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.

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.

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.

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;

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.

Objectives: In December 2019, a pneumonia like illness was first reported in Wuhan-China caused by a new coronavirus named corona virus disease -2019 (COVID-19) which then spread to cause a global pandemic. Most of the available data in the literature is derived from Chinese cohorts and we aim to contribute the clinical experience of a single British clinical centre with the characteristics of a British cohort. Design: A prospective case series. Setting: A single clinical centre in the UK. Methods: We have collected the demographics and medical characteristics of all COVID-19 positive cases admitted over two-week period. All cases were diagnosed by PCR. Results: Total of 71 COVID-19 patients were included in this case series. Majority of patients (75%) were ≥75 years old and 58% were men. Pre-existing comorbidities was common (85% of patients). Most patients presented with respiratory symptoms such as fever (59%), shortness of breath (56%) and cough (55%). Gastrointestinal symptoms were second most common presenting compliant such as diarrhoea (10%) and abdominal pain (7%). Opacification in chest X-rays were demonstrated in 45% of patients. All patients received supportive treatment and no specific antiviral therapy was administered in this cohort. So far, 18 (25%) patients have fully recovered, 9 patients (13%) escalated to a higher level of care and 10 (14%) have died. Patients who died were non-significantly older than those who have recovered (78.0 v 69.2 years, p=0.15) but they had a significantly higher clinical frailty scores (5.75 v 3.36, p=0.005). Conclusion: This case series demonstrated that the characteristics of British COVID-19 patients were generally similar to what is published in literature although we report more gastrointestinal symptoms at presentation. We have identified frailty as a risk factor for adverse outcome in COVID-19 patients and suggest that it should be included in the future vaccination recommendations.

Hundreds of researchers are working to develop a vaccine and are evaluating drugs to mitigate the adverse health and economic consequences of COVID-19 (Coronavirus disease 19) worldwide. If novel compounds are found, geopolitical and economic variables will determine their introduction to communities. Therefore, finding low-cost and widely accessible drugs for prevention or treatment of COVID-19 would be ideal.A recent study found that ivermectin, an FDA-approved anti-parasitic drug, has inhibitory effects on replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Ivermectin has broad anti-viral activity through inhibition of viral proteins including importin α/β1 heterodimer and integrase protein2. Caly and colleagues reported that the addition of ivermectin at a concentration of 5 micromolar (μM) (twice the reported IC50) to Vero-hSLAM cells, 2 hours post infection with SARS-CoV-2, resulted in a reduction in the viral RNA load by 99.98% at 48 hours1. The authors suggested that this drug could reduce the viral load in infected patients, with potential effect on disease progression and spread.While the findings by Caly and colleagues provide some promise, there is no evidence that the 5 μM concentration of ivermectin used by Caly and colleagues in their in vitro SARS-CoV-2 experiment, can be achieved in vivo . The pharmacokinetics of ivermectin in humans is well described (Figure 1)3-5, and even with the highest reported dose of approximately 1700 µg/kg (i.e. 8.5 times the FDA-approved dose of 200 μg/kg), the maximum plasma concentration was only 0.28 µM5. This is 18 times lower than the concentration required to reduce viral replication of SARS-CoV-2in vitro . Ivermectin accumulation in tissues is mild and would not be sufficient to achieve the antiviral effect with conventional doses6. Although high doses of ivermectin in adults or children are well tolerated5,7, the clinical effects of ivermectin at a concentration of 5 μM range are unknown and may be associated with toxicity. Consequently, ivermectin has in vitroactivity against SARS-CoV-2 but this effect is unlikely to be observedin vivo using current dosing.Amidst fear of the pandemic, the public and some physicians are now using ivermectin off-label for prophylaxis or as adjuvant therapy for COVID-19. Because ivermectin is only commercially available as a 3 or 6 mg tablets or a 6 mg/ml oral suspension, in order to administer a high dose, some people may experiment with more concentrated veterinary formulations. These actions are not based on clinical trials and have motivated cautionary statements from institutions such as the FDA against the use of pharmaceutical formulations of ivermectin intended for animals as therapeutics in humans 8.Potential avenues for further investigation into repurposing ivermectin for SARS-CoV-2 may be to: (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure; and (ii) evaluate more potent ivermectin analogs (e.g. doramectin) which may also inhibit SARS-CoV-2. These are areas for research – clearly, further studies are needed before ivermectin can be used for the prevention and treatment of COVID-19. As recently discussed in BJCP, this highlights the critical need to consider pharmacological principles to guide in vitro testing when repurposing old drugs for therapeutic use against COVID-199.

BACKGROUND: the outbreak of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 150000 infected individuals and more than 20000 deaths in Italy. Viral acute pneumonitis is the major cause of morbidity and mortality, but there is increasing evidence that COVID-19 patients show a variable degree of vascular complications, due to a possible hypercoagulability status. OBJECTIVE: to report thrombotic events in abdominal and lower-limb arteries of COVID-19 patients (abdominal aorta, superior mesenteric artery, femoral arteries, cardiac, spleen and kidney). METHODS: we retrospectively reviewed our clinical records of patients with confirmed SARS-CoV-2 infection, admitted from March 1st to April 6th, 2020, to a tertiary care center in Brescia, Italy. We selected five patients with major arterial thrombo-embolic manifestations. RESULTS AND CONCLUSION: In our opinion, arterial thrombotic events may be more common in COVID-19 patients than in general population, possibly resulting in rapid worsening of patient conditions.

Objective: Numerous clinical practice guidelines (CPGs) for the corona virus disease 2019 (COVID-19) have been developed since its outbreak. To date, however, the methodological quality of these guidelines has not been fully evaluated. Quality evaluation of the guidelines is to facilitate the clinic practitioners in diagnosis and treatment of the COVID-19. Methods: The evaluation was conducted by searching seven databases and government organizations websites (December 2019 to March 2020). Four assessors assessed the quality of the CPGs independently with the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. For domain scores (0-100%), >60% were considered of sufficient quality, and >80% of good quality. Results: Of 471 retrieved records, 20 guidelines were included. The median score for the domain of scope and purpose was 56.9% (range 40.3–90.3%) and nine guidelines scored >60%, among which three guidelines scored >80%. The median score for the stakeholder involvement domain was 7% (range 0–65.3%) and only two guidelines scored >60%. Nine guidelines scored 0% in this domain. The median score for the rigour of development domain was 0% (range 0–91.7%) and fourteen guidelines scored 0% in this domain. The median score for the clarity of presentation domain was 30.6% (range 13.9–91.7%) and six guidelines scored >60%, among which three guidelines scored >80%. The median score for the applicability domain was 0% (0–57.3%) and eleven guidelines scored 0% in this domain. The median score for the editorial independence domain was 0% (0–100%): four guidelines scored >80%. Discussions：Three guidelines were recommendable, and four were recommendable with modification in the stakeholder involvement, the rigour of development, and the applicability domains. Our results could contribute to improve development of future guidelines, and affect the reasonable selection and use of guidelines in clinical practice.

Background The COVID-19 pandemic has led to radical political control of social behaviour. The purpose of this paper is to explore data trends from the pandemic regarding infection rates/policy impact, and draw learning points for informing the unlocking process. Methods The daily published cases in England in each of 149 Upper Tier Local Authority (UTLA) areas were converted to Average Daily Infection Rate(ADIR), an R-value - the number of further people infected by one infected person during their infectious phase with Rate of Change of Infection Rate(RCIR) also calculated. Stepwise regression was carried out to see what local factors could be linked to differences in local infection rates. Results By the 19th April 2020 the infection R has fallen from 2.8 on 23rd March before the lockdown and has stabilised at about 0.8 sufficient for suppression. However there remain significant variations between England regions. Regression analysis across UTLAs found that the only factor relating to reduction in ADIR was the historic number of confirmed number infection/000 population, There is however wide variation between Upper Tier Local Authorities (UTLA) areas. Extrapolation of these results showed that unreported community infection may be >200 times higher than reported cases, providing evidence that by the end of the second week in April, 29% of the population may already have had the disease and so have increased immunity. Conclusion Analysis of current case data using infectious ratio has provided novel insight into the current national state and can be used to make better-informed decisions about future management of restricted social behaviour and movement.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

During the COVID-19 pandemic, ER visits have drastically decreased for non-COVID conditions such as appendicitis, heart attack and stroke. Patients may be avoiding seeking medical attention for fear of catching the deadly condition or as an unintended consequence of stay-at-home orders. This delay in seeking care can lead to increased morbidity and mortality, which has not been figured in the assessment of the extent of damage caused by this pandemic. This case illustrates an example of “collateral damage” caused by COVID-19 pandemic. What would have been a standard STEMI treated with timely and successful stenting of a dominant right coronary artery occlusion, became a much more dangerous post-infarction VSD; all because of a 2-day delay in seeking medical attention by an unsuspecting patient.

COVID-19, the disease resulting from infection by a novel coronavirus: SARS-Cov2 that has rapidly spread since November 2019 leading to a global pandemic. SARS-Cov2 has infected over 2.8 million people and caused over 180,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of Acute Respiratory Distress Syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti-inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS and thus chronotherapy may be used to effectively manage ARDS in COVID-19 patients.

I moved out of our shared bedroom of nearly 10 years on 3/22/2020. It was not a difficult decision as we have two young children and wondered what would happen if both of us became ill at the same time. As a Maternal-Fetal medicine physician in New York City, I was acutely aware of the coming COVID-19 crisis, and its potential ramifications on the health of my family, friends, patients and community. I am trained to function well in emergencies, and in this case, it was a quick and seemingly logical next-step to sleep separately.This decision also comes along with an already in place full-scale decontamination effort that begins as soon as I enter our home. This involves minimizing what jewelry, clothing, food and bags go back and forth between the hospital and my home, 3-shoe changes, stripping off my clothing and placing everything into the wash, and then running to the shower. None of these choices were rooted in years of medical science, given the novelty of the virus, and paucity of data on the SARS-CoV-2 (COVID-19). I used early data regarding transmission as well as anecdotal reports from friends in Asia who seemed to suggest that it was highly contagious and highly transmissible. Thus, when I recently learned that there is a science and a history surrounding how pathogens have shaped human psychological adaptations. As we are forced to confront the longstanding evolutionary pressure of pathogen avoidance regarding what to eat, and touch and who to be intimate with, it no longer feels theoretical.1Looking back at what I’ve gained and what I’m missing over this last month, I am acutely aware of how much less we are touching as a family and in my medical practice, and I miss it. As I say goodnight to my family and retreat to our windowless den, I am both thankful for a place to sleep that is near enough to be able to peek at their beautiful sleeping faces, while sad that I feel less at ease hugging or kissing them. While every health care worker on the front-line of this crisis has drawn different boundaries (some more or less extreme), my decision to sleep in a separate room, create a decontamination routine, and be less physically affectionate with my children was the only way I could feel in control in an uncontrollable situation.Medical professionals know that touch, rooted in the amygdala of the brain, cannot be separated from the expression of empathy and solidarity that it provides.2 In medicine, touch has long been hypothesized to have an impact on health and development over our lifespan. Dr. Cascio and her team at the Vanderbilt Kennedy Center for Human Development describe social touch as “a powerful force in human development, shaping social reward, attachment, cognitive, communication, and emotional regulation from infancy and throughout life.3” Many of the babies of the mothers I care for will begin their lives in the Neonatal Intensive Care Unit where the science surrounding touch as part of healthcare is widely accepted and engrained in the culture. Skin-to-skin and kangaroo care, the act of carrying your child in a pouch-like device, have been shown to improve breastfeeding, bonding, and neurocognitive development4,5 In fact, the World Health Organization currently has an ongoing international trial looking at the benefits of survival on low-birthweight infants of kangaroo care initiated immediately after birth on survival of low birth weight infants.6 Later in life, touch, relationship quality and intimacy continue to drive good health and have been associated with improved cognitive function in the Rotterdam Study7,8and improved cardiovascular outcomes in the National Social Life Health and Aging Project.8 Their findings suggest physical touch may have positive health implications for older adults.Prior to the pandemic, physicians were already sounding alarms about the loss of medical touch in modern medicine. In a 2011 TED talk with over 1.7 million views, renowned author and physician Abraham Verghese discussed the power of physician touch and the physical exam as he tried to revive the culture of bedside medicine.9 With this pandemic all of that has changed. We are all exceedingly careful to prevent transmission and yet try to provide care and solace in new ways. At the bedside, a gloved hand continues to provide care and comfort. I am happily finding ways to connect with patients through smiling eyes behind a mask, and jokes or phrases that now replace touch. I find myself more commonly expressing words of empathy in telemedicine visits to fill in for the gaps that touch might have provided before. I ask many, many questions to understand symptoms if I cannot see the patient in person. Due to the surrounding events, I am undertaking the fulfilling process of learning a new skill in medicine, to express my emotions on a screen and affect patients’ lives in ways similar to that of an in-person visit.As we raise our family in this time of pandemic, I am thankful that my husband is doing “double-duty” in the realm of hugging and kissing, and has always been a physically affectionate father to our children. I try to tell them how much I love them with greater frequency and despite the concerted effort there are days it’s almost impossible to share our apartment without being physically close. The psychological impact this crisis will have on them is yet to be determined. I hope time will find them healthy, more resilient and grateful at the end of this journey.But tonight, as they sleep soundly in their beds for another night, I am still saddened that I’m not doing the usual kissing and hugging as I tuck them into bed, and it feels like a true loss, among the many others. I am not sleeping as soundly these days for a multitude of reasons including the guest bed, the strangeness of being alone after so many years, and the exponential rise in screen time for work and media consumption. I am truly hopeful we will return to a time when we can more freely touch and care for the people we love and the patients we value so much. In the simplest of internet searches, touch has so many definitions. Touch can mean to be in close contact, but it can also mean to affect.10 COVID-19 has affected us in innumerable ways, and as healthcare workers navigate a post-COVID landscape, I’m hopeful we can continue to innovate and find safe ways to incorporate medical touch into a practice that will be forever changed.Acknowledgements : I would like to acknowledge our patients for their immense flexibility in this changing landscape, the support of my division and department, and my family. I’d like to thank Dr. Gwendolyn Quinn and my husband David Lee, for their significant editorial assistance.

We report a case of COVID-19 with only atypical CT findings; tree-in-bud appearance and centri-lobular nodules. Some COVID-19 cases show only atypical CT findings. Physicians should make comprehensive judgements.

Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials. Drugs with previous efficacy against related betacoronaviruses like SARS and MERS were also systematically evaluated as potentially promising candidates for drug repositioning.

Viruses are considered as one of the primary drivers for human evolution. Humans in return have also offered them an ideal habitat for their growth and evaluation. However, both, humans and viruses are diverse, astute, competitive, and avaricious in nature, which engage them in a never-ending battle. Today, the world goes to win the battle against COVID-19 for sure. However, this never ending merciless battle between viruses and humans looks like an arms race for their survival in which neither a virus wins nor a human but each battle provides them an opportunity to bounce back for the next.

Aims In the absence of a commonly agreed dosing protocol based on pharmacokinetic considerations, the dose and treatment duration for hydroxychloroquine (HCQ) COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. Methods We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. Results Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800mg day on D1 followed by 600mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. Conclusion Our results were clear indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best the benefit/risk balance.

Since coronavirus disease 2019 (COVID-19) was reported globally pandemic, dentistry is known as one of the most critical disciplines. Teledentistry as a sub branch of telemedicine which can be a useful modality is defined by using any telecommunication technology facility, including digital photo and video to deliver oral care to isolated patients in distant places by low cost(1). Although teledentistry has been introduced as a valid tool to prevent unnecessary referrals, policy makers have not shown much interest on it yet (2,3).Diagnosis, treatment, and monitoring could be performed, meanwhile research and continuing education or public education could be done via teledentistry. In COVID-19 pandemic, teledentistry can prevent human and non-human resources burden. Oral chronic diseases like vesiculobullous and painful conditions are so dreadful and exhausting needing more care. Pediatric patients and those who are suffering from cancer are no more exceptions to this point. Tablets, smart phones, and all types of electronic gadgets can facilitate virtual communication which is helpful in telehealth.Traditional visual examination is a gold standard, in order to reach a better diagnosis and treatment plan. In teledentistry, intra oral or other high quality cameras can provide essential documents. There are so many investigations to compare visual and virtual examination, which showed only some problems in diagnosing interproximal carious lesions which is solved by digital radiography (3).Teledentistry examinations are valid, feasible, and comparable to visual examination for oral screening. Data storage is another crucial part in teledentistry due to privacy policies (2,3).Pediatric dentistry, oral medicine, orthodontics, and periodontics are the most common disciplines that have studied the efficacy of teledentistry rather than effectiveness. In developing countries, where emergency care is more important than preventive care, conservatism of decision makers, lack of resources and ICT infrastructure are the most common problems in providing teledentistry (4).Meanwhile there is a hidden advantage for teledentistry and telemedicine that it can avoid feelings of isolation and stress for patients; so, it can be more useful during COVID-19 quarantine (5).Teledentistry performs in two ways; asynchronous by transmission intraoral or extraoral images that are not used in real time; also, known as the store and forward method, synchronous by use of real-time interactive technologies, such as video or photoconferencing, and mobile health care services via smartphone apps and text messages.All the process should be recorded in patients file for further information. Accurate triage is another prominent advantage of teledentistry, which is so important during COVID-19.For people in need of care like geriatrics or patients with special needs telemedicine can eliminate some barriers (6).Besides to teledentirstry’s advantages, especially in a situation like a pandemic infection even with very primary facilities teledentistry can be performed and be useful for triage. By introducing dentistry as a very dangerous discipline, teledentistry can play a very specific role to solve the majority of patients’ problems as a helpful facility in this crisis and may be it can also persuade policy makers to perform teledentistry in a vast program.

Event-based surveillance (EBS) systems monitor a broad range of information sources to detect early signals of disease emergence, including new and unknown diseases. Following the emergence of a newly identified coronavirus –so-called COVID-19, in humans in December 2019 in Wuhan, China, we conducted a retrospective analysis of the capacity of three Event-Based Systems (EBS) systems (ProMED, HealthMap and PADI-web) to detect early signals of this emergence. We evaluated the changes in the online news vocabulary coinciding with the period before / after the identification of COVID-19, as well as the assessment of its contagiousness and pandemic potential. ProMED was the timeliest EBS, detecting signals one day before the official notification. At this early stage, the specific vocabulary was related to “pneumonia symptoms” and “mystery illness”. Once COVID-19 was identified, the vocabulary changed to virus family and specific COVID-19 acronyms. Our results suggest the three EBS systems are complementary regarding data sources, and all need improvements regarding timeliness. EBS methods should be adapted to the different stages of disease emergence to improve the early detection of future emergence of unknown pathogens.

The coronavirus disease 2019 (COVID-19) pandemic has touched almost every continent. Personal protective equipment (PPE) is the final line of protection of healthcare workers (HCW). There is variation as well as controversy of infection control recommendation with regards to the use of PPE for HCW between institutions. The aim of this narrative review is to of examine and summarise the available evidence to guide recommendation for the safety of HCW. A literature search was conducted on the PubMed, MedLine, and Embase databases with the keywords “personal protective equipment”, “COVID 19”, “n95”, “health care worker”, and “mortality”. SARS-nCoV-2 is highly contagious. 3.5-20% of HCW has been reported to be infected. The mortality ranges from 0.53-1.94%. PPE is part of the measure within a package of prevention and control of pandemic, rather than a replacement of. Respirators are more effective than masks in preventing aerosol transmission to HCWs. Extended use may be considered if guidelines are adhered. PAPRs if available should be used in high risk procedures. Transmission of viruses is multimodal, and in the setting of a novel pathogen with high case fatality with no proven effective interventions, PPE that affords the best protection should be available to HCWs.

Background The WHO recommends testing any suspected person with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), in order to limit the spread of the epidemic. In Italy, some Regions opted for extensive testing, whereas others limited tests to selected subjects. To assess the influence of different strategies, we examined the incidence of death and severe cases in Italy. Methods Data on new cases of SARS-CoV-2, number of tests, deaths, and admissions to Intensive Care Units (ICU) were retrieved in each Italian Region, from February 24th to March 18th, 2020. As an index of different screening strategies, the number of tests/positive test results (T/P) ratio as of March 7th, 2020, was considered. The cumulative number of deaths and of new severe cases, between March 23thand 25th was recorded. The association of those two outcomes with the number of T/P ratio was assessed using linear regression models. Results In the interval between March 23th-25th, recorded deaths (*million inhabitants) were 14(3-54), whereas severe cases were 31(10-112). Both the number of deaths and that of severe cases showed a significant correlation (R2 .38 and .37, with p<.01) with the T/P ratio. Deaths and severe cases were associated with higher mean personal income and lower density of General Practioners (GPs). The association of T/P with severe cases and deaths retained statistical significance after adjusting for mean personal income (R2 .20 and .21, respectively; both p=.04) and GPs density (R2.22 and .21, respectively; both p=.03). Conclusions A more aggressive screening strategy for SARS-Cov-2, was associated with lower rates of death and severe disease in Regions of Italy.

The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (2019-nCoV) with so far mortality cases of 100,000 all over the world. Currently, there are no effective enough treatment options for this previously unknown virus. The current drugs in pipline and some plausible drug are overviewed in this paper. The potential molecular targets of each steps of the 2019-nCoV drug life cycle is discussed and highlights here. Although different types of anti-viral targets are applicable for 2019-nCoV drug screenings, the more promising targets can be considered as protease and RNA polymerase. Based on the results from antiviral agents repurposing and clinical studies, the remdesivir could be an encouraging drug in the frontline to be administrated for 2019-nCoV. Much progress in understanding the 2019-nCoV the molecular details of its life cycle followed by the identification of therapeutic targets seems to be an efficient approach in discovering potential drugs.

Two papers in this issue, on births to Covid-19 infected mothers, are important additions to this rapidly evolving literature. They are both broadly reassuring.The paper from Lombardy, the epicentre of the pandemic in Italy, is the first detailed report of pregnancies from this large region (Ferrazzi et al. BJOG 2020 xxxx). Among 42 affected women, 19 developed pneumonia, of whom seven required oxygen and four critical care. Eighteen babies were delivered by Caesarean, although in eight the indication was unrelated to Covid-19. Three babies tested positive for SARS-COV-2. Two to women who had developed Covid-19 postnatally and had breast-fed without a mask; the presumed source was the mother. One baby who delivered vaginally and did not breast-feed, developed respiratory symptoms requiring one day’s ventilation and tested positive. No mothers or babies died.The paper from China reports SARS-COV-2 viral tests in a range of body fluids from mothers and babies with COVID-19, cared for at Renmin Hospital of Wuhan University (RHWU) (Yanting Wu et al. BJOG 2020 xxxx). This hospital appears on the Global Research Identifier Database (GRID) here https://grid.ac/institutes/grid.412632.0. Readers should know that the GRID database reports that RHWU has the following English aliases “People’s Hospital of Wuhan University”, “Hubei Provincial People’s Hospital”, “First Affiliated Hospital of Wuhan University”, “Wuhan University Renmin Hospital” and “Hubei General Hospital”. This raises the possibility that some or all of the cases may have been reported previously.With this proviso, the detailed information that 1/9 stool samples, 0/13 vaginal samples, and 1/3 breast milk samples were positive is important. Of the five babies who have delivered, none tested positive for Covid-19, although two, both preterm, had pneumonia diagnosed on chest x ray. Apart from one biochemical pregnancy in the first trimester in which a serum human chorionic gonadotrophin of 25.9 IU/L reverted to negative, no mothers or babies died.Taken together with other accumulating data, it is already clear that Covid-19 is less severe in pregnancy than the two previous coronavirus infections, Severe Acute Respiratory Syndrome-related coronavirus (SARS) and Middle East Respiratory Syndrome-related coronavirus (MERS). Nevertheless, four of the mothers from Lombardy required critical care, and there have been other reports of both mother and baby deaths in association with Covid-19. It remains an important disease in pregnancy, which should be taken seriously.No disclosures. A completed disclosure of interest form is available to view online as supporting information.