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.

SARS-CoV-2 has infected millions of people around the world, with most cases recorded among adults. The cases reported among children have been acknowledged to be minimal in comparison to adults. Nevertheless, COVID-19 has been reported to affect children at all ages, including newborns. The symptoms among children have also been identified to be similar to those observed among adults, although pediatric patients have been noted to display spectrum of clinical features ranging from asymptomatic through mild to moderate symptoms. Despite ample publications on the ongoing pandemic, the literature is only replete with guidelines on treating SARS-CoV-2 infection among older people. In this narrative review, comprehensive updates on the infection in children have been discussed. The latest information on the spread of the disease among children around the world, the clinical features observed among the pediatric population, as well as recommended pharmaceutical treatments of COVID-19 among this special group of patients have been covered. Further, expert consensus statements regarding the management of this highly contagious disease among pregnant women and neonates have been discussed. It is believed that this comprehensive review will provide updated information on the epidemiology and clinical features of the ongoing pandemic among pediatric patients. Additionally, the guidelines for handling SARS-CoV-2 among pregnant women and children, as reviewed in this article, are anticipated to be useful to frontline clinicians battling this fatal disease around the globe.

Background : Critically ill patients with coronavirus disease 2019（COVID-19）was surging and far outnumbered existing beds. Aims :  To describe how to rapidly convert general wards to intensive care units for critically ill patients with COVID-19. Materials & Methods :  Comprehensive assessment and analysis of available resources and standard requirements. Results : The ICUs were successfully assembled in four days. The conversion included environment reconstruction, configuration and management of equipment, information system construction and human resource allocation. A total of 172 critically ill patients had been admitted to the contemporary ICUs and none medical staff was infected. Discussion :  The epidemic situation of COVID-19 poses a great challenge to various management departments of the hospital, especially for critically ill patients with high mortality rate. To save more critically ill patients, the conversion of a general ward to a quarantine ICU ward must be completed in a short time, and the optimal allocation of resources must be appropriate to ensure that the medical team works effectively and is of high quality. In face of the overloaded medical system, the ideal non-negative pressure ward is hard to achieve. However, we have demonstrated with evidence that our conversions are effective in both providing care to the critical patients and protecting the safety of our staff. Conclusion:  The conversion is successful and the running experience would be a reference for hospitals in other areas nationally or globally.

Acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid-19) for which as of now there is no effective treatment. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung edema, inflammatory cell infiltraton and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid-19-associated ARDS.

Aims 1. To systematically review the currently available evidence investigating the association between olfactory dysfunction (OD) and the novel coronavirus (COVID-19). 2. To analyse the prevalence of OD in patients who have tested positive on Polymerase Chain Reaction (PCR) for COVID-19. 2. To perform a meta-analysis of patients presenting with olfactory dysfunction, during the pandemic, and to investigate the Positive Predictive Value for a COOVID-19 positive result in this population. 3. To assess if olfactory dysfunction could be used as a diagnostic marker for COVID-19 positivity and aid public health approaches in tackling the current outbreak. Methods We systematically searched MedLine (PubMed), Embase, Health Management Information Consortium (HMIC), Medrxiv, the Cochrane Library, the Cochrane COVID-19 Study Register, NIHR Dissemination centre, Clinical Evidence, National Health Service Evidence and the National Institute of Clinical Excellence to identify the current published evidence which associates coronaviridae or similar RNA viruses with anosmia. The initial search identified 157 articles. 145 papers were excluded following application of our exclusion criteria. The 12 remaining articles, that presented evidence on the association between COVID-19 and olfactory dysfunction, were critically analysed. Results OD has been shown to be the strongest predictor of COVID-19 positivity when compared to other symptoms in logistic regression analysis. In patients who had tested positive for COVID-19 there was a prevalence of 62% of OD. In populations of patients who are currently reporting OD there is a positive predictive value of 61% for a positive COVID-19 result. Conclusion Our review has shown that there is already significant evidence which demonstrates an association between OD and the novel coronavirus – COVID-19. It is unclear if this finding is unique to this coronavirus as individual viral phenotypes rarely present in such concentrated large numbers. We have demonstrated that OD is comparatively more predictive for COVID-19 positivity compared to other associated symptoms. We recommend that people who develop OD during the pandemic should be self-isolate and this guidance should be adopted internationally to prevent transmission.

A recent commentary published in BJCP used lopinavir/ritonavir as an example to highlight the importance of the clinical pharmacology principles in the repurposing of old drugs for therapeutic use against Coronavirus disease 19 (COVID-19).1 Here, we provide another example to support this point.A recent study found that ivermectin, an FDA-approved anti-parasitic drug, has inhibitory effects on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).2 Ivermectin has broad anti-viral activity through inhibition of viral proteins including importin α/β1 heterodimer and integrase protein.3 In the in vitro study reported by Caly and colleagues, the addition of ivermectin at a concentration of 5 micromolar (μM) (twice the reported IC50) to Vero-hSLAM cells 2 hours post infection of with SARS-CoV-2 resulted in a reduction in the viral RNA load by 99.98% at 48 hours.2Large trials of mass drug administration of ivermectin in adults and children have shown that ivermectin is well tolerated.4 Even at doses that are 10 times greater than the highest FDA-approved dose of 200 μg/kg, central nervous system toxicity has not been reported.5 However, following the oral administration of supra-therapeutic doses of ivermectin (i.e. 120 mg) the maximum plasma concentration achieved was 0.28 ± 0.18 (standard deviation) μM, a value 18 times lower than the reported 5 μM ivermectin concentration used by Caly et al in their SARS-CoV-2 experiment.5 To date, the clinical effects of ivermectin at a concentration of 5 μM range are unknown, but likely to be toxic. Furthermore, ivermectin is only commercially available as a 3 mg oral tablet.6 These factors hinder our ability to immediately repurpose ivermectin in its current form for the treatment of COVID-19.While the findings by Caly and colleagues provide some promise, viral suppression was not seen at concentrations observed with standard doses in humans. Further preclinical in vivo studies should evaluate the pharmacokinetics and pharmacodynamics to determine the kill pattern of ivermectin. A potential alternate solution may be to develop an inhaled formulation of ivermectin to efficiently deliver a high local concentration in the lung, whilst minimising systemic toxicity. As therapeutic agents to tackle the COVID-19 pandemic are urgently sought, careful consideration of the pharmacokinetics of these drugs should be considered to guide in vitro testing.

Dear Editor,Since December 2019, coronavirus 2019 (COVID-19) has spread worldwide.1 Some data have suggested that the prevalence and mortality of COVID-19 are different among races. 2However, this analysis did not account for potential confounding factors.Since chronic kidney disease (CKD) is common, the number of COVID-19 patients with CKD will increase. However, there are scarce data about outcomes in CKD patients. We herein investigated the outcomes from COVID-19 in AAs compared to those in whites.We analyzed Mount Sinai Health System (MSHS) medical records up to April 5, 2020, using Epic SlicerDicer software. We extracted data from patients who had positive for the COVID-19 reverse-transcription polymerase chain reaction (RT-PCR) test. Sex, age, race, and comorbidities (hypertension, diabetes mellitus, ischemic heart disease, heart failure, and atrial fibrillation) were extracted using the 10th revision of the International Statistical Classification of Diseases code. Mortality and intensive care unit (ICU) admission were tracked through April 12, 2020. Relative risks (RR) and 95 % confidence interval (CI) in each race stratified by age groups and comorbidities were calculated using a Fisher’s exact test. MSHS waived Institutional Review Board approval since this research used only deidentified, aggregate-level data.During the study period, 1,269 AAs COVID-19 patients with 105 CKD patients and 1,450 whites COVID-19 patients with 80 CKD patients were detected. AAs were younger (median 66, IQR 55-76) than whites (median 75, IQR 65-83) (p< 0.001). There was no significant difference in mortality between AAs and whites (0.65 [0.36-1.15]). This tendency was observed after stratification by age and medical conditions. Similarly, AAs did not have an increased risk of ICU admission (0.84 [0.6-1.18])) even after stratification by age and comorbidities (Table).To the best of our knowledge, this is the first study that compared the risk of severe outcomes among races in CKD patients. Although it has been suggested that there might be racial disparity in COVID-19, our study did not show any significant differences in outcomes, even after stratifying patients by age and comorbidities. Our data suggested that we do not need to stratify these patients by race.The racial and ethnic diversity in NYC enabled us to investigate differences in outcomes among races in the same cohort. However, our study has several limitations. First, the number of patients was relatively small. Second, we did not access individual data, which prevented us from performing multivariate analyses. The fact that AAs were younger might mask differences among races.In conclusion, AAs with CKD did not have a higher risk of mortality or ICU admission than whites with CKD. This trend was consistent after stratification by age, sex, or comorbidities.Acknowledgements: noneConflict of Interest Disclosures: TY reports no conflict of interest. TM reports no conflict of interest. NC reports no conflict of interest. HM reports no conflict of interest. SC repots no conflict of interest. SM reports no conflict of interest.Reference1. Team CC-R. Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 - United States, February 12-March 28, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(13):382-386.2. Health N. Age adjusted rate of fatal lab confirmed COVID-19 cases per 100,000 by race/ethnicity group as of April 6, 2020 (Accessed Aprio 12, 2020). 2020.

Patient selection and cannulation arguably represent the key steps for the successful implementation of Extracorporeal Membrane Oxygenation (ECMO) support. Cannulation is traditionally performed in the operating room or the catheterization laboratory for a number of reasons, including physician preference and access to real-time imaging, with the goal of minimizing complications and ensuring appropriate cannula positioning. Nonetheless, the patients’ critical and unstable conditions often require emergent initiation of ECMO and preclude the safe transport of the patient to a procedural suite. Therefore, with the objective of avoiding delay with initiation of therapy and reducing the hazard of transport, we implemented a protocol for bedside ECMO cannulation. In the current pandemic, this strategy may have additional benefits for the care of patients with refractory acute respiratory distress syndrome (ARDS) due to COVID-19 decreasing risk of healthcare worker or other patients exposure to the novel SARS-CoV-2 virus occurring during patient transport, preparation, or during disinfection of the procedural suite and the transportation pathway after ECMO cannulation.

I have some comments on TBED recently published paper titled “Serological survey of SARS-CoV-2 for experimental, domestic, companion and wild animals excludes intermediate hosts of 35 different species of animals” by Deng JH, et al.

Aim: A worldwide pandemic of coronavirus disease 2019 (COVID-19) which emerged in China in December 2019 affects the world very seriously. We aimed to evaluate the benign prostatic hyperplasia (BPH) patients who were admitted and treated to our hospital due to COVID-19. Methods: Between March 18, 2020 and April 5, 2020 , 18 patients admitted with COVID-19 who has BPH and are using medication for this were included in the study and analyzed retrospectively. Diagnosis was confirmed by COVID-19 nucleic acid test by sampling sputum or nasopharyngeal swab. Standard COVID-19 treatment protocol determined by our Ministry of Health was applied to all patients according to their risk groups. Epidemiological, clinical, radiological features, additional diseases, laboratory tests, complications and outcome data of all patients were recorded. Results: Mean age of patients was 59.6 (range: 56-73). As the mode of transmission, 10 (55.5%) of patients were infected in hospital, 5 (27.7%) patients had a relative with COVID-19 and 3 (16,6%) was unknown. During follow-up, 2 (11.1%) patients were transferred to intensive care unit (ICU). One of these patients dramatically progressed and died. Patients who survived and were not transferred to ICU had lesser comorbidities and were relatively young. Mean duration of hospitalization was 14.2 days (range 12-19). Conclusion: We think that COVID-19 patients with BPH had a low mortality rate and did not have a poor prognosis in this patient group. It is crucial to take comprehensive preventive measures to control COVID-19 transmission via hospital route.

This is the first report of a case of COVID-19 after allogeneic stem cell transplantation. Our case suggests that COVID-19 may exist without characteristic CT images, especially in immunocompromised hosts, such as patients after transplantation.

The pandemic caused by SARS-CoV-2 has affected communities throughout the world. The global nature of health care disparities is exacerbated by COVID-19. Patients in Low-and Middle-Income Countries have limited health care resources and marginal support for the evaluation and treatment of cardiac rhythm disorders. Heart Rhythm Societies and their members need to advocate for increased subsidies and assistance for these patients.

As the pandemic of Coronavirus Disease 2019 (COVID-19) rages throughout the world, accurate modeling of the dynamics thereof is essential. However, since the availability and quality of data varies dramatically from region to region, accurate modeling directly from a global perspective is difficult, if not altogether impossible. Nevertheless, via local data collected by certain regions, it is possible to develop accurate local prediction tools, which may be coupled to develop global models. In this study, we analyze the dynamics of local outbreaks of COVID-19 via a coupled system of ordinary differential equations (ODEs). Utilizing the large amount of data available from the ebbing outbreak in Hubei, China as a testbed, we estimate the basic reproductive number, R0 of COVID-19 and predict the total cases, total deaths, and other features of the Hubei outbreak with a high level of accuracy. Through numerical experiments, we observe the effects of quarantine, social distancing, and COVID-19 testing on the dynamics of the outbreak. Using knowledge gleaned from the Hubei outbreak, we apply our model to analyze the dynamics of outbreak in Turkey. We provide forecasts for the peak of the outbreak and the total number of cases/deaths in Turkey, for varying levels of social distancing, quarantine, and COVID-19 testing.

The coronavirus disease 2019 (COVID-19) is an infectious disease which has rapidly evolved into a pandemic. Though it has affected all disciplines of medical sciences but it has some serious implications pertaining to cardiovascular sciences which have presented unique challenges in front of cardiac surgeons in particular. To flatten the curve of this pandemic, routine cardiac surgeries are being deferred indefinitely resulting in the pool of sick cardiac patients rising day by day. A different perspective is presented on this global catastrophe from the viewpoint of a cardiac surgeon.

Aim: The COVID pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation. Result: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible. Conclusion: These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection. What is known about this topic? Nothing is known about the health significance of the D614G SARS-CoV-2 variant. What does this article add? A molecular clue to viral molecular pathogenesis of COVID-19 disease.

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 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.

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!”

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

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.

The current Covid-19 pandemic is a significant global health threat. The outbreak has profoundly affected all healthcare professionals, including heart surgeons. To adapt to these exceptional circumstances, cardiac surgeons had to change their practice significantly. We herein discuss the challenges and broad implications of the Covid-19 pandemic from the perspective of the heart surgeons.

Angiotensin converting enzyme-2 (ACE2) is the receptor for the coronavirus SARS-CoV-2, which causes COVID-19. We propose the following hypothesis: Imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing Angiotensin-II (ANG II) signaling, a primary driver of COVID-19 pathobiology. ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of ANG II to ANG peptides that counteract pathophysiological effects of ACE1-generated ANGII. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: 1) ANG II receptor blockers (ARBs); 2) ACE1 inhibitors (ACEIs); 3) Agonists of receptors activated by ACE2-derived peptides [e.g., ANG (1-7), which activates MAS1]; 4) Recombinant human ACE2 or ACE2 peptides as decoys for the virus. Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients. Importantly, approved ARBs and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19.

In this review, we identify opportunities for drug discovery in the treatment of COVID-19 and in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targetting key host and viral targets in the mid-term, by first screening these targets against drugs already licensed; an agenda for drug re-purposing, which should allow rapid translation to clinical trials. A simultaneous, multi-pronged approach using conventional drug discovery methodologies aimed at discovering novel chemical and biological means targetting a short-list of host and viral entities should extend the arsenal of anti-SARS-CoV-2 agents. This longer-term strategy would provide a deeper pool of drug choices for future-proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide.