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856 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Please note: These are preprints and have not been peer reviewed.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.
COVID-19 in a child with severe aplastic anemia
Yunus Akçabelen
Ayça Koca Yozgat

Yunus Akçabelen

and 3 more

May 09, 2020
COVID-19 in a child with severe aplastic anemiaYunus Murat Akçabelen1, Ayça Koca Yozgat1, Aslı Nur Parlakay2, Nese Yarali11 Department of Pediatric Hematology, Ankara City Hospital Children’s Hospital, Turkiye2 Department of Pediatric Infectious Disease, Ankara City Hospital Children’s Hospital, TurkiyeArticle type: Letter to the editörRunning Title: COVID-19 in pediatric aplastic anemiaKey words: COVID-19, children, aplastic anemiaDisclosures: noneWord counts: 625
A lesson from an old friend: high molecular weight kininogen (HMWK) impact in COVID-1...
Chiara Colarusso
Michela Terlizzi

Chiara Colarusso

and 3 more

May 09, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 (COVID-19). It has fatality rate that floats from 5 to 15% and the symtoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. Thus, we propose to pharmacologically block the kallicrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.
Early Respiratory Outcomes Following Cardiac Surgery in Patients with COVID-19
khosro barkhordari
mohamad reza  khajavi

khosro barkhordari

and 7 more

May 09, 2020
Abstract The objective of this study was to describe early respiratory outcomes of asymptomatic COVID-19 patients after cardiac surgery. In this retrospective clinical study (case series) we reviewed and analyzed patient clinical data of 25 covid-19 asymptomatic patients that underwent urgent or emergent cardiac surgery between February 29 and April 10, 2020 in Tehran Heart Center Hospital. Median of age was 63 years (IQR, 52-67), Euro SCORE 7.50 (IQR, 6.5-8.5) and body mass index 26.3 (IQR, 22.5-28.6). 68% of patients had one or more comorbidities. Hypertension (56%) was the most common followed by Diabetes type 2 (40%). Off-pump cardiac surgery was done in 4 patients and on-pump on 21 patients with median CPB time of 85 minutes (IQR, 50-147.50). Median anesthesia time was 4.5 hours (IQR, 4-5). Median oxygen index and Fio2 on ventilator were 10 cmH20 (IQR, 9.5-10.5) and 0.64(IQR, 0.60-0.64) respectively. Median pao2/Fio2 was 231(IQR, 184-261). There was one case of extubation failure. The Median intubation time and length of ICU stay were 13 hours (IQR, 9.5-18) and 3 days (IQR, 2-4) respectively. Overall mortality was 16%. Readmission rate to ICU was 16% with. In this group respiratory outcome was worse with median Pao2/Fio2 84.5 (75-122), oxygen index of 4.38(IQR, 3.77-5.1) and morality rate of 75%. Conclusion: Based on the results of this study, very early post-cardiac surgery respiratory outcomes in asymptomatic COVID-19 patients are apparently smooth; nonetheless, readmission to the ICU is high. Overall respiratory outcomes are poor especially for those who readmitted to ICU.
Oncology care during COVID-19 pandemic in a low middle-income country
Amita Trehan
Richa Jain

Amita Trehan

and 2 more

May 09, 2020
The 2019 novel coronavirus disease (COVID-19) has affected all aspects of life globally and care of children with malignancies is no exception. We are part of a large tertiary care 2000 bedded university hospital in North India. Approximately 450 new malignancies are diagnosed annually, translating to 10 patients per week. About 200 children attend the clinics every week. Additionally, 15-20 walk-in patients are evaluated daily in the daycare. Patients travel from distances as far as 500 km to reach our center.  Merely 20% live within 50 km of the hospital, and approximately 35% reside at a distance exceeding 200 km. Two-third of the patients hail from urban areas and one third belong to rural areas. The majority of families stay in a patient hostel in the hospital premises, and a few rent a flat in the city for the 4-9 months duration of intensive phase of therapy. The Government of India mandated a lockdown on the 24th March 2020 in response to the coronavirus pandemic and the outpatient services of the hospital were closed. The borders with the neighboring states were sealed & vehicular movement curtailed with barring of public transport & suspension of all interstate and intercity travel. The citizens were advised to maintain social distancing. The unit was faced with the formidable challenge of ensuring the well-being of children under our care from a wide geographical spread with minimal access to Pediatric Oncology services in their   hometowns. How did we manage our patients?
Diagnosis and management of the drug hypersensitivity reactions in Coronavirus diseas...
aslı gelincik
Knut Brockow

aslı gelincik

and 9 more

May 08, 2020
Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.
Asthma and COVID-19 in children -- a systematic review and call for data
Jose A. Castro-Rodriguez
Erick Forno

Jose Castro-Rodriguez

and 1 more

May 08, 2020
Rationale: Whether asthma constitutes a risk factor for COVID-19 is unclear. Here we aimed to assess whether asthma, the most common chronic disease in children, is a risk factor for COVID-19 in pediatric populations. Methods: We performed a systematic literature search in three stages: First, we reviewed PubMed, EMBASE and CINAHL for systematic reviews of SARS-CoC-2 and COVID-19 in pediatric populations, and reviewed their primary articles; second, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; third, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma. Results: In the first search, eight systematic reviews were found, of which five were done in pediatric population; after reviewing 67 primary studies we found no data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 34 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 23 pre-prints in MedRxiv were identified with data on asthma, but again none with pediatric data. We found only one report by the U.S. CDC stating that 40/345 (~11.5%) children with data on chronic conditions had “chronic lung diseases including asthma”. Conclusion: There is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range.
The potential of cannabidiol in the COVID-19 pandemic: a hypothesis letter
Giuseppe Esposito
Marcella Pesce

Giuseppe Esposito

and 6 more

May 08, 2020
Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High-CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPARΥ agonist, it can display a direct antiviral activity 4) PPARΥ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID-19 pandemic.
Acute Complicated Type B Aortic Dissection during the New York City COVID-19 Surge.
Shinichiro Ikeda
Michael Shih

Shinichiro Ikeda

and 3 more

May 08, 2020
The impact of the COVID-19 pandemic in New York City (NYC) is dramatic. COVID-19 cases surged, hospitals expanded to meet capacity, and NYC remains the global epicenter of this pandemic. During this unprecedented time, a young woman with known Marfan syndrome presented with an acute complicated type B aortic dissection to our Aortic Center. Using the Provisional Extension to Induce Complete Attachment technique, we treated this patient and quickly discharged her the next day to decrease the risk of COVID-19 infection. Her progress was monitored using frequent phone calls and one office visit at two weeks.
Comment on Matricardi PM et al.: The first, holistic immunological model of COVID-19:...
Antonio Mirijello
Maria D'Errico

Antonio Mirijello

and 4 more

May 07, 2020
Comment on Matricardi PM et al.: The first, holistic immunological model of COVID-19: implications for prevention, diagnosis, and public health measuresTO THE EDITOR:We read with great interest the review article by Matricardi and colleagues [1] depicting mechanisms of disease for COVID-19 and analyzing both viral and host factors influencing its course. We particularly agree with Authors on the pivotal role of innate immunity in the very early phase of disease, being crucial for the subsequent evolution. Most known weapons of innate immune system are represented by natural antibodies, non-specific antimicrobial proteins, interferons, cytokines and cellular elements (i.e. natural killer cells).[1] However, innate immunity could be influenced by other, still underrecognized, factors.At present, a solid proof of evidence is available on the ability of vitamin D in modulating immune response.[2] Most of data are available from the field of bacterial infections and sepsis,[3] being low vitamin D levels associated with a higher risk of infection and mortality.[4]In addition, vitamin D could play a role against viruses by maintaining physical barriers (i.e. tight junctions, gap junctions, etc.), enhancing natural immunity (i.e. production of cathelicidin, defensins, etc.) and modulating adaptive immune response (i.e. modulation of TH1/TH2 response and inflammation).[5] On this connection, emerging data support the role of vitamin D supplementation in reducing the risk and severity of influenza.[5] Both influenza and COVID-19 show their maximum spread in winter season and the highest severity in elderly people. Reduced vitamin D levels could represent a possible pathophysiological explanation, among others, in both cases.[5,6] With this regard, it has been hypothesized that variations in vitamin D status across countries and latitudes could, at least in part, explain variations of mortality from COVID-19.[6,7]However, at present the exact vitamin D status among COVID-19 patients is unknown.[7] Moreover, the role and mechanisms of vitamin D in the treatment of COVID-19 are still unexplored and several interventional trials are ongoing. Should these hypotheses be confirmed, universal vitamin D supplementation would represent a possible and inexpensive strategy to enhance natural immunity against COVID-19.Antonio Mirijello, MDMaria Maddalena D’Errico, MDAntonella Lamarca, MDPamela Piscitelli, MDSalvatore De Cosmo, MDDepartment of Medical Sciences, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy
Pediatric Cancer Research: Surviving COVID-19
Jeffery Auletta
Peter Adamson

Jeffery Auletta

and 11 more

May 07, 2020
A diverse panel of pediatric cancer advocates and experts, whose collective experience spans the continuum of international academic medicine, industry, federal research, and cancer advocacy, recently discussed challenges for pediatric cancer research in the context of Coronavirus Disease 2019 (COVID-19). Specifically, this special report addresses the following focus areas: (1) the critical role that translational research has played in transforming pediatric cancer outcomes; (2) the current and potential future impact of COVID-19 on pediatric cancer research; (3) target areas of COVID-19 research that may have application in immunity, oncogenesis and therapeutic discovery; and (4) future considerations and directions in maintaining pediatric cancer research during and after COVID-19.
Lost ground: female academics face an uphill battle in post-pandemic world
Tricia Stadnyk
Kerry Black

Tricia Stadnyk

and 1 more

May 07, 2020
A document by Tricia Stadnyk, written on Authorea.
Mental health of healthcare workers during the COVID-19 pandemic in Italy
Marialaura Di Tella
Annunziata Romeo

Marialaura Di Tella

and 3 more

May 06, 2020
Background: The COVID-19 pandemic represents one of the most stressful events of recent times. Among the population, healthcare professionals who treat COVID-19 patients are most likely to develop psychological distress and posttraumatic stress symptoms (PTSS). The present study thus aimed to investigate the psychological impact of the COVID-19 outbreak on Italian healthcare workers. Methods: The responses of 145 healthcare workers (72 medical doctors and 73 nurses) were included in the final dataset. Participants were asked to provide sociodemographic and clinical information, and to complete: 1) quality of life and health-related Visual Analogue Scales, 2) State-Trait Anxiety Inventory-Form Y1, 3) Beck Depression Inventory, and 4) PTSD Checklist for DSM-5. Results: A comparison between healthcare professionals working in COVID-19 wards and other units revealed that the former reported higher levels of both depressive symptoms and PTSS. Moreover, the results of regression analyses showed that in healthcare professionals working with COVID-19 patients, gender and marital status, and gender and age significantly predicted depressive symptoms and PTSS, respectively. Particularly, being female and not in a relationship were found to be associated with higher levels of depressive symptoms, whereas being female and older were found to be related to higher levels of PTSS. Conclusions: The current findings suggest that specific predisposing factors could identify healthcare workers who are at high risk of developing mental health symptoms when faced with COVID-19 patients.
“Water pumps, not Wars” – From emotive to rational language in managing the Covid-19...
Mike Stedman
Mark Davies

Mike Stedman

and 2 more

May 06, 2020
At the date of writing this editorial, there is growing agreement amongst experts that the first wave of the COVID-19 pandemic is in decline. The number of deaths reported each day is now around 1% of the cumulative total and falling. In general, the approach to predicting pandemic policy has been through a comparison of inter-country performance in managing this crisis. While all countries are paying a high price in economic slowdown and lives lost, the health consequences in terms of cases and deaths have varied considerably. Countries with lower relative mortality and infection numbers have shown a more structured logical approach to pandemic management. There is a very real urgency to learn lessons immediately given the pressure to reduce the home confinement policy as soon as possible. While this is clearly a challenging time for policy makers, public health messaging is often emotive around concepts such ‘being at war’ with the virus, and other similar statements. We propose that a more rational approach to moving forward is required to avoid a second wave. Understanding this rational approach can be found through an evaluation of not only how other countries are approaching this challenge, but also from history.
The Role of Climate During the COVID-19 epidemic in New South Wales, Australia
Michael Ward
Shuang Xiao

Michael Ward

and 2 more

May 05, 2020
Previous research has identified a relationship between climate and occurrence of SARS-CoV and MERS-CoV cases, information that can be used to reduce the risk of infection. Using COVID-19 notification and postcode data from New South Wales, Australia during the exponential phase of the epidemic in 2020, we used time-series analysis to investigate the relationship between 749 cases of locally-acquired COVID-19 and daily rainfall, 9am and 3pm temperature, and 9am and 3pm relative humidity. Lower 9am relative humidity (but not rainfall or temperature) was associated with increased case occurrence; a reduction in relative humidity of 1% was predicted to be associated with an increase of COVID-19 cases by 6.11%. During periods of low relative humidity, the public health system should anticipate an increased number of COVID-19 cases.
PEDIATRIC CORONAVIRUS DISEASE 2019: HOW TO ASSESS CHEST DISEASE?
Adele Corcione
Federica Annunziata

Adele Corcione

and 3 more

May 05, 2020
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a serious health problem worldwide. In the pediatric population, currently available epidemiological data seem reassuring as the incidence of coronavirus disease 2019 (COVID-19) is much lower than in adults, with less critical cases and very few deaths. At present, there are no evidence-based studies on chest imaging in pediatric COVID-19. Chest X-rays showed non-specific findings and chest computed tomography (CT) exhibited similar, but fairly less severe CT changes compared to adult. Moreover, in approximately 50% of pediatric patients no correlation was found between chest CT imaging results and clinical characteristics. Lung ultrasound is rarely used, despite its unquestionable benefits as it can be performed at bed-side with a portable device, which minimizes virus transmission, is cheap and can be easily repeated. In conclusion, the chest imaging use in children, who are typically spared from severe infection, deserve recommendations different than adults also considering the increased risk of radiations exposure. In view of this, pediatric comparative studies among different chest imaging techniques, either less or more invasive, are urgently needed possibly after standardization of interpretation criteria of lung ultrasound.
Considerations on Cardiac Patients During Covid-19 Outbreak
Fabiola Sozzi
Marta Belmonte

Fabiola Sozzi

and 3 more

May 05, 2020
SARS-CoV-2 not only causes viral pneumonia but has major implications for the cardiovascular system. Nevertheless, we assisted to a drastic reduction in the number of ACS during this period. Telemedicine and telecardiology, intended as integration to the traditional management appear precious tools especially in Covid-19 era. Given the decrease in new Covid-19 cases worldwide20, now we are approaching the so-called “Phase 2” challenge of a gradual return to pre-Covid-19 life. The epidemiological and clinical situation is rapidly evolving and practice patterns with policies depend on institutions and local availability.
Tackling COVID-19 infection through complement-targeted immunotherapy
Sonata Jodele
Jörrg  Köhl

Sonata Jodele

and 1 more

May 05, 2020
The complement system is an ancient part of innate immunity sensing highly pathogenic coronaviruses by Mannan-binding lectin resulting in lectin pathway-activation and subsequent generation of the anaphylatoxins (AT) C3a and C5a as important effector molecules. Complement deposition in endothelial cells and high blood C5a serum levels have been reported in COVID-19 patients with severe illness, suggesting vigorous complement activation leading to systemic thrombotic microangiopathy (TMA). Strikingly, SARS-CoV-2-infected African Americans suffer from high mortality. Complement regulator gene variants prevalent in African Americans have been associated with a higher risk for severe TMA and multi-organ injury. These findings allow us to apply our knowledge from other complement-mediated diseases to COVID-19 infection to better understand severe disease pathogenesis. Here we will discuss the multiple aspects of complement activation, regulation, crosstalk with other parts of the immune system and the options to target complement in COVID-19 patients to halt disease progression and death.
Safe Nasoendoscopy Assisted Procedure in the Post COVID-19 Pandemic Era
Ajith George
Christopher Coulson

Ajith George

and 2 more

May 04, 2020
For centuries it has been humankind’s instinct to cover the mouth and nose when coughing or sneezing. Common sense would dictate this instinctively reduces the dispersion of aerosol and droplets and thus the spread of contact and airborne infections.Aerosol generating procedures (AGPs) have become a new byword for procedures that put clinicians at increased risk of contracting COVID-19. Whilst the title suggests the risk is simply in aerosols, the science is much more interesting. Droplets and aerosols are different, with the distinction between them based on size. Whilst experts disagree on the absolute size when an aerosol becomes a droplet, the general acceptance is that anything bigger than 50 microns (0.05mm) is a droplet and those smaller are aerosols.In most contagious respiratory infections, the principal transmission agents are droplets (1). This is due to the relatively high viral load in a droplet, purely due to its large size, and also the fact that large droplets have weight, and so gravity pulls them down onto surfaces that others can touch – so passing it on. This is why washing hands is so effective against droplet spread.Aerosol transmission is thought to be a much less frequent cause of transmission, mainly due to the very small viral load (given the aerosol itself is by definition very small). However, it is clearly more concerning as these very small, and therefore very light particles, can travel large distances on air currents and can be directly inhaled. That said, it is thought to only play a minor role in transmission compared to droplet spread.During the COVID-19 pandemic PHE (Public Health England) updated guidance on what it considers (AGPs) Aerosol Generating Procedures. Included within this list were examinations of the upper aerodigestive tract in ENT. Any procedure enacting air over a fluid mucosal surface therefore poses a risk of viral dispersion within both droplets and aerosol. Healthcare workers were recommended to reduce endoscopy of the nose and throat. Any essential examination had to be performed using high level PPE including an respirator (N95 or FFP3)(2).Anfinrud et al (3) graphically represented a visual reduction in aerosol production by creating light sheet from a 532-nm green LASER. Comparisons were made between a person talking with and without a cover for the mouth, in their instance, a slightly dampened wash cloth. Light flashes were recorded to evaluate the number of droplets ranging between 5-200 microns. They showed that by covering the mouth, virtually no light flashes were seen. This observation supports the well-known concept that covering the mouth does indeed reduce droplet production.On impact with smooth surfaces droplets disperse to smaller sizes and can aerosolise. Similarly impact onto soft surfaces absorbs droplets reducing their projection as well as the tendency to aerosolise (3).As the pandemic plateaus in countries across the world various strategies are to be considered to return to a new normal. This would facilitate the resumption of diagnostic services whilst maintaining the protection to healthcare workers. One suggestion is the use of facemasks to help reduce the risk of inadvertent droplet dispersion (2). Despite the ‘soft surface’ barrier masks create, in the ENT setting, facemasks obscure access to the nasal cavity thus preventing nasoendoscopy.The ‘SNAP’ (Safe Nasoendoscopic Airway Procedure) developed by endoscope-i Ltd (West Midlands, UK) is a single-use, valved endoscopic port, retrofitted to any surgical mask (Figure 1), permitting entry of a 4mm flexible and rigid endoscope to examine the naso and pharyngolarynx. The valve, a 10.9 mm cylindrical tube truncated by two opposing 45 degree inclined membranes 700 microns thick, approaches a point but terminates in a 700 micron thick and 500 micron wide plateau, creating a ‘duck bill’ formation The valves are formed using a FFF (fused filament fabrication) 3D printing technique with a Flashforge Creator Pro 3D printer. The plateau atop the valve serves to provide a reference for introducing a slit using a hardened steel razor blade that is 400 microns thin. The blade is mounted in a jig to ensure angle, penetration depth and position are controlled as it is driven through the membrane. These measures ensure that the valve opening is observably consistent and less than 50 microns. Once the SNAP is fitted to a surgical mask, any cough or sneeze generated during the procedure is caught within the mask. The valve is configured such that pressure from the patient side will serve to collapse the walls of the valve membrane thereby further sealing the slit in the valve. This seal has been in vitro tested with aerosolised fluorescein(figure 2). The 45-degree angle of the valve walls from the non-patient side similarly allows the blunt tip of the nasoendoscope to deform the valve walls with ease. The cylindrical form of the walls encourages the valve membranes to return to their original flat shape following withdrawal of the endoscope.During the COVID-19 pandemic our tertiary head and neck cancer referral centre managed 120 urgent 2ww cases. Using the Tikka et al calculator (4) 40% of referrals were redirected back to the GP. The remaining 60% either went direct for imaging or underwent endoscopy. In total 40 cases were endoscoped, 9 of which using the SNAP. All 9 cases scoped with the SNAP were completed without any adverse effect. No cough or sneeze was elicited during any of the examinations and observations between the two groups were identical. Subsequently one consultant lead FEES examination was performed under controlled conditions. Again, the procedure was completed without any complications. The patient self-remarked on the comfort of the endoscopy as a result of the stability provided by the SNAP device in the alar region the prevented inadvertent movement during the chin tuck and head turn exercises.Our observations demonstrate the SNAP device is a practical and safe tool to aid reduction in droplet dispersion whilst performing nasoendoscopy. We hope to see the inclusion of such a device in recovery guidelines by national bodies in order to facilitate the return of safe nasoendoscopy in the post COVID Pandemic era.
Comment on “ACE inhibitors and COVID-19: We don’t know yet”
Tevfik Ilcol
Erkan Cure

Tevfik Ilcol

and 2 more

May 02, 2020
We read with great interest the article by Khashkhusha TR et al “ACE inhibitors and COVID-19: We don’t know yet”. The authors discuss whether the use of angiotensin-converting enzyme (ACE) inhibitors (ACEIs) in novel coronavirus disease‐19 (COVID‐19) patients is beneficial or harmful. ACEIs and angiotensin receptor antagonists (ARBs) both upregulate ACE2 levels. We believe that ARBs should be preferred since, unlike ARBs, ACEIs may increase angiotensin II through the chymase pathway. We would like to discuss potential harms ACEI may cause through secondary bradykinin-chymase pathways.
Animal models of SARS-CoV-2 infection and mechanisms of COVID-19
Simon Cleary
Simon Pitchford

Simon Cleary

and 8 more

May 02, 2020
The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 infections has led to substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS-CoV-2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID-19. At the time of writing, in vivo studies of SARS-CoV-2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partially model the mechanisms implicated in human severe COVID-19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID-19. These models need to recapitulate key mechanisms of COVID-19 severe acute respiratory distress syndrome and reproduce the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS-CoV-2 infection and COVID-19-related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID-19 pathogenesis and for assessing potential treatments.
Converting a standard internal medicine ward into an isolation unit during the COVID-...
iftach sagy
Elli Rosenberg

iftach sagy

and 2 more

May 01, 2020
The COVID-19 pandemic has substantial implications on almost every aspect of life. Its ongoing influence on health care, as well as other financial, social, psychological, educational and emotional aspects are yet to be fully recognized. Although the COVID-19 outbreak emerged in China at the end of December 2019, the first patient arrived in Israel on February 21st. This nearly two month gap enabled the Israeli health system to implement preparations at a both national and institutional level. Every hospital established an isolated internal medicine ward, which was assigned to treat only COVID-19 patients. Since there was no previous experience or recommended published guidelines, on a national level the Ministry of Health instructed each hospital to convert at least one standard internal medicine ward into a specialized isolated COVID 19 unit, usually within a few days. Although several series of protocols to treat critical COVID-19 patients in ICUs have been proposed, similar recommendations for treatment in internal medicine wards are scarce (1,2). Hence, we would like to summarize our experience in the organizational aspects of managing COVID-19 patients in an isolated internal medicine ward of a tertiary medical center.Minimal exposure . The major concept of working in the isolation ward is minimal exposure to the pathogen. The medical and nursing staff are essential resources and it is crucial to minimize their risk of SARS-COV-2 infection. The staff are also instructed to minimize social contacts outside of working hours to avoid infection risk outside of the hospital. The ward’s staff is divided into two separate ”capsules”, each capsule with consistent personnel (nursing and medical staff) that work at separate shifts without physical interaction between the shifts. In this manner, if one member is accidently infected, only one capsule is isolated instead of the entire staff.Minimal exposure concept is facilitate in the following methods:Medical staff enter the ward the least as possible – usually once for morning rounds and later only for new admissions or for deteriorating patients.Every entrance to the ward is carried out only with the minimal staff needed (e.g. two physicians and two nurses). Communication with the remaining team situated outside of the isolation unit is continuous.Every entrance is planned ahead and equipment (e.g. PCR swabs, fluids) are prepared a priori.We conduct minimal procedures and only on an as-need bases.We use point-of-care ultrasound for lung and heart physical examination instead of stethoscope use(3)Situation room. We facilitate a situation room (SR) manned 24/7 by a physician or nurse. Patients’ vital signs and medical follow-up are transmitted from the isolated ward to the SR. The are multiple communication channels for facilitating transmission of medical data to and from the SR. In addition, the SR is connected to other units inside and outside of the hospital who used as needed.Telemedicine. Telemedicine devices allow the staff to monitor patients with little SARS COV 2 exposure(4). The ward is interconnected with cameras which broadcast to the SR, allowing continued monitoring of the patients. In a addition, mobile sensors are attached to the patients, which wirelessly transmit vital signs, via wifi, to the SR. A remote control mobile robot with a screen, microphone and camera, can be remotely moved around the isolated ward, allowing constant communication with the patients.Patients examination. Due to the use of personal protective equipment (PPE) the routine physical examination of COVID 19 patients is limited. Instead, we recommend focusing on appreciating the general condition of the patients, his/her speech flow, mobility level and in mild to moderate cases on POCUS of the lungs.Inter-disciplinary approach. The significance of inter-disciplinary cooperation cannot be more emphasized. During rounds physicians assist nursing staff in their routine tasks: e.g. measuring vital signs, feeding patients and replacing bed ridden patient’s diaper. We also are aided by social workers with routine talks with patients and family members for daily updates and for psychological support (5). In addition, a physiotherapist is involved to perform respiratory and ambulatory physiotherapy as needed.Research. We initiated several small-scale studies in our ward. Data of the admitted COVID 19 patients are collected to evaluate possible association with demographical and clinical characteristics. We also evaluate several compounds with minimal adverse evets, which were recently reported to have possible positive effect on disease progression, such as hydroxychloroquine, Zinc, vitamin C and N-acetyl-cysteine(6,7).In conclusion, treating COVID-19 patients create unique clinical and institutional challenges. These challenges can be managed with minimal exposure to the medical staff, but without losing the therapeutic Continuum. Notwithstanding, the basic concept of internal medicine remain the same: maximal treatment with minimal risk for the patients (Primum non nocere), but also to the treating team. More studies are needed to investigate the functioning of the isolated COVID-19 wards in larger scales, and the preparedness of health systems to this pandemic at national levels.All authors declare no conflict of interest(1) Xie J, Tong Z, Guan X, Du B, Qiu H, Slutsky AS. Critical care crisis and some recommendations during the COVID-19 epidemic in China. Intensive Care Med 2020:1-4.(2) Wang H, Wang S, Yu K. COVID-19 infection epidemic: the medical management strategies in Heilongjiang Province, China. Crit Care 2020 Mar 18;24(1):107-020-2832-8.(3) Peng QY, Wang XT, Zhang LN, Chinese Critical Care Ultrasound Study Group (CCUSG). Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic. Intensive Care Med 2020 Mar 12.(4) Wendelboe AM, Amanda Miller J, Drevets D, Salinas L, Miller E, Jackson D, et al. Tabletop exercise to prepare institutions of higher education for an outbreak of COVID-19. Journal of Emergency Management 2020;18(2):1-20.(5) Lima CKT, de Medeiros Carvalho, Poliana Moreira, Lima, Igor de Araújo Silva, de Oliveira Nunes, José Victor Alexandre, Saraiva JS, de Souza RI, et al. The Emotional Impact Of Coronavirus 2019-Ncov (New Coronavirus Disease). Psychiatry Res 2020:112915.(6) Matthay MA, Aldrich JM, Gotts JE. Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med 2020 Mar 20.(7) Razzaque M. COVID-19 Pandemic: Can Maintaining Optimal Zinc Balance Enhance Host Resistance? 2020.
COVID-19 infection thrombosis due to hemagluttination of antibodies and COVID-19 anti...
kevin.roe@att.net

Kevin Roe

April 30, 2020
A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality. COVID-19 has also shown about 80% genetic similarity to the Severe Acute Respiratory Symptom (SARS) virus, which is already known to be derived from a bat virus. Arterial thrombosis and venous thrombosis, variously attributed to long term patient immobilizations, inflammation, autoimmune reactions or endothelial cell damage to the blood vessels, have also been reported for COVID-19 infections. However, there is another explanation for thrombosis (blood clots) in many patients infected with COVID-19.
When Public Health Crises Collide: Social Disparities and COVID-19
Richard Stein
Oana Ometa

Richard Stein

and 1 more

April 30, 2020
In To Have or to Be? , psychoanalyst Erich Fromm writes about pursuit after domination of nature, material abundance, and unlimited happiness, which made modern society become more interested inhaving than in being . Income, in his view, should not be as accentuated as to create different experiences of life for different groups [1]. Of the concepts that Fromm presents, the domination of nature, which facilitates zoonotic spillover events by increasing the overlap between the habitat of various species with that of humans [2-5], and the gap between the rich and the poor, which recently has become the widest in years [6], become particularly relevant in context of the COVID-19 pandemic.Even though susceptibility to COVID-19 does not know socioeconomic boundaries, a critical and worrisome finding is emerging from preliminary data and may re-shape infectious disease outbreak management strategies for the future. An early analysis of COVID-19 data from several jurisdictions in the United States found that counties with a majority of African American residents had three-times higher infection rates and six-times higher mortality rates than counties with a majority of Caucasian residents [7]. Another analysis, of March 2020 COVID-19 hospitalization data from 14 states in the United States, found more African American individuals among hospitalized patients whose race or ethnicity was recorded [8]. These and other findings reveal a disproportionately higher risk of serious or fatal COVID-19 in minorities. What makes these observations remarkable is that hypertension, diabetes, and obesity, which are risk factors for more severe or fatal COVID-19 [9-13], are exactly the chronic conditions that have long been recognized as disproportionately affecting racial/ethnic minorities and socioeconomically disfavored individuals and groups [14].Obesity affects minorities and low-socioeconomic-status groups disproportionately at all ages [15], a finding that was reported in several countries [16-19]. Some of the risk factors that account for disparities in obesity include low socioeconomic status [20], food insecurity, restricted access to healthy diet and recreational facilities [21-24], residence in areas with fast food restaurants [25], a high neighborhood density of small grocery stores [26], distance to a store [27], exposure to obesogenic environments [28, 29], shift work [30] and irregular sleep patterns [31-33].Obesity increases the risk for other chronic diseases [12], including diabetes and hypertension [34]. African American adults in the United States have among the highest rates of hypertension worldwide [35]. Several factors were implicated in disparities in hypertension, including socioeconomic status [36], differences in awareness [37], residence in a food desert [38], chronic stress [39, 40], fewer healthcare resources [41], and income [42]. Disparities for diabetes were described in minority populations in terms of increased prevalence [43, 44], worse management and control [45, 46], and higher rates of complications [45, 47]. Over the past three decades the socioeconomic disparities for type 2 diabetes have widened [48].Racial, ethnic and socioeconomic disparities also shape inequities in the access to mental health care [49-52]. This is very relevant for COVID-19, in context of the quarantine that was implemented in many countries in various forms, including school closures, allowing non-essential personnel to work from home, closure of mass transit systems, cancellation of public events, and restrictions on the assembly of groups of people [53-55]. Social isolation negatively impacts mental health and, with > 70% of the young people and adults not receiving adequate mental health treatment from health care personnel worldwide [56], the implications in the wake of COVID-19 are extensive and far-reaching. The 2002-2003 SARS pandemic revealed that a substantial proportion of the quarantined individuals may display PTSD and depression symptoms, with longer duration of the quarantine being associated with more severe PTSD [57]. During the same pandemic, hospital employees from Beijing who were quarantined had higher PTSD levels than those who were not, even three years later [58]. Among individuals from South Korea isolated for two weeks during the 2015 MERS outbreak, anxiety and anger were still present 4-6 months after the quarantine [59].The disproportionately higher suffering of socio-economically disadvantaged individuals at a moment of crisis is, unfortunately, nothing new. In the 14th century, in the Black Death pandemic, the poorest populations were also the most extensively impacted ones in terms of mortality [60, 61], and low-income individuals had a considerably worse outcome after the 1918 flu pandemic [62]. The disproportionate effect on socio-economically disadvantaged individuals was also apparent in the wake of natural disasters, such as Hurricane Katrina [63] or the Deepwater Horizon oil spill [64]. One aspect that makes COVID-19 different is that several segments of the population become more vulnerable not simply due to socioeconomic disparities, but as a result of chronic medical conditions that these disparities have at least partly fueled over decades. The partial overlap between the risk factors for these two groups of diseases is reminiscent of debates on whether the broad classification of diseases into non-communicable and communicable ones is a meaningful one, considering that the two groups often overlap and interact markedly with one another [65-67]. Another aspect that sets COVID-19 aside from other pandemics in recent history is the extent and the duration of the quarantine and the resulting increase in unemployment rates [68, 69], which only promise to prolong and exacerbate the extent of social inequities and the burden of chronic diseases.COVID-19 provides a steep and perplexing learning curve that underscores the imperative need to envision infectious diseases not simply from a biomedical perspective, but as part of a complex framework that incorporates ethnic, socioeconomic, and political dimensions. Racial/ethnic and socioeconomic disparities are conducive to the development of chronic medical conditions that could increase the risk of severe COVID-19, widening the disparities and accentuating the chronic disease burden and, as a result, further marginalizing already vulnerable individuals and groups. The implications of this positive feedback loop for individuals, groups, and society, extend beyond COVID-19 and beyond infectious diseases in general. The current pandemic eloquently demonstrates, albeit at a high cost, that societies function on the basis of a social contract, as described by Jean-Jacques Rousseau and, undoubtedly, offers an important moment to reflect on the profound, far-reaching, and multi-layered consequences of disparities in society.References1. Fromm E. To Have or to be. Continuum: New York 1977;
COVID-19 treatment in patients with comorbidities: Awareness of drug-drug interaction...
David Back
Catia Marzolini

David Back

and 7 more

April 30, 2020
In a recent issue of Br J Clin Pharmacol Smith et al1 published an outstanding commentary titled ‘Dosing will be a key success factor in repurposing antivirals for Covid-19’. They highlighted that the success in our repurposing efforts will be dependent on ‘getting the dose right’ for drugs which have been developed for different indications and stressed some of the unique challenges of treating this particular disease. They pointed the reader to lopinavir/ritonavir (LPV/r) as an example of a repurposed antiviral and the limited experience of this drug regimen (and other treatments) in the elderly population with comorbidities – ie those most at risk from Covid-19. It is on the issue of comorbidities, polypharmacy and drug-drug interactions (DDIs) that we wish to comment.
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