REDACS: Regional emergency-driven adaptive cluster sampling for effective COVID-19 management

As COVID-19 is spreading, national agencies need to monitor and track several metrics. Since we do not have perfect testing programs on the hand, one needs to develop an advanced sampling strategies for prevalence study, control and management. Here we introduce REDACS: Regional emergency-driven adaptive cluster sampling for effective COVID-19 management and control and justify its usage for COVID-19. We show its advantages over classical massive individual testing sampling plans. We also point out how regional and spatial heterogeneity underlines proper sampling. Fundamental importance of adaptive control parameters from emergency health stations and medical frontline is outlined. Since the Northern hemisphere entered Autumn and Winter season (this paper was originally submitted in November 2020), practical illustration from spatial heterogeneity of Chile (Southern hemisphere, which already experienced COVID-19 winter outbreak peak) is underlying the importance of proper regional heterogeneity of sampling plan. We explain the regional heterogeneity by microbiological backgrounds and link it to behavior of Lyapunov exponents. We also discuss screening by antigen tests from the perspective of "on the fly" biomarker validation, i.e., during the screening. [ FROM AUTHOR] Copyright of Stochastic Analysis & Applications is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Propensity-Matched Comparison of Robotic-Assisted Pulmonary Lobectomy Outcomes in Pre-COVID-19 Patients versus COVID-19-Era Patients

INTRODUCTION: The COVID-19 pandemic has presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the COVID-19 pandemic has affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). METHOD(S): We retrospectively analyzed 721 consecutive patients who underwent RAPL between September 2010 and March 2022 by one surgeon at one institution. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as PreCOVID-19 and 83 patients as COVID-19-Era based on surgical date. An optimal variable ratio matching method of one to four PreCOVID-19 patients (with average of three) were matched to each COVID-19-Era patient. Variables used for matching were age, gender, smoking history in pack-years, and preoperative diabetes mellitus, coronary artery disease or myocardial infarction, and FEV1%. Variables of interest were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p<=0.05. Multivariable generalized linear regression was used to investigate predictors of the presence of postoperative complications and report odds ratios (OR). RESULT(S): COVID-19-Era patients had higher incidences of preoperative atrial fibrillation (p=0.027), peripheral vascular disease (p=0.0425), and pancreatitis (p=0.0349) compared to PreCOVID-19 patients. Differences in tumor size and histology, nodal status, and AJCC v8 pathologic stage were statistically insignificant. COVID-19-Era patients experienced a high incidence of effusion or empyema postoperatively (p< 0.0001). The PreCOVID-19 and COVID-19-Era cohorts had comparable odds for developing a postoperative complication. Older age, longer intraoperative skin-to-skin duration, and preoperative COPD are all predictive of an increased risk of developing a postoperative complication (Table 1). CONCLUSION(S): Despite our COVID-19-Era patients having greater indices of preoperative comorbidities, our analysis showed that they had a similar risk of developing a postoperative complication when compared to our PreCOVID-19 patients. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Patient age, skin-to-skin duration of the procedure, and preoperative COPD should be considered when planning for complication risk following RAPL.

The Effects of Statins on Respiratory Symptoms and Pulmonary Fibrosis in COVID-19 Patients with Diabetes Mellitus: A Longitudinal Multicenter Study.

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM.

Virtual reality for surgical planning, training and patient engagement in the field of congenital heart disease: a single centre experience

Introduction: The treatment of congenital heart disease (CHD) is complex and often requires a personalised approach involving several surgical interventions. Despite advancements in imaging, understandingCHDin 3D can still be a major challenge, especially for atypical cases spanning multiple pathologies. Virtual reality (VR) is a rapidly growing technology allowing the user to be completely immersed within a simulated environment. At our centre, we pioneered the use of VR for CHD to: (i) aid surgical planning (ii) enhance teaching and (iii) improve patient communication. Methods: A VR application has been designed in house specifically to meet these aims over the last year at our centre. The VR software allows the user to import multiple models of patient-specific anatomies reconstructed from medical images. The application uses a commercial headset with controllers to allow the user to interact with the virtual heart. Different tools were implemented to help the planning (measuring, cutting, device interaction), improve teaching (labelling, ultrasound simulators, multi-user experiences) and patient engagement (labelling, colours, splitting). The development was a collaborative process between clinicans, engineers and educators, allowing for tailored tools to be developed to address the clinical/educational needs. Results: In clinical practice, our VR app was successfully used for planning more than 20 cases, including: (i) double-outlet right ventricle repairs (ii) aortic root replacements for Marfan syndrome (iii) percutaneous pulmonary valve implantations (iv) stenting of pulmonary arteries. In an educational setting, VR has been routinely added to a specialised cardiac morphology course for healthcare professionals, over 90% of whom found it “extremely/very useful” in aiding their understanding of CHD. In addition, it was implemented in an undergraduate course during COVID- 19 to support remote learning, with the use of online multi-user teaching. Over the course of two years, more than 100 students were taught using VR. Finally, our app was found to be particularly engaging by patients and their families in understanding the complexity of CHD during public events held at our Centre. Conclusions: Our preliminary research with in-house developed VR software showed how this can be used in facilitating the understanding of CHD for treatment planning, education and communication.

An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.

The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.

Autophagy: The Potential Link between SARS-CoV-2 and Cancer.

COVID-19 infection survivors suffer from a constellation of symptoms referred to as post-acute COVID-19 syndrome. However, in the wake of recent evidence highlighting the long-term persistence of SARS-CoV-2 antigens in tissues and emerging information regarding the interaction between SARS-CoV-2 proteins and various components of the host cell macroautophagy/autophagy machinery, the unforeseen long-term consequences of this infection, such as increased risk of malignancies, should be explored. Although SARS-CoV-2 is not considered an oncogenic virus, the possibility of increased risk of cancer among COVID-19 survivors cannot be ruled out. Herein, we provide an overview of the possible mechanisms leading to cancer development, particularly obesity-related cancers (e.g., colorectal cancer), resulting from defects in autophagy and the blockade of the autophagic flux, and also immune escape in COVID-19 survivors. We also highlight the potential long-term implications of COVID-19 infection in the prognosis of patients with cancer and their response to different cancer treatments. Finally, we consider future directions for further investigations on this matter.

Quercetin as a Natural Therapeutic Candidate for the Treatment of Influenza Virus.

The medical burden caused by respiratory manifestations of influenza virus (IV) outbreak as an infectious respiratory disease is so great that governments in both developed and developing countries have allocated significant national budget toward the development of strategies for prevention, control, and treatment of this infection, which is seemingly common and treatable, but can be deadly. Frequent mutations in its genome structure often result in resistance to standard medications. Thus, new generations of treatments are critical to combat this ever-evolving infection. Plant materials and active compounds have been tested for many years, including, more recently, active compounds like flavonoids. Quercetin is a compound belonging to the flavonols class and has shown therapeutic effects against influenza virus. The focus of this review includes viral pathogenesis as well as the application of quercetin and its derivatives as a complementary therapy in controlling influenza and its related symptoms based on the targets. We also touch on the potential of this class of compounds for treatment of SARS-COV-2, the cause of new pandemic.

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. RESULTS: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61-2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07-2.33), P = 0.312]. CONCLUSIONS: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

Quercetin as a Natural Therapeutic Candidate for the Treatment of Influenza Virus

The medical burden caused by respiratory manifestations of influenza virus (IV) outbreak as an infectious respiratory disease is so great that governments in both developed and developing countries have allocated significant national budget toward the development of strategies for prevention, control, and treatment of this infection, which is seemingly common and treatable, but can be deadly. Frequent mutations in its genome structure often result in resistance to standard medications. Thus, new generations of treatments are critical to combat this ever-evolving infection. Plant materials and active compounds have been tested for many years, including, more recently, active compounds like flavonoids. Quercetin is a compound belonging to the flavonols class and has shown therapeutic effects against influenza virus. The focus of this review includes viral pathogenesis as well as the application of quercetin and its derivatives as a complementary therapy in controlling influenza and its related symptoms based on the targets. We also touch on the potential of this class of compounds for treatment of SARS-COV-2, the cause of new pandemic.

Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management?

In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection.

FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.

In December 2019, a novel SARS-CoV-2 coronavirus emerged, causing an outbreak of life-threatening pneumonia in the Hubei province, China, and has now spread worldwide, causing a pandemic. The urgent need to control the disease, combined with the lack of specific and effective treatment modalities, call for the use of FDA-approved agents that have shown efficacy against similar pathogens. Chloroquine, remdesivir, lopinavir/ritonavir or ribavirin have all been successful in inhibiting SARS-CoV-2 in vitro. The initial results of a number of clinical trials involving various protocols of administration of chloroquine or hydroxychloroquine mostly point towards their beneficial effect. However, they may not be effective in cases with persistently high viremia, while results on ivermectin (another antiparasitic agent) are not yet available. Interestingly, azithromycin, a macrolide antibiotic in combination with hydroxychloroquine, might yield clinical benefit as an adjunctive. The results of clinical trials point to the potential clinical efficacy of antivirals, especially remdesivir (GS-5734), lopinavir/ritonavir, and favipiravir. Other therapeutic options that are being explored involve meplazumab, tocilizumab, and interferon type 1. We discuss a number of other drugs that are currently in clinical trials, whose results are not yet available, and in various instances we enrich such efficacy analysis by invoking historic data on the treatment of SARS, MERS, influenza, or in vitro studies. Meanwhile, scientists worldwide are seeking to discover novel drugs that take advantage of the molecular structure of the virus, its intracellular life cycle that probably elucidates unfolded-protein response, as well as its mechanism of surface binding and cell invasion, like angiotensin converting enzymes-, HR1, and metalloproteinase inhibitors.