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991 covid-19 Wiley Open Research Preprints

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Please note: These are preprints and have not been peer reviewed. Data may be preliminary. Preprints should not be relied on to guide medical practice or health-related decisions. News media reporting on preprints should stress that the research should not yet be considered conclusive.
From a crisis to an opportunity: Eight insights for doing science in the Covid-19 era...
Julia Chacón Labella
Mickey Boakye

Julia Chacón Labella

and 11 more

July 25, 2020
The COVID-19 crisis has forced researchers in Ecology to change the way we work almost overnight. Nonetheless, the pandemic has provided us with several novel components for a new way of conducting international Science. In this perspective piece, we summarize eight central insights that are helping us, as early career researchers, navigate the uncertainties, fears and challenges of advancing Science during the COVID-19 pandemic. We highlight how innovative, collaborative and often Open Science-driven developments that have arisen from this crisis can form a blueprint for a community reinvention in academia. Our insights include personal approaches to managing our new reality, maintaining capacity to focus and resilience in our projects, and a variety of tools that facilitate remote collaboration. We also highlight how, at a community level, we can take advantage of online communication platforms for gaining accessibility to conferences and meetings, and for maintaining research networks and community engagement while promoting a more diverse and inclusive community. Overall, we are confident that these practices can support a more inclusive and kinder scientific culture for the longer term.
COVID 19 - An Indian Perspective
Bashi Velayudhan
Mohammed Idhrees

Bashi Velayudhan

and 1 more

July 24, 2020
Abstract Lockdown, quarantine, self-isolation, personal protection equipment, social distancing have become words of daily usage ever since the world health organisation declared COVID-19 as a pandemic. The impact of COVID 19 extends over the medical field, economy, education and politics. Though the knowledge of the virus is evolving, we are yet to find a solution. India, country with the 2nd largest population, went into a phase of lockdown from 25th March 2020 to 31st May 2020. There was phased measure to “Unlock” starting from1st June 2020. This has affected the clinical practise and training of the resident. The challenges faced during this unprecedented time are multi-faceted which includes overcrowding, health care system, educational background. Indian Association of Cardiovascular-Thoracic Surgeons kept continuing the educational program through a series of “Masterclass”.
Diagnosis, Management and Recovery of COVID 19: a Case Report in Bangladesh
Lutfa Akther
Shaila  Shahnewaz

Lutfa Akther

and 3 more

July 24, 2020
A 30-year-old man, who had no travel history to COVID-19 prone areas whereas he had the characteristics signs and symptoms of COVID-19. Chest X-ray and rRT-PCR revealed his confirmed COVID-19. This study recommends the early identification and management of COVID-19.
A Case Series of Inferior Vena Cava Filter Implantation in Three COVID-19 Patients wi...
chuanqi cai
Yi Guo

chuanqi cai

and 6 more

July 24, 2020
Three COVID-19 cases were simultaneously confirmed as deep venous thrombosis (DVT). Ultrasound-guided IVCF implantation is an effective method that can be considered as a precautionary strategy for preventing lethal pulmonary embolism occurrence, especially for critical DVT-COVID-19 patients who are not suitable to be transferred to a routine X-ray operation room.
Severe Coronavirus Disease 2019 (COVID-19) Pneumonia Patients Treated Successfully wi...
Hayato Koba
Taro Yoneda

Hayato Koba

and 5 more

July 24, 2020
Three COVID-19 patients who were received lopinavir/ritonavir plus favipiravir got to improved without any severe adverse events. Two patients harboring high fever, severe pneumonia and respiratory failure obtained dramatic improvement. The combination therapy might be a treatment option; earlier therapy onset may have needed to avoid lung sequela.
Impact of the COVID-19 pandemic in Radiopharmacy Activities: Preliminary report: firs...
Fatma Al-Saeedi

Fatma Al-Saeedi

July 23, 2020
Rationale, aims, and objectives: The coronavirus pandemic has disrupted normal activities across the world, from economy to socialization, and claiming hundreds of thousands of lives. The activities in radiopharmacy laboratories across the globe have been affected significantly. This survey was conducted to assess the effect of COVID-19 on radiopharmacy and activities going on in the laboratories around the world. This was meant to undertake a preliminary record of the continuing survey. Methods: A three-sectioned questionnaire with 12 questions was distributed to the professional working on radiopharmacy laboratories. The sections included demographic information, the effect of the pandemic on the regular operation on a radiopharmacy, and the measures taken to prevent the spread of the virus among the laboratory staff. Random sampling approach was used to select 100 respondents, including staff and radiochemists, across different parts of the world. Results: The survey demonstrated that the pandemic hugely impacted activities in a radiopharmacy laboratory. 98% of the respondents reported major disruptions in the normal schedule in the laboratory. Even though some laboratories continued working normally, strict measures were put in place to prevent the spread of the virus among the staff. In many radiopharmacy laboratories, diagnostic procedures and tests quantitatively decreased. The survey reported positron emission radiopharmaceutical fluorodeoxyglucose F-18 (F18-FDG) as the frequently organ imaging radiopharmaceutical during the pandemic. Conclusions: The survey showed that COVID-19 has negatively impacted activities in a radiopharmacy laboratory, consequently affecting research activities.
Acute Pancreatitis in a COVID-19 Patient- An Unusual Presentation.
Goutam Kumar Acherjya
Md Masudur  Rahman

Goutam Kumar Acherjya

and 7 more

July 23, 2020
Initially, Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 virus is strikingly thought to be manifested by respiratory illness such as cough, chest tightness, and dysponea. Therefore, we are presenting a confirmed case of COVID-19 who developed acute pancreatitis-a rare manifestation during disease process without any known aggravating factors
A neonate born to an infected COVID-19 mother was tested positive just 24 hours after...
Roya Huseynova
Latifa A.Bin Mahmoud

Roya Huseynova

and 6 more

July 22, 2020
Coronavirus disease (COVID-19) is a highly contagious disease with a rapid increase in cases and mortality all over the world. We report a neonate born to the pregnant woman with COVID tested positive for SARS-CoV-2 infection just 24 hours after its birth.
Increased Mortality in COVID-19 Patients Following Cardiac Surgery
Anastasia Katsiampoura
Cesar Perozo

Anastasia Katsiampoura

and 7 more

July 22, 2020
In this report we describe the clinical presentation, laboratory findings and outcomes of four patients that were referred for urgent cardiothoracic intervention and tested positive for COVID-19. Though the majority of the patients undergoing surgery had low Society of Thoracic Surgeons score and uneventful operating time, mortality was very high and driven primarily by the viral syndrome. Laboratory markers that have been associated with disease severity in the general population were also prognostic in our population. Our study shows that these patients have very high mortality, whereas prevention and preoperative screening is required in preventing nosocomial spreading of the disease.
The COVID Pandemic - Potential Collateral Damage in a Less Focused Dimension
Hans-Joachim Schäfers
Carolin Kunz

Hans-Joachim Schäfers

and 2 more

July 22, 2020
Protective measures against Covid have a relevant impact on communication. This will have be to be considered in the future.
Mini-commentary on BJOG-20-0939.R2
Miho Iida
Mamoru Tanaka

Miho Iida

and 1 more

July 21, 2020
With no end in sight to the convergence of COVID-19, countries are struggling with strategies to halt the “second wave” and mitigate economic decline. Estimated to account for around half of the infections, asymptomatic transmission of SARS-CoV-2 has been hampering the containment of the virus. A positive case rate of 10% was reported by Prabhu et al. among 625 pregnant women who were universally screened for SARS-CoV-2 on the day of admission for delivery at 3 institutions in New York City, of which 80% were asymptomatic at the time of testing including pre- and post-symptomatic patients. As evidence shows that virus sheds before symptoms appear and even after their cessation, these populations may have increased the chances of COVID-19 outbreak in the hospitals. Utilization of testing results for isolation practices was not mentioned in the report, possibly given the long turnaround time for the testing platforms at the time.While the risk of nosocomial transmission is affected by clinical settings, the intimate and prolonged nature of childbirth elevates the risk of cross-infection between midwives and women. The role of nosocomial transmission has been increasingly recognized, and its severity risk may be greater than those of community-acquired infections. A recent report has suggested facilities to consider testing pregnant women for SARS-CoV-2 at the time of admission (Rasmussen SA, et al. JAMA. 2020). International Confederation of Midwives has also called for governments to prioritize testing for all pregnant women and their care providers. Identification of infectious women prior to delivery could contribute to prevention of further transmission to patients and healthcare workers. Importance should also be emphasized on evaluating contact history due to the nature of false-negative PCR results (Woloshin S, et al. NEJM. 2020).Another significance of performing testing for SARS-CoV-2 on pregnant women is for the adequate medical management of the women and the fetuses. While outcome for mothers and neonates seems generally favorable, data suggest that pregnancy can be associated with increased risk for severity, including intensive care unit admission and receipt of mechanical ventilation (Ellington S, et al., MMWR Morb Mortal Wkly Rep 2020;69:769–775). Furthermore, a recent article has raised concerns over transplacental transmission of SARS-CoV-2 to the fetus (Vivanti AJ, et al. Nat Commun. 2020;11:3572). Collection of longitudinal data is crucial to understand the effects of SARS-CoV-2 infection on maternal and neonatal outcomes. Results of large-scale prospective cohort studies, such as INTERCOVID study, are expected to add high-quality evidence on the effects of COVID-19 in pregnancy on the health of the mothers, fetuses, and newborns.Screening a maternity population under a pandemic can be a way to provide a glimpse of the distribution of the population, since capacity constraints still impede widespread testing in many countries. Recent development of faster diagnostic testing could bring improvement, but test sensitivity will remain a challenge. Fundamental preventive measures and clinical management should be continued; that is, hygiene and social distancing practices for women themselves, and careful evaluation of each mother and fetus for care providers.
Diabetes in COVID-19 pandemic-prevalence, patient characteristics and adverse outcome...
Ahmed Hafiz
demelza emmerton

Ahmed Hafiz

and 2 more

July 21, 2020
Abstract Background: Current literature on COVID-19 pandemic has identified diabetes as a common comorbidity in patients affected. However, the evidence that diabetes increases the risk of infection, effect of diabetes on outcomes and characteristics of patients at risk is not clear. Objectives: To explore the prevalence of diabetes in COVID-19 pandemic, effect of diabetes on clinical outcomes and to characterise the patients with diabetes affected by COVID-19. Methods: A literature review of articles published in English language and reported outcomes on prevalence and effect of diabetes on outcomes and patients characteristics. Results: The prevalence of diabetes in COVID-19 patients appears similar to that in the general population. The evidence of diabetes increasing the risk of severe infection and adverse outcomes is substantial. The progression of the disease into acute respiratory distress syndrome, the requirement for intensive care admission or mechanical ventilation and mortality all have been increased by the presence of diabetes. Patients with diabetes at risk of COVID-19 appear to be obese, of older age, have uncontrolled glycaemia and have coexisting comorbidities especially cardiovascular disease and hypertension. Tight glycaemic control on admission to hospital using insulin infusion has shown some beneficial effects however, the role of hypoglycaemic medications in the management of these patients is not yet clear. Conclusion: High risk group should be identified and prioritised in future vaccination programmes. Future research is required to optimise management of patients with diabetes and develop new ways to manage them via technological developments such as telecare.
Authors’ reply re: Maternal transmission of SARS-COV-2 to the neonate, and possible r...
Kate Walker
Keelin ODonoghue

Kate Walker

and 6 more

July 20, 2020
Authors’ reply re: ’Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis (Response to BJOG-20-1416)Kate F Walker1, Keelin O’Donoghue2, Nicky Grace3, Jon Dorling4, Jeannette L Comeau4, Wentao Li5 Jim G Thornton11Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham2The Irish Centre for Maternal and Child Health, University College Cork, Cork University Maternity Hospital, Cork, Ireland3 School of English, University of Nottingham4Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada5Department of Obstetrics and Gynaecology, Monash University, Clayton, AustraliaThank you for the opportunity to comment on the letter by Dr Xue from Shanghai Jiao Tong University. We agree there are many weaknesses in the data we reviewed. Dr Xue has identified one. Others are the incomplete reporting of infant feeding and mother-child interactions, and the frequent lack of infant testing to confirm or refute the possibility of vertical transmission of COVID-19. Finally, although we simply provided summary totals, it would be statistically preferable to combine series using the Mantel-Haenszel method and calculate a relative risk. We judged that doing this in light of the uncertainties around the data which Dr Xue has identified, might give a spurious precision to our results. As he says, more work is needed. For now we think it remains reasonable to not regard COVID-19 in itself, as an indication for Caesarean, artificial feeding or separation, in the mother and baby’s interest.
Tocilizumab for treating severe COVID-19 pneumonia refractory to combined hydroxychlo...
Manoon  Surabotsophon
Yingyot  Klai-On

Manoon Surabotsophon

and 11 more

July 20, 2020
Three patients with COVID-19 pneumonia received treatment with hydroxychloroquine combined with lopinavir plus ritonavir and favipiravir. Two patients early diagnosed with COVID-19 pneumonia received tocilizumab at severe pneumonia diagnosed and survived. The third patient was late diagnosed and received tocilizumab when the disease progressed to ARDS, and passed away.
Are Children with SARS-CoV-2 Infection at High Risk for Thrombosis? Viscoelastic Test...
Maha Al-Ghafry
Banu Aygun

Maha Al-Ghafry

and 11 more

July 20, 2020
The coagulopathy of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well documented in adults, with increases in D-dimer and prothrombin time strong predictors of mortality and anticoagulation shown to decrease this mortality. Viscoelastic parameters such as elevations in maximum clot firmness (MCF) on rotational thromboelastometry (ROTEM) have correlated with a hypercoagulable state in adults with SARS-CoV-2. We report our experience in children infected with SARS-CoV-2, with noted elevations in D-dimer and MCF on ROTEM (indicating hypercoagulability). Exploration of viscoelastic testing to provide additional laboratory-based evidence for pediatric-specific risk-assessment for thromboprophylaxis in SARS-CoV-2 is warranted.
Shielding against SARS-Cov-2 infection is not justified in children with severe asthm...
Michael Kabesch

Michael Kabesch

July 20, 2020
To the Editor, For the EU funded project PERMEABLE (PERsonalized MEdicine Approach for Asthma and Allergy Biologicals SeLEction), which addresses the availability of and access to advanced therapy of asthma in children across Europe, we performed a survey including 37 major pediatric asthma and allergy centers between September 2019 and July 2020. In total, the centers contributing to the survey treated approximately 1.000 young patients with severe asthma in 25 major European countries and Turkey with biologicals. In the light of the Corona Pandemic, we extended our survey asking the responsible clinicians if they experienced a SARS-CoV-2 infection in any of the children they are caring for. The questions pertaining to Corona infections were asked between March and July 2020.Given the prevalence of SARS-CoV-2 infections in the general population and in children, one would expect that at least 1% of the patients would be affected (1). In fact, none of the centers was aware of any symptomatic COVID-19 case in their patient populations or any positive SARS-CoV-2 tests.This leads to the conclusion, that either SARS-CoV-2 infections have a mild or even asymptomatic course also in children with severe asthma or that children with severe asthma (and their parents) were extremely successful in avoiding SARS-CoV-2 infections. Thus, we investigated by structured interview, how centers in those 26 countries had instructed their patients to avoid COVID-19. Interestingly, only 4 European countries (UK, Ireland, Portugal and Malta) had a strict, so called shielding policy in place which followed a principle of maximal segregation of severe asthmatics from the rest of the population: not leaving the house at all, not attending school even when they reopened, wearing face masks also at home, and social distancing even with family members. All other countries followed the principle of continuing or even enforcing asthma treatment in patients and advising to follow the same Corona rules as the general population.Both strategies led to the same result: An absence of COVID-19 cases in children with severe asthma. We conclude from this observation, that shielding is not necessary in children with severe asthma as they and their families are perfectly able to avoid Corona infections. The harm done to children by enforcing seclusion, separation and stigmatization needs to be acknowledged. Deprivation of school, social contact and friends weights heavy on children and the absence of any COVID-19 cases in major European centers for severe asthma in children does not justify a policy of compulsory shielding of children with severe asthma, neither in the first nor in any further Corona wave.Michael Kabesch, M.D.University Children’s Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany.Member of the Research and Development Campus Regensburg (WECARE) at the Hospital St. Hedwig of the Order of St. John, Regensburg, Germany.ReferencesStringhini S, Wisniak A, Piumatti G, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study [published online ahead of print, 2020 Jun 11]. Lancet . 2020;S0140-6736(20)31304-0.
Evaluation of the US governors' decision when to issue stay-at-home orders
Benjamin Djulbegovic
Iztok Hozo

Benjamin Djulbegovic

and 2 more

July 17, 2020
Rationale, aims and objectives In the US, the reluctance of the federal government to impose a national stay-at-home policy in wake of COVID19 pandemic has left the decision of how to achieve social distancing to individual state governors. We hypothesized that in the absence of formal guidelines, the decision to close a state reflects the classic Weber-Fechner law of psychophysics- the amount by which a stimulus (such as number of cases or deaths) must increase in order to be noticed as a fraction of the intensity of that stimulus. Methods On April 12, 2020 we downloaded data from the New York Times database from all 50 states and the District of Columbia; by that time all but 7 states had issued the stay-at-home orders. We fitted the Weber-Fechner logarithmic function by regressing the log2 of cases and deaths respectively against the daily counts. We also conducted Cox regression analysis to determine if the probability of issuing the stay-at-home order increases proportionally as the number of cases or deaths increases. Results We found that the decision to issue the state-at-home order reflects the Weber-Fechner law. Both the number of infections (p=<0.0001; R2=0.79) and deaths (p<0.0001; R2=0.63) were significantly associated with the decision to issue the stay-at-home orders. The results indicate that for each doubling of infections or deaths, an additional 4 to 6 states will issue stay-at-home orders. Cox regression showed that when the number of deaths reached 256 and the number of infected people were over 16,000 the probability of issuing “stay-at-home” order was close to 100%. We found no difference in decision-making according to the political affiliation; the results remain unchanged on July 16,2020. Conclusions when there are not clearly articulated rules to follow, decision-makers resort to simple heuristics, in this case one consistent with the Weber-Fechner law.
Unfractionated heparin inhibits live wild-type SARS-CoV-2 cell infectivity at therape...
Julia Tree
Jeremy Turnbull

Julia Tree

and 11 more

July 20, 2020
Background and Purpose: Currently there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently being used to treat anticoagulant anomalies in COVID-19 patients. In addition, in the UK, nebulised unfractionated heparin (UFH) is currently being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild-type SARS-CoV-2, in vitro, is thus urgently needed. Experimental Approach: A range of heparin preparations both UFH (n=4) and low molecular weight heparins (LMWH) (n=3) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Victoria/01/2020) using a plaque reduction neutralisation assay and Vero E6 cells. ND50 values for each heparin were calculated using a mid-point probit analysis. Key Results: UFH had potent antiviral effects, with ND50 values of 12.5 and 23 μg/ml for two porcine mucosal UFH tested. Bovine mucosal UFH had similar antiviral effects although it was ~50% less active (ND50, 50-75 μg/ml). In contrast, LMWHs such as Clexane and Fragmin were markedly less active by ~100-fold (ND50 values of 2.6-6.8 mg/ml). Conclusions and Implications: This comparison of a panel of clinically relevant heparins, including the UFH preparation under trial in the UK, demonstrated that distinct products exhibit different degrees of antiviral activity against live SARS-CoV-2. Porcine mucosal UFH has the strongest antiviral activity followed by bovine mucosal UFH, whereas LMWHs had the lowest amount of antiviral activity (by 100-fold). Overall the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19.
Pigs are not susceptible to SARS-CoV-2 infection but are a model for viral immunogeni...
Júlia Vergara-Alert
Jordi Rodon

Júlia Vergara-Alert

and 13 more

July 16, 2020
Conventional piglets were inoculated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through different routes, including intranasal, endotracheal, intramuscular and intravenous ones. Although piglets were not susceptible to SARS-CoV-2 and lacked lesions or viral RNA in tissues/swabs, seroconversion was observed in pigs inoculated parenterally (intramuscularly or intravenously).
Dexamethasone, pro-resolving lipids and resolution of inflammation in COVID-19
Evangelos Andreakos
Maria Papadaki

Evangelos Andreakos

and 2 more

July 16, 2020
EDITORIAL Coronavirus disease‐19 (COVID‐19) is a new disease caused by SARS‐CoV2. Since the beginning of 2020, it has become one of the main challenges of our times, causing a high incidence of severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure and death1. At the root of COVID-19 lies the sudden development of ‘cytokine storms’, hyper-inflammatory responses involving the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-1, IL-8, and MCP-1) that impair the gas exchange function of the lung and lead in select patients, mostly with underlying comorbidities, to multiorgan failure and death1,2. Additional complications triggered by ‘cytokine storms’ include endothelial dysfunction and hypercoagulation, increasing the risk of thromboembolytic events, and life-threatening cardiovascular complications. Anti-inflammatory therapies are thus being considered for alleviating the damaging side effects of hyper-inflammation with many trials including anti-cytokine biologicals, disease-modifying antirheumatic drugs (DMARDs) and corticosteroids being ongoing3. Surprisingly, among them dexamethasone has taken center stage as initial results from the RECOVERY trial, a large multicenter randomized open-label trial for hospitalized patients run in the United Kingdom, revealed notable efficacy in the treatment of critically ill COVID-19 patients4.Dexamethasone is one of the oldest synthetic glucocorticoid agonists synthesized in 1957 and introduced into the clinic in 1961. When administered at 6 mg daily, either orally or intravenously for 10 days, dexamethasone was shown in the RECOVERY trial to improve survival rates of hospitalized patients with severe COVID-19 receiving oxygen or being on mechanical ventilation by a remarkable 30%4. Benefit was restricted to patients requiring respiratory support whereas in milder cases this was not clear. This notable efficacy of dexamethasone treatment goes against the current view of corticosteroid use in respiratory viral infections which remains contradictory. Although corticosteroids improve ventilator weaning and can lower the intensity of the host response to the virus, tempering the ‘cytokine storm’ and limiting immunopathology, they can also reduce viral clearance and lead to more severe disease. Understanding therefore how dexamethasome mediates its effects is of paramount importance.Dexamethasone, as other corticosteroids, is held to mediate its anti-inflammatory and immunosuppressive effects via the glucocorticoid receptor. Upon ligand binding, the receptor-corticosteroid molecule complex moves into the cell nucleus, where it dimerizes and binds to glucocorticoid response elements (GRE), acting as transcriptional repressor or transactivator of diverse sets of genes. This results in the inhibition of inflammatory cell activity, including neutrophils, macrophages and lymphocytes, and the suppression of pro-inflammatory cytokines such as TNF and interleukins and other genes such as cyclooxygenase-2 and inducible nitric oxide synthase5. However, we have recently uncovered that dexamethasone can also induce the D-series proresolving lipid mediator pathway leading to the production of 17-HDHA and the protectins D1 and DX6. These are potent major players of the molecular machinery driving the resolution of inflammation, i.e. the proper regulated termination of pro-inflammatory responses involving the catabolism of pro-inflammatory mediators, the removal of inflammatory cells and the restoration of the tissue in a timely and highly coordinated manner7. Although resolution of inflammation has long been considered to occur spontaneously as a result of the waning of pro-inflammatory responses, this is now known to be an ordered and highly regulated process involving the timely production of enzymatically oxygenated lipid-derived mediators such as protectins, D-series resolvins and maresins derived from the omega-3 fatty acid docosahexaenoic acid (DHA), E-series resolvins derived from eicosapentaenoic acid (EPA), and lipoxins biosynthesized from omega-6 fatty acids following eicosanoid class switching7. Interestingly, certain lipid mediators have been shown to exert additional non-conventional functions; resolvin D4 can attenuate pathologic thrombosis, reduce NETosis and promote clot removal8 which is now recognized as a key pathology of COVID-19 infection, while resolvin E4 (RvE4) stimulates efferocytosis of senescent erythrocytes in hemorrhagic exudates especially under hypoxic conditions that characterize COVID-199. Moreover, corticosteroids have been reported to reduce fibrinogen and procoagulant factors under pro-inflammatory conditions and increase anticoagulant factors10.The ability of viral infections to induce proresolving lipids has been reported earlier. Toll-like receptor 7 (TLR7), a major pattern recognition receptor of viral RNA, activates PD1 and PDX production11. Moreover, influenza virus infection has been demonstrated to drive proresolving lipid mediator networks including the production of PD1 which limits influenza pathogenicity by directly interacting with the RNA replication machinery to inhibit viral RNA nuclear export12,13. Notably, in particularly virulent strains of influenza virus such as the H5N1 avian strain, PD1 formation is not sufficiently upregulated, leading to more efficient viral replication and host demise12. It is therefore plausible that the efficacy of dexamethasone in COVID-19 is due at least in part to its ability to induce proresolving lipid mediators that possess multiple anti-inflammatory and proresolving actions tempering down inflammation and promoting its resolution, preventing coagulation and enhancing viral and bacterial clearance (Figure 1) yet are not immunosuppressive . Whether other corticosteroids beyond dexamethasone can also mediate such effects, and to what extent, is not known. Whether inhalable corticosteroids, such as those given to asthmatic patients, can also induce proresolving lipid mediator networks locally and thus prevent the development of severe SARS‐CoV‐2 infection remains to be determined. There is evidence that asthmatic patients exhibit reduced incidence of severe and/or critical COVID-1914.Recently, COVID-19 patients showed increased association of serum arachidonate-derived proinflammatory lipid mediators, e.g. prostaglandins, in severe COVID -19 infections while some pro-resolving mediators such as resolvin E3 were up-regulated in the moderate COVID-19 group suggesting that an imbalance in lipid mediators with a swift toward pro-inflammatory mediators in severe disease may contribute to COVID-19 disease severity15. Although the involvement of proresolving lipid mediator pathways in COVID-19 is an attractive hypothesis, further evidence from human trials is needed as there are no studies at present reporting the induction or modulation of such networks in the context of the various disease stages and treatments. It is thus of uttermost priority to investigate proresolving lipid mediators in COVID-19, in a temporal and longitudinal manner, as modulating these networks either through drug treatment or direct administration of resolvin and protectins agonists has the potential to affect this highly lethal and devastating disease in a way other approaches cannot. Such studies are therefore eagerly awaited.
Sulforaphane: from death rate heterogeneity in countries to candidate for prevention...
Jean Bousquet
Josep Anto

Jean Bousquet

and 8 more

July 16, 2020
To the Editor, Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] is a clinically relevant nutraceutical compound present in cruciferous vegetables (Brassicaceae). It is used for the prevention and treatment of chronic diseases and may be involved in ageing.1Along with other natural nutrients, sulforaphane has been suggested to have a therapeutic value for the treatment of the coronavirus disease 2019 (COVID-19).2 Sulforaphane is an isothiocyanate stored in its inactive form glucoraphanin.3 The enzyme myrosinase, found in plant tissue and in the gut microbiome, is involved in the conversion of glucoraphanin to its active form sulforaphane.4
Convalescent plasma for pediatric patients with COVID-19 associated acute respiratory...
Caroline Diorio
Elizabeth Anderson

Caroline Diorio

and 28 more

July 16, 2020
There are no proven safe and effective therapies for children who develop life-threatening complications of SARS-CoV-2. Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2 but has theoretical risks. We report on the first use of CP in children with life-threatening COVID-19, providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.
CLINICAL MANAGEMENT OF LUNG CANCER PATIENTS WITH RESPIRATORY SYMPTOMS DURING EPIDEMIC...
Pınar Kabalak
Derya Kızılgöz

Pınar Kabalak

and 3 more

July 16, 2020
Objective: There are many clinical conditions that need to be followed and treated during pandemic like lung cancer. Carrying out health care for these patients who are immune-suppresive require extra care. Method: Among 108 lung cancer patients who has been hospitalized during pandemic, 18 of them with respiratory symptoms were evaluated. Results: Median age was 64±9.4 with male predominance (male n=16, female n=2). Thirteen of them was non-small cell lung cancer (NSCLC) and 5 of them was small cell lung cancer (SCLC). Nine (50%) patients were receiving chemotherapy. The most common symptom was shortness of breath (n=14, 77.8%), followed by fever (n=10, 55.6%). Findings confirmed on computed thorax tomography (CTT) were as follows: Consolidation (n=8, 44.4%), ground glass opacities (n=8, 44.4%) and thoracic tumour/mediastinal-hilar lymphadenopathy (n=3, 16.7%). Hypoxia was seen in 11 patients (61.1.%). Twelve patients had elevation of LDH (median=302±197) and lymphopenia (median=1055±648). There were 5 (27.7%) highly suspected cases for COVID-19. Any of their nasopharyngeal swap was positive. Two of these 5 patients received COVID-19 specific treatment even they have negative PCR results for 3 times. They responded well both clinical and radiological. For one case with SCLC receiving immunotherapy metil-prednisolone was initiated for radiation pneumonitis after excluding COVID-19. Conclusion: In line with the health policies of the countries and the adequacy of the health system, the necessity of a multidisciplinary approach in the management and treatment of complications in patients with lung cancer becomes even more important in this pandemic.
Easily accessible, up-to-date and standardized training model in Urology: E-Learning...
Volkan Sen
Huseyin Eren

Volkan Sen

and 9 more

July 16, 2020
Objectives: There is no standardized and up-to-date education model for urology residents in our country. We aimed to describe our National E learning education model for urology residents. Methodology: The ERTP working group; consisting of urologists was established by Society of Urological Surgery to create E-learning model and curriculum at April 2018. Learning objectives were set up in order to determine and standardize the contents of the presentations. In accordance with the Bloom Taxonomy, 834 learning objectives were created for a total of 90 lectures (18 lectures for each PGY year). Totally 90 videos were shoot by specialized instructors and webcasts were prepared. Webcasts were posted at uropedia.com.tr, which is the web library of Society of Urological Surgery. Satisfaction of residents and instructors was evaluated with feedbacks. An assessment of knowledge was measured with multiple-choice exam. Results: A total of 43 centers and 250 urology residents were included in ERTP during the academic year 2018/2019. There were 93/38/43/34/25 urology residents at 1st/2nd/3rd/4th and 5th year of residency, respectively. Majority of the residents (99.1%) completed the ERTP. The overall satisfaction rate of residents and instructors were 4,29 and 4,67(min:1 so bad, max:5 so good). An assessment exam was performed to urology residents at the end of the ERTP and the mean score was calculated as 57.99 points (min:20, max:82). Conclusion: Due to the Covid-19 pandemic, most of the educational programs had to move online platforms. We used this reliable and easily accessible e-learning platform for standardization of training in urology on national basis. We aim to share this model with international residency training programs.
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