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1015 covid-19 Wiley Open Research Preprints

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covid-19 pandemic turkey wildlife children childhood cancer viral nitric oxide (no) aorta and great vessels malperfusion nose and throat marfan syndrome cardiovascular research zoonosis/zoonotics pharmacotherapy clinical pharmacology disease control education paediatric airways respiratory pharmacology drug safety intercellular signaling cancer sar-cov-2 letter + show more keywords
head and neck surgery covid-19 respiratory failure infant guanylate cyclase prescribing virus obstetrics and gynaecology ear infectious disease: virology paediatric orl general asthma & early wheeze respiratory distress syndrome & ards termination of pregnancy drug information respiratory syncytial viruses bronchiolitis health services research otology immunopharmacology veterinary epidemiology research ethics epidemiology tb rhinology low and middle income contries emerging diseases sars-cov-2 therapeutics delivery: caesarean section transmission human viral challenge studies cytokines disease characteristics lung infectious diseases infections: pneumonia vaccination communication controlled human infection studies inflammation tevar clinical studies neurology oxygenation and therapy coronary artery disease mobile ecmo evidence-based medicine drug regulation s-nitrosylation pulmonary hypertension statistics and study design
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Please note: These are preprints and have not been peer reviewed.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.
Timing and volume of information relevant to the Otolaryngologist during the COVID-19...
Cristina Cernei
Manu Shrivastava

Cristina Cernei

and 3 more

July 16, 2020
Background: The SARS-CoV-2 was first reported in December 2019 in Wuhan, China and has been declared a pandemic in March 2020. COVID-19 has caused unprecedented and lasting biopsychosocial effects worldwide. All healthcare professionals have faced life threatening risks by attending their daily jobs. The daily emergence of advice and guidelines was necessary to ensure the safety of patients and staff. To this effect, all elective services came to a halt to preserve hospitals’ capacity for dealing with the sickest. This retrospective, descriptive review aims to assess the volume and timing of the advice released specifically relevant to the UK Otolaryngologist. Methods: The search included online advice published in English by international, national and ENT-specific organisations between the 1st of January to the 31st of May. The date, title, source, type of advice and link to the advice was recorded in Excel. The resources were analysed per week of publication. A separate search for peer-reviewed publications was conducted using PubMed Central and Cochrane databases. Findings: 175 covid-19 related guidance’s were identified. 52/175 (29.7%) articles were published by international organisations. 56/175 (32%) were produced by national organisations and 67/175 (38.28%) were produced by ENT specific organisations. The peak guidance production took place in the third and fourth week of March (16/03/2020- 29/03/2020) with 72/175 publications. Of these, 27/72 came from the international category, 17/72 from national bodies and 28/72 from ENT-specific organisations. 13,863 total publications relating to COVID-19 were found using PubMed and Cochrane search strategies; 76% were relevant to ENT surgeons. Conclusion: The challenges faced by the Otolaryngologist relate to the unprecedented, sudden and daily changes to clinical practice. Multiple bodies interpreted the guidance giving an opportunity for confusion and delays in treatments for patients. Implementing a system with clear lines of communication and dissemination of information will improve our response in future pandemic events whilst maintaining a commercial awareness to better use the human and financial resources of an already financially-restricted NHS.
Interoperable medical data: the missing link for understanding COVID-19
Denis C Bauer
Alejandro Metke-Jimenez

Denis Bauer

and 9 more

July 13, 2020
Being able to link clinical outcomes to SARS-CoV-2 virus strains is a critical component of understanding COVID-19. Here we discuss how current processes hamper sustainable data collection to enable meaningful analysis and insights. Following ‘Fast Healthcare Interoperable Resource’ implementation guide, we introduce an ontology-based standard questionnaire to overcome these shortcomings and describe patient “journeys” in coordination with the World Health Organization. We identify steps in the clinical health data acquisition cycle and workflows that likely have the biggest impact in the data-driven understanding of this virus.
Limitations of Telemedicine- a Gynecologist's Perspective
Sarah Werner
Adi Katz

Sarah Werner

and 1 more

July 13, 2020
A Gynecologist's perspective on the limitations of telemedicine in the setting of early pregnancy diagnosis during the COVID-19 Pandemic.
Factors determining COVID-19 pneumonia severity in a country with routine BCG vaccina...
Kurtuluş Aksu
Tuğba Naziroğlu

Kurtuluş Aksu

and 2 more

July 13, 2020
Background: Bacillus Calmette-Guérin (BCG) vaccination policies of countries are postulated to have effect on the course of coronavirus disease 2019 (COVID-19) pandemic. Methods: Retrospective cross-sectional study was conducted between March 11-June 10, 2020 in a chest clinic in a state hospital in Istanbul,Turkey. Adults with diagnosis of COVID-19 pneumonia confirmed with severe acute respiratory syndrome coronavirus 2 polymerase chain reaction positivity in a nasopharyngeal sample and pulmonary infiltrates in computed chest tomography were included consecutively. Sociodemographic characteristics, body-mass index, smoking status, comorbid diseases, income rates, and BCG-vaccination status were compared between severe and mild patients with COVID-19 pneumonia. Results: Study population consisted of 123 adults (mean age, 49.7 years [standard deviation, 13.3 years]; 82 (66.7%) male). The proportion of BCG-vaccinated cases was significantly lower among severe patients than mild patients with COVID-19 pneumonia (68.5% vs 88.2%; p=.026). Mean age (54.0 ± 11.5 years vs 38.3 ±10.7 years; p <.001), diabetes rate (32.6% vs 5.9%; p=.002) and low-income (84.3% vs 52.9% p<.001) are higher in patients with severe COVID-19 pneumonia than in patients with mild COVID-19 pneumonia. Multivariate logistic regression analysis showed that increasing age (odds ratio [OR], 1.112; 95% confidence interval [CI], 1.058 – 1.169; p<.001) and low income (OR, 3.369; 95% CI, 1.074 – 10.570; p =.037) are associated with severe COVID-19 pneumonia. Conclusion: Clinical data does not support that being vaccinated with BCG is associated with disease severity in COVID-19 pneumonia. Age and low-income are the major predictors for disease severity.
Prognosis of olfactory and gustatory dysfunctions in COVID-19 Patients: A case series
Po-Yu Liu
Rong-San Jiang

Po-Yu Liu

and 1 more

July 13, 2020
Olfactory and gustatory dysfunctions are common presentations in COVID-19 patients. We present three patients who received smell and taste tests after recovery. The smell test suspected persistent impairment of olfactory function in these patients. The report proposes continued evaluation of olfactory function by a smell test in COVID-19 patients.
Evaluation of the novel coronavirus disease in Turkish Children; Preliminary Outcomes
kamil YILMAZ
Ayfer Gozu Pirinccioglu

kamil YILMAZ

and 20 more

July 13, 2020
Background: The novel coronavirus disease (Covid-19) can progress with mild to moderate or self-limiting clinical findings in children. The aim of this study was to investigate the disease features of Covid-19 in Turkish children. Methods: Children diagnosed by the method of RT-PCR for Covid-19 at the Dicle University Department of Pediatric, between April and June 2020, were evaluated. Hospital records were investigated retrospectively. Results: One hundred and five patients children with the mean age of 108.64±65.61 were enrolled in this study. The most common cause of transmission in pediatric patients was contacting with a family member diagnosed with COVID-19 (n=91, 86.7%).The most common admission complaints were dry cough (n=17, 16.2%), fever (n=16, 15.2%), lassitude and fatigue (n=14, 13.3%) respectively. More than 95 % of all children with Covid-19 had asymptomatic, mild, or moderate cases. CRP was identified only independent factor associated with long duration of hospitalization. Conclusion: The results of this study show preliminary results of a study investigating the effect of Covid-19 on Turkish children. A clear understanding of the local epidemiology of corona virus infections and identification of risk factors is critical for the successful implementation of the prevention and control program.
Tracing the Path of Inhaled Nitric Oxide: Biological Consequences of Protein Nitrosyl...
Vikram Bhatia
Lara Elnagary

Vikram Bhatia

and 2 more

July 13, 2020
Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension, especially in neonates, and has been recently proposed for treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID-19. In this review, we summarize the effects of endogenous and exogenous NO on protein S-nitrosylation, which is the selective and reversible covalent attachment of a nitrogen monoxide group to the thiol side chain of cysteine. This post-translational modification targets specific cysteines based on the acid/base sequence of surrounding residues, with significant impacts on protein interactions and function. S-nitrosothiol (SNO) formation is tightly compartmentalized and enzymatically controlled, but also propagated by non-enzymatic transnitrosylation of downstream protein targets. Redox-based nitrosylation and denitrosylation pathways dynamically regulate the equilibrium of SNO-proteins. We review the physiological roles of SNO proteins, including nitrosohemoglobin and autoregulation of blood flow through hypoxic vasodilation, and pathological effects of nitrosylation including inhibition of critical vasodilator enzymes; and discuss the intersection of NO source and dose with redox environment, in determining the effects of protein nitrosylation.
COVID-19 IN PEDIATRIC CANCER PATIENTS IN A RESOURCE-LIMITED SETTING: NATIONAL DATA FR...
Jacqueline Montoya
Cecilia Ugaz

Jacqueline Montoya

and 20 more

July 09, 2020
A document by Jacqueline Montoya. Click on the document to view its contents.
A COVID-19 Human Viral Challenge Model? Learning from Experience.
Robert Lambkin-Williams
John DeVincenzo

Robert Lambkin-Williams

and 1 more

July 08, 2020
Abstract. The Controlled Human Infection Model and specifically the Human Viral Challenge Model are not dissimilar to standard clinical trials while adding another layer of complexity and safety considerations. The models deliberately infect volunteers, with an infectious challenge agent (CA) to determine the effect of the infection and the potential benefits of the experimental interventions. The Human Viral Challenge Model studies can shorten the time to assess the efficacy of a new vaccine or treatment by combining this with the assessment of safety. The newly emerging SARS-COV-2 virus is highly contagious and the cause pandemic disease COVID-19. An urgent race in is on to develop a new vaccine against this virus in a timeframe never attempted before. The use of the Human Viral Challenge Model has been proposed to accelerate the development of the vaccine. In the early 2000’s the authors successfully developed a pathogenic Human Viral Challenge Model for another virus for which there was no effective treatment and established it to evaluate potential therapies and vaccines against Respiratory Syncytial Virus. The authors feel that the experience gained in the development of that model can help with the development of a COVID-19 HVCM and describe it here. Word count: 197
Can SARS-CoV-2 cause life-threatening bronchiolitis in infants?
Maya Andre
Konrad Pätzug

Maya Andre

and 5 more

July 08, 2020
This letter is meant to inform the community of pediatricians/pediatric intensivists that we suspect SARS-CoV-2 to cause life-threatening bronchiolitis in infants and we therefore suggest maintaining a high level of suspicion of COVID-19, irrespective of an initially negative SARS-CoV-2 RT-PCR testing, when other causes of bronchiolitis are unidentifiable in young children.
Lockdown, Social Media exposure regarding COVID-19 and the relation with self-assessm...
Ariana-Anamaria Cordos
Sorana D. Bolboacă

Ariana-Anamaria Cordos

and 1 more

July 07, 2020
Introduction. Locking the humanity in their homes, COVID-19 forced people to use the technology at hand to keep informed about the outbreak and to keep close to their loved ones. During this time, even if physical health is theoretically unaffected, keeping calm and sane can be challenging. The aim of this research was to evaluate whether exposure to COVID-19 information available in the digital space has a different impact on the mental condition of Romanian medical staff, compared to general population, particularly searching for depression and anxiety symptoms. Materials and methods. An online survey was conducted from April 6 to 16, 2020 within the Romanian users of Social Media platforms. The questionnaire assessed depression with the WHO-Five Well-Being Index, anxiety with the Generalized Anxiety Disorder Scale and Social Media exposure by asking how often the respondents saw COVID-19 related information on the most popular Social Media channels in Romania. Information about: gender, age, educational level, occupation, area of living and risk category was also collected. The risk categories were defined as no risk, medium risk, and medical staff. Results. Almost 90% of the 402 participants received daily through at least one Social Media channel information related to the COVID-19 outbreak. The Social Media Exposure significantly associated with the risk group only for Facebook and LinkedIn. However, exposure to information regarding COVID-19 was neither associated with anxiety nor depression. No significant association was identified neither between age class and self-assessed anxiety nor self-assessed depression. The self-assessment of depression was significantly more frequent as compared to self-assessment of anxiety. Conclusion. The results of this research are opposite to most of the already published literature. Depression and anxiety could not be correlated with the context of lockdown and excessive COVID-19-related information.
International Study on Impact of COVID 19 on Cardiac and Thoracic Aortic Aneurysm Sur...
Mohammed Idhrees
Professor Mohamad Bashir

Mohammed Idhrees

and 3 more

July 07, 2020
Background: The COVID19 pandemic gripped every nation’s healthcare system and provisions on all levels. In cardiac and aortic surgery, as it is with most specialities, elective surgeries were halted. Aims of the study: We captured reflections, contingencies, and current practices across of high-volume centres in cardiac and aortic surgery globally. We also aimed this study to assess decision on prioritization of the surgical patients, the need for personal protection equipment and choice of preoperative investigations in current dynamic and fluid climate. Methods: A validated web-based questionnaire was constructed and was circulated to the international surgeons amongst high volume cardiac and aortic surgery centres. Their intrinsic feedback on decision making, impact of the lockdown and perspectives for the future ahead us all were noted. Mixed method approach was constructed. Qualitative data analysis was introduced to signify the impact globally. Results: Overall, 23 centers from 18 countries participated in this international study. 91.7% of the respondents stopped operating on elective patients during the pandemic. Majority of the surgeons agreed that acute aortic dissection (87.1%) should be operated as emergency procedure and stable triple vessel disease (87.1%) to be considered as elective procedure. Three-fifth (60%) of the respondents relied on CT chest as a preoperative screening modality. Conclusion: In the present climate where there is paucity of evidence, this will give an interim consensus for the cardiac surgeons. With the increase in cumulative number of COVID19 patients, careful utilization of the resources regarding hospital beds and manpower is of paramount importance.
Animals and SARS-CoV-2: Species susceptibility and viral transmission in experimental...
Emma Hobbs
Tristan Reid

Emma Hobbs

and 1 more

July 07, 2020
The current COVID-19 global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of probable bat origin, has highlighted the ongoing need for a One Health response to emerging zoonotic disease events, which are significantly increasing over time. Understanding the human-animal interface and its relevance to disease transmission remains a critical control point for many emerging zoonoses. Determination of the susceptibility of various animal species to infection with SARS-CoV-2 and the role of animals in the epidemiology of the disease will be critical to informing appropriate human and veterinary public health responses to this pandemic. A scoping literature review was conducted to collect, evaluate and present the available research evidence regarding SARS-CoV-2 infections in animals. Experimental studies have successfully demonstrated SARS-CoV-2 infection and transmission in cats, ferrets, hamsters, bats and non-human primates under experimental settings. Dogs appear to have limited susceptibility to SARS-CoV-2, while other domestic species including pigs and poultry do not appear susceptible. Naturally occurring SARS-CoV-2 infections in animals appear uncommon, with 14 pets, 8 captive big cats and an unreported number of farmed mink testing positive to date. Infections typically appear asymptomatic in dogs, while clinical signs of respiratory and/or gastrointestinal disease tend to be mild to moderate in felines, and severe to fatal in mink. Most animal cases have been infected by close contact with COVID-19 patients. In domestic settings, viral transmission is self-limiting, however in high density animal environments there can be sustained between-animal transmission. To date, two potential cases of animal-to-human transmission are being investigated, on infected mink farms. Given the millions of COVID-19 cases worldwide and ongoing potential for further zoonotic and anthroponotic viral transmission, further research and surveillance activities are needed to definitively determine the role of animals in community transmission of SARS-CoV-2.
Lessons for teaching from the pandemic
Jan Strojil
Hana Suchánková

Jan Strojil

and 1 more

July 07, 2020
In the context of the current COVID-19 pandemic, what are the lessons clinical pharmacology could learn to improve our teaching practice and involvement in research and ethics committees to make sure we are better prepared for the next emergency. Is there something in the light of the hydroxychloroquine hype that we as clinical pharmacologists or our professional societies could have done better? We propose updating the way we teach about drug development, rules and ethics of off-label prescribing and critical appraisal of primary sources when guidelines and top-level evidence are not available. Clinical pharmacology should play a leading role in the future re-definition of processes and guidelines for emergencies such as the one we faced in 2020.
Humidity is a consistent climatic factor contributing to SARS-CoV-2 transmission
Michael Ward
Shuang Xiao

Michael Ward

and 2 more

July 07, 2020
There is growing evidence that climatic factors could influence the evolution of the current COVID-19 pandemic. Here, we build on this evidence base, focusing on the southern hemisphere summer and autumn period. The relationship between climatic factors and COVID-19 cases in New South Wales, Australia was investigated during both the exponential and declining phases of the epidemic in 2020, and in different regions. Increased relative humidity was associated with decreased cases in both epidemic phases, and a consistent negative relationship was found between relative humidity and cases. Overall, a decrease in relative humidity of 1% was associated with an increase in cases of 7-8%. Overall, we found no relationship with between cases and temperature, rainfall or wind speed. Information generated in this study confirms humidity as a driver of SARS-CoV-2 transmission.
Hypothesis Article: The Potential Therapeutic Effects of Colchicine for Prevention of...
mohammad hablolvarid

mohammad hablolvarid

July 07, 2020
Background and Purpose. Since the onset of COVID-19 many clinical trials of drugs and/or vaccines are continuing and new ones are introduce daily. Yet the international research process failed to develop a preventative vaccine or potent therapeutic drugs for relieving the severity of the disease. Therefore, at present the best recommendation to people to slow the spread of the disease is; please stay at home and maintain social distancing! Experimental approach. Many aspects of pharmacotherapeutic mechanism of action of some previously approved drugs with anti-inflammatory effects, such as colchicine, in various disorders is not fully understood. Therefore, many potential therapeutic uses for these drugs and its analogues can be imagined. In this hypothesis article, an attempt has been made to evaluate some potential therapeutic effects of colchicine that may be benefit against COVID-19. Key Results. Prophylactic therapy with colchicine regulates the innate inflammatory response by blocking intracellular signaling pathways. This can inhibit respiratory alveolar destruction following COVID-19 pneumonia, which is the main cause of ARDS and death in these patients. Conclusion and Implications Since the macrophage and granulocytes are the main pro-inflammatory mediators in the lung, it seems application of therapeutic doses of colchicine, before the onset of respiratory problems, will protect the lung against severe damages and respiratory failure in COVID-19 patients. Obviously, many clinical trials are required to prove the validity of this claim.
Response to letter to the editor; TEVAR for a Marfan patient during COVID-19 pandemic...
Shinichiro Ikeda
Michael Shih

Shinichiro Ikeda

and 3 more

July 07, 2020
Dear Dr Harky et. al,We appreciate your inquiry regarding our case report. Dr Harky et. al suggested that TEVAR for a Marfan patient could be an unnecessary approach even during the COVID-19 pandemic.We believe in this particular case, the endovascular approach was fully justified as the patient had clear signs of end organ ischemia at presentation. He presented with extreme right leg ischemia with diffuse numbness. There was no detectable distal arterial flow of the right extremity by a Doppler and physical evaluation. Contrast computed tomography scan showed a completely occluded right common iliac artery and diminished flow to the right renal and celiac arteries due to the compression of the true lumen from the false lumen. Preoperative creatinine was elevated to 1.2 mg/dl. She was also suffering ongoing right kidney malperfusion.It was during the time when COVID-19 epidemic started spreading rapidly in New York City. Our hospital beds were filled with COVID-19 patients and there was a shortage of medical supplies with no ventilators immediately available. It was important to reduce exposure of the individual to the hospital environment and minimize length of stay and ventilator needs. As such, we chose to proceed with TEVAR to minimize the risk of lung injury which can occur in open repair. Postoperative respiratory failure is a major issue in open thoracic aortic repair [1]. The patient did not have a risk of respiratory comorbidities but we believed that this pandemic placed all patients at risk for contracting COVID-19 and subsequent acute respiratory distress [2].Due to the high risk of spinal cord ischemia in this particular patient, we performed TEVAR with a distal bare metal component to preserve the blood flow into spinal cord arteries [3]. The initial clinical treatment plan was to perform the TEVAR as a bridge to open repair. We obviously will need to follow-up with her carefully and if any signs of failure of TEVAR is detected, open repair will ultimately be required.Dr Harky et. al suggested axillary femoral artery bypass to rescue the ischemic leg, however, this patient also suffered malperfsuion of the renal and celiac arteries, so further intervention was required.Thank you for your insightful suggestions.References1) Khan FM, Naik A, Hameed I, et al. Open repair of descending thoracic and thoracoabdominal aortic aneurysms: a meta-analysis. Ann Thorac Surg . 2020;S0003-4975(20)30865-1.2) Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA.  2020;323:1406–7.3) Lombardi JV, Cambria RP, Nienaber CA, et al. Five-year results from the study of Thoracic Aortic Type B Dissection Using Endoluminal Repair (STABLE I) study of endovascular treatment of complicated type B aortic dissection using a composite device design. J Vasc Surg. 2019; 70:1072-81.
Successful Mobile Extracorporeal Membrane Oxygenator for COVID-19 Severe Respiratory...
Nicolas Brozzi
Jaime Hernandez-Montfort

Nicolas Brozzi

and 9 more

July 07, 2020
High volume ECMO centers have developed mobile ECMO programs in recent years to facilitate implementation of ECMO support at hospitals with lower capabilities, and transfer these patients for further care. We report a case of mobile ECMO on patient with COVID-19 related ARDS, and discuss the potential application in current SARS-CoV-2 pandemic.
Chasing COVID-19 chemotherapeutics without putting the cart before the horse
Steven Rannard
Thomas McDonald

Steven Rannard

and 2 more

July 07, 2020
Dear editor,Given time, drug discovery programmes will undoubtedly yield highly potent drugs to form the basis of optimised COVID-19 regimens. However, if efficacious therapies can be identified from current medicines, repurposing represents the fastest route to establish deployable interventions and buy time for vaccine and novel drug development. It is important to note that effective medicines were rigorously optimised for the treatment of specific indications. Route of administration, dosage and schedules for existing therapies were optimised to provide adequate plasma/tissue pharmacokinetics and safety for their target disease or condition. These cannot be assumed to be optimal for COVID-19 but are often highly predictable from pre-existing data and clinical experience. For example, hydroxychloroquine and lopinavir/ritonavir recently failed to deliver benefits in RCTs for mild/moderate and severe disease,1, 2 but the clear disconnect between reportedin vitro antiviral activity and known human pharmacokinetics after administration of approved doses was predictable.3Interpretation of laboratory-based antiviral activity assessments is complicated by current uncertainty regarding the appropriateness of the existing model systems. The majority of in vitro antiviral screening assays have utilised Vero cells, which were derived from the kidney of African Green Monkey in the 1970s, and the lack of clinical evidence for which to validate the exposure-response relationship in humans is problematic. Evidence is emerging that the anti-SARS-CoV-2 activity of drugs may be higher in cells derived from humans. However, the question of which cell types are most representative of in vivo performance is yet to be addressed, and all that can really be concluded from current knowledge is that the susceptibility of SARS-CoV-2 to antivirals is cell-type-dependent. The consequences of this in terms of the variety of cell types known to be infected and/or sustain productive infection in vivo is equally uncertain, and further exacerbated by the lack of robustly validated animal models. However, repurposed drugs cannot be assumed to be active against SARS-CoV-2 at a dose that was optimised on the basis of potency for and accumulation at their initial therapeutic target.Nucleoside/nucleotide polymerase inhibitors have proven highly successful for other viruses, but usually require combination with another drug class. Remdesivir and favipiravir have in vitro anti-SARS-CoV-2 activity across multiple studies, and the unprecedented speed at which they have transitioned through COVID-19 RCTs can only be commended.4, 5, 6 Daily IV infusion may make inherent sense for severely ill patients, but a transformational impact for COVID-19 can only be realised if wide compatibility with global healthcare systems and equitable access across all country contexts is achieved. While reduction in symptom duration may mitigate healthcare saturation in high-income countries, the absence of a clear benefit for mortality diminishes game-changing potential. However, the clinical validation of the antiviral activity of such drugs will make them clear candidates for implementation as part of community-based interventions if other challenges are addressed. Importantly, the combination of nucleoside analogues with a secondary target such as the protease has stood the test of time in antiviral pharmacology. The recent reports of low-dose dexamethasone leading to an impact on mortality7 is a significant step forward but long-term mitigation of viral transmission, with subsequent economic and social restrictions, requires antiviral treatment or prevention to minimise hospitalisation through a community-targeted approach.Focussing on existing single drugs, and not appropriately formulated medicines, will require the rethinking of a number of medicine development parameters such as posology, reformulation and therapeutic index (Figure 1); current HIV medicines, for example, are formulated for chronic (life-long) dosing to moderate and control disease but a successful COVID-19 therapy will likely require only a short term acute administration to rapidly cure the patient. Conversely, different considerations are required for longer-term applications in COVID-19 chemoprophylaxis, which could have a dramatic effect on control of the pandemic.Many advanced drug delivery technologies have emerged in recent years. Long-acting drug delivery involving injectable, implantable or microarray patch mediated delivery have attracted enormous recent interest for prevention of other infectious diseases,8, 9 and the ability to deliver potent antiviral combinations for a period of months could play a transformational role in the absence of a safe and efficacious vaccine. The physicochemistry and activity of the polymerase inhibitors, and other drugs with known anti SARS-Cov-2 activity, also warrants investigation of pulmonary delivery via nebuliser or metered dose inhaler for direct dosing to the upper airways to supplement systemic drug delivery as pre- or post-exposure prophylaxis. Several advanced drug delivery strategies can be applied rapidly and do not need to be prohibitively expensive for global community programmes. It seems unlikely that a global pandemic can be ended if effective medicines are only available to the few and equitable access is therefore of benefit to all. Importantly, relying solely upon pre-existing formulations and posologies optimised for other diseases carries inherent risk of rejecting drug candidates with an otherwise high potential for global impact.
Re: Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such...
Rui-Hong Xue

Rui-Hong Xue

July 02, 2020
Sir, We read with interests the article by Kate F Walker and colleagues, entitled ”Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis”. In the article, the authors systematically analyzed the mode of delivery on the infection rates of COVID-19 in the newborn. Despite the limitations, especially the retrospective nature of studies examined, this study provided important information about the selection of mode of delivery of women with COVID-19. It suggests that neonatal infection rates are not different after Caesarean birth or vaginal delivery. However, the severity of the COVID-19 infection of the mothers was not considered. Clinically, pregnant women with the more severe COVID-19 infection appear to prefer delivery by Caesarean delivery rather than vaginal birth. Therefore, it is possible that any beneficial effects of Caesarean birth in reducing transmission of COVID-19 might not be apparent because the severity of COVID-19 infection was greater in these women. This selective bias would weaken the conclusions of current studies. We feel that prospective evaluation the safety of mode of delivery with COVID-19 is required.Rui-hong Xue11Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Management of life-threatening acute respiratory syndrome and severe pneumonia second...
Salwa  Yaqoub
Shamsa  Ahmad

Salwa Yaqoub

and 15 more

July 02, 2020
Through this case, we present the thought process, team-based strategy and sequel of managing a complex, critically ill pregnant with ARDS and COVID-19 pneumonia. This case also confirms the feasibility of using convalescent plasma and ECMO during early postnatal period in acutely ill parturient with respiratory failure.
Teaching An Experiential Field Course Via Online Participatory Science Projects: A CO...
Laci Gerhart
Christopher Jadallah

Laci Gerhart

and 3 more

July 01, 2020
Experience and training in field work is a critical component of undergraduate education in ecology, and many university courses incorporate field-based or experiential components into the curriculum in order to provide students hands-on experience. Due to the onset of the COVID-19 pandemic and the sudden shift to remote instruction in the spring of 2020, many instructors of such courses found themselves struggling to identify strategies for developing rigorous field activities that could be completed online, solo, and from a student’s backyard. This case study illustrates the process by which one field-based course, a UC California Naturalist certification course offered at the University of California, Davis, transitioned to fully remote instruction. The transition relied on established, publicly available, online participatory science platforms (e.g., iNaturalist) to which the students contributed data and observations remotely. Student feedback on the course and voluntary continued engagement with the participatory science platforms indicates that the student perspective of the experience was on par with previous traditional offerings of the course. This case study also includes topics and participatory science resources for consideration by other faculty facing a similar transition from group field activities to remote, individual field-based experiences.
A virtual bird’s eye view: Live streaming nest boxes to continue outreach in the era...
Jennifer Houtz
Rachael Mady

Jennifer Houtz

and 2 more

July 01, 2020
COVID-19 created a host of challenges for science education; in our case, the pandemic halted our in-person elementary school outreach project on bird biology. This project was designed as a year-long program to teach fifth grade students in Ithaca, New York, USA about bird ecology and biodiversity, using outdoor demonstrations and in-person games and activities to engage students in nature. As a central part of this effort, we set up nest boxes on school property and had planned to monitor them with students during bird breeding in the spring. Here, we describe our experiences transitioning this program online: we live streamed nest boxes to students’ virtual classrooms and used them as starting points for virtual lessons on bird breeding and nestling development. We suggest that instituting similar programs at local schools can promote equitable learning opportunities for students across geographical locations and with various living situations. In an era of social distancing and isolation, we propose that nest box live streaming and virtual lessons can support local communities by providing access to the outdoors and unconventional science learning opportunities for all students.
Utility of the FebriDx point-of-care test for rapid triage and identification of poss...
Nawazish Karim
Srikumar Mallik

Nawazish Karim

and 11 more

July 01, 2020
Abstract Background Differentiating viral from bacterial acute respiratory infections (ARIs) remains challenging, due to the non-specific clinical manifestations. The COVID-19 pandemic is putting extraordinary strain on healthcare resources. To date, molecular testing is available but has a long turnaround time and therefore cannot provide results at the point-of-care (POC) thereby exposing COVID-19/Non-COVID-19 patients to each other while awaiting diagnosis. Methods This observational study prospectively evaluated the utility of a triage strategy including FebriDx, a POC fingerstick blood test that differentiates viral from bacterial ARIs through simultaneous detection of Myxovirus-resistance protein A (MxA) and C-reactive protein (CRP), in rapidly determining viral cases requiring immediate isolation and confirmatory molecular testing, from non-infectious patients or bacterial infections requiring antibiotics. Results 75 consecutive patients were screened, 48 eligible cases were tested with FebriDx, 36 were confirmed viral infection and 35/36 had COVID-19. 31/35 COVID-19 cases tested positive for SARS-CoV-2 via rRT-PCR and (4/35) had a clinical diagnosis of probable COVID-19 based on symptoms, epidemiological history, and chest imaging (PPV 100% (35/35)). 13 cases were FebriDx viral negative and rRT-PCR was also negative. In one case, it was not possible to determine the exact cause of infection, although a viral infection could not be excluded. Including this patient, FebriDx NPV was 92.3% (12/13), exceeding the NPV of rRT-PCR a 68.3% (13/19), and diagnostic sensitivity was conservatively calculated at 97% (35/36) compared to 82.9% (29/35) for initial rRT-PCR. The diagnostic specificity of both FebriDx and rRT-PCR was 100%. Conclusions: FebriDx could be deployed as part of a reliable triage strategy for identifying possible COVID-19 patients with symptomatic ARI in the COVID-19 pandemic. Key words: Pandemic; COVID-19; SARS-CoV-2; pneumonia; viral; point of care; infection
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Wiley Open Research

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