Question: Does SARS-CoV-2 have any subtypes, and if so what are they?

Title: Masking the general population might attenuate COVID-19 outbreaks Content: The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed"one-mask protection") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.

Title: Is SARS-CoV-2 Vertically Transmitted? Content: At the end of 2019, in Wuhan (China), the onset of a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed. The disease, named COVID-19, has a wide spectrum of clinical presentations, ranging from asymptomatic or mild to critical, and for some patients the disease is even fatal. Apparently, being a child or being pregnant does not represent an additional risk for adverse outcomes. The purpose of this mini-review was to investigate what is in the scientific literature, so far, in regard to vertical transmission of SARS-CoV-2. Data were obtained independently by the two authors, who carried out a systematic search in the PubMed, Embase, LILACS, Cochrane, Scopus and SciELO databases using the Medical Subject Heading terms “coronavirus,” “COVID-19,” and “vertical transmission.” Few studies about the vertical transmission of SARS-CoV-2 are found in the literature. In all case reports and case series, the mothers' infection occurred in the third trimester of pregnancy, there were no maternal deaths, and most neonates had a favorable clinical course. The virus was not detected in the neonate nasopharyngeal swab samples at birth, in the placenta, in the umbilical cord, in the amniotic fluid, in the breast milk or in the maternal vaginal swab samples in any of these articles. Only three papers reported neonatal SARS-CoV-2 infection, but there is a bias that positive pharyngeal swab samples were collected at 36 h and on the 2nd, 4th, and 17th days of life. The possibility of intrauterine infection has been based mainly on the detection of IgM and IL-6 in the neonates' serum. In conclusion, to date, no convincing evidence has been found for vertical transmission of SARS-CoV-2.

Title: Genetic Grouping of SARS-CoV-2 Coronavirus Sequences using Informative Subtype Markers for Pandemic Spread Visualization Content: We propose an efficient framework for genetic subtyping of SARS-CoV-2, the novel coronavirus that causes the COVID-19 pandemic. Efficient viral subtyping enables visualization and modeling of the geographic distribution and temporal dynamics of disease spread. Subtyping thereby advances the development of effective containment strategies and, potentially, therapeutic and vaccine strategies. However, identifying viral subtypes in real-time is challenging: SARS-CoV-2 is a novel virus, and the pandemic is rapidly expanding. Viral subtypes may be difficult to detect due to rapid evolution; founder effects are more significant than selection pressure; and the clustering threshold for subtyping is not standardized. We propose to identify mutational signatures of available SARS-CoV-2 sequences using a population-based approach: an entropy measure followed by frequency analysis. These signatures, Informative Subtype Markers (ISMs), define a compact set of nucleotide sites that characterize the most variable (and thus most informative) positions in the viral genomes sequenced from different individuals. Through ISM compression, we find that certain distant nucleotide variants covary, including non-coding and ORF1ab sites covarying with the D614G spike protein mutation which has become increasingly prevalent as the pandemic has spread. ISMs are also useful for downstream analyses, such as spatiotemporal visualization of viral dynamics. By analyzing sequence data available in the GISAID database, we validate the utility of ISM-based subtyping by comparing spatiotemporal analyses using ISMs to epidemiological studies of viral transmission in Asia, Europe, and the United States. In addition, we show the relationship of ISMs to phylogenetic reconstructions of SARS-CoV-2 evolution, and therefore, ISMs can play an important complementary role to phylogenetic tree-based analysis, such as is done in the Nextstrain [1] project. The developed pipeline dynamically generates ISMs for newly added SARS-CoV-2 sequences and updates the visualization of pandemic spatiotemporal dynamics, and is available on Github at https://github.com/EESI/ISM and via an interactive website at https://covid19-ism.coe.drexel.edu/. Author Summary The novel coronavirus responsible for COVID-19, SARS-CoV-2, expanded to reportedly 8.7 million confirmed cases worldwide by June 21, 2020. The global SARS-CoV-2 pandemic highlights the importance of tracking viral transmission dynamics in real-time. Through June 2020, researchers have obtained genetic sequences of SARS-CoV-2 from over 47,000 samples from infected individuals worldwide. Since the virus readily mutates, each sequence of an infected individual contains useful information linked to the individual’s exposure location and sample date. But, there are over 30,000 bases in the full SARS-CoV-2 genome—so tracking genetic variants on a whole-sequence basis becomes unwieldy. We describe a method to instead efficiently identify and label genetic variants, or “subtypes” of SARS-CoV-2. Applying this method results in a compact, 11 base-long compressed label, called an Informative Subtype Marker or “ISM”. We define viral subtypes for each ISM, and show how regional distribution of subtypes track the progress of the pandemic. Major findings include (1) covarying nucleotides with the spike protein which has spread rapidly and (2) tracking emergence of a local subtype across the United States connected to Asia and distinct from the outbreak in New York, which is found to be connected to Europe.

Title: SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? Content: In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected. The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence. Any existing pools of SARS-CoV-2 progenitors would be particularly dangerous if similarly well adapted for human transmission. To look for clues regarding intermediate hosts, we analyze recent key findings relating to how SARS-CoV-2 could have evolved and adapted for human transmission, and examine the environmental samples from the Wuhan Huanan seafood market. Importantly, the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources. We conclude by describing and advocating for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population(s) of progenitor virus.

Title: Podcast: Beating a killer coronavirus Content: As COVID-19 continues to spread, so does the effort to find treatment and vaccinations against SARS-CoV-2, the coronavirus that causes the disease Around the world, scientists are working nonstop on therapies they hope will stem the loss of life during this pandemic while trying to set us up to prevent future outbreaks What’s not clear is which of these treatments will work Much about SARS-CoV-2 remains unknown In this episode of Stereo Chemistry, we dig into the efforts to beat the novel coronavirus and why in some cases it’s like throwing spaghetti against the wall to see what sticks Learn more at http://cenm ag/coronapodcast

Title: Understanding Coronavirus Content: Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience

Title: The Coronavirus Pandemic: What Does the Evidence Show? Content: Coronavirus disease 2019 (COVID-19) is a newly emerged disease that has become a global public health concern as it rapidly spread around the world. The etiologic agent responsible for this disease has been named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses as it shows similar genomic features to that of SARS-CoV which caused a pandemic in 2002. This disease first appeared in Hubei province of China and it follows human-to-human transmission but the path this virus took to set up human infection remains a mystery. By 17 April 2020, globally there have been 2,074,529 confirmed cases with 139,378 deaths because of COVID-19. SARS-CoV-2 shows several similarities with SARS?CoV, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) with its clinical presentations. This can vary from asymptomatic infection to severe disease and mortality. Real-time reverse-transcription polymerase chain reaction (rRT-PCR) screening is considered as the standard laboratory test for the diagnosis of COVID-19. There is no proven antiviral agent against SARS-CoV-2 so the treatment for COVID-19 is symptomatic, aiming for the management of the symptoms and prevention of the complications. The outbreak of COVID-19 has led to the implementation of extraordinary public health measures throughout the world. Numerous antiviral compounds used to treat other infections are being clinically researched to find possible treatment. Similarly, the traditional public health outbreak response strategy of isolation, quarantine, social distancing and community containment has been implemented in multiple countries and has played an important role in the prevention of new outbreaks. This review aims to enhance our understanding of COVID 19. Keywords: Coronavirus disease 2019; COVID-19; SARS-CoV-2; novel coronavirus 2019; severe acute respiratory syndrome-2.

Title: In the pipeline Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer Content: Let’s take inventory on the therapies that are being developed for the coronavirus epidemic Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they’re making all their Covid-19 content free to all readers during this crisis I’d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons The Biocentury list doesn’t cover these, but here’s an article at Nature Biotechnology that goes into detail Clinical trials are a huge time sink – they sort of have to be, in most cases, if they’re going to be any good – and if you’ve already done all that stuff it’s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right This has been in development for a few years as an RNA virus therapy – it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit The compound is a prodrug – that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524 It mechanism of action is to get incorporated into viral RNA, since it’s taken up by RNA polymerase and it largely seems to evade proofreading This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited

Title: In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03 Content: The recent outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV and Middle East respiratory Syndrome CoV (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.

Title: A Novel Synonymous Mutation of SARS-CoV-2: Is This Possible to Affect Their Antigenicity and Immunogenicity? Content: The S glycoprotein of coronaviruses is important for viral entry and pathogenesis with most variable sequences. Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes (SARS-CoV-2a and -b) were confirmed within SARS-CoV-2 strains. These two subtypes were divided by a novel synonymous mutation of D614G. This may play a crucial role in the evolution of SARS-CoV-2 to evade the host immune system. The region containing this mutation point was confirmed as a B-cell epitope located in the S1 domain, and SARS-CoV-2b strains exhibited severe reduced antigenic indexes compared to SARS-CoV-2a in this area. This may allow these two subtypes to have different antigenicity. If the two subtypes have different serological characteristics, a vaccine for both subtypes will be more effective to prevent COVID-19. Thus, further study is urgently required to confirm the antigenicity of these two subtypes.

Title: Complications and outcomes of SARS-CoV-2 in pregnancy: where and what is the evidence? Content: OBJECTIVES: To add to the growing evidence on SARS-CoV-2 infection during pregnancy, so as to better inform clinical decision making and optimize patient outcomes. METHODS: A systematic search of relevant databases was perfomed on 25 March 2020 and a repeat search, on 10 April 2020. Reports of pregnant patients with SARS-CoV-2 infection at any time during their pregnancy were reviewed and summarized . RESULTS: We summarized the outcomes of a total of 155 pregnant women and 118 neonates. The evidence suggests a similar rate of severe COVID-19 cases in pregnant women and the general population. The frequency of cesarean deliveries is high, against guidelines recommendations. CONCLUSION: Limited data on COVID-19 during preganacy, associated with a wide variation in the methodology make accurate data interpretation difficult.

Title: Complications and outcomes of SARS-CoV-2 in pregnancy: where and what is the evidence? Content: OBJECTIVES To add to the growing evidence on SARS-CoV-2 infection during pregnancy, so as to better inform clinical decision making and optimize patient outcomes. METHODS A systematic search of relevant databases was perfomed on 25 March 2020 and a repeat search, on 10 April 2020. Reports of pregnant patients with SARS-CoV-2 infection at any time during their pregnancy were reviewed and summarized . RESULTS We summarized the outcomes of a total of 155 pregnant women and 118 neonates. The evidence suggests a similar rate of severe COVID-19 cases in pregnant women and the general population. The frequency of cesarean deliveries is high, against guidelines recommendations. CONCLUSION Limited data on COVID-19 during preganacy, associated with a wide variation in the methodology make accurate data interpretation difficult.

Title: What we know about the novel coronavirus’s proteins Content: Scientists across the globe are gunning to understand the novel coronavirus, called SARS-CoV-2, and what makes it so contagious and deadly Several members of the coronavirus family infect humans: four cause the common cold, and two—SARS-CoV and MERS-CoV—have triggered dangerous epidemics The novel coronavirus’s closest kin is SARS-CoV, which jumped species from bats to civets to humans to cause the severe acute respiratory syndrome (SARS) epidemic of 2002–3 That SARS outbreak infected just over 8,000 people The current coronavirus pandemic has infected more than 2 million people and killed more than 130,000 as of April 15, according to data from Johns Hopkins University “From a molecular perspective, figuring out why the virus is so much more transmissible than past viruses is where we should be looking right now,” says Robert Kirchdoerfer, a structural biologist at the University of Wisconsin–Madison who studies how coronaviruses fuse with host cells While people infected

Title: Are your cash-flow tools recession ready? Content: Abstract In good times like those most businesses have enjoyed for the past decade, business owners have typically watched their income statements with pleasure, as year-to-year performance gains have fattened their dividend payouts and increased the valuation of the companies they own and run. All too often in such times, scant attention is paid to what’s between the top line and the bottom line of the income statement. Worse, most business owners, in my experience, give little more than a cursory nod to the balance sheet. Why does this matter? When a recession lands on their doorstep with a sudden thud, as it apparently just has, many of these same people will find themselves having sailed too close to the wind, with cash running out and a dearth of tools to help them weather the storm and understand what has gone wrong. But it need not be so, for there are four simple tools to help any business owner answer these four important questions: (1) Where is cash going in my business, and where is it coming from? (2) To what extent are my profit margins improving or declining, and why? (3) To what extent am I effectively managing the cash-flow relationships with my customers and my suppliers? (4) What, if anything, can I do to better manage the cash that flows into and out of my business? If your business is threatened by the COVID-19 pandemic, here are some tools to help it survive.

Title: GPS Tracking App for Police to Track Ambulances Carrying COVID-19 Patients for Ensuring Safe Distancing Content: The outbreak of the SARS-CoV-2 virus is causing loss of lives and property all over the world. There have been more than 2.1 million cases of COVID-19 with a death of more than 1.2 lakh patients worldwide and the numbers are still rising. The virus spreads rapidly by the droplets coming out from the nose and mouth of an infected person (Sandoiu in Why does SARS-CoV-2 spread so easily? Medical news today, 2020 https://www.medicalnewstoday.com/articles/why-does-sars-cov-2-spread-so-easily). In this situation, proper quarantining and monitoring of the already infected patients are very essential. In cases where patients need to be transferred to different locations by ambulances, monitoring of these ambulances by the traffic police can help to ensure distancing and faster movement of the vehicle inside the city. This paper presents the development of a Real-time Global Positioning System-based tracking app for the ambulances carrying COVID-19 patients which would help traffic police to ensure distancing the patients from the public.

Title: Aerosol generating procedures and infective risk to healthcare workers: SARS-CoV-2 – the limits of the evidence Content: The transmission behaviour of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being defined. It is likely that it is transmitted predominantly by droplets and direct contact and it is possible that there is at least opportunistic airborne transmission. In order to protect healthcare staff adequately is necessary that we establish whether aerosol generating procedures (AGPs) increase the risk of transmission of SARS-CoV-2. Where we do not have evidence relating to SARS-CoV-2, guidelines for safely conducting these procedures should consider what risk procedures would have of transmitting related pathogens. Currently there is very little evidence detailing the transmission of SARS-CoV-2 associated with any specific procedures. Regarding aerosol generating procedures and respiratory pathogens in general, there is still a large knowledge gap that will leave clinicians unsure what risk they are putting themselves in when offering these procedures. This review aimed to summarise the evidence (and gaps in evidence) around AGPs and SARS-CoV-2.

Title: Aerosol generating procedures and infective risk to healthcare workers: SARS-CoV-2 - the limits of the evidence Content: The transmission behaviour of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being defined. It is likely that it is transmitted predominantly by droplets and direct contact and it is possible that there is at least opportunistic airborne transmission. In order to protect healthcare staff adequately is necessary that we establish whether aerosol generating procedures (AGPs) increase the risk of transmission of SARS-CoV-2. Where we do not have evidence relating to SARS-CoV-2, guidelines for safely conducting these procedures should consider what risk procedures would have of transmitting related pathogens. Currently there is very little evidence detailing the transmission of SARS-CoV-2 associated with any specific procedures. Regarding aerosol generating procedures and respiratory pathogens in general, there is still a large knowledge gap that will leave clinicians unsure what risk they are putting themselves in when offering these procedures. This review aimed to summarise the evidence (and gaps in evidence) around AGPs and SARS-CoV-2.

Title: Ultraviolet irradiation doses for coronavirus inactivation – review and analysis of coronavirus photoinactivation studies Content: Background: To slow the increasing global spread of the SARS-CoV-2 virus, appropriate disinfection techniques are required. Ultraviolet radiation (UV) has a well-known antiviral effect, but measurements on the radiation dose necessary to inactivate SARS-CoV-2 have not been published so far. Methods: Coronavirus inactivation experiments with ultraviolet light performed in the past were evaluated to determine the UV radiation dose required for a 90% virus reduction. This analysis is based on the fact that all coronaviruses have a similar structure and similar RNA strand length. Results: The available data reveals large variations, which are apparently not caused by the coronaviruses but by the experimental conditions selected. If these are excluded as far as possible, it appears that coronaviruses are very UV sensitive. The upper limit determined for the log-reduction dose (90% reduction) is approximately 10.6 mJ/cm(2) (median), while the true value is probably only 3.7 mJ/cm(2) (median). Conclusion: Since coronaviruses do not differ structurally to any great exent, the SARS-CoV-2 virus – as well as possible future mutations – will very likely be highly UV sensitive, so that common UV disinfection procedures will inactivate the new SARS-CoV-2 virus without any further modification.

Title: Severe Acute Respiratory Syndrome Coronavirus Elicits a Weak Interferon Response Compared to Traditional Interferon-Inducing Viruses Content: The aim of the present study is to investigate changes of interferon (IFN) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (PBMCs) with severe acute respiratory syndrome (SARS) coronavirus (CoV) and to compare these changes to those induced by well-established IFN-inducing viruses, such as vesicular stomatitis (VSV) and Newcastle viruses (NDV). Experiments have been carried out using PBMCs of 10 different healthy donors. The results showed that the antiviral activity of IFN contained in the supernatant of SARS-CoV-infected PBMCs was lower than those induced by VSV and NDV. Consequently, SARS-CoV induces a lower synthesis of IFN-α, -β and -γ compared to VSV and NDV. Characterization of the profile of IFN-α subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-α2 and −6 subtypes were higher compared to other IFN-α subtypes namely, IFN-α5, −8, −10, −13/1, −17, and −21. In conclusion, SARS-CoV induces IFNs to a less extent compared to VSV and NDV, thus suggesting that the IFN system does play a limited role in early host defense against SARS-CoV infection.

Title: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19 Content: Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any ”normal” post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.

Title: What’s new in the renin-angiotensin system?: Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus Content: Cellular entry of enveloped viruses is often dependent on attachment proteins expressed on the host cell surface. Viral envelope proteins bind these receptors, and, in an incompletely understood process, facilitate fusion of the cellular and viral membranes so as to introduce the viral core into the cytoplasm. Only a small fraction of viral receptors have been identified so far. Recently, a novel coronavirus was identified as the etiological agent of severe acute respiratory syndrome (SARS). The fusion protein gene of SARS coronavirus (SARS-CoV) was cloned and characterized, and shortly thereafter, angiotensin-converting enzyme 2 (ACE2) was shown to be its functional receptor. Identification of ACE2 as a receptor for SARS-CoV will likely contribute to the development of antivirals and vaccines. It may also contribute to the development of additional animal models for studying SARS pathogenesis, and could help identify the animal reservoir of SARS-CoV.

Title: Glycosylation of the severe acute respiratory syndrome coronavirus triple-spanning membrane proteins 3a and M. Content: The severe acute respiratory syndrome coronavirus (SARS-CoV) open reading frame 3a protein has recently been shown to be a structural protein. The protein is encoded by one of the so-called group-specific genes and has no sequence homology with any of the known structural or group-specific proteins of coronaviruses. It does, however, have several similarities to the coronavirus M proteins; (i) they are triple membrane spanning with the same topology, (ii) they have similar intracellular localizations (predominantly Golgi), (iii) both are viral structural proteins, and (iv) they appear to interact with the E and S proteins, as well as with each other. The M protein plays a crucial role in coronavirus assembly and is glycosylated in all coronaviruses, either by N-linked or by O-linked oligosaccharides. The conserved glycosylation of the coronavirus M proteins and the resemblance of the 3a protein to them led us to investigate the glycosylation of these two SARS-CoV membrane proteins. The proteins were expressed separately using the vaccinia virus T7 expression system, followed by metabolic labeling. Pulse-chase analysis showed that both proteins were modified, although in different ways. While the M protein acquired cotranslationally oligosaccharides that could be removed by PNGaseF, the 3a protein acquired its modifications posttranslationally, and they were not sensitive to the N-glycosidase enzyme. The SARS-CoV 3a protein, however, was demonstrated to contain sialic acids, indicating the presence of oligosaccharides. O-glycosylation of the 3a protein was indeed confirmed using an in situ O-glycosylation assay of endoplasmic reticulum-retained mutants. In addition, we showed that substitution of serine and threonine residues in the ectodomain of the 3a protein abolished the addition of the O-linked sugars. Thus, the SARS-CoV 3a protein is an O-glycosylated glycoprotein, like the group 2 coronavirus M proteins but unlike the SARS-CoV M protein, which is N glycosylated.

Title: Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? Content: Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.

Title: The global population of SARS-CoV-2 is composed of six major subtypes Content: The World Health Organization characterized the COVID-19 as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory (ORF8) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.

Title: What's the plan? The unique challenges facing the home and community care sector in preparing for a pandemic. Content: Recent experience with the outbreak of severe acute respiratory syndrome (SARS) in Canada and the global threat of the H5N1 virus (avian "flu") have increased the appetite for and urgency of pandemic planning as a policy issue. The healthcare setting is one of the most important areas to prepare for such an event, and it is crucial that discussions around doing so include all settings in which care is delivered. As the home and community care sector is increasingly utilized and likely to be relied upon even more during a pandemic, addressing the challenges to occupational health and safety uniquely faced by this sector will be vitally important to the entire health system. A pandemic plan that does not consider healthcare outside of the institutional setting is incomplete and will be likely to fail. This commentary outlines the challenges to providing care in the home and community that must be considered in any plan designed to deal with a pandemic on a system-wide level.

Title: Does SARS-CoV-2 has a longer incubation period than SARS and MERS? Content: The outbreak of a novel coronavirus (SARS-CoV-2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), highlighting the need for larger and well-annotated datasets.

Title: Does SARS‐CoV‐2 has a longer incubation period than SARS and MERS? Content: The outbreak of a novel coronavirus (SARS‐CoV‐2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS‐CoV‐2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS‐CoV‐2, severe acute respiratory syndrome coronavirus (SARS‐CoV), and middle east respiratory syndrome coronavirus (MERS‐CoV), highlighting the need for larger and well‐annotated datasets.

Title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization Content: STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? SUMMARY ANSWER ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization. WHAT IS KNOWN ALREADY ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells. STUDY DESIGN, SIZE, DURATION Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS ACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression. MAIN RESULTS AND THE ROLE OF CHANCE In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1 (P < 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri more than vehicle or estrogen (P < 0.05). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss. STUDY FUNDINGS/COMPETING INTEREST(S) This study was supported by National Institutes of Health / National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest.

Title: Mutations strengthened SARS-CoV-2 infectivity Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.

Title: Mutations on COVID-19 diagnostic targets Content: Effective, sensitive, and reliable diagnostic reagents are of paramount importance for combating the ongoing coronavirus disease 2019 (COVID-19) pandemic at a time there is no preventive vaccine nor specific drug available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It would be an absolute tragedy if currently used diagnostic reagents are undermined in any manner. Based on the genotyping of 7818 SARS-CoV-2 genome samples collected up to May 1, 2020, we reveal that essentially all of the current COVID-19 diagnostic targets have had mutations. We further show that SARS-CoV-2 has the most devastating mutations on the targets of various nucleocapsid (N) gene primers and probes, which have been unfortunately used by countries around the world to diagnose COVID-19. Our findings explain what has seriously gone wrong with a specific diagnostic reagent made in China. To understand whether SARS-CoV-2 genes have mutated unevenly, we have computed the mutation ratio and mutation $h$-index of all SARS-CoV genes, indicating that the N gene is the most non-conservative gene in the SARS-CoV-2 genome. Our findings enable researchers to target the most conservative SARS-CoV-2 genes and proteins for the design and development of COVID-19 diagnostic reagents, preventive vaccines, and therapeutic medicines.

Title: Meaning of dangerous goods Content: The parties to a contract for the carriage of goods by sea, whether this is embodied in a bill of lading or one of the standard charterparty forms, customarily negotiate its terms against a background of both commercial and legal considerations. The parties’ respective liability for risks to which the vessel and its cargo might be exposed during the course of the contracted voyage will be of paramount importance. Should they arise, the potential risks might expose the parties, through their insurance, to expensive damage claims. Therefore, the description of the cargo for shipment is one of the crucially important components of the negotiations between the parties to any shipping contract.(1) This requirement becomes especially relevant when it has been estimated that more than 50% of the cargoes transported by sea today may be regarded as dangerous, hazardous, and/or harmful and need to be handled with special care. As a result, a shipper does not have unlimited freedom as to what he may transport by sea. Restrictions on goods which a charterer or shipper may ship are imposed by law, the terms of the contract and statutes. These restrictions are commonly elided into a general proposition that a person sending goods by sea must not ship dangerous goods. Yet it is the case that dangerous goods are often shipped and legitimately so; and the carrier should discharge his normal duties in respect of whatever cargo he has agreed to carry. The real issues, therefore, are to identify what risks are involved in the carriage of the cargo in question, how these risks are allocated between the parties and what the consequences of shipping dangerous goods are.(2)

Title: BCG is a good immunotherapeutic agent for viral and autoimmune diseases: Is it a new weapon against coronavirus (COVID-19)? Content: Now nearly a century old, the Bacillus Calmette-Guérin (BCG) vaccine is used routinely in humans for the prophylaxis of tuberculosis and to clear up leprosy. As the immune response to the vaccine shows some degree of cross-antigenicity, the vaccine also affects a level of resistance to a range of unrelated diseases and pathogens. Clinical studies data have shown that the BCG vaccine has effects on autoimmune and inflammatory diseases. Although the vaccine does not possess any inherent antiviral activity, it engages in the host immune system such that many types of viral infections are considerably reduced. Hence, we expect that the frequency and severity of many microbial diseases, including COVID-19, will be lower in counties in which mass BCG vaccination programs are implemented. So the BCG vaccine may prove useful in the coming months especially in countries where already have mass BCG vaccination, as the COVID-19 pandemic has placed an unprecedented strain on health services across the world. Currently, countless front-line healthcare staff is in immediate danger of exposure to the SARS-CoV-2 virus. Furthermore, as oral zinc sulfate as immunomodulator has proved an effective means to treat various viral diseases (including viral warts and herpes), parasitic infections, and diseases with autoimmune reactions such as Behcet’s disease and recurrent aphthous stomatitis, it could be employed in combination with the BCG vaccine to enhance the immunological functions of patients with COVID-19. So BCG immunotherapy combined with oral zinc sulfate will be encouraging protective programs in societies where coronavirus is going to spread.

Title: Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far Content: Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.

Title: Coronavirus in pregnancy. What we know so far? Content: Coronaviruses are a group of viruses which, even if they are affecting mainly mammals and birds, could be transmitted to humans, generating common cold The new virus strain is named SARS-CoV-2 and has 85% sequence similarity to SARS-CoV Until now, it has caused more than 100 000 confirmed cases of infection and almost 5000 deaths, having a mortality rate of 4% All information (symptoms, signs, management, complications) are taken from the other pandemic infections (SARS, MERS) Information about viral infection concerning pregnant women are limited and are common to other SARS infections There are very few cases of pregnant patients infected with SARS-CoV-2 and studies are ongoing

Title: The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis Content: Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.

Title: Tuberculosis and COVID-19 in 2020: lessons from the past viral outbreaks and possible future outcomes Content: Background. The threat of contagious infectious diseases is constantly evolving, as demographic explosion, travel globalization and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. PubMed electronic database was requested for relevant articles linking TB, influenza and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (with a focus on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from the past outbreaks (other coronaviruses), as well as influenza pandemic / seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their harmful synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead.

Title: SARS-CoV-2, COVID-19, skin and immunology - what do we know so far? Content: The pandemic condition Coronavirus-disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2 positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial and maculopapular eruptions as well as livedo, necrosis and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical and histologic features of virus- as well as drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.

Title: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? Content: INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. SUMMARY: Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

Title: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19? Content: INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

Title: Analysis of the susceptibility of lung cancer patients to SARS-CoV-2 infection Content: Recent studies have reported that COVID-19 patients with lung cancer have a higher risk of severe events than patients without cancer. In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Lung cancer patients in each age stage, subtype, and pathological stage are susceptible to SARS-CoV-2 infection, except for the primitive subtype of LUSC. LUAD patients are more susceptible to SARS-CoV-2 infection than LUSC patients. The findings are unanimous on tissue expression in gene and protein levels.

Title: Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.

Title: Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection? Content: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.

Title: Host Immune Response and Immunobiology of Human SARS-CoV-2 Infection Content: One of the most serious viral outbreaks of the decade, infecting humans, originated from the city of Wuhan, China, by the end of December 2019, has left the world shaken up. It is the successor infection of severe acute respiratory syndrome coronavirus (SARS-CoV) named as SARS-CoV-2 causing a disease called as COVID-19 (Coronavirus disease-19). Being one of the most severe diseases in terms of transmission, this disease agitates the immune system of an individual quite disturbingly which at times leads to death, which is why it has become the need of the hour to step forward to extensively involve in understanding the genetics, pathogenesis, and immunopathology of SARS-CoV-2 in order to design drugs to treat or to design a vaccine to prevent. In this chapter, we have tried to review and summarize the studies done so far to understand the host–pathogen relationship and the host immune response during COVID-19 infection. One of the recent developments regarding the understanding of SARS-CoV-2 infection is the mechanism of immune evasion involved during the pathogenesis and cytokine storm syndrome during infection in the patient against which a drug called as Hydroxychloroquine has been designed. Comprehensively, we have tried to give an immunological insight into the SARS-CoV-2 infection in order to understand the possible outcome for any therapeutic advancement.

Title: Cancer immunotherapy does not increase the risk of death by COVID-19 in melanoma patients Content: Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies. There are no clinical data about the safety of immune check point antibodies in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies, are an effective treatment for most melanoma patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma. Methods: In Spain we have started a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age is 69 years (range 6 to 94 years), 27 (54%) patients are males and 36 (70%) patients have stage IV melanoma. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death in those patients undergoing treatment with anti PD-1 antibodies does not exceed the global risk of death in this population. These results could be relevant in order to select melanoma therapy during the COVID-19 pandemic

Title: Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes Content: Our researchers took a look at a sequence of DNA known as the ACE2 gene. This gene is most well known for its role in regulating blood pressure. But in recent times, it’s drawn a lot of attention from the scientific community because it may also serve as a doorway of sorts, enabling viruses like SARS-CoV-2 to infect cells. Our researchers looked at the ACE2 gene in more than 200,000 people, comparing their exact DNA sequences to see where there are differences among people. Variation in the DNA sequence of a gene is common and is sometimes meaningless. But other times, small changes in the DNA sequence can alter the protein that is made from that gene. In this case the ACE2 gene makes the ACE2 protein, which is what the SARS-CoV-2 virus interacts with. We found a lot of variation between individuals and checked to see if that variation coincided with any traits (i.e., people with variant X tend to have high blood pressure more often than people without variant X). All of the traits we looked at were non-COVID-19-related traits, meaning we haven’t asked these people anything about COVID-19 yet (this is because these DNA sequences were collected before the pandemic). We found that there are a number of variations observed among people in a specific part of the ACE2 gene. These variations are expected to alter the shape or functionality of a specific part of the ACE2 protein: The part that interacts with the SARS-CoV-2 virus. We don’t yet know what the real-life significance of this variation is, but it’s possible that these variants decrease the protein’s ability to interact with the SARS-CoV-2 virus, thus decreasing the person’s likelihood of being infected. We can speculate that there will be a spectrum of vulnerability to COVID-19 among people, where some people are more vulnerable than others, and that variants in this part of the ACE2 gene may be one of the reasons. The research we presented here shines a light on this part of the ACE2 gene and may give future researchers a direction to go in as they try to figure out what makes people vulnerable to COVID-19 and similar viruses.

Title: A generalized overview of SARS-COV-2: Where does the current knowledge stand? Content: The novel coronavirus known to have brought the world to a standstill is responsible for many deaths throughout the globe as of now. The causative agent (SARS-CoV-2) for coronavirus disease 2019 (COVID-19) has been recognized as a zoonotic transfer. Although, the medium of animal-human transmission is still unknown, bats maybe a potential reservoir of this novel strain. Due to its high rate of transmission the most favorable way of limiting the outbreak’s extent is by early diagnosis followed by isolation of the infected individuals. So far, the most widely used diagnosis methods are RT-qPCR which detects specific sequences of the viral RNA. Some other methods include serological tests and the recently introduced CRISPR-CAS-12 based assays. As of now, no specific therapeutic treatments are known for COVID-19 however the use of some broad-spectrum antiviral drugs and convalescent plasma therapy have demonstrated positive outcomes. Apart from these treatments, vaccine development for SARS-CoV-2 is also in progress by 17 known companies. This article provides a comprehensive insight on the recently emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) including its origin, transmission mechanism, pathophysiology and updated treatment methods.

Title: SARS-CoV-2 and human milk: what is the evidence? Content: The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical, and public health communities have rapidly engaged to find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. While respiratory droplets are a known mechanism of transmission, other mechanisms are possible. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronavirus (including SARS-CoV-2) via human milk and/or breastfeeding. There is a single study providing some evidence of vertical transmission of human coronavirus 229E, a single study evaluating presence of SARS-CoV in human milk (it was negative), and no published data on MERS-CoV and human milk. There are 9 case studies of human milk tested for SARS-CoV-2; none detected the virus. Importantly, none of the published studies on coronaviruses and human milk report validation of their analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.

Title: No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2 Content: The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised reservoir. Due to this extremely recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that some lineages of SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible candidate mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any of the recurrent mutations that have been observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we developed a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a carefully curated set of recurrent mutations identified within a dataset of over 23,000 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent SARS-CoV-2 mutations currently in circulation appear to be evolutionary neutral. Recurrent mutations also seem primarily induced by the human immune system via host RNA editing, rather than being signatures of adaption to the novel human host. We find no evidence at this stage for the emergence of more transmissible lineages of SARS-CoV-2 due to recurrent mutations.

Title: Replication of SARS-CoV-2 in human respiratory epithelium. Content: Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there are also a plethora of animal coronaviruses, which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002 SARS-CoV emerged, to rapidly disappear in May 2003. In 2012 MERS-CoV was identified as a possible threat to humans, but its pandemic potential so far is minimal, as the human-to-human transmission is ineffective. The end of 2019 brought us information about the SARS-CoV-2 emergence, and the virus rapidly spread in 2020 causing an unprecedented pandemic.At present, the studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for the understanding of virus biology and evolution.Here we show that fully differentiated human airway epithelium cultures constitute an excellent model to study the infection with the novel human coronavirus SARS-CoV-2. We observed an efficient replication of the virus in the tissue, with the maximal replication at 2 days post-infection. The virus replicated in ciliated cells and was released apically.IMPORTANCE SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2.

Title: Replication of SARS-CoV-2 in human respiratory epithelium Content: Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there are also a plethora of animal coronaviruses, which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002 SARS-CoV emerged, to rapidly disappear in May 2003. In 2012 MERS-CoV was identified as a possible threat to humans, but its pandemic potential so far is minimal, as the human-to-human transmission is ineffective. The end of 2019 brought us information about the SARS-CoV-2 emergence, and the virus rapidly spread in 2020 causing an unprecedented pandemic.At present, the studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for the understanding of virus biology and evolution.Here we show that fully differentiated human airway epithelium cultures constitute an excellent model to study the infection with the novel human coronavirus SARS-CoV-2. We observed an efficient replication of the virus in the tissue, with the maximal replication at 2 days post-infection. The virus replicated in ciliated cells and was released apically.IMPORTANCE SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2.

Title: Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models Content: Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized replication competent SARS-CoV-2 with exceptional potency as measured by two different assays. There was no enhancement of pseudovirus infection in cells expressing Fcγ receptors at any concentration. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 potently neutralized mouse ACE2 adapted SARS-CoV-2 in wild type BALB/c mice and native virus in hACE2 expressing transgenic mice. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.

Title: [What is the origin of SARS-CoV-2?] Content: Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.

Title: Enfermedad pulmonar obstructiva crónica e infección por SARS-CoV-2. ¿Qué sabemos hasta ahora?/ Enfermedad pulmonar obstructiva crónica e infección por SARS-CoV-2. ¿Qué sabemos hasta ahora?/ Chronic Obstructive Pulmonary Disease and SARS-CoV-2 Infection. What Do We Know so Far? Content:

Title: Extrapulmonary Manifestations of SARS-CoV-2: A Brief Review Content: On December 30, 2019, the first reports of a group of patients with unknown etiology pneumonia appeared in Wuhan city, Hubei province, China Taking into consideration the large amount of similar nucleotide sequences between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the past epidemic coronavirus, it will be appropriate to expect that such pathogens share the same cell line tropism and systemic pathology Although several studies have, so far, identified the clinical characteristics of COVID-19 cases, there is very little knowledge on the extrapulmonary affection of SARS-CoV-2 In this review, we summarize reports of the main affected organs besides the pulmonary system such as the liver and kidneys, as well as the cardiovascular and nervous system The mechanisms of lesion remain largely unclear The approach of this investigation is to suggest multisystemic work-up in patients with SARS-CoV-2 infection, aside from its respiratory management Correspondence to: María Fernanda Osorio Pesantes, MD, School of Medicine, Universidad Espíritu Santo-Ecuador, Av Samborondón S/N, Guayaquil 092301, Ecuador E-mail: maferosorio@uees edu ec The authors have no funding or conflicts of interest to disclose Author Statement: M F O and R G V participated in writing the original draft, and review and editing This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections Copyright © 2020 Wolters Kluwer Health, Inc All rights reserved

Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: Background: This study’s aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. Methods: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, “What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?” Results: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. Conclusions: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.

Title: Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence? Content: BACKGROUND: This study's aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. METHODS: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, "What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?" RESULTS: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. CONCLUSIONS: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.

Title: Discharged COVID-19 Patients Testing Positive Again for SARS-CoV-2 RNA: A Minireview of Published Studies from China Content: In the ongoing COVID-19 pandemic, one potential cause of concern is that some discharged COVID-19 patients are testing positive again for SARS-CoV-2 RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS-CoV-2 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive RT-PCR test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including for example, fecal specimens, from COVID-19 patients before and after they are discharged from hospitals. This article is protected by copyright. All rights reserved.

Title: Discharged COVID‐19 Patients Testing Positive Again for SARS‐CoV‐2 RNA: A Minireview of Published Studies from China Content: In the ongoing COVID‐19 pandemic, one potential cause of concern is that some discharged COVID‐19 patients are testing positive again for SARS‐CoV‐2 RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS‐CoV‐2 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive RT‐PCR test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including for example, fecal specimens, from COVID‐19 patients before and after they are discharged from hospitals. This article is protected by copyright. All rights reserved.

Title: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19) Content: Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays.

Title: Current laboratory diagnostics of coronavirus disease 2019 (COVID-19). Content: Laboratory medicine provides an almost irreplaceable contribution to the diagnostic reasoning and managed care of most human pathologies. The novel coronavirus disease 2019 (COVID-19) is not an exception to this paradigm. Although the relatively recent emergence does not allow to draw definitive conclusions on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics, some standpoints can be conveyed. First and foremost, it seems now clear that we will be living together with this virus for quite a long time, so that our vigilance and responsiveness against the emergence of new local outbreaks shall be maintained at the highest possible levels. The etiological diagnosis of COVID-19 is, and will remain for the foreseeable future, deeply based on direct identification of viral RNA by means of molecular biology techniques in biological materials, especially upper and lower respiratory tract specimens. Whether other materials, such as blood, urine, stools, saliva and throat washing, will become valid alternatives has not been unequivocally defined so far. As concerns serological testing, promising information can be garnered from preliminary investigations, showing that the vast majority of COVID-19 patients seem to develop a sustained immune response against the virus, characterized especially by emergence of anti-SARS-CoV-2 IgG and IgA, 1 to 2 weeks after the onset of fever and/or respiratory symptoms. Whether these antibodies will have persistent neutralizing activity against the virus is still to be elucidated on individual and general basis. The availability of rapid tests for detecting either viral antigens or anti-SARS-CoV-2 antibodies are a potentially viable opportunity for purposes of epidemiologic surveillance, though more information is needed on accuracy and reliability of these portable immunoassays.

Title: Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not? Content: Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic

Title: Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not Content: Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.

Title: On the sensitivity of non-pharmaceutical intervention models for SARS-CoV-2 spread estimation Content: Introduction: A series of modelling reports that quantify the effect of non pharmaceutical interventions (NPIs) on the spread of the SARS-CoV-2 virus have been made available prior to external scientific peer-review. The aim of this study was to investigate the method used by the Imperial College COVID-19 Research Team (ICCRT) for estimation of NPI effects from the system theoretical viewpoint of model identifiability. Methods: An input-sensitivity analysis was performed by running the original software code of the systems model that was devised to estimate the impact of NPIs on the reproduction number of the SARS-CoV-2 infection and presented online by ICCRT in Report 13 on March 30 2020. An empirical investigation was complemented by an analysis of practical parameter identifiability, using an estimation theoretical framework. Results: Despite being simplistic with few free parameters, the system model was found to suffer from severe input sensitivities. Our analysis indicated that the model lacks practical parameter identifiability from data. The analysis also showed that this limitation is fundamental, and not something readily resolved should the model be driven with data of higher reliability. Discussion: Reports based on system models have been instrumental to policymaking during the SARS-CoV-2 pandemic. With much at stake during all phases of a pandemic, we conclude that it is crucial to thoroughly scrutinise any SARS-CoV-2 effect analysis or prediction model prior to considering its use as decision support in policymaking. The enclosed example illustrates what such a review might reveal.

Title: Treatment and research lines for the patient with COVID-19. What do we have and where are we going? Content: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the most significant global public health crisis of this generation. From the beginning of the pandemic, several publications and on-line resources about different treatment lines have been done, and development effort in response to the COVID-19 pandemic to investigate potential therapies is unprecedented. Unfortunately, until now, there is not enough evidence to recommend any specific anti-COVID19 treatment. Randomized clinical trials and high-quality evidence, even in the middle of a pandemic, are needed. We provide a review of the latest published literature on the therapeutic strategies and current investigational lines for SARS-CoV-2.

Title: Why does Japan have so few cases of COVID-19? Content: The COVID-19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS-CoV-2 infections.

Title: An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies Content: Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to nearly 190 countries. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood lab profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.

Title: An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies Content: Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to more than 200 countries or territories. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood laboratory profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.

Title: Biological Warfare: Infectious Disease and Bioterrorism Content: The term biological warfare typically conjures images of medieval warriors tossing dead cattle over city walls or clandestine government agents secretly releasing mysterious microbes into enemy territory. Of course, biological warfare does encompass such activity, but the vast majority of what constitutes biological warfare is far more mundane. Ever since life evolved on earth about 3.8 billion years ago, organisms have constantly devised new ways to kill each other. Any organism that makes use of toxins—from bacteria to snakes—is engaging in a form of biological warfare. Humans who engage in biological warfare do so by taking advantage of these toxin-producing organisms.

Title: COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Content: A severe outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019, and spread so rapidly that more than 200,000 cases have so far been reported worldwide; on January 30, 2020, the WHO declared it the sixth public health emergency of international concern. The two previously reported coronavirus epidemics (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) share similar pathogenetic, epidemiological and clinical features as COVID-19. As little is currently known about SARS-CoV-2, it is likely that lessons learned from these major epidemics can be applied to the new pandemic, including the use of novel immunosuppressive drugs.

Title: Why does the coronavirus spread so easily between people? Content: As the number of coronavirus infections approaches 100,000 people worldwide, researchers are racing to understand what makes it spread so easily A handful of genetic and structural analyses have identified a key feature of the virus — a protein on its surface — that might explain why it infects human cells so readily Other groups are investigating the doorway through which the new coronavirus enters human tissues — a receptor on cell membranes Both the cell receptor and the virus protein offer potential targets for drugs to block the pathogen, but researchers say it is too early to be sure “Understanding transmission of the virus is key to its containment and future prevention,” says David Veesler, a structural virologist at the University of Washington in Seattle, who posted his team’s findings about the virus protein on the biomedical preprint server bioRxiv on 20 February1 The new virus spreads much more readily than the one that caused severe acute respiratory syndrome, or SARS (also a coronavirus), and has infected more than ten times the number of people who contracted SARS

Title: What we know so far: COVID-19 current clinical knowledge and research Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.

Title: What we know so far: COVID-19 current clinical knowledge and research. Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.

Title: Why does Japan have so few cases of COVID‐19? Content: The COVID‐19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS‐CoV‐2 infections.[Image: see text]

Title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results Content: Testing for RNA viruses such as SARS-CoV-2 requires careful handling of inherently labile RNA during sample collection, clinical processing, and molecular analysis. Tests must include fail-safe controls that affirmatively report the presence of intact RNA and demonstrate success of all steps of the assay. A result of “no virus signal” is insufficient for clinical interpretation: controls must also say “The reaction worked as intended and would have found virus if present.” Unfortunately, a widely used test specified by the US Centers for Disease Control and Prevention (CDC) incorporates a control that does not perform as intended and claimed. Detecting SARS-CoV-2 with this assay requires both intact RNA and successful reverse transcription. The CDC-specified control does not require either of these, due to its inability to differentiate human genomic DNA from reverse-transcribed RNA. Patient DNA is copurified from nasopharyngeal swabs during clinically-approved RNA extraction and is sufficient to return an “extraction control success” signal using the CDC design. As such, this assay fails-unsafe: truly positive patient samples return a false-negative result of “no virus detected, control succeeded” following any of several readily-encountered mishaps. This problem affects tens-of-millions of patients worth of shipped assays, but many of these flawed reagents have not yet been used. There is an opportunity to improve this important diagnostic tool. As demonstrated here, a re-designed transcript-specific control correctly monitors sample collection, extraction, reverse transcription, and qPCR detection. This approach can be rapidly implemented and will help reduce truly positive patients from being incorrectly given the all-clear. One Sentence Summary A widely-used COVID-19 diagnostic is mis-designed and generates false-negative results, dangerously confusing “No” with “Don’t know” – but it’s fixable

Title: Sars-CoV-2: A clinical update - II Content: INTRODUCTION: A covid-19 pandemic decreed by WHO has raised greater awareness of it EPIDEMIOLOGY: The infection, reached the mark of 2,000,000 patients in 33 countries and caused the risk of the presence of comorbidities and advanced age TRANSMISSIBILITY: The transmissibility calculated so far is similar to the H1N1 epidemic, but with lower mortality rates PHYSIOPATHOLOGY: The SARS-CoV-2 virus, of the Coronaviridae family, has the capacity for cellular invasion through the angiotensin-converting enzyme 2 does not have a lower respiratory epithelium and in the cells of the small intestine mucosa CLINICAL MANIFESTATIONS: a presentation can be divided into mild (fever, fatigue, cough, myalgia, and sputum) and severe (cyanosis, dyspnoea, tachypnea, chest pain, hypoxemia and need for clinical measurement) and has an estimated estimate of 2% DIAGNOSIS: allows the detection of viral load in CRP-TR of patients with high clinical suspicion TREATMENT: based on supportive measures and infection control In severe cases, the use of medications such as hydroxychloroquine and azithromycin or medication can be promising Take care to avoid the use of corticosteroids There are no restrictions on the use of resources and IECAs / BRAs

Title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done? Content: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.

Title: What we know so far: COVID-19 current clinical knowledge and research Content: In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features , Copyright Notice (C) 2020 Royal College of Physicians

Title: Dermatologists and SARS‐CoV‐2: The impact of the pandemic on daily practice Content: Since the first case of “pneumonia of unknown aetiology” was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognised thereafter as “severe acute respiratory syndrome coronavirus 2” (SARS‐CoV‐2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease‐19 (COVID‐ 19) and satisfying the epidemiological criteria for a label of “pandemic.” The ongoing SARS‐CoV‐2 pandemic is having a huge impact on dermatological practice including the marked reduction of face‐to‐face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID‐19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID‐19 care for patients assistance and new research needs to be addressed. It is not known yet, if skin lesions and derangement of the skin barrier could make it easier for SARS‐CoV‐2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS‐CoV‐2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS‐CoV‐2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID‐19 disaster. Learning from experience may help to cope with future major societal changes.

Title: Dermatologists and SARS-CoV-2: the impact of the pandemic on daily practice Content: Since the first case of 'pneumonia of unknown aetiology' was diagnosed at the Wuhan Jinyintan Hospital in China on 30 December 2019, what was recognized thereafter as 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2) has spread over the four continents, causing the respiratory manifestations of coronavirus disease-19 (COVID-19) and satisfying the epidemiological criteria for a label of 'pandemic'. The ongoing SARS-CoV-2 pandemic is having a huge impact on dermatological practice including the marked reduction of face-to-face consultations in favour of teledermatology, the uncertainties concerning the outcome of COVID-19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in COVID-19 care for patient assistance and new research needs to be addressed. It is not known yet if skin lesions and derangement of the skin barrier could make it easier for SARS-CoV-2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with SARS-CoV-2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. SARS-CoV-2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. The consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the COVID-19 disaster. Learning from experience may help to cope with future major societal changes.

Title: COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions Content: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.

Title: On the evolutionary epidemiology of SARS-CoV-2 Content: There is no doubt that the novel coronavirus SARS-CoV-2 that causes COVID-19 is mutating and thus has the potential to adapt during the current pandemic. Whether this evolution will lead to changes in the transmission, the duration, or the severity of the disease is not clear. This has led to considerable scientific and media debate, from raising alarms about evolutionary change to dismissing it. Here we review what little is currently known about the evolution of SARS-CoV-2 and extend existing evolutionary theory to consider how selection might be acting upon the virus during the COVID-19 pandemic. While there is currently no definitive evidence that SARS-CoV-2 is undergoing further adaptation, continued, evidence-based, analysis of evolutionary change is important so that public health measures can be adjusted in response to substantive changes in the infectivity or severity of COVID-19.

Title: Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes Content: COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.

Title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing Content: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 Mpro for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 Mpro active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 Mpro protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.

Title: In silico prediction of potential inhibitors for the Main protease of SARS-CoV-2 using molecular docking and dynamics simulation based drug-repurposing Content: BACKGROUND: The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 M(pro) (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding. METHODS: For the study, we have targeted the SARS-CoV-2 M(pro) for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 M(pro) active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries. RESULTS: The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 M(pro) protein. CONCLUSIONS: In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.

Title: Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. Content: UNLABELLED Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2. IMPORTANCE The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.

Title: Fight against novel coronavirus: A perspective of medicinal chemists Content: The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents.

Title: INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA Content: SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.

Title: INFECTIONS IN PREGNANCY WITH COVID-19 AND OTHER RESPIRATORY RNA VIRUS DISEASES ARE RARELY, IF EVER, TRANSMITTED TO THE FETUS: EXPERIENCES WITH CORONAVIRUSES, HPIV, hMPV RSV, AND INFLUENZA. Content: SARS-CoV-2, the agent of COVID-19, is similar to two other coronaviruses, SARS-CoV and MERS-CoV, in causing life-threatening maternal respiratory infections and systemic complications. Because of global concern for potential intrauterine transmission of SARS-CoV-2 from pregnant women to their infants, this report analyzes the effects on pregnancy of infections caused by SARS-CoV-2 and other respiratory RNA viruses, and examines the frequency of maternal-fetal transmission with SARS-CoV-2, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, respiratory syncytial virus (RSV), parainfluenza (HPIV) and metapneumovirus (hMPV). There have been no confirmed cases of intrauterine transmission reported with COVID-19 or any other coronavirus infections. Influenza virus, despite causing approximately one billion annual infections globally, has only a few cases of confirmed or suspected intrauterine fetal infections reported. RSV is in an unusual cause of illness among pregnant women, and with the exception of one premature infant with congenital pneumonia, no other cases of maternal-fetal infection are described. Parainfluenza virus and human metapneumovirus can produce symptomatic maternal infections but do not cause intrauterine fetal infection. In summary, it appears that the absence thus far of maternal-fetal transmission of the SARS-CoV-2 virus during the COVID-19 pandemic is similar to other coronaviruses, and is also consistent with the extreme rarity of suggested or confirmed cases of intrauterine transmission of other respiratory RNA viruses. This observation has important consequences for pregnant women as it appears that if intrauterine transmission of SARSCoV-2 does eventually occur, it will be a rare event. Potential mechanisms of fetal protection from maternal viral infections are also discussed.

Title: Potential for elimination of SAR-CoV-2 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination Content: The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, future vaccination against COVID-19 may fall into long-term costly guerrilla warfare between SARS-CoV-2 and humans. Elimination of SARS-CoV-2 through vaccination to avoid the potential long-term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to the elimination of three human influenza viruses, which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggest that the rapid establishment of global herd immunity through mass vaccination using an appropriate vaccine could eliminate SARS-CoV-2. The coming 2 years are a golden time for elimination through vaccination, which requires tremendous national and international collaboration. This review also prioritizes the efficacy of vaccines for COVID-19 and elucidates the importance of the development of more live vaccines for COVID-19.

Title: Novel coronavirus SARS-CoV-2 and COVID-19. Practice recommendations for obstetric anaesthesia: what we have learned thus far Content: • Pregnancy does not seem to be associated with more severe COVID-19 infections. • Risk of antenatal vertical transmission of COVID-19 is low. • Epidural analgesia should be considered, provided platelet counts are not low. • Droplet precautions are indicated for all women with suspected COVID-19. • Airborne precautions recommended for general anaesthesia or higher risk thereof.

Title: SARS-CoV-2 from faeces to wastewater treatment: What do we know? A review Content: SARS-CoV-2, the virus that causes COVID-19, has been found in the faeces of infected patients in numerous studies. Stool may remain positive for SARS-CoV-2, even when the respiratory tract becomes negative, and the interaction with the gastrointestinal tract poses a series of questions about wastewater and its treatments. This review aims to understand the viral load of SARS-CoV-2 in faeces and sewage and its fate in wastewater treatment plants (WWTPs). The viral load in the faeces of persons testing positive for SARS-CoV-2 was estimated at between 5·103 to 107.6 copies/mL, depending on the infection course. In the sewerage, faeces undergo dilution and viral load decreases considerably in the wastewater entering a WWTP with a range from 2 copies/100 mL to 3·103 copies/mL, depending on the level of the epidemic. Monitoring of SARS-CoV-2 in sewage, although no evidence of COVID-19 transmission has been found via this route, could be advantageously exploited as an early warning of outbreaks. Preliminary studies on WBE seem promising; but high uncertainty of viral loads in wastewater and faeces remains, and further research is needed. The detection of SARS-CoV-2 in sewage, based on RNA sequences and RT-PCR, requires a shared approach on sample pre-treatment and on-site collection to ensure comparable results. The finding of viral RNA in stools does not imply that the virus is viable and infectious. Viability of CoVs such as SARS-CoV-2 decreases in wastewater - due to temperature, pH, solids, micropollutants - but high inactivation in WWTPs can be obtained only by using disinfection (free chlorine, UVC light). A reduction in the quantity of disinfectants can be obtained by implementing Membrane-Bioreactors with ultrafiltration to separate SARS-CoV-2 virions with a size of 60-140 nm. In sludge treatment, thermophilic digestion is effective, based on the general consensus that CoVs are highly sensitive to increased temperatures.

Title: SARS-CoV-2 from faeces to wastewater treatment: What do we know? A review Content: Abstract SARS-CoV-2, the virus that causes COVID-19, has been found in the faeces of infected patients in numerous studies. Stool may remain positive for SARS-CoV-2, even when the respiratory tract becomes negative, and the interaction with the gastrointestinal tract poses a series of questions about wastewater and its treatments. This review aims to understand the viral load of SARS-CoV-2 in faeces and sewage and its fate in wastewater treatment plants (WWTPs). The viral load in the faeces of persons testing positive for SARS-CoV-2 was estimated at between 5·103 to 107.6 copies/mL, depending on the infection course. In the sewerage, faeces undergo dilution and viral load decreases considerably in the wastewater entering a WWTP with a range from 2 copies/100 mL to 3·103 copies/mL, depending on the level of the epidemic. Monitoring of SARS-CoV-2 in sewage, although no evidence of COVID-19 transmission has been found via this route, could be advantageously exploited as an early warning of outbreaks. Preliminary studies on WBE seem promising; but high uncertainty of viral loads in wastewater and faeces remains, and further research is needed. The detection of SARS-CoV-2 in sewage, based on RNA sequences and RT-PCR, requires a shared approach on sample pre-treatment and on-site collection to ensure comparable results. The finding of viral RNA in stools does not imply that the virus is viable and infectious. Viability of CoVs such as SARS-CoV-2 decreases in wastewater - due to temperature, pH, solids, micropollutants - but high inactivation in WWTPs can be obtained only by using disinfection (free chlorine, UVC light). A reduction in the quantity of disinfectants can be obtained by implementing Membrane-Bioreactors with ultrafiltration to separate SARS-CoV-2 virions with a size of 60–140 nm. In sludge treatment, thermophilic digestion is effective, based on the general consensus that CoVs are highly sensitive to increased temperatures.

Title: Potential for elimination of SAR‐CoV‐2 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination Content: The ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by the novel virus SARS‐CoV‐2 has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, the future vaccination against COVID‐19 may fall into long‐term costly guerrilla warfare between SARS‐CoV‐2 and humans. Elimination of SARS‐CoV‐2 through vaccination to avoid the potential long‐term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to elimination of three human influenza viruses which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggested that rapid establishment of global herd immunity through mass vaccination using a proper vaccine could eliminate SARS‐CoV‐2. The coming two years is the golden time for the elimination through vaccination which requires tremendous national and international collaboration. This review also prioritized the efficacy of vaccines for COVID‐19 and elucidated the importance for development of more live vaccines for COVID‐19. This article is protected by copyright. All rights reserved.

Title: Epidemiological and clinical features of asymptomatic patients with SARS‐CoV‐2 infection Content: Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS‐CoV‐2 without any symptoms. Patients with confirmed SARS‐CoV‐2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS‐CoV‐2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS‐CoV‐2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0‐15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS‐CoV‐2 in throat swabs, while one patient was only tested positive for SARS‐CoV‐2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS‐CoV‐2 tested negative from admission was 7.0 days (IQR: 4.0‐9.0 days). Patients without any symptoms but with SARS‐CoV‐2 exposure should be closely monitored and tested for SARS‐CoV‐2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS‐CoV‐2 have favorable outcomes.

Title: Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection Content: Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.

Title: Neurological Insights of COVID-19 Pandemic Content: The novel coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The virus is unlike its previous counterparts, SARS-CoV and MERS-CoV, or anything the world has encountered before both in terms of virulence and severity of the infection. If scientific reports relevant to the SARS-CoV-2 virus are noted, it can be seen that the virus owes much of its killer properties to its unique structure that has a stronger binding affinity with the human angiotensin-converting enzyme 2 (hACE2) protein, which the viruses utilize as an entry point to gain accesses to its hosts. Recent reports suggest that it is not just the lung that the virus may be targeting; the human brain may soon emerge as the new abode of the virus. Already instances of patients with COVID-19 have been reported with mild (anosmia and ageusia) to severe (encephalopathy) neurological manifestations, and if that is so, then it gives us more reasons to be frightened of this killer virus. Keeping in mind that the situation does not worsen from here, immediate awareness and more thorough research regarding the neuroinvasive nature of the virus is the immediate need of the hour. Scientists globally also need to up their game to design more specific therapeutic strategies with the available information to counteract the pandemic. In this Viewpoint, we provide a brief outline of the currently known neurological manifestations of COVID-19 and discuss some probable ways to design therapeutic strategies to overcome the present global crisis.

Title: Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis. Content: Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host's antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests,this could drive researchers to find effective treatments against the virus.

Title: COVID-19 and the Cerebro-Cardiovascular Systems: What do we Know so Far? Content: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of 2019-2020 has resulted in multiple hospitalizations, deaths and economic hardships worldwide. Though respiratory involvement in patients with coronavirus disease 2019 (COVID-19) is well-known, the potential cardiovascular and cerebrovascular manifestations are less-understood. We performed a PubMed and Google Scholar search and reviewed relevant literature regarding COVID-19 and cardiovascular system involvement. SARS-CoV-2 possesses high-affinity for angiotensin converting enzyme 2 (ACE2) receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID-19 cases. Pre-existing cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk-factor for severe infection. Based on our review of published studies, COVID-19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects and acute stroke and are likely to have poorer outcomes as a result. As the COVID-19 pandemic continues, more data regarding potential cardiovascular and cerebrovascular manifestations of the disease is required.

Title: SARS‐CoV‐2: What do we know so far? Content: We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia. Older patients and patients with underlying comorbidities are at a higher risk of death. We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia.

Title: Acute Coronary Syndromes and Covid-19: Exploring the Uncertainties. Content: Since an association between myocardial infarction (MI) and respiratory infections has been described for influenza viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. The initial data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss the pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; and learnings that have emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.