Internet could be effectively used by the media outlets for risk and outbreak communication in the current crisis. The news stories and videos must be tagged keeping the search terms of people in consideration. This audience-centric approach may be used to supply people with more credible information and guidelines time-to-time. This article analyses the keywords used by the public to search the content related to pandemic so that media outlets may produce and disseminate the related content accordingly via their digital platforms. A paired sample t-test was used to compare Google News and YouTube searches on selected keywords related to COVID-19.

Here, we propose a basic model that could be helpful to foresee the spread of COVID-2019. We performed linear regression, Multilayer perceptron and Vector autoregression model for expectation on the COVID-19 kaggle information to anticipate the epidemiological pattern of the disease and rate of COVID-2019 cases in India. Predicted the possible trends of COVID-19 impacts in India based on data collected from Kaggle. With the prevailing data about confirmed, recovered and death across India for over the time duration helps in predicting and forecasting the near future. For additional examination or future point of view, case definition and information assortment must be kept up continuously.

SARS-CoV-2 has been shown to bind the host cell ACE2 receptor through its spike protein receptor binding domain (RBD), required for its entry into the host cells. We have screened phytocompounds from a medicinal herb, Tinospora cordifolia, for their capacities to interrupt the viral RBD and host ACE2 interactions. We employed molecular docking to screen phytocompounds in T. cordifolia against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy. ‘Tinocordiside’ docked very well at the center of the interface of AEC2-RBD complex, and was found to be well stabilized during MD simulation. Tinocordiside incorporation significantly decreased electrostatic component of binding free energies of ACE2-RBD complex (23.5 and 17.10 kcal/mol in the trajectories without or with the ligand, respectively). It indicates that such an interruption of electrostatic interactions between the RBD and ACE2 would weaken or block COVID-19 entry and its subsequent infectivity. We postulate that natural phytochemicals like Tinocordiside could be the viable options for controlling COVID-19 contagion and its entry into host cells.

Recent observations suggest that COVID-19 causes an “atypical” form of acute respiratory distress syndrome with impaired pulmonary circulation and enhanced thromboembolism. In this letter we have proposed that the interaction between erythrocytes and endothelial cells may have a crucial role in pathogenesis of COVID-19. Acknowledging this interaction suggests new targets for transnational research during the pandemic.

Amid the 2020 Coronavirus pandemic, hydroxychloroquine sulfate (brand name Plaquenil or abbreviated HCQ) is being explored as a potential treatment for those affected with Covid-19 disease. Based on a limited in-vitro and anecdotal clinical data, the U.S. Food and Drug Administration (FDA) approved emergency use of hydroxychloroquine sulfate as an off- label medication for hospitalized COVID-19 patients weighing 50kg or more.1 Research Questions: 1. What is the safety profile of hydroxychloroquine sulfate compared to common outpatient medications such as acetaminophen and ibuprofen in terms of major and minor adverse effects? 2. Could hydroxychloroquine sulfate be used as an outpatient medication to treat COVID- 19?

There is an urgent need for targeted and effective COVID-19 treatment. A number of medications, including hydroxychloroquine, remdesivir, lopinavir-ritonavir, fapiravir, and tocilizumab, have been identified as potential treatments for COVID-19. Bringing these repurposed medications to the public for COVID-19 will require robust and high-quality clinical trials. This article reviews translational science principles and strategies for conducting clinical trials in a pandemic and evaluates recent trials for each drug candidate. We hope that this knowledge will help focus efforts during this crisis and lead to the expedited development and approval of COVID-19 therapy.

The SARS-CoV-2, the causative agent of COVID-19, has been established to gain access to the human cell via the ACE2 receptor similar to its familial coronavirus SARS-CoV which led to the outbreak in 2003. A concern with the newer 2019 coronavirus is its 10-20-fold higher affinity to the ACE2 receptor that of SARS-CoV, aiding its effective human-to-human transmission which has led to this pandemic. ACE2 receptor expression is thought to be upregulated in use with ACE inhibitors. As ACE inhibitors are known to be a used extensively in the treatment of hypertension it was a concern regarding the risk of using these medications alongside a SARS-COV-2 infection. ACE inhibitors are also used in the treatment regime of other common conditions including diabetes and Cardiovascular disease (CVD). It is worth noting that ACE2 expression has found to be upregulated by the use of thiazolidinediones and ibuprofen too. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. Therefore, it would hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs would increase the risk of developing severe and fatal COVID-19.

The COVID-19 pandemic is upon us and although currently the epicenters are Europe and United States of America the prospects of consequences for health systems, health workers and populations in low and middle-income countries are daunting.One of the major challenges in a pandemic is reaching health workers with essential information on epidemiology, clinical guidelines, personal protection measures and infection control. This is particularly the case for resource constraint environments in low and middle-income countries. Mobile health solutions have the last decade claimed ability to reach large volumes of health workers in resource constraint environments with up-to-date clinical guidelines and health information. It is now time to raise up to expectations.In-service training has long been used to improve health workers’ competences with varying degrees of success (1, 2). However traditional in-service trainings are designed as a group-based workshop design removes the health care providers from their facilities. Evidence also show that the one-time training does not always improve providers performance (1, 3) and it is suggested onsite repetitive, targeted skill-based learning activities which are spaced overtime improves learning outcome (3). With the current COVID-19 emergency where face to face training and mentoring is a challenge, use of mobile technology could help to fill the gap in training of front line health workers (4). Most emergencies also in the COVID-19 era likely take place peripherally where health workers have inadequate access to clinical guidelines and reference materials to handle situations that are beyond their skills (5). Promotion of health services via mobile electronic media (mHealth) like mobile phones has been suggested as a means to bridge this outreach gap (6). In 2019, 98% of adult people in low and middle income countries had a cellular subscription, and approximately 72% of people in Sub-Saharan Africa have a cellular subscription and more than half of people in remote areas have a mobile phone (7). Mobile devices are in increasing number being used to provide continued training support to frontline health workers and remote providers, through access to educational videos, information, interactive exercises, and can allow for continued clinical and skills monitoring (8). Necessity is a driver for technological innovation as previously seen in sub Saharan Africa with development of the mobile banking systems and dual sim cards, and we are now witnessing examples of health care innovation in the wake of the COVID-19 pandemic.We have, in a consortium of non-governmental organizations, academia and the private sector, and in a collaboration with International Confederation of Midwifes (ICM) and UNFPA, responded to the COVID-19 pandemic by rapid development of a COVID-19 module in an existing mobile job and training aid called the Safe Delivery App (SDA) (9). The SDA, a freely available tool, is an emergency obstetric and neonatal care training aid for skilled birth attendants in low- and middle-income countries. Launched in 2015 it uses animated videos for clinical instructions and provides access to evidence-based and up-to-date clinical guidelines. In addition to the animated videos four basic features guide health workers in the App: action cards, drug lists, practical procedures, and MyLearning an individualised e-learning component. MyLearning, was developed in 2016 in response to requests from partners to move beyond push messages and simulate self-learning within the App through gamification principles. The app is free of charge and follows WHO guidelines. Through continuous development it currently exists in two global versions (English, French) and 14 language versions and has more than 120,000 downloads globally, with greater use across Africa and South East Asia.The COVID-19 module in the SDA contains an animated short movie on infection prevention and personal protection equipment during COVID-19, figure 1. It also contains latest evidence on COVID-19 consequences for pregnant women and newborns and practical procedures for handling deliveries and newborns during the pandemic. The language and illustrations are simple with a focus on local adaptable measures such as recipes and procedures for making your own alcohol rub. One challenge is the rapid evolving evidence and ever-changing guidelines. To make ongoing changes cost-effective the film speaks and visual is held in general terms while written text in the film and action cards/practical procedures is changeable in a content management system. User patterns of the module in the app will be monitored continuously.mHealth responses to the COVID-19 are emerging. The potential for telemedicine is obvious as well as health information systems support for outbreak monitoring and management (10, 11). Interestingly, there is also a push towards open sharing of not only clinical and epidemiological data but also social media data from technological compagnies that can support community surveillance, contact tracing, social mobilization and health promotion (12). The global community claim that mHealth have the potential for rapid response, real time data, up-to-date clinical guidelines in the hands of health workers. The ultimate test is here in the COVID-19 pandemic. We are calling for the mobile health community and global partners – it is time to raise up to expectations of the potentials of mobile health.

A deep neural network-based program for sequence-based prediction of supersecondary structure codes (SSSCs), called SSSCPrediction (SSSCPred) was constructed. Furthermore, to predict the flexibility and conformational change of proteins, a comparison program of three deep-neural-network-based prediction systems (SSSCPred200, SSSCPred100, and SSSCPred) was developed. I compared the predicted and observed flexible conformations of SARS-CoV-2 and SARS-CoV spike proteins by using SSSCs and the comparison program. The SARS-CoV SSSC sequences of the receptor-binding motif predicted by the three deep-neural-network-based systems well reproduced those of the Protein Data Bank (PDB) data, including the structured loops. In contrast, the receptor-binding motif SSSCs of SARS-CoV-2 differs greatly from those of SARS-CoV, with that of SARS-CoV-2 being more flexible. Only one common identical motif (SSSC: SSSHSSHHHH) among all of the compared SSSC sequences, including predicted and observed ones, was found at the S2 subunit. This motif has an extremely rare and relatively undeformable conformation. The comparison program may be helpful to explore undeformable drug discovery targets of many unsolved protein structures.

Background: Since the declaration of the global pandemic of COVID-19 by the World Health Organization on March 11, 2020; we have continued to see a steady rise in the numbers of people infected by SARS-CoV-2. However, there is still very limited data on the course and outcomes of this serious infection in a vulnerable population of pregnant patients and their fetuses. International perinatal societies and institutions including SMFM, ACOG, RCOG, ISUOG, CDC, CNGOF, ISS/SIEOG and CatSalut have released guidelines for the care of these patients. Objectives: We aim to summarize these current guidelines in a comprehensive review for patients, healthcare workers and healthcare institutions. Search Strategy: A literature search was performed through PubMed, and direct review of professional society’s website and journal publications. A total of 15 papers were identified from 10 societies and reviewed by two authors who were in agreement. Selection Criteria: The most updated guideline including information on antepartum, intrapartum and postpartum care put forth by each society was included. Data Collection and Analysis: Data specific to antepartum, intrapartum, and postpartum were abstracted from the publications and summarized into tables 2, 3 and 4 respectively. Main Results: The summary of guidelines for management of COVID-19 in pregnancy across different perinatal societies is consistent, with some variation in the strength of recommendations. Conclusions: It is important to recognize that these guidelines are frequently updated, as we continue to learn more about the course and impact of COVID-19 in pregnancy. The references to access all these guidelines are provided.

The pandemic outbreaks of coronavirus disease 2019 (COVID-19) was first discovered in Wuhan, Hubei, China in December 2019. The COVID-19 was caused by the novel coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It took 30 days to spread to all provinces of China [1]. Recently, the confirmed cases of COVID-19 have been reported from about 200 countries or regions on March 30, 2020, and killed almost 30 thousand people [2]. Efficient identification of the infection by SARS-CoV-2 has been one of the most important tasks to facilitate all the following counter measurements in dealing with infectious disease. In Taiwan, a COVID-19 Open Science Platform adhering to the spirit of open science: sharing sources, data, and methods to promote progress in academic research while corroborating findings from various disciplines has established in mid-February 2020, for collaborative research in support of the development of detection methods, therapeutics, and a vaccine for COVID-19. Research priorities include infection control, epidemiology, clinical characterization and management, detection methods (including viral RNA detection, viral antigen detection, and serum antibody detection), therapeutics (neutralizing antibody and small molecule drugs), vaccines, and SARS-CoV-2 pathogenesis. In addition, research on social ethics and the law are included to take full account of the impact of the COVID-19 virus.

The (COVID-19) coronavirus disease 19 is a highly transmittable and pathogenic viral infection that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has recently emerged in Wuhan province of China and rapidly spread throughout the world. Though the intermediate source of origin and its transfer to humans is not very well known, but the fast human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine developed so far to be used against COVID-19. In the current review, we summarize and comparatively analyse the deadly virus and how it poses a constant threat to sub continental nations especially India. A number of ecological interventions are also suggested to protect humans and keep the virus carrying bats at a distance.

Nitric oxide (NO) is a unique signaling molecule in the mammalian species. NO is produced by a variety of cell types to elicit distinct physiological actions. In the vascular system, NO is produced by the endothelium, a single layer of cells forming the inner lining of all blood vessels. Endothelium-derived NO has several different functions, one of which is vascular smooth muscle relaxation, resulting in vasodilation and a consequent decrease in blood pressure and increase in local blood flow. In the erectile tissue, NO is released as a neurotransmitter from the nerves innervating the corpus cavernosum during sexual stimulation, and causes profound smooth muscle relaxation and increased blood flow to the erectile tissue. This results in engorgement with blood and consequent penile erection.The uniqueness of NO as a signaling molecule derives, at least in part, by the fact that it is a gaseous molecule in its native state. However, despite being a gas, NO, like oxygen (O2), elicits its pharmacological effects as a solute in aqueous solution. Another unique characteristic of NO is its fleeting action because of its highly unstable chemical nature and reactivity. Unlike many other signaling molecules, NO elicits its wise array of physiological effects by distinct mechanisms. For example, vascular and nonvascular smooth muscle relaxation, and inhibition of platelet function are mediated by intracellular cyclic GMP (cyclic 3’, 5’-guanosine monophosphate). NO elicits many cyclic GMP-independent effects as well. For example, nitric oxide is a reactive free radical that can covalently modify protein function. One good example is protein S-nitrosylation, which can result in both regulatory and aberrant effects. By this and a variety of other mechanisms, NO also reacts with other molecules, such as reactive oxygen species, in invading cells such as bacteria, parasites and viruses to kill them or inhibit their replication or spread.The first pharmacological action of nitric oxide, demonstrated several years before it’s production in mammals was actually discovered, was vascular and nonvascular smooth muscle relaxation. One of many examples of the latter is the smooth muscle enveloping the sinusoidal cavities within the corpus cavernosum. Another important example is the airway smooth muscle in the trachea and bronchioles of the lungs. Indeed, inhalation of NO gas causes bronchodilation and increased delivery of air into the lungs. However, perhaps more significant than the bronchodilator effect of inhaled NO is its vasodilator effect. In fact, advantage was taken of the vasodilator action of NO in the lungs by Warren Zapol, MD, from the Massachusetts General Hospital in Boston, who discovered that inhalation of very small amounts of NO gas by newborn babies with life-threatening, persistent pulmonary hypertension (PPHN) results in a dramatic and permanent reversal of pulmonary vasoconstriction. Inhaled NO (INO) literally turned blue babies into pink babies. Without INO, most babies would have died while others would have required highly invasive procedures (extracorporeal membrane oxygenation; ECMO) to oxygenate their lungs, and may not have survived.Regarding its antiviral action, NO has been shown to increase the survival rate of mammalian cells infected with SARS-CoV (Severe Acute Respiratory Syndrome caused by coronavirus). In an in vitrostudy, NO donors (i.e., S-nitroso-N-acetylpenicillamine) greatly increased the survival rate of SARS-CoV-infected eukaryotic cells, suggesting direct antiviral effects of NO (1). In this study, NO significantly inhibited the replication cycle of SARS CoV in a concentration-dependent manner. NO also inhibited viral protein and RNA synthesis. Furthermore, NO generated by inducible nitric oxide synthase inhibited the SARS CoV replication cycle. The coronavirus responsible for SARS-CoV shares most of the genome of COVID- 19 indicating potential effectiveness of inhaled NO therapy in these patients.In 2004, during the SARS-CoV outbreak in China, the administration of inhaled NO reversed pulmonary hypertension, improved severe hypoxia and shortened the length of ventilatory support as compared to matched control patients with SARS-CoV (2). The mechanism of action was thought to be pulmonary vasodilation and consequent improved oxygenation in the blood of the lungs, thereby killing the virus, which does not do well in a high oxygen environment. In addition, however, I would offer the opinion that the NO also interacts directly with the virus to kill it and/or inhibit its replication, as shown in a prior study (1).Although studies have not yet been reported with COVID-19, NO has been shown to have an antiviral effect on several DNA and RNA virus families (3). The NO-mediated S-nitrosylation of viral molecules might be an intriguing general mechanism for the control of the virus life cycle. In this regard, it is conceivable that NO could nitrosylate cysteine-containing enzymes and proteins, including nucleocapsid proteins and glycoproteins, present in the coronavirus.In view of the knowledge gained by treating SARS-CoV patients with INO, it follows that INO might be effective in patients with the current SARS CoV-2 (COVID-19) infection. Indeed, a clinical trial of inhaled nitric oxide in patients with moderate to severe COVID-19 with pneumonia and under assisted ventilatory support recently received IRB (Institutional Review Board) approval at the Massachusetts General Hospital. Warren Zapol is director of this project. This trial has now been expanded to include at least two additional hospitals in the U.S. In the successful treatment of persistent pulmonary hypertension in newborns, the amount of NO inhaled is generally one ppm (part per million). In the clinical trial using COVID-19 patients, the amount of NO will be approximately 100-fold higher, about 100 ppm. This is a safe dose of INO, which could prove to be effective in killing the virus and allowing recovery of the patient. The effective use of INO would also lessen the need for oxygen, ventilators, and beds in the ICU.One thing I urge everyone to practice during this coronavirus pandemic is to breathe or inhale through your NOSE and exhale through your mouth. Swedish investigators at the Karolinska Institute in Stockholm have shown that the cells and tissues in the nasal sinusoids, but not the mouth, constantly and continuously produce nitric oxide, which is a gas, and can be easily detected in the exhaled breath. The physiological significance of this is that nasally-derived NO, when inhaled through the nose, improves oxygen delivery into the lungs by causing bronchodilation. This physiological action of inhaled NO is well-known by competitive athletes, especially runners. Moreover, when inhaling through the nose, your nasal nitric oxide is inhaled into your lungs where it stands a chance of meeting up with the coronavirus particles and killing them or inhibiting their replication. Inhaling through your mouth will NOT accomplish this. By the same token, exhaling through your nose is highly wasteful in that you would be expelling the NO away from the lungs, where it is needed most.“INHALE THROUGH YOUR NOSE, AND EXHALE THROUGH YOUR MOUTH!”

Aim: Many concerns still existed about the safety of hydroxychloroquine (HCQ) in the treatment of Corona Virus Disease 2019 (COVID-19). The purpose of this study was to evaluate the safety of HCQ by performing a systematic review and meta-analysis. Methods: Randomized controlled trials reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved from the establishment of the database to February 27, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. Results: We identified 34 eligible studies that involved 3,639 patients. The difference in the cumulative number of AEs between the HCQ and control group was statistically significant (P<0.0001). The pooled incidence of gastrointestinal AEs, which occurred most frequently in the HCQ group was higher than that in the control group (P<0.0001) according to the system organ class. In addition, the risks of skin and subcutaneous tissue AEs (P = 0.011), renal and urinary disorders (P=0.011), ear and labyrinth AEs (P = 0.045) and surgical and medical procedures AEs (P = 0.020) in HCQ group are also significantly increased compared with the control group. Meanwhile, the cumulative number of SAEs was similar between the two groups (P=0.222). Meta-analysis results indicated that the pooled incidences of all the AEs reported by two or more studies were similar except for the treatment discontinuation caused by AEs (RD 0.02, 95% CI: 0.00 to 0.06). Conclusion: HCQ was well tolerated and might be safe for clinical application under the outbreak of COVID-19.

More than one million patients worldwide have been diagnosed with coronavirus disease 19 (COVID-19) to date (WHO situation report, 8th April 2020). There is neither a vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing drugs is a key route of action. In this review we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilised in traditional Chinese medicine, could be repurposed to treat COVID-19. We collate and review evidence for tetrandrine’s putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two-pore channel 2 (TPC2). Consideration of its pharmacodynamics and pharmacokinetics suggests that oral tetrandrine at doses currently used in clinical practice could be an effective agent for the treatment of SARS-CoV-2 infection in humans.

IntroductionThe coronavirus disease 2019 (COVID-19) first outbreak at the end of 2019 in Wuhan, China, and quickly spread into more than 200 countries worldwide, turning into a global pandemic. As a new emerging and severe contagious disease, all people are vulnerable to it. Therefore, it’s not surprising that more and more pregnant patients are being reported.1, 2 The maternal and fetus outcomes of COVID-19 pregnant women are the focus of our attention. Fortunately, based on the results of current studies, the clinical characteristic and outcomes of COVID-19 maternal patients are similar to that of non-pregnant women. No maternal death has been reported.1, 2 But the consequences of infection with SARS-CoV-2 for fetus or newborn are uncertain; especially, there is still huge controversy regarding whether SARS-CoV-2 can be transplacentally transmitted from infected pregnant women to their fetuses. A previous review, through analyzing a total of 38 pregnant women with COVID-19 in China, didn’t found intrauterine transmission of SARS-CoV-2.2 However, a recent study by L Dong et al3 described a newborn born to a COVID-19 mother with elevated IgM antibody level to SARS-CoV-2, indicating a possible transplacental transmission.Here, we reported a newborn born to a convalescent COVID-19 mother has a viral pneumonia on the day of birth and elevated IgM/IgG antibody levels to SARS-CoV-2 at 3 days age.

Viruses are non-living particles containing genetic information in the form of DNA or RNA. They are fascinating because they are not considered a form of life even though they evolve in the same way all living organisms do. Viruses are so-called obligate pathogens because they cannot multiply unless they infect and hijack the cellular machinery in living organisms. 

The ongoing wide spread of Covid-19, also referred to as 2019-nCoV or SARS-CoV-2, is undoubtedly one of the deadliest zoonotic diseases the whole world has grappled with. As of April 10, 2020, this disease has infected above 1.6 million people in over 200 countries worldwide, and claimed the lives of more than 96,000.1 Figure 1 shows the distribution of confirmed cases in the first 20 nations with the highest number of Covid-19 patients as of April 10, 2020, the least of which has over 9,000 cases.**Figure 1**With the increasing trend of daily new cases and daily death from the beginning of March to April 9, 2020, as displayed on Figure 2, it could be predicted that this fatal pandemic could last well beyond a year. According to the modeling completed by pandemic intelligence experts at the Imperial College, London, the 2019 novel coronavirus is likely to remain for another 12-18 months.2 Typically, past pandemics have lasted between one to three years.3Examples of such recent pandemics are the H1N1 influenza,4 SARS-CoV,5Ebola,6 and MERS-CoV,7 which all lasted for more than 12 months. As the emergence of these novel viruses keep increasing, how could biosafety and biosecurity measures guard against the introduction of the harmful causative organisms to humans in the future?**Figure 2**The terms biosafety and biosecurity are broadly used in diverse frameworks and refer not only to protection of humans and their surrounding environment against lethal biological agents, but also to global deactivation of arms of mass destruction.8 In the concept of biorisk management, these two terms refer to best practices that prevent the spillover of toxic organisms to human beings and into the environment.9,10 Although these two terms have been used interchangeably and often denoted with similar meanings, scientists have distinguished between the two concepts. According to Zaki,11 biosafety involves all the preventive measures undertaken to eradicate strains of pathogenic microorganisms and their potential toxins. On the other hand, biosecurity includes a set of preventive strategies intended to reduce the risk of transmission of infectious diseases in humans, crops, livestock, isolated pests and genetically modified organisms.12The World Health Organization (WHO) has classified disease-causing microorganisms into four different groups based on their principal characteristics, hazardous threat to individuals and the community, and their route of transmission.13,14 Table 1 presents the four different groups with their associated risk levels.**Table 1**Concluding from the descriptions for the various pathogenic organisms and their risk levels to individuals and the community in Table 1, the novel coronaviruses that cause Covid-19, SARS-CoV, MERS-CoV, and many other pandemic-causing pathogens, could be classified as risk level 4 pathogens. As spillover events keep occurring in recent years, and more of these high-risk emerging infectious diseases (EIDs) are likely to be introduced into the environment, it is necessary for the general public and stakeholders around the globe to institute biosafety and biosecurity measures in preventing the transmission of these biological toxins to mankind, livestock and their inhabitations. Among the core elements of the principles of biosafety measures and biosecurity strategies, the following are principal in guiding against EIDs:Effective regulations have to be put in place to avoid and manage intentional exposures to the sources and hosts of pathogenic organisms of medium to high risk levels. Strict observation of such policies around the world will minimize human activities that have caused several spillover events in the past.As the sources of novel pathogens have been identified in the past, it is necessary for scientists to inform the general public about the sources and hosts of such toxic organisms. Further research should also be targeted towards identifying these pathogens in animals and plants which are usually exposed to the environment. Such knowledge will help stakeholders and policymakers to notify the general public about the potential spillover events that are likely from contacts with identified sources and hosts of these pathogens.The risk assessment of pathogenic diseases of the past and a predicted assessment of likely EIDs in the future should be made available to the general public. Such awareness will inform the mass about the economic, social, and health impacts of these diseases. This will reinforce public adherence to policies and regulations which are instituted to limit contacts with pathogenic sources as people are aware of the potential losses to national and global economy, and the adverse effects on social life and health facilities.As health personnel, scientists, and leaders in various capacities often find themselves in the frontline during the emergence of epidemic and pandemic diseases, they need to be trained adequately to guarantee proper apprehension and execution of biosafety procedures to ensure the maintenance of a safe working environment for individuals and the wider community. This will ensure appropriate measures are taken to limit the spread of infections.Finally, routine upgrades are required to render instituted biosafety and biosecurity measures more effective and efficient in this ever-changing world. As the etiology and epidemiology of EIDs keep evolving, constant updates to safe practices in health centers around the world are required to adapt these practices to effectively manage the emerging diseases.As various country-based mitigation measures are being implemented around the world to contain and control the course of Covid-19,15 it is essential that the above biosafety and biosecurity measures are adopted and implemented to effectively manage the ongoing outbreak, and prevent future emerging infections.

Angiotensin converting enzyme 2 activation: a novel potential Covid-19 therapeutic strategyIn late December 2019, the Covid-19 epidemic, caused by a novel coronavirus SARS-CoV-2, emerged in Wuhan, Hubei province, China. This epidemic has a doubling period of 1.8 days, and there are concerns about its progression to pandemic scales due to its exponential rate of spread. No specific drugs or vaccines are currently available for the treatment and/or prevention of SARS-CoV-2 infection. Hence, there is an imperative need to search for a safe and effective therapeutic strategy for Covid-19 infected patients, especially the critically ill individuals.Angiotensin-converting enzyme 2 (ACE2) is a crucial component of the renin-angiotensin-system (RAS) axis because it converts Angiotensin II into angiotensin (1–7), which exerts an antifibrotic, antihypertrophic and vasodilatory effect. ACE2 is a membrane-bound aminopeptidase which has been reported to be a functional receptor for coronaviruses, including SARS-CoV and SARS-CoV-2. The first step of SARS-CoV-2 infection is binding of the spike protein of the virus to ACE2 which is widely distributed on the alveolar type II cells and capillary endothelium (Lu et al., 2020). It has been demonstrated that SARS-CoV downregulates ACE2 protein in mice, contributing to severe lung injury (Kuba et al., 2005). This suggests that augmented ACE2 activation may result in enhanced binding with SARS-CoV-2. Thus, increasing ACE2 activation may have a dual function to both neutralize the virus and rescue cellular ACE2 activity protecting the lung from damage.Diminazene (DIZE) is an antitripanosomal drug which has been shown to serve as an ACE2 activator and reduce bleomycin-induced pulmonary fibrosis (Shenoy, Qi, Gupta, Katovich & Raizada, 2012). In addition, it has been reported that activation of ACE2 by DIZE prevented asthma progression in rats by altering AKT, p38, NF-κB and other inflammatory markers. DIZE also halted the development and progression of experimentally induced pulmonary hypertension in rats, improved right ventricular function, and diminished proinflammatory cytokines effects that were accompanied with increased lung ACE2 activity. Given the reported safety of DIZE administration in humans (Hutchinson & Watson, 1962; Pepin & Milord, 1994) and the pressing need for Covid-19 therapeutic, in addition to the well-documented pharmacological effects of DIZE, clinical studies are warranted to elucidate the potential safety and efficacy of DIZE in Covid-19 infected patients.In conclusion, SARS-CoV-2 represents a global health challenge. Unfortunately, no specific therapeutic options are currently available. Thus, there is an imperative need for a safe and effective drug in order to put this pandemic to an end. DIZE has a reported acceptable safety profile. Moreover, DIZE increased lung ACE2 activity in different experimental models, an effect which conferred lung protection against various insults. Taking into consideration the reported effect of SARS-CoV-2 on pulmonary ACE2 activity, it could be suggested that DIZE administration could offer some therapeutic merit for SARS-CoV-2 infected patients. However, clinical studies are required to unravel the potential safety and efficacy of DIZE administration in Covid-19 infected patients.Competing interests The author declares no competing interests.

Streamline maternal health care provision to mitigate the risk for pregnant women under COVID-19 pandemicHong Jiang1, Mu Li2, Huijing Shi1*, Xu Qian11School of Public Health; Global Health Institute; National Health Commission Key Laboratory of Health Technology Assessment, Fudan University, Mailbox 175, No. 138 Yixueyuan Road, Shanghai 200032, China;2School of Public Health; China Studies Centre, Room 313, Edward Ford Building, University of Sydney, Sydney 2006, Australia*Corresponding author: Huijing Shi, hjshi@fudan.edu.cn, School of Public Health; Global Health Institute; NHC Key Laboratory of Health Technology Assessment, Fudan University, Mailbox 175, No. 138 Yixueyuan Road, Shanghai 200032, China;The novel Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan City China in early December 20191,2, and has rapidly spread across the world. The pandemic has strained health system3, which presents a huge challenge to maintain other essential health services, including maternal health care. As the first country to experience the COVID-19 outbreak, there are lessons could be learnt for establishing a better preparedness mechanism from a service delivery perspective to provide essential maternal health care and mitigate health risk for pregnancy women.First, all health facilities providing antenatal care should apply high standard of precaution to ensure pregnant women are not exposed to the COVID-19 transmission. This includes setting up a triage area to screen for COVID-19 symptoms and contact history with confirmed cases before pregnant women entering antenatal clinics. People with COVID-19 exposure history, suspected cases or COVID-19 patients should be separated from other pregnant women and placed in designated areas. This will also protect antenatal care providers. Appointment is required in advance for antenatal service to ensure adequate social distancing and manage the patient flow in health facilities.Second, as routine service provision might be disrupted, perinatal care availability and any changes to service provision should be disseminated widely, preferably through online platforms4. Women with low risk pregnancy may reduce the risk of contracting COVID-19 by reducing the number of antenatal visits. Women with pregnancy complications and other health conditions should contact their antenatal care provider to seek specific advice. Communication and counselling can be provided to pregnant and postnatal women online, including recognizing warning signs of going to hospital urgently. During movement restriction or self-isolation guidance of keeping healthy diet and physical activity, and mental health support are important for the well-being of pregnant women.Third, balancing the demands of emergency responding to COVID-19 and maintaining essential perinatal health service at national, provincial and local levels. Guidelines on conditions that require continuing antenatal care and those can be delayed should be developed5. Designated hospitals for treating pregnant women with COVID-19 should be enlisted to ensure they will receive appropriate care from a multi-disciplinary team6. At the provincial/regional level, health authorities should adapt to local context and develop uniformed perinatal operational guidelines across all local health facilities and monitor the equitable access to service and service quality. Local health facilities are responsible for disseminating service information via official channels, e.g. account on social media platforms such as WhatsApp, Facebook, and providing services following the provincial/regional operational guidelines.As the pandemic intensifies globally7,8, the experience and lessons of China on the response and streamline health system may help other counties to mitigate adverse impact of the pandemic on maternal and newborns.Disclosure of interestsWe declare no competing interests.

Lopinavir combined with ritonavir were reported to benefit the patients with SARS by reducing the viral loads. However, in the latest clinical trials, no benefit was observed with lopinavir-ritonavir treatment beyond standard care in patients with COVID-19. We comment here that this disappointed result of clinical trial might result from the low volume of the lung distribution of lopinavir. The major reasons were listed below: 1) The binding affinity of ACE2 with SARS-CoV-2 spike protein is ~10- to 20-fold higher than the binding affinity of ACE2 with SARS-CoV spike protein, indicating that SARS-CoV-2 can enter AT2 cells in lung much easier than SARS-CoV. Therefore, the viral loads of SARS-CoV-2 might be much higher than viral loads of SARS-CoV in the lung tissue. 2) The concentration of lopinavir in the lung tissue was 1.18 μg equiv/ml in rats. The low volume of the lung distribution of lopinavir might not be enough to inhibit the coronavirus replication due to the high viral loads in the lung tissue. 3) In contrast, the concentration of chloroquine in the lung tissue was much higher (30.76 ± 0.85 μg equiv/ml) in rats, which might lead to its clinical and virologic benefits in the treatment of COVID-19 patients. Together, we proposed here that anti-SARS-CoV-2 drug repurposing studies should pay more attentions to the lung tissue distribution of antiviral drugs. The efficacy of antiviral drugs might depend on their lung tissue distributions

Dear Editor,Although a worldwide phenomenon, severe acute respiratory syndrome (SARS)-coronavirus (Cov)-2 infection is apparently less severe in some parts of the world. However, some countries present a surprisingly low death toll (https://coronavirus.jhu.edu/map.html downloaded in March 22, 11:00 AM). Epidemiology is crucial to tackle this pandemic as well as the search for compounds to treat. Turmeric (Indian saphron), a much-appreciated spice has India is by far the greater producer, and consumer, together with Pakistan, Malaysia, Bangladesh, Sri Lanka, Taiwan, China, Burma (Myanmar), and Indonesia (http://www.fao.org/fileadmin/user_upload/inpho/docs/Post_Harvest_Compendium_-_Turmeric.pdf downloaded in March 21, 2020). Curcuma or curcuminoids isolated from Turmeric have long been reported to have anti-inflammatory and immunomodulatory activity. Due to its very low bioavailability, alternatives to improve turmeric absorption have been developed. That is not to say that edible consumption would be of no effect (Aggarwal, Gupta & Sung, 2003). A world coronavirus map reveals that countries in southeast Asia present very low numbers of SARS-Cov-2 infections. Although numbers of infected people may not be reliable, the death rate is hard to be hidden. We focused our list on the major turmeric consumers but Taiwan given the strict rules for isolation implemented there. As of March 26, the death covid-19 toll reported in Indonesia, Malaysia, India, Pakistan, Bangladesh, Sri Lanka, and Burma, that represent over one-quarter of the world population was 128, being 78, 23, 14, 8, 5, 0, 0, respectively. On the other hand, Iran, which was a greater consumer of Turmeric, has experienced a shortage of this product due to economic sanctions, and had 2,234 deaths in March 22 (https://economictimes.indiatimes.com/news/economy/foreign-trade/turmeric-exports-hit-by-us-sanctions-against-iran/articleshow/70446034.cms?from=mdr). Community isolation has been hard to be implemented in Iran, which probably has shortage of health facilities and supplies to face this epidemic. Faced with data from developing countries, the death coronavirus disease (covid)-19 toll from high curcumin consumers is apparently very low as compared to those from developed countries, some of them with severe rules restricting social activities and better health infrastructure to treat patients. Would this just be coincidental? There are claims that drugs acting in the angiotensin converting enzyme (ACE) pathway may worsen the clinical picture of patients affected by SARS-Cov-2 (https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19 downloaded in March 21, 2020). ACE blocking compounds may lead to upregulation of the ACE2 gene receptor expression. It follows that ACE2 receptors are used by SARS-Cov-2 as a cell entry. It has been previously shown that rats subjected to thioacetamide induced hepatotoxicity are protected by Curcumin administration, an effect that was associated with down-regulation of the ACE gene (Akinyemi et al., 2015). Further, rats subjected to induced systemic arterial hypertension were protected by pre-treatment with ginger and turmeric rhizome supplementation, that led to reduction in ACE activity (Fazal, Fatima, Shahid & Mahboob, 2015). Hence, it might well be that Curcumin, by down-regulating ACE gene expression, can be of help against covid-19 disease. Notwithstanding, previous reports have shown that curcumin presents both direct and indirect antiviral activity against the human immunodeficiency virus (HIV) by inhibiting virus replication or via blocking inflammatory pathways operating in the acquired immunodeficiency syndrome (Prasad & Tyagi, 2015). Hard times pose hard problems that demand urgent policies. Health authorities worldwide are struggling to decide which is best to prevent people from getting covid-19 infection and, when the disease unleashes, which attitudes to preserve lives. There are various compounds being tested against covid-19. Hydroxychloroquine, given the safety profile of this well-known immunomodulating compound used in rheumatology for prolonged periods, is being indicated pending robust data to document its efficacy, if any, on the basis that it may be a non-expensive life-saving strategy posing no additional harm to an already affected SARS-Cov-2 patient (Touret & de Lamballerie, 2020). Using the best rationale to look for evidence about the therapeutic effects of turmeric in COVID19, we can do an exercise on Hill’s causality criteria. The strength of the association is high, based on the incidence map, and has been a repeated pattern in many countries with similar consumption of turmeric. There is some consistency between epidemiological and laboratory findings given that Curcumin apparently down-regulates ACE2 gene receptor expression, a major pathway in covid-19 cell entry (see above). We cannot yet claim specificity or biological gradient (dose-response relationship). Temporality is guaranteed because the consumption of saffron has long been incorporated into the culture of those countries. Similarly, chloroquine appears to interfere with the terminal glycosylation of the ACE2 cell receptor (Touret & de Lamballerie, 2020). At this time, we do not believe a ginger tea or adding turmeric to our meal would be of any harm. If in vitro data prove curcumin to be effective, clinical studies could be then proposed.

Since December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2（SARS-CoV-2）has swept 200 countries and regions worldwide1 and has become a ”Public Health Emergency of International Concern” (PHEIC). Pregnant women are susceptible to COVID-19 due to the changes in their physiology and the adaptability of their immune system2. During the outbreak of COVID-19, prenatal examinations may be postponed, however, delivery cannot be delayed, and the delivery room should work as usual. During this period, it is particularly important to quickly identify high-risk groups and to provide appropriate protection for childbirth and the puerperium. In accord with experience in China (Guidelines for the Prevention and Control of New Coronavirus Infections in Medical Institutions issued by the National Health Commission ), we strongly recommend that during the outbreak of COVID-19, all medical institutions should conduct graded, staged, comprehensive and continuous training of all staff, based on the particular epidemic prevention and control needs of for of different positions, to constantly improve staff’s awareness of the prevention and control of COVID-19. To strengthen staff comprehension of the necessary precautions during a COVID-19 epidemic, an assessment method that combines theory with scenario testing should also be applied 3,4. At the same time, based on our experience of delivery room management, we recommend a delivery room processing flow (Fig.1) and graded protection 5 (Table 1) for pregnant women with different infection risks，as detailed below:(1) Primary screening of all women (First level protective equipment should be applied): Check the axillary temperature and the fetal heart rate, and enquire whether there is fever, respiratory symptoms (cough, chest tightness, etc.), gastrointestinal symptoms (vomiting, diarrhea, etc.) and other symptoms before allowing women to sit in the maternity waiting area. Ask whether there is increased risk of contact with a COVID-19 positive patient (fever of any family member within two weeks, a history of traveling to the epidemic area or contact with a suspected or confirmed patient). Any positive history of the above indicates ‘potential risk’ status.(2) Pregnant women with potential-risk and/or suspected infection merit further screening (Second level protective equipment should be applied): attending staff should immediately apply second or third level of protective equipment, screening tests (which include respiratory pathogens tests like adenovirus, respiratory syncytial virus, influenza A virus, influenza B virus and parainfluenza virus, Mycoplasma pneumoniae and Chlamydia pneumoniae, blood routine tests, and C-reactive protein) should be undertaken and the new coronavirus nucleic acid test for pregnant women with potential-risk/suspected infection should be performed. A chest CT scan with informed consent to observe the lungs should be performed if signs or symptoms provide any indication (inform the patients about the necessity of chest CT and ask them to cover their abdomen properly). Obstetric management should not be delayed by testing for COVID-19.(3) Delivery room management (for vaginal delivery): ① Pregnant women suspected to be COVID-19 positive should be immediately transferred to an isolated delivery room (avoiding contact with other patients) or negative pressure delivery room and be required to wear surgical mask6. Accompanying family must not be permitted. Patients should be managed by specific experienced senior medical specialists, and third level protective equipment must be applied to avoid cross-infection; ② pregnant women at potential risk of infection: Accompanying family should not be allowed. Patients are recommended to wear surgical masks6 and should be transferred to isolated delivery rooms, with management/supervision by specific experienced senior medical specialists. Second level protective equipment should be applied to prevent cross-infection, if availability of protective materials is adequate. ③ low-risk pregnant women (those without any history of epidemiological exposure or clinical symptoms) should be transferred to an ordinary delivery room for delivery (avoiding contact with other patients). Second level protective equipment should be applied. It is recommended that these women wear disposable medical masks 6. Only family members who have no history of epidemiological contact and clinical symptoms within the past 2 weeks are allowed to attend the childbirth, and accompanying family members are also required to wear disposable medical masks.As fetal compromise is relatively common in pregnancies complicated by COVID-19 infection, continuous electronic fetal monitoring in labor is recommended for all women suspected with COVID-19, following transfer to the appropriate delivery room.7We advocate attempts to deliver vaginally without undue obstetric intervention and recommend caution regarding procedures such as episiotomy and ventouse/forceps delivery. Currently, we do not recommend water deliveries for pregnant women with suspected infection. There is no evidence that epidural analgesia or spinal anesthesia is contraindicated, therefore, epidural analgesia should be recommended to pregnant women suspected of COVID-19 infection before or in early labor to minimize the need for general anesthesia in emergency situations7.(4) Emergency caesarean section treatment：Suspected COVID-19 infection is not an indication for cesarean section, unless the woman’s respiratory condition demands urgent delivery, or pregnant women have other indications. Multi-disciplinary consultation involving anaesthetists, neonatologists, obstetricians, and infectious disease physicians is required before deciding to deliver prematurely in cases of suspected infection, and if Caesarean section is indicated, the procedure should be performed in a negative pressure isolation operating room (third level protective equipment should be applied). The choice of anesthetic mode is determined by the anaesthetist, based on the patient’s respiratory function. For pregnant women with potential infection (potential-risk), their pregnancy can be terminated in the isolated operating room (second level protective equipment should be applied) if properly protected. First level protective equipment is recommended when performing cesarean section for pregnant women with low-risk infection.(5) Postpartum management: postpartum vital signs, uterine contractions, maternal mental health and other conditions of the mother should be monitored, and attention paid to the prevention of postpartum hemorrhage, thrombosis, etc. For pregnant women with suspected infection, the neonatologist should be notified at least half an hour before delivery to take appropriate measures to isolate the newborn. Delayed cord clamping is still recommended given a lack of evidence to the contrary, unless there are other contraindications7. 14 days of isolation for newborns is recommended8; there is currently no evidence to support the suspension of breastfeeding in pregnant women with suspected infection, indeed, we advocate breastfeeding, as the wider benefits outweigh the potential risks of transmission through breastmilk 7. Isolation and preventive measures should be undertaken if referral is needed 5. If there are no abnormal signs/symptoms within two hours after delivery, mothers with suspected infection can be transferred to an isolation ward for further observation; ‘potential-risk’ pregnant women can be transferred to the isolation ward (avoiding contact with other patients) and low-risk mothers managed according to conventional procedures. Pregnant woman with suspected or potential infection should undergo diagnostic testing immediately. If infection is confirmed, the corresponding management should follow the previous guidelines for dealing with confirmed cases of COVID-192.(6) After-delivery protection procedures: After the mother was transferred to the ward, routine cleaning should be undertaken. The surfaces of the equipment (including the obstetric table, ultrasound machine, and neonatal warm bed) in the isolation delivery room and the negative-pressure delivery room need to be wiped and disinfected immediately, preferably with 1000 mg/L chlorine-containing disinfectant; 75% ethanol can be used for the non-corrosion resistance instruments7,9. Spraying is not a recommended method of disinfecting the equipment as this can affect the components. Dedicated cleaning tools are required to avoid cross contamination. The inspection room should be disinfected with ultraviolet light, ≥60 min each time, once or twice a day, with at least 30 min ventilation after irradiation. The ultrasound probe should be protected with a dark cloth during the irradiation. The room should be vacated when ultraviolet lamps are used.(7) Medical waste disposal: Protective supplies used by medical personnel and all patient waste should be regarded as infectious medical waste, which requires double-layer sealing, clear labeling, and airtight transport 10. If testing of the placenta and/or amniotic fluid is required, strict sampling and sealing should be carried out to avoid contamination of the surface of the container and the spread of infection. The surface of the container should be disinfected before sample inspection to further avoid infection of any personnel.

COVID-19 is a disease which is sweeping the globe, often with devastating consequences. The more we understand, the more it appears that infection has a very wide clinical spectrum from totally asymptomatic to life threatening. Without widespread community testing it is impossible to ascertain true infection rates and develop strategies which reduce or prevent transmission without the need for on-going draconian measures such as complete national lockdown. These measures are mandatory at the time of writing, however widespread adoption of face masks has been shown to help prevent transmission of other respiratory pathogens, and also infections acquired by healthcare staff. Combining mass testing with a combination of social distancing and face mask use might offer a way forward until a mass COVID-19 vaccination programme can be established.