosis. Coinfection of Mycobacterium tuberculosis (TB) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has implications beyond morbidity at the individual level and can lead to unintended TB exposure to others. We present six cases of COVID-19 with newly diagnosed cavitating pulmonary tuberculosis to highlight the significance of this phenomenon and favorable outcomes if recognized early.