title: High speed large scale automated isolation of SARS-CoV-2 from clinical samples using miniaturized co-culture coupled with high content screening

text: SARS-CoV-2, a novel coronavirus infecting humans, is responsible for the current COVID-19 global pandemic. If several strains could be isolated worldwide, especially for in-vitro drug susceptibility testing and vaccine development, few laboratories routinely isolate SARS-CoV-2. This is due to the fact that the current co-culture strategy is highly time consuming and requires working in a biosafety level 3 laboratory. In this work, we present a new strategy based on high content screening automated microscopy (HCS) allowing large scale isolation of SARS-CoV-2 from clinical samples in 1 week. A randomized panel of 104 samples, including 72 tested positive by RT-PCR and 32 tested negative, were processed with our HCS procedure and were compared to the classical isolation procedure. Isolation rate was 43 % with both strategies on RT-PCR positive samples, and was correlated with the initial RNA viral load in the samples, where we obtained a positivity threshold of 27 Ct. Co-culture delays were shorter with HCS strategy, where 80 % of the positive samples were recovered by the third day of co-culture, as compared to only 25 % with the classic strategy. Moreover, only the HCS strategy allowed us to recover all the positive elements after 1 week of co-culture. This system allows rapid and automated screening of clinical samples with minimal operator work load, thus reducing the risks of contamination.


title: Limited SARS-CoV-2 diversity within hosts and following passage in cell culture

text: Since the first reports of pneumonia associated with a novel coronavirus (COVID-19) emerged in Wuhan, Hubei province, China, there have been considerable efforts to sequence the causative virus, SARS-CoV-2 (also referred to as hCoV-19) and to make viral genomic information available quickly on shared repositories. As of 30 March 2020, 7,680 consensus sequences have been shared on GISAID, the principal repository for SARS-CoV-2 genetic information. These sequences are primarily consensus sequences from clinical and passaged samples, but few reports have looked at diversity of virus populations within individual hosts or cultures. Understanding such diversity is essential to understanding viral evolutionary dynamics. Here, we characterize within-host viral diversity from a primary isolate and passaged samples, all originally deriving from an individual returning from Wuhan, China, who was diagnosed with COVID-19 and subsequently sampled in Wisconsin, United States. We use a metagenomic approach with Oxford Nanopore Technologies (ONT) GridION in combination with Illumina MiSeq to capture minor within-host frequency variants ≥1%. In a clinical swab obtained from the day of hospital presentation, we identify 15 single nucleotide variants (SNVs) ≥1% frequency, primarily located in the largest gene – ORF1a. While viral diversity is low overall, the dominant genetic signatures are likely secondary to population size changes, with some evidence for mild purifying selection throughout the genome. We see little to no evidence for positive selection or ongoing adaptation of SARS-CoV-2 within cell culture or in the primary isolate evaluated in this study. Author Summary Within-host variants are critical for addressing molecular evolution questions, identifying selective pressures imposed by vaccine-induced immunity and antiviral therapeutics, and characterizing interhost dynamics, including the stringency and character of transmission bottlenecks. Here, we sequenced SARS-CoV-2 viruses isolated from a human host and from cell culture on three distinct Vero cell lines using Illumina and ONT technologies. We show that SARS-CoV-2 consensus sequences can remain stable through at least two serial passages on Vero 76 cells, suggesting SARS-CoV-2 can be propagated in cell culture in preparation for in-vitro and in-vivo studies without dramatic alterations of its genotype. However, we emphasize the need to deep-sequence viral stocks prior to use in experiments to characterize sub-consensus diversity that may alter outcomes.


title: Potential involvement of monoamine oxidase activity in SARS-COV2 infection and delirium onset

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of extra-respiratory signs and symptoms. One such manifestation is delirium, an acute confusional state occurring in 60-70% of severe SARS-CoV-2 cases. Delirium is also a common clinical syndrome following planned orthopedic surgery. This investigation initially explored the underlying role of metabolism in delirium-susceptibility in this setting. Metabolomics profiles of cerebrospinal fluid (CSF) and blood taken prior to surgery found significant concentration differences of several amino acids, acylcarnitines and polyamines were observed in delirium-prone patients. Phenethylamine (PEA) concentrations in delirium-prone patients was significantly lower in CSF than in blood, whilst in age- and gender-matched controls the opposite was observed (adjusted p values: 1.8x10-6 (control) and 1.788x10-10 (delirium)). PEA is metabolised by monoamine oxidase B (MAOB), a putative enzyme target for the treatment of Alzheimers disease, Parkinsons disease and depression. Our computational structural comparisons of MAOB and angiotensin converting enzyme (ACE) 2 found high similarity, specifically within the SARS-CoV-2 spike protein. MAOB structural alignment to ACE2 was 51% overall, but this was over 95% in the ACE2-spike protein binding region. Thus, it is possible that the spike protein interacts with MAOB on a molecular level. A previously published metabolomic dataset of control subjects and patients with either mild or severe COVID-19 was then analysed. Major concentration differences in some metabolites attributed to altered MAO activity were detected. Therefore, our hypothesis is that the SARS-CoV-2 influences MAOB activity, which is one potential cause for the many observed neurological and platelet based complications of SARS-CoV-2 infection.


title: Communal News Work: COVID-19 Calls for Collective Funding of Journalism

text: It is widely held that journalism, journalists and news all play important roles for democracy and an informed citizenry. News publishers have journalistic authority and are oftentimes seen as one of the most important knowledge-producing institutions in society, routinely carrying out epistemic practices that strive towards producing verified and reliable news about public affairs. The COVID-19 pandemic has forcefully reminded us about this vital information function of the news media, with a surge in traffic to mobile applications and news sites around the world. Unfortunately, the COVID-19 pandemic is simultaneously crushing the advertising business that plays such a vital role in funding news production. This commentary argues that many journalistic institutions - particularly on the local level - currently face an existential crisis, one that calls for immediate and collective action. With a normative desire of saving journalism, we put forward that society should engage in what we refer to as communal news work as an attempt to financially sustain journalism during the COVID-19 pandemic crisis and well into the future.


title: Citywide Nucleic Acid Screening of SARS-CoV-2 Infections in Post-lockdown Wuhan, China: Results and Implications

text: Background: After the outbreak of Coronavirus disease in 2019 (COVID-19), stringent lockdown measures were imposed in Wuhan between January 23, 2020 and April 8, 2020. To provide evidence on the post-lockdown risk of COVID-19 epidemic in Wuhan, the city government conducted a citywide nucleic acid screening of SARS-CoV-2 infection between May 14 and June 1, 2020. Methods: All city residents aged [≥]6 years were potentially eligible to participate the screening programme. The rate of detection of asymptomatic infected cases was calculated, and their demographic and geographic distributions were investigated. ArcGIS 10.0 was used to draw a geographic distribution of asymptomatic infected persons. Results: The screening programme recruited a total of 9,899,828 persons (response rate, 92.9%). The screening found no newly confirmed patients with COVID-19, and identified 300 asymptomatic infected cases (detection rate 0.303/10,000). In addition, 107 of 34,424 previously recovered patients with a history of COVID-19 diagnosis were tested positive (relapse rate, 0.31%). Virus culture of SARS-CoV-2 was negative for all 300 asymptomatic cases and all 107 recovered COVID-19 patients. A total of 1,174 close contacts of asymptomatic cases were traced and all of them had a negative nucleic acid testing result. Conclusions: Prevalence of COVID-19 nucleic acid test positivity was very low in the Wuhan general population, in recovered cases and in contacts of asymptomatic cases, five to eight weeks after the end of lockdown. These findings help resolve concerns about the post-lockdown risk of COVID-19 epidemic, and promote the recovery of economy and normal social life in Wuhan.


title: Tracing two causative SNPs reveals SARS-CoV-2 transmission in North America population

text: During the COVID-19 pandemic, precisely tracing the route of the SARS-CoV-2 transmission in human population remains challenging. Because this RNA virus can mutate massively without a specifically tracing maker. Herein, using a geographic stratified genome-wide association study (GWAS) of 2599 full-genome sequences, we identified that two SNPs (i.e., 1059.C>T and 25563.G>T) of linkage disequilibrium were presented in approximately half of North America SARS-CoV-2 population (p = 2.44 x 10−212 and p = 2.98 x 10−261), resulting two missense mutations (i.e., Thr 265 Ile and Gln 57 His) in ORF1ab and ORF3a, respectively. Interestingly, these two SNPs exclusively occurred in the North America dominated clade 1, accumulated during mid to late March, 2020. We did not find any of these two SNPs by retrospectively tracing the two SNPs in bat and pangolin related SARS-CoV-2 and human SARS-CoV-2 from the first epicenter Wuhan or other regions of China mainland. This suggested that the SARS-CoV-2 population of Chinese mainland were different from the prevalent strains of North America. Time-dependently, we found that these two SNPs first occurred in Europe SARS-CoV-2 (26-Feb-2020) which was 3 days early than the occurring date of North America isolates and 17 days early for Asia isolates (Taiwan China dominated). Collectively, this population genetic analysis highlights a well-confidential transmission route of the North America isolates and the two SNPs we newly identified are possibly novel diagnosable or druggable targets for surveillance and treatment.


title: Entrepreneurship as the unsung hero during the current COVID-19 economic crisis: Australian perspectives

text: The COVID-19 pandemic has not only had a significant and catastrophic effect on business and economies globally, but has identified the external and internal enablement of new venture creation. This paper aims to provide entrepreneurship insights, implementations and dynamics to demonstrate the role of entrepreneurship in times of such adversity within an Australian context. We provide emergent enquiry narratives from leading Australian scholars, identifying entrepreneurial initiatives as a catalyst to new venture creation and growth. Narratives include insights associated with the entrepreneurial mindset, the multidimensional effects of resilience and entrepreneurship, entrepreneurship education, entrepreneurship enablers and the entrepreneurial ecosystem. Opportunities for further research are identified, particularly regarding context and empirical outcomes. We postulate that entrepreneurship may well be the unsung hero during the current COVID-19 economic crisis.


title: Temperature, humidity, and wind speed are associated with lower Covid-19 incidence

text: In absence of empirical research data, there has been considerable speculative hypothesis on the relationship between climatic factors (such as temperature and humidity) and the incidence of Covid-19. This study analyzed the data from 310 regions across 116 countries that reported confirmed cases of Covid-19 by March 12, 2020, and found that temperature, humidity, and wind speed were inversely associated with the incidence rate of Covid-19 after adjusting for the regional and temporal trend in the incidence of Covid-19, columnar density of ozone, precipitation probability, sea-level air-pressure, and length of daytime.


title: The race to find a SARS-CoV-2 drug can only be won by a few chosen drugs: a systematic review of registers of clinical trials of drugs aimed at preventing or treating COVID-19

text: Considering the massive amount of clinical trial registers aimed to find effective drugs for the prevention and treatment of COVID-19, it is challenging to have a comprehensive view of which drugs are being studied more extensively and when is expected that we will have consistent results regarding their effectiveness. This systematic review included all clinical trials on pharmacological therapy related to COVID-19 and SARS-CoV-2 registered at the International Clinical Trials Registry Platform (WHO-ICTRP) up to April 22, 2020. Clinical trials characteristics (country, design, sample size, main outcomes, expected completion data, type of participants, length of the interventions, main outcomes). How many trials and he accumulated sample size by drug or combination of drugs, and by month in 2020 was depicted. We identified 412 clinical trials registers addressing the effect of pharmacological treatments on COVID-19, predominantly from Asia and Europe (42.2% and 31.1% of clinical trials registers, respectively). The most main outcomes studied were clinical recovery (54.4% of the clinical trials registers, respiratory recovery (28.2%) mortality (27.4%), viral load/negativity (20.4%). During 2020, a huge amount of clinical trials are expected to be completed: 41 trials (60,366 participants) using hydroxychloroquine, 20 trials (1,588 participants) using plasma, 18 trials (6,830 participants) using chloroquine, 12 trials (9,938 participants using lopinavir/ritonavir, 11 trials (1,250 participants) using favipiravir, 10 trials ( 2,175 participants) using tocilizumab and 6 trials (13,540 participants) using Remdesivir. The distribution of the number of registered clinical trials among the different therapeutic options leads to an excess of sample size for some and a lack for others. Our data allow us to conclude that by the end of June we will have results of almost 20 trials involving 40000 patients for hydroxychloroquine and 5 trials with 4500 patients for remdesivir; however, low statistical power is expected from the 9 clinical trials testing the efficacy of favipiravir or the 5 testing tocilizumab, since they will recruit less than 1000 patients each one.


title: PROTECTIVE ANTIBODIES AGAINST HPIV3 INFECTION

text: Human parainfluenza virus type III (HPIV3) is a common respiratory pathogen that afflicts children and can be fatal in vulnerable populations, including the immunocompromised. Unfortunately, an effective vaccine or therapeutic is not currently available, resulting in tens of thousands of hospitalizations per year. In an effort to discover a protective antibody against HPIV3, we screened the B cell repertoires from peripheral blood, tonsils, or spleen from healthy children and adults. These analyses yielded five monoclonal antibodies that potently neutralized HPIV3 in vitro. These HPIV3 neutralizing antibodies targeted two non-overlapping epitopes of the HPIV3 F protein, with most targeting the apex. Importantly, prophylactic administration of one of these antibodies, named PI3-E12, resulted in potent protection against HPIV3 infection in cotton rats. Additionally, PI3-E12 could also be used therapeutically to suppress HPIV3 in immunocompromised animals. These results demonstrate the potential clinical utility of PI3-E12 for the prevention or treatment of HPIV3 in both immunocompetent and immunocompromised individuals.


title: MicrobioLink: An integrated computational pipeline to infer functional effects of microbiome-host interactions

text: Microbiome-host interactions play significant roles in health and in various diseases including auto-immune disorders. Uncovering these inter-kingdom cross-talks propels our understanding of disease pathogenesis, and provides useful leads on potential therapeutic targets. Despite the biological significance of microbe-host interactions, there is a big gap in understanding the downstream effects of these interactions on host processes. Computational methods are expected to fill this gap by generating, integrating and prioritizing predictions - as experimental detection remains challenging due to feasibility issues. Here, we present MicrobioLink, a computational pipeline to integrate predicted interactions between microbial and host proteins together with host molecular networks. Using the concept of network diffusion, MicrobioLink can analyse how microbial proteins in a certain context are influencing cellular processes by modulating gene or protein expression. We demonstrated the applicability of the pipeline using a case study. We used gut metaproteomic data from Crohn’s disease patients and healthy controls to uncover the mechanisms by which the microbial proteins can modulate host genes which belong to biological processes implicated in disease pathogenesis. MicrobioLink, which is agnostic of the microbial protein sources (bacterial, viral etc), is freely available on GitHub (https://github.com/korcsmarosgroup/HMIpipeline).


Coronavirus disease (COVID-19): The need to maintain regular physical activity while taking precautions


title: Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster

text: Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding. Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response. Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week. Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.


title: Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19

text: Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki's disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.


title: COVID-19 Pandemic Response Simulation: Impact of Non-pharmaceutical Interventions on Ending Lockdowns

text: As many federal and state governments are starting to ease restrictions on non-pharmaceutical interventions (NPIs) used to flatten the curve, we developed an agent-based simulation to model the incidence of COVID-19 in King County, WA under several scenarios. While NPIs were effective in flattening the curve, any relaxation of social distancing strategies yielded a second wave. Even if daily confirmed cases dropped to one digit, daily incidence can peak again to 874 cases without import cases. Therefore, policy makers should be very cautious in reopening society.


title: SARS-CoV-2 and Norovirus Co-Infection after Lung Transplantation

text: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading as a pandemic in 2020 Few reports on infections in thoracic transplantation have been published so far We present a case of COVID-19 in a 55-year old female lung transplant recipient infected 5 months posttransplant, who additionally was co-infected with a Norovirus Respiratory and gastrointestinal symptoms were observed without need of therapeutic escalation except for antibiotic therapy We observed a moderate disease evolution likely due to triple immunosuppression


title: Predicting COVID-19 malignant progression with AI techniques

text: Background: The coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since mid-December 2019, which greatly challenge public medical systems. With limited medical resources, it is a natural strategy, while adopted, to access the severity of patients then determine the treatment priority. However, our work observes the fact that the condition of many mild outpatients quickly worsens in a short time, i.e. deteriorate into severe/critical cases. Hence, it has been crucial to early identify those cases and give timely treatment for optimizing treatment strategy and reducing mortality. This study aims to establish an AI model to predict mild patients with potential malignant progression. Methods: A total of 133 consecutively mild COVID-19 patients at admission who was hospitalized in Wuhan Pulmonary Hospital from January 3 to February 13, 2020, were selected in this retrospective IRB-approved study. All mild patients at admission were categorized into groups with or without malignant progression. The clinical and laboratory data at admission, the first CT, and the follow-up CT at severe/critical stage of the two groups were compared with Chi-square test, Fisher's exact test, and t test. Both traditional logistic regression and deep learning-based methods were used to build the prediction models. The area under ROC curve (AUC) was used to evaluate the models. Results: The deep learning-based method significantly outperformed logistic regression (AUC 0.954 vs. 0.893). The deep learning-based method achieved a prediction AUC of 0.938 by combining the clinical data and the CT data, significantly outperforming its counterpart trained with clinical data only by 0.141. By further considering the temporal information of the CT sequence, our model achieved the best AUC of 0.954. The proposed model can be effectively used for finding out the mild patients who are easy to deteriorate into severe/critical cases, so that such patients get timely treatments while alleviating the limitations of medical resources.


title: A COVID-19 epidemic model integrating direct and fomite transmission as well as household structure

text: This paper stresses its base contribution on a new SIR-type model for COVID-19 including direct and fomite transmission as well as the effect of distinct household structures. To what extent increasing the physical-distancing-related contact radius and enhancing mass control (public curfew, lockdown, workplace clearance, and school closure) reduce the number of predicted active cases is studied via parameter estimation.


title: Where is Boris Johnson? When and why it matters that leaders show up in a crisis

text: Now, more than at any time in our recent history, we will be judged by our capacity for compassion. (Rishi Sunak, UK Chancellor of the Exchequer, 20 March 2020). 1In this piece, I draw on an ethics of care and compassion to address a question that has been asked almost daily in UK politics over the past weeks and months, namely: Where is Boris Johnson? Johnson is a leader with a long-standing reputation for being selective about whether and when he shows up. On 16 March 2020, as the severity of the coronavirus finally seemed to register, Johnson agreed to start holding daily press briefings, bringing his previous track-record and apparent instinct for no-shows into sharp relief. Criticism was understandably stilled during his hospitalisation for the virus, but it was not long after his discharge from hospital before the question of his absences came back into focus, with renewed concern about his non-attendance at key COBRA meetings and his decision to go on holiday in mid-February as the virus had been taking hold. 2Through the prism of the psychoanalytic caring leader, I reflect on some of the explanations for, and implications of, his absences, arguing that they do not always have the same function or effect. Some absences may be politically astute, as a way of promoting an anti-establishment message and/or reassuring his constituents of their own competence and efficacy. Other absences are decidedly risky, because they send a message that he does not care. In times of crisis, the scales of separation versus proximity – absence versus presence – tip differently to normal, and leaders who appear not to care risk triggering especially powerful anxieties about betrayal and abandonment. When it is impossible for us to be carefree, leaders must avoid being perceived or experienced as careless.


title: Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

text: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,600 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.


title: COVID-19 diagnosis and study of serum SARS-CoV-2 specific IgA, IgM and IgG by a quantitative and sensitive immunoassay

text: Background The current pandemic of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a great loss in lives and economy. Detecting viral RNAs on nasopharyngeal and throat swabs is the standard approach for SARS-CoV-2 diagnosis with variable success. Currently, there are only a few studies describing the serological diagnostic methods that involve the detection of SARS-CoV-2-specific IgM and IgG. Here, we aimed to develop a more quantitative and sensitive serological test for COVID-19 diagnosis, monitoring and clinical investigation, based on the detection of antigen-specific IgA as well as IgM and IgG in blood in response to SARS-CoV-2 infection. Methods In this investigation, we report the development of a set of validated diagnostic kits for detecting serum IgA, IgM, and IgG specific to SARS-CoV-2 nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein by chemi-luminescence immuno-analysis. The kits were tested with a cohort of 216 sera from 87 laboratory-confirmed COVID-19 patients, and 483 sera from SARS-CoV-2 negative or healthy individuals as negative controls. A standard receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic accuracy. Using the kits, serum levels of IgA, IgM, and IgG were analyzed, in response to SARS-CoV-2 infection and COVID-19 pathogenesis. Findings The diagnostic kits based on the RBD antigen outperformed those based on the NP. RBD-specific IgA, IgM, and IgG detection kits showed sensitivities of 98.6%, 96.8%, and 96.8%, and specificities of 98.1%, 92.3%, and 99.8%, respectively. In addition, using purified RBD-specific immunoglobulins from a serum pool of COVID-19 patients as standards, the serum concentrations of RBD-specific IgA, IgM, and IgG proteins were determined. The concentrations varied widely among different patients. Median concentration of IgA and IgM reached peaks at 16-20 days after illness onset at 8.84 μg/mL and 7.25 μg/mL, respectively, while median concentration of IgG peaked during 21-25 days after illness onset at 16.47 μg/mL. Furthermore, the serum IgA level positively correlates with COVID-19 severity. Interpretation Our immunoassay of measuring SARS-CoV-2 specific antibodies IgA, IgM, and IgG in serum provides a better serological testing with improved sensitivity and specificity. Data of IgA, IgM, and IgG responses in blood of COVID-19 patients may provide novel insight for the monitoring and treatments of COVID-19. The kits are also suitable for epidemiological studies and vaccine validations.


title: Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

text: Circular DNA of chromosomal origin form from all parts of eukaryotic genomes. In yeast, circular rDNA accumulates as cells divide, contributing to replicative aging. However, little is known about how other chromosome-deri ved circles segregate and contribute to geneticvariation as cells age. We identified circular DNA across the genome of young S. cerevisiae populations and their aged descendants. Young cells had highly diverse circular DNA populations, but lost 94% of the different circular DNA after 20 divisions. Circles present in both young and old cells were characterized by replication origins and included circles from unique regions of the genome, rDNA circles and telomeric Y’ circles. The loss in genetic heterogeneity in aged cells was accompanied by massive accumulation of rDNA circles >95% of all circular DNA. We discovered circles had flexible inherence patterns. Glucose limited conditions selected for cells with glucose-transporter gene circles, [HXT6/7circle], and up to 50% of cells in a population carried them. [HXT6/7circle] cells were eventually substituted by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNA were intermediates in chromosomal amplifications. In conclusion, DNA circles can offer a flexible adaptive solution but cells lose genetic heterogeneity from circular DNA as they undergo replicative aging.


title: Could preventing thromboembolism be a new hope for COVID-19 patients?

text: Several researches have been conducted in order to study treatment effects for COVID-19. Nevertheless, some of the current treatments have not been effective or recommended for severe cases. In this perspective article, we briefly discuss the latest developments in the COVID-19 management.


title: Genetic Grouping of SARS-CoV-2 Coronavirus Sequences using Informative Subtype Markers for Pandemic Spread Visualization

text: 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: Are men who smoke at higher risk for a more severe case of COVID-19 than women who smoke? A Systematic Review

text: Background: The novelty of the Covid-19 pandemic is reflected in the lack of literature available for the impact of smoking on the intensity of the COVID-19 clinical manifestations. Our study tries to address this gap. Method: Six cohorts from China were analysed and a crude odds ratio was manually calculated. Results: Patients with a smoking history were approximately 2 times (95% CI= 1.036-1.883) as likely to suffer from severe clinical manifestations of COVID-19 compared to patients without a smoking history. A higher percentage of males suffer more severe symptoms of COVID-19 in comparison to females, but this could be associated with the gender specific smoking trends observed in China. Conclusion: The gender specific smoking trends could be associated with the increased severity of COVID-19 disease manifestations in the male population.


title: SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

text: The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 from the Chinese province of Hubei and its subsequent pandemic spread highlight the importance of understanding the full molecular details of coronavirus infection and pathogenesis. Here, we compared a variety of replication features of SARS-CoV-2 and SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-infected cells established extensive cross-reactivity of antisera previously raised against a variety of nonstructural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron microscopy revealed that the ultrastructural changes induced by the two SARS viruses are very similar and occur within comparable time frames after infection. Furthermore, we determined that the sensitivity of the two viruses to three established inhibitors of coronavirus replication (Remdesivir, Alisporivir and chloroquine) is very similar, but that SARS-CoV-2 infection was substantially more sensitive to pre-treatment of cells with pegylated interferon alpha. An important difference between the two viruses is the fact that - upon passaging in Vero E6 cells - SARS-CoV-2 apparently is under strong selection pressure to acquire adaptive mutations in its spike protein gene. These mutations change or delete a putative ‘furin-like cleavage site’ in the region connecting the S1 and S2 domains and result in a very prominent phenotypic change in plaque assays.


title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel

text: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (SARS-CoV-2) and represents the causative agent of a potentially fatal disease that is of public health emergency of international concern. Coronaviruses, including SARS-CoV-2, encode an envelope (E) protein, which is a small, hydrophobic membrane protein; the E protein of SARS-CoV-2 has high homology with that of severe acute respiratory syndrome coronavirus. (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Our results suggest that the pentameric E protein promotes the penetration of monovalent ions through the channel. Analysis of the potential mean force (PMF), pore radius and diffusion coefficient reveals that Leu10 and Phe19 are the hydrophobic gates of the channel. In addition, the pore demonstrated a clear wetting/dewetting transition with monovalent cation selectivity under transmembrane voltage, which indicates that it is a hydrophobic voltage-dependent channel. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel.


title: Next-generation diagnostics: virus capture facilitates a sensitive viral diagnosis for epizootic and zoonotic pathogens including SARS-CoV-2

text: Background The detection of pathogens in clinical and environmental samples using high-throughput sequencing (HTS) is often hampered by large amounts of background information, which is especially true for viruses with small genomes. Enormous sequencing depth can be necessary to compile sufficient information for identification of a certain pathogen. Generic HTS combining with in-solution capture enrichment can markedly increase the sensitivity for virus detection in complex diagnostic samples. Methods A virus panel based on the principle of biotinylated RNA-baits was developed for specific capture enrichment of epizootic and zoonotic viruses (VirBaits). The VirBaits set was supplemented by a SARS-CoV-2 predesigned bait set for testing recent SARS-CoV-2 positive samples. Libraries generated from complex samples were sequenced via generic HTS and afterwards enriched with the VirBaits set. For validation, an internal proficiency test for emerging epizootic and zoonotic viruses (African swine fever virus, Ebolavirus, Marburgvirus, Nipah henipavirus, Rift Valley fever virus) was conducted. Results The VirBaits set consists of 177,471 RNA-baits (80-mer) based on about 18,800 complete viral genomes targeting 35 epizootic and zoonotic viruses. In all tested samples, viruses with both DNA and RNA genomes were clearly enriched ranging from about 10-fold to 10,000-fold for viruses including distantly related viruses with at least 72% overall identity to viruses represented in the bait set. Viruses showing a lower overall identity (38% and 46%) to them were not enriched but could nonetheless be detected based on capturing conserved genome regions. The internal proficiency test supports the improved virus detection using the combination of HTS plus targeted enrichment but also point to the risk of carryover between samples. Conclusions The VirBaits approach showed a high diagnostic performance, also for distantly related viruses. The bait set is modular and expandable according to the favored diagnostics, health sector or research question. The risk of carryover needs to be taken into consideration. The application of the RNA-baits principle turned out to be user-friendly, and even non-experts (without sophisticated bioinformatics skills) can easily use the VirBait workflow. The rapid extension of the established VirBaits set adapted to actual outbreak events is possible without any problems as shown for SARS-CoV-2.


title: Evaluation of the potential incidence of COVID-19 and effectiveness of contention measures in Spain: a data-driven approach

text: Our society is currently experiencing an unprecedented challenge, managing and containing an outbreak of a new coronavirus disease known as COVID-19. While China - were the outbreak started - seems to have been able to contain the growth of the epidemic, different outbreaks are nowadays being detected in multiple countries. Much is currently unknown about the natural history of the disease, such as a possible asymptomatic spreading or the role of age in both the susceptibility and mortality of the disease. Nonetheless, authorities have to take action and implement contention measures, even if not everything is known. To facilitate this task, we have studied the effect of different containment strategies that can be put into effect. Our work specifically refers to the situation in Spain as of February 28th, 2020, where a few dozens of cases have been detected. We implemented an SEIR-metapopulation model that allows tracing explicitly the spatial spread of the disease through data-driven stochastic simulations. Our results are in line with the most recent recommendations from the World Health Organization, namely, that the best strategy is the early detection and isolation of individuals with symptoms, followed by interventions and public recommendations aimed at reducing the transmissibility of the disease, which although not efficacious for disease eradication, would produce as a second-order effect a delay of several days in the raise of the number of infected cases


title: Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach

text: Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.


title: Ad-hoc Assembly of Lean Extracorporeal Membrane Oxygenation Systems for COVID-19

text: Background: The COVID-19 epidemic is overwhelming intensive care units with bilateral pneumonia patients requiring respiratory assistance. Bottlenecks in availability of ventilators and extracorporeal membrane oxygenation may contribute to mortality, implying ethically difficult rationing decisions. It is unclear if accelerated equipment production will meet demand, calling for fallback solutions for life support in worst-case scenarios. Methods: Veno-venous extracorporeal gas exchange (VV-ECMO) can provide vital support in bilateral lung failure. VV-ECMO essentially comprises large flow venous accesses, membrane gas exchange, and a blood pump. As thousands of FDA and CE certified Impella blood pumps and consoles are distributed globally for cardiac support, we explored ad-hoc assembly of lean ECMO systems by embedding Impella pumps coaxially in tubes in combination with standard gas exchangers. Results: Ad-hoc integration of Impella blood pumps with gas exchange modules, standard cannulas for large bore venous access, regular ECMO tubing, Y-pieces and connectors led to lean ECMO systems with stable performance over several days. Oxygenation of 2.5-5 L of blood/minute is realistic. Benefit/risk analysis appears favorable if a patient requires respiratory support but cannot be supported because of lack of ventilators or unavailability of a required ECMO system. Conclusion: Ad-hoc assembly of veno-venous ECMOs using Impella pumps is feasible and results in stable blood flow across gas exchange modules. However, such off-label use of the devices calls for specific ethical and regulatory considerations prior to their use as last resort in patients for whom no other treatment modalities are available.


title: Sensitivity of RT-PCR testing of upper respiratory tract samples for SARS-CoV-2 in hospitalised patients: a retrospective cohort study.

text: Objectives: To determine the sensitivity and specificity of RT-PCR testing of upper respiratory tract (URT) samples from hospitalised patients with COVID-19, compared to the gold standard of a clinical diagnosis. Methods: All URT RT-PCR testing for SARS-CoV-2 in NHS Lothian, Scotland, United Kingdom between the 7th of February and 19th April 2020 (inclusive) was reviewed, and hospitalised patients were identified. All URT RT-PCR tests were analysed for each patient to determine the sequence of negative and positive results. For those who were tested twice or more but never received a positive result, case records were reviewed, and a clinical diagnosis of COVID-19 allocated based on clinical features, discharge diagnosis, and radiology and haematology results. For those who had negative URT RT-PCR tests but a clinical diagnosis of COVID-19, respiratory samples were retested using a multiplex respiratory panel, a second SARS-CoV-2 RT-PCR assay, and a human RNase P control. Results: Compared to the gold standard of a clinical diagnosis of COVID-19, the sensitivity of an initial URT RT-PCR for COVID-19 was 82.2% (95% confidence interval 79.0-85.1%). Two consecutive URT RT-PCR tests increased sensitivity to 90.6% (CI 88.0-92.7%). A further 2.2% and 0.9% of patients who received a clinical diagnosis of COVID-19 were positive on a third and fourth test. Conclusions: The sensitivity of a single RT-PCR test of an URT sample in hospitalised patients is 82.2%. Sensitivity increases to 90.6% when patients are tested twice. A proportion of cases with clinically defined COVID-19 never test positive on URT RT-PCR despite repeated testing.


title: SARS-CoV-2 / COVID-19 and its Transmission, Prevention, Treatment and Control - An Update

text: Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2), pandemic has caused huge panic, havoc and global threats worldwide The origin of this virus has been linked to animals, intermediate host is still to be identified, and studies are being carried out that how it got transmitted to humans and acquired rapid human-to-human transmission Within a short time period of only 05 months, SARS-CoV-2 has spread to 213 countries, and till 28th May, 2020, nearly 5 8 million confirmed cases have been reported while taking lives of 0 36 million persons Seeing the current situation of rapid increase in COVID-19 cases daily in many countries, this seems to be the deadliest pandemic after the 1918 Spanish Flu There is currently no specific effective treatment for COVID-19 and also in absence of vaccine the radical cure of the disease is far away Researchers are pacing high to design and develop effective vaccines, drugs and therapeutics to counter COVID-19, however such efforts, clinical trials, necessary approvals and then to reach the level of bulk production of many millions of doses may still take much time Prevention and control of COVID-19 outbreaks requires an evidence-based, multi-factorial and effective mitigation strategy to be adopted The current review discusses on the research advancements, challenges and opportunities in COVID 19 management with a focus on its transmission, prevention, treatment and control


title: Therapeutic Management of COVID-19 Patients: A systematic review

text: Background: SARS-CoV-2 is the cause of the COVID-19 that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study: this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods: A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed full articles in English published from December 1 st , 2019 to March 26 th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral, antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results: As of March 26, 2020, of the initial manuscripts identified (n=449) articles. Forty-one studies were included, of which clinical trials (n=3), (case reports n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most common mentioned and reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and oseltamivir (n=16). Conclusions: This is the first systematic review up to date related to the therapeutics used in COVID-19 patients. Only forty-one research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China, corticosteroid therapy was found to be the most used medicine in these studies.


An Expert Discussion on Autism in the COVID-19 Pandemic


The Impact of Novel Coronavirus on Dermatology.


title: Effect of gamma sterilization on filtering efficiency of various respiratory face-masks

text: Three types of respiratory masks viz N95, non-woven fabric and double layer cotton cloth are being used as an essential inhalation protective measure against COVID-19 by suppressing the entry of respiratory droplets. The filtering efficiency of these masks were tested before and after sterilisation using gamma radiation for the two flow rate conditions corresponding normal breath rate (20lpm) and during sneezing/coughing (90lpm).Sterilisation is carried out using a gamma irradiator containing Co-60 source for the two dose exposures viz. 15kGy and 25kGy. The filtering efficiency for surgical (non-woven fabric) and double layer cotton cloth mask is found to vary from 18% to 22% for the cumulative particle of size [≥] 0.3 micron in both un-irradiated and irradiated condition. The filtration efficiency of N95 mask is found to be reduced to 70% for the most penetrating particle size (0.3 micron) with the flow rate of 20lpm and further reduced for particles in the range of 0.1 and 0.2 micron with flow rate of 90 lpm. The reduction in efficiency after gamma sterilization is associated with reduction of electrostatic interaction of filter medium with particles laden in the air stream. Even with reduced filtering efficiency due to gamma sterilisation, the N95 masks are much superior than the surgical and cloth masks. Instead of disposing N95 mask after single use, they can be reused a few times as N70 mask during this pandemic crisis after sterilisation using gamma radiation.


title: Toward in vivo-relevant hERG safety assessment and mitigation strategies based on relationships between non-equilibrium blocker binding, three-dimensional channel-blocker interactions, dynamic occupancy, dynamic exposure, and cellular arrhythmia

text: The human ether-a-go-go-related voltage-gated cardiac ion channel (commonly known as hERG) conducts the rapid outward repolarizing potassium current in cardiomyocytes (IKr). Inadvertent blockade of this channel by drug-like molecules represents a key challenge in pharmaceutical R&D due to frequent overlap between the structure-activity relationships of hERG and many primary targets. Building on our previous work, together with recent cryo-EM structures of hERG, we set about to better understand the energetic and structural basis of promiscuous blocker-hERG binding in the context of Biodynamics theory. We propose a two-step blocker binding process consisting of: Diffusion of a single fully solvated blocker copy into a large cavity lined by the intracellular cyclic nucleotide binding homology domain (the initial capture step). Occupation of this cavity is a necessary but insufficient condition for ion current disruption. Translocation of the captured blocker along the channel axis (the IKr disruption step), such that: The head group, consisting of a quasi-linear moiety, projects into the open pore, accompanied by partial de-solvation of the binding interface. One tail moiety packs along a kink between the S6 helix and proximal C-linker helix adjacent to the intra-cellular entrance of the pore, likewise accompanied by mutual de-solvation of the binding interface (noting that the association barrier is comprised largely of the total head + tail group de-solvation cost). Blockers containing a highly planar moiety that projects into a putative constriction zone within the closed channel become trapped upon closing, as do blockers terminating prior to this region. A single captured blocker molecule may associate and dissociate from the pore many times before exiting the CNBHD cavity. Lastly, we highlight possible flaws in the current hERG safety index (SI) and propose an alternate in vivo-relevant strategy factoring in: Benefit/risk. The predicted arrhythmogenic fractional hERG occupancy (based on action potential simulations of the undiseased human ventricular cardiomyocyte). Alteration of the safety threshold due to underlying disease. Risk of exposure escalation toward the predicted arrhythmic limit due to patient-to-patient pharmacokinetic variability, drug-drug interactions, overdose, and use for off-label indications in which the hERG safety parameters may differ from their on-label counterparts.


title: Needs and concerns of patients in isolation care units - learnings from COVID-19: A reflection

text: With strict measures in place to contain the spread of coronavirus disease 2019, many have been isolated as suspected or confirmed cases. Being isolated causes much inconvenience for the patients and family. Patients' and next-of-kins’ needs and concerns during isolation will be shared together with suggestions for key process improvements. Our hospital’s Senior Patient Experience Managers contact all patients admitted to the isolation wards on a daily basis to provide some form of support. Common issues raised were gathered and strategies to help with their needs and concerns were discussed. Being in isolation is a challenging period for both patients and family. Nonetheless, we can implement measures to mitigate against the adverse effects of isolation. Patient education, effective and efficient means of communication, close monitoring for signs of distress and anxiety, and early intervention could help patients cope better with the whole isolation experience. Nursing management may want to consider implementing the measures shared in the article to manage patient’s stress while not compromising on staff safety.


title: Sequential Vaccination for Containing Epidemics

text: The dynamics of infectious diseases spread is crucial in determining their risk and offering ways to contain them. We study sequential vaccination of individuals in networks, where there is a limit on the number of individuals that can be vaccinated every day. Effective allocation of vaccine will play a critical role in preventing the spread and reducing the effects of a future pandemic. We derive methods for calculating upper and lower bounds of the expected number of infected individuals, as well as provide estimates on the number of vaccinations that is needed for containment. We calculate these explicitly on trees, d-dimensional grids, and Erdős Rényi graphs. Finally, we construct a time-dependent budget allocation strategy and demonstrate its superiority over constant budget allocation on real networks following first acquaintance vaccination. Our results provide a principled approach to assess the needed vaccination rate given the social graph topology.


title: The support needs of Australian primary health care nurses during the COVID-19 pandemic

text: Aim: To identify Australian primary healthcare nurses immediate support needs during the COVID-19 pandemic. Background: COVID-19 has had widespread implications for primary healthcare nurses. Supporting these nurses' capacity to deliver quality care ensures that ongoing health needs can be met. Methods: Primary healthcare nurses were recruited to an online survey via social media and professional organisations in April 2020. Results: Six-hundred and thirty-seven responses were included in analysis. Participants provided 1213 statements about perceived supports required to provide quality clinical care. From these, seven key categories emerged, namely; personal protective equipment, communication, funding, industrial issues, self-care, workplace factors and valuing nurses. Conclusion: A number of key issues relating to personal health and safety, care quality, and job security need to be addressed to support primary healthcare nurses during the COVID-19 pandemic. Addressing these support issues can assist in retaining nurses and optimising the role of primary healthcare nurses during a pandemic. Implications for nursing management: Responding to the needs of primary healthcare nurses has the potential to facilitate their role in providing community-based healthcare. This knowledge can guide the provision of support for primary healthcare nurses during the current pandemic, as well as informing planning for future health crises.


title: Analysis of codon usage and evolutionary rates of the 2019-nCoV genes

text: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV), which first broke out in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a mortality ranging from 3% to 6%. To better understand the evolution of the newly emerging 2019-nCoV, in this paper, we analyze the codon usage pattern of 2019-nCoV. For this purpose, we compare the codon usage of 2019-nCoV with that of other 30 viruses belonging to the subfamily of orthocoronavirinae. We found that 2019-nCoV shows a rich composition of AT nucleotides that strongly influences its codon usage, which appears to be not optimized to human host. Then, we study the evolutionary pressures influencing the codon usage and evolutionary rates of the sequences of five conserved genes that encode the corresponding proteins (viral replicase, spike, envelope, membrane and nucleocapsid) characteristic of coronaviruses. We found different patterns of both mutational bias and nature selection that affect the codon usage of these genes at different extents. Moreover, we show that the two integral membrane proteins proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins are important targets for the development of vaccines and antiviral drugs, tend to evolve faster as compared to other ones. Taken together, our results suggest that the higher evolutionary rate observed for these two genes could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.


title: What variables can better predict the number of infections and deaths worldwide by SARS-CoV-2? Variation through time

text: Lack of knowledge is the main problem we face in the global Covid-19 pandemic. SARS-CoV-2 is a new virus of which there were no previous studies. Using data from 50 very different countries and by means of a regression analysis, we studied the degree to which a series of variables (health indicators, environmental parameters, economic and social indicators, general characteristics of the country) were able to predict the number of people infected and killed by Covid-19. We also studied how these variables were changing their ability to predict the number of infected and dead by covid-19 during a 3 months period (March, April, May). The number of deaths by Covid-19 can always be predicted with great accuracy from the number of infected, regardless of the characteristics of the country (which has better or worse health, greater or lesser wealth, regardless of its population structure, etc.). Epidemiological measures to prevent transmission, mainly travel and mobility restrictions, proved to be much more efficient than having large hospital and medical resources. Inbound tourism turned out to be the variable that best predicts the number of infected (and, consequently, the number of deaths) happening in the different countries. Electricity consumption and degree of air pollution of a country (CO2 emissions, nitrous oxide and methane) are also capable of predicting, with great precision, the number of infections and deaths from Covid-19 in that country. Characteristics such as the area and population of a country also can predict, although to a lesser extent, the number of infected and dead. In contrast, a series of variables, which in principle would seem to have a greater influence on the evolution of Covid-19 (hospital bed density, Physicians per 1000 people, Researches in R & D, urban population, etc.), turned out to have very little ability to predict both the number of infected and the number of deaths from Covid-19. All this may explain why the countries that opted for social withdrawal policies since the start of the pandemic outbreak obtained better results.


title: Including people with disability in the COVID-19 outbreak emergency preparedness and response in China

text: With the outbreak of the COVID-19, China had to declare a public health emergency within a short time. In order to control and prevent further spread of the disease, China activated the highest emergency response level and has been implementing many draconian measures based on the Law on Prevention and Treatment of Infectious Diseases (LPTID). However, the LPTID lacks a disability perspective and overlooks the needs of people with disabilities during emergencies to a large extent. Combining the law and disability perspectives, this article analyzes different Articles of the LPTID and points out its inadequacies regarding the emergency preparedness and response plans in the midst of a major public health crisis. Besides, the experiences of some people with disabilities being affected are shared in the article. This article calls for nations to ensure amendments of their legal frameworks regarding public health and emergency preparedness fully engage a rights-based disability perspective.


title: Photosynthetic protein classification using genome neighborhood-based machine learning feature

text: Identification of novel photosynthetic proteins is important for understanding and improving photosynthetic efficiency. Synergistically, genomic context such as genome neighborhood can provide additional useful information to identify the photosynthetic proteins. We, therefore, expected that applying the computational approach, particularly machine learning (ML) with the genome neighborhood-based feature should facilitate the photosynthetic function assignment. Our results revealed a functional relationship between photosynthetic genes and their genomic neighbors, indicating the possibility to assign functions from their genome neighborhood profile. Therefore, we created a new method for extracting the patterns based on genome neighborhood network (GNN) and applied for the photosynthetic protein classification using ML algorithms. Random forest (RF) classifier using genome neighborhood-based features achieved the highest accuracy up to 94% in the classification of photosynthetic proteins and also showed better performance (Mathew’s correlation coefficient = 0.852) than other available tools including the sequence similarity search (0.497) and ML-based method (0.512). Furthermore, we demonstrated the ability of our model to identify novel photosynthetic proteins comparing to the other methods. Our classifier is available at http://bicep.kmutt.ac.th/photomod_standalone, https://bit.ly/2S0I2Ox and DockerHub: https://hub.docker.com/r/asangphukieo/photomod


title: Structural basis to design multi-epitope vaccines against Novel Coronavirus 19 (COVID19) infection, the ongoing pandemic emergency: an in silico approach

text: The 2019 novel coronavirus (COVID19 / Wuhan coronavirus), officially named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded RNA coronavirus. SARS-CoV-2 causes the contagious COVID19 disease also known as 2019-nCoV acute respiratory disease and has led to the ongoing 2019–20 pandemic COVID19 outbreak. The effective counter measures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidate. In the present study, we have screened and shortlisted 38 CTL, 33 HTL and 12 B cell epitopes from the eleven Protein sequences of SARS-CoV-2 by utilizing different in silico tools. The screened epitopes were further validated for their binding with their respective HLA allele binders and TAP (Transporter associated with antigen processing) molecule by molecular docking. The shortlisted screened epitopes were further utilized to design novel two multi-epitope vaccines (MEVs) composed of CTL, HTL and B cell epitopes overlaps with potential to elicit humoral as well as cellular immune response against SARS-CoV-2. To enhance the immune response for our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has been utilized as an adjuvant at N terminal of both the MEVs. Further molecular models for both the MEVs were prepared and validated for their stable molecular interactions with Toll-Like Receptor 3 (TLR 3). The codon-optimized cDNA of both the MEVs were further analyzed for their potential of high level of expression in a human cell line. The present study is very significant in terms of molecular designing of prospective CTL and HTL vaccine against SARS-CoV-2 infection with the potential to elicit cellular as well as humoral immune response. (SARS-CoV-2), Coronavirus, Human Transporter associated with antigen processing (TAP), Toll-Like Receptor (TLR), Epitope, Immunoinformatics, Molecular Docking, Molecular dynamics simulation, Multi-epitope Vaccine Graphical abstract The designed CTL (Cytotoxic T lymphocyte) and HTL (Helper T lymphocyte) multi-epitope vaccines (MEV) against COVID19 infection. Both the CTL and HTL MEV models show a very stable and well fit conformational complex formation tendency with the Toll like receptor 3. CTL and HTL MEVs: ribbon; Toll like receptor 3: gray cartoon; Adjuvant [truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1]: orange ribbon regions; Epitopes: cyan ribbons regions; 6xHis Tag: magenta ribbon regions.


title: A scientometric overview of CORD-19

text: As the COVID-19 pandemic unfolds, researchers from all disciplines are coming together and contributing their expertise. CORD-19, a dataset of COVID-19 and coronavirus publications, has recently been published alongside calls to help mine the information it contains, and to create tools to search it more effectively. Here, we focus on the delineation of the publications included in CORD-19, and analyse this delineation from a scientometric perspective. We find that CORD-19 contains research not only on COVID-19 and coronaviruses, but on viruses in general. Publications from CORD-19 mostly focus on a few, well-defined areas, including: coronaviruses (primarily SARS, MERS, COVID-19); public health and viral epidemics; the molecular biology of viruses; influenza and other families of viruses; immunology and antivirals; methodology (testing, diagnosing, clinical trials). CORD-19 publications published in 2020, especially focused on topics of pressing relevance (spread, infection, efficacy of counter-measures), are disproportionately popular on social media. While we fully endorse the initiative that led to CORD-19, we also advise to consider its relatively broad content critically.


title: False positives in reverse transcription PCR testing for SARS-CoV-2

text: Background: Large-scale testing for SARS-CoV-2 by RT-PCR is a key element of the response to COVID-19, but little attention has been paid to the potential frequency and impacts of false positives. Method: From a meta-analysis of external quality assessments of RT-PCR assays of RNA viruses, we derived a conservative estimate of the range of false positive rates that can reasonably be expected in SARS-CoV-2 testing, and analyzed the effect of such rates on analyses of regional test data and estimates of population prevalence and asymptomatic ratio. Findings: Review of external quality assessments revealed false positive rates of 0-16.7%, with an interquartile range of 0.8-4.0%. Such rates would have large impacts on test data when prevalence is low. Inclusion of such rates significantly alters four published analyses of population prevalence and asymptomatic ratio. Interpretation: The high false discovery rate that results, when prevalence is low, from false positive rates typical of RT-PCR assays of RNA viruses raises questions about the usefulness of mass testing; and indicates that across a broad range of likely prevalences, positive test results are more likely to be wrong than are negative results, contrary to public health advice about SARS-CoV-2 testing. There are myriad clinical and case management implications. Failure to appreciate the potential frequency of false positives and the consequent unreliability of positive test results across a range of scenarios could unnecessarily remove critical workers from service, expose uninfected individuals to greater risk of infection, delay or impede appropriate medical treatment, lead to inappropriate treatment, degrade patient care, waste personal protective equipment, waste human resources in unnecessary contact tracing, hinder the development of clinical improvements, and weaken clinical trials. Measures to raise awareness of false positives, reduce their frequency, and mitigate their effects should be considered.


title: COVID-19 patient firstly visiting eye doctor due to tarsadenitis and subconjunctival hemorrhage: A case report/ 以急性睑板腺炎和结膜下出血首诊于眼科的新型冠状病毒肺炎一例

text: A 35-year-old female patient with a history of significant epidemiological exposure firstly visited eye doctor due to acute tarsadenitis in the right eye.Subsequently, she developed subconjunctival hemorrhage, fever and cough and received topical administration of antibiotics and systemic treatment of antiviral drug.Shortly thereafter, both his mother and father, who denied COVID-19 associated epidemiological history, appeared fever, fatigue and other symptoms and diagnosed as COVID-19.This female patient was diagnosed as COVID-19 by CT image of lung and COVID-19 RNA detection 17 days and 24 days after firstly visited eye doctor, respectively, and received specialized isolation treatment.The symptoms of COVID-19 are very varied, eye doctors should keep alert and pay attention to personal protection.


title: Initial Study of Human Genetic Contribution to COVID-19 Severity and Susceptibility

text: The COVID-19 pandemic has accounted for more than five million infections and hundreds of thousand deaths worldwide in the past six months. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed inter-individual phenotypic variability. Here, we report the first host genetic study in China by deeply sequencing and analyzing the 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Based on a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among the five severity groups including asymptomatic, mild, moderate, severe and critical ill patients after the correction of potential confounding factors. The most significant gene loci associated with severity is located in TMEM189-UBE2V1 involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We also identified that the HLA-A*11:01, B*51:01 and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial study of Chinese patients provides a comprehensive view of the genetic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study was also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.


title: Predicting the COVID-19 epidemic in Algeria using the SIR model

text: The aim of this study is to predict the daily infected cases with Coronavirus (COVID-19) in Algeria. We apply the SIR model on data from 25 February 2020 to 29 April 2020 for the prediction. We estimate the parameters of our model by minimizing the negative log likelihood function using the Nelder- Mead method. We found that the epidemic peak reach July month and the COVID-19 disease will disappear in the month of October. We suggest that Algerian authorities need to implement a strict containment strategy over a long period to effectively reduce the epidemic size.


title: Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs

text: COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.


title: Characterizing key attributes of the epidemiology of COVID-19 in China: Model-based estimations

text: Background: A novel coronavirus strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in late 2019. The resulting disease, Coronavirus Disease 2019 (COVID-2019), soon became a pandemic. This study aims to characterize key attributes of the epidemiology of this infection in China. Methods: An age-stratified mathematical model was constructed to describe the transmission dynamics and estimate the age-specific differences in the biological susceptibility to the infection, age-assortativeness in transmission mixing, case fatality rate (CFR), and transition in rate of infectious contacts (and reproduction number R0) following introduction of mass interventions. Results: The model estimated the infectious contact rate in early epidemic at 0.59 contacts per day (95% uncertainty interval (UI)=0.48-0.71). Relative to those 60-69 years of age, susceptibility to the infection was only 0.06 in those ≤19 years, 0.34 in 20-29 years, 0.57 in 30-39 years, 0.69 in 40-49 years, 0.79 in 50-59 years, 0.94 in 70-79 years, and 0.88 in ≥80 years. The assortativeness in transmission mixing by age was very limited at 0.004 (95% UI=0.002-0.008). Final CFR was 5.1% (95% UI=4.8-5.4%). R0 rapidly declined from 2.1 (95% UI=1.8-2.4) to 0.06 (95% UI=0.05-0.07) following onset of interventions. Conclusion: Age appears to be a principal factor in explaining the patterns of COVID-19 transmission dynamics in China. The biological susceptibility to the infection seems limited among children, intermediate among young to mid-age adults, but high among those >50 years of age. There was no evidence for differential contact mixing by age, consistent with most transmission occurring in households rather than in schools or workplaces.


Defining a ‘Risk Group’ and Ageism in the Era of COVID-19


title: Obstetric Anaemia in Africa in the Time of COVID-19: A Call to Action

text: Abstract As we face the COVID-19 pandemic, shortages of blood and components are a global concern Yet Africa has struggled to maintain a sustainable safe blood supply prior to the pandemic The impact of COVID-19 on an already fragile blood supply could result in devastating consequences for obstetric patients, adding to the burden of maternal mortality on the African continent Application of the principles of Patient Blood Management in the obstetric population has previously been recommended In the light of the COVD-19 pandemic, these cost effective and safe principles should be applied with urgency in Africa in an attempt to reduce maternal mortality in the wake of the pandemic


title: A “Deep Dive” into the SARS-Cov-2 Polymerase Assembly: Identifying Novel Allosteric Sites and Analyzing the Hydrogen Bond Networks and Correlated Dynamics

text: Replication of the SARS-CoV-2 genome is a fundamental step in the virus life cycle and inhibiting the SARS-CoV2 replicase machinery has been proven recently as a promising approach in combating the virus. Despite this recent success, there are still several aspects related to the structure, function and dynamics of the CoV-2 polymerase that still need to be addressed. This includes understanding the dynamicity of the various polymerase subdomains, analyzing the hydrogen bond networks at the active site and at the template entry in the presence of water, studying the binding modes of the nucleotides at the active site, highlighting positions for acceptable nucleotides’ substitutions that can be tolerated at different positions within the nascent RNA strand, identifying possible allosteric sites within the polymerase structure and studying their correlated dynamics relative to the catalytic site. Here, we combined various cutting-edge modelling tools with the recently resolved SARS-CoV-2 cryo-EM polymerase structures to fill this gap in knowledge. Our findings provide a detailed analysis of the hydrogen bond networks at various parts of the polymerase structure and suggest possible nucleotides’ substitutions that can be tolerated by the polymerase complex. We also report here three “druggable” allosteric sites within the nsp12 RdRp that can be targeted by small molecule inhibitors. Our correlated motion analysis shows that the dynamics within one of the newly identified sites are linked to the active site, indicating that targeting this site can significantly impact the catalytic activity of the SARS-CoV-2 polymerase.


title: Presence of SARS-Coronavirus-2 in sewage

text: In the current COVID-19 pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 is present in sewage during the emergence of COVID-19 in the Netherlands, sewage samples of 7 cities and the airport were tested using RT-PCR against three fragments of the nucleocapsid protein gene (N1-3) and one fragment of the envelope protein gene (E). No SARS-CoV-2 was detected in samples of February 6, three weeks before the first case was reported in the Netherlands on February 27. On March 5, the N1 fragment was detected in sewage of five sites. On March 15/16, the N1 fragment was detected in sewage of six sites, and the N3 and E fragment were detected at 5 and 4 sites respectively. This is the first report of detection of SARS-CoV-2 in sewage. The detection of the virus in sewage, even when the COVID-19 incidence is low, indicates that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.


title: Social contact and inequalities in depression and loneliness among older adults: A mediation analysis of the English Longitudinal Study of Ageing

text: Background: Social contact, including remote contact (by telephone, email, letter or text), could help reduce social inequalities in depression and loneliness among older adults. Design: Cross-sectional survey. Participants: 8th wave of the English Longitudinal Study of Aging (2016/17), stratified by age (n=1,635 aged <65; n=4,123 aged 65+). Methods: Inverse probability weighted estimation of average effects of weekly in-person and remote social contact on depression (score of 3+ on 8-item CES-D scale) and two measures of loneliness (sometimes/often feels lonely vs hardly ever/never; and top quintile of UCLA loneliness scale vs all others). We also estimated controlled direct effects of education, partner status, and wealth on loneliness and depression under two scenarios: 1) universal infrequent (<weekly) in-person social contact; and 2) universal weekly remote social contact. Results: Weekly in-person social contact was associated with reduced odds of depression and loneliness, but associations with remote social contact were weak. Lower education raised odds of depression and loneliness, but differences were attenuated with infrequent in-person contact. Respondents living alone experienced more depression and loneliness than those living with a partner, and less wealth was associated with more depression. With universal infrequent in-person contact, differences narrowed among those aged under 65 but widened among those aged 65+. Universal weekly remote contact had little impact on inequalities. Conclusions: Reduced in-person social contact may increase depression and loneliness among older adults, especially for those aged 65+ who live alone. Reliance on remote social contact seems unlikely to compensate for social inequalities.


title: Effective containment explains sub-exponential growth in confirmed cases of recent COVID-19 outbreak in Mainland China

text: The recent outbreak of COVID-19 in Mainland China is characterized by a distinctive algebraic, sub-exponential increase of confirmed cases with time during the early phase of the epidemic, contrasting an initial exponential growth expected for an unconstrained outbreak with sufficiently large reproduction rate. Although case counts vary significantly between affected provinces in Mainland China, the scaling law t^μ is surprisingly universal, with a range of exponents μ = 2.1 ± 0.3. The universality of this behavior indicates that, in spite of social, regional, demographical, geographical, and socio-economical heterogeneities of affected Chinese provinces, this outbreak is dominated by fundamental mechanisms that are not captured by standard epidemiological models. We show that the observed scaling law is a direct consequence of containment policies that effectively deplete the susceptible population. To this end we introduce a parsimonious model that captures both, quarantine of symptomatic infected individuals as well as population wide isolation in response to mitigation policies or behavioral changes. For a wide range of parameters, the model reproduces the observed scaling law in confirmed cases and explains the observed exponents. Quantitative fits to empirical data permit the identification of peak times in the number of asymptomatic or oligo-symptomatic, unidentified infected individuals, as well as estimates of local variations in the basic reproduction number. The model implies that the observed scaling law in confirmed cases is a direct signature of effective contaiment strategies and/or systematic behavioral changes that affect a substantial fraction of the susceptible population. These insights may aid the implementation of containment strategies in potential export induced COVID-19 secondary outbreaks elsewhere or similar future outbreaks of other emergent infectious diseases.


ER Goddess: The Coronavirus Doesn't Care


title: Anxiety, depression, attitudes, and internet addiction during the initial phase of the 2019 coronavirus disease (COVID-19) epidemic: A cross-sectional study in Mexico.

text: Abstract Objectives: To describe the prevalence and distribution of anxiety and depression among Mexican population, and to examine its association with internet addiction during the COVID-19 outbreak. Design: A web-based cross-sectional study. Setting: General population in Mexico. Participants: 561 subjects were recruited (71% female, mean age of was 30.7 {+/-} 10.6 years). Interventions: An online survey to assess personal attitudes and perceptions towards COVID-19, sleep-disorders related, the Mexican version of the Hospital Anxiety and Depression Scale (HADS) and the Internet Addiction Test (IAT) was applied. Primary and secondary outcome measures: Prevalence of anxiety, depression, internet addiction and sleep disorders and associated factors. Also, prevalence for anxiety and depression were compared to an historic control group. Results: During the initial phase of the COVID-19 pandemic the prevalence for anxiety and depression was 50% (95% CI, 45.6% to 54.1%) and 27.6%, (95% CI 23.8% to 31.4%), respectively. We found a 51% (33% to 50%) increase in anxiety and up to 86% increase in depression uring the initial weeks of the lock-down compared to the control group. According to the IAT questionnaire, 62.7% (95% CI 58.6% to 68.8%) of our population had some degree of internet addiction. Odds ratio for development of anxiety symptoms was 2.02 (95% CI1.56-2.1, p=0.0001) and for depression was 2.15 (95% CI 1.59-2.9, p=0.0001). In the multivariate analysis, younger age (p=0.006), sleep problems (p=0.000), and internet addiction ( p=0.000) were associated with anxiety and depression. Conclusions: Our study provides valuable information on the psychological impact that the COVID-19 pandemic has had on the Mexican population. As in other parts of the globe, in Mexico, fear of SARS-CoV-2 infection has had devastating consequences on mental health, such as anxiety, depression and sleeping disturbances. Internet abuse and the consequent overexposure to rapidly spreading misinformation (infodemia) are associated to anxiety and depression.


title: A critical analysis of corona related data: What the more reliable data can imply for Western-Europe

text: We present a less common type of discussion about COVID-19 data, beginning with the observation that the number of people reported deceased following COVID-19 infection is currently the most reliable dataset to be used. When the available real-life data are visualized for a number of European countries, they reveal the commonly seen exponential increase, though with different absolute rates, and over time different periods. More interesting information is obtained upon inspection of the daily increments in deaths. These curves look very similar to those for China, and seem to indicate that in European countries that have imposed more strict human-human contact measures, in particular Italy and Spain, where we have seen a decrease in daily deaths since early April, it is to be expected it will take 40-50 days from the end of March until this number has fallen to negligible levels. Taking the initial increase in the number of deaths for Germany, and combining this with typical values for the mortality reported in the literature and the published number of daily contacts for the working population, we calculated an initial increase in infections of 20 per day by a single infected person with an average human-human contact number of 22, decreasing to 5.5 after the first 10 days. The high number at the outset is likely related to outbreaks in a high local concentration of people.


title: Firearm Purchasing and Firearm Violence in the First Months of the Coronavirus Pandemic in the United States

text: Importance. Firearm violence is a significant public health and safety problem in the United States. A surge in firearm purchases following the onset of the coronavirus pandemic may increase rates of firearm violence. Objective. To estimate the association between changes in firearm purchasing and interpersonal firearm violence during the coronavirus pandemic. Design. Cross-sectional time series study. We estimate the difference between observed rates of firearm purchases and those predicted by seasonal autoregressive integrated moving average models. Using negative binomial models, we then estimate the association between excess firearm purchases and rates of interpersonal firearm violence within states, controlling for confounders. Setting. The 48 contiguous states and the District of Columbia. Hawaii and Alaska are excluded due to missing or incomplete data. Exposure. The difference between observed and expected rates of firearm purchases in March through May 2020, approximated by National Instant Criminal Background Check System records. Main Outcome and Measure. Fatal and nonfatal injuries from interpersonal firearm violence, recorded in the Gun Violence Archive. Results. We estimate that there were 2.1 million excess firearm purchases from March through May 2020--a 64.3% increase over expected volume, and an increase of 644.4 excess purchases per 100,000 population. We estimate a relative rate of death and injury from firearm violence of 1.015 (95% Confidence Interval (CI): 1.005 to 1.025) for every 100 excess purchases per 100,000, in models that incorporate variation in purchasing across states and control for effects of the pandemic common to all states. This reflects an increase of 776 fatal and nonfatal injuries (95% CI: 216 to 1,335) over the number expected had no increase in purchasing occurred. Conclusions and Relevance. We find a significant increase in firearm violence in the United States associated with the coronavirus pandemic-related surge in firearm purchasing. Our findings are consistent with existing research. Firearm violence prevention strategies may be particularly important during the pandemic.


title: Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome

text: Defects in histone methyltransferases (HMTs) are major contributing factors in neurodevelopmental disorders (NDDs). Heterozygous variants of SETD1A involved in histone H3 lysine 4 (H3K4) methylation were previously identified in individuals with schizophrenia. Here, we define the clinical features of the Mendelian syndrome associated with haploinsufficiency of SETD1A by investigating 15 predominantly pediatric individuals who all have de novo SETD1A variants. These individuals present with a core set of symptoms comprising global developmental delay and/or intellectual disability, subtle facial dysmorphisms, behavioral and psychiatric problems. We examined cellular phenotypes in three patient derived lymphoblastoid cell lines with three variants: p.Gly535Alafs*12, c.4582-2_4582delAG, and p.Tyr1499Asp. These patient cell lines displayed DNA damage repair defects that were comparable to previously observed RNAi-mediated depletion of SETD1A. This suggested that these variants, including the p.Tyr1499Asp in the catalytic SET domain, behave as Loss-of-Function (LoF) alleles. Previous studies demonstrated a role for SETD1A in cell cycle control and differentiation. However, individuals with SETD1A variants do not show major structural brain defects or severe microcephaly, suggesting that defective proliferation and differentiation of neural progenitors is unlikely the single underlying cause of the disorder. We show here that the Drosophila Melanogaster SETD1A orthologue is required in postmitotic neurons of the fly brain for normal memory, suggesting a role in post development neuronal function. Together, this study defines a neurodevelopmental disorder caused by dominant de novo LoF variants in SETD1A and further supports a role for H3K4 methyltransferases in the regulation of neuronal processes underlying normal cognitive functioning.


title: Ending coronavirus lockdowns will be a dangerous process of trial and error

text: The world is holding its breath After the novel coronavirus made its way from China around the world, one country after another adopted harsh measures to stop SARS-CoV-2 from spreading and overwhelming hospitals They have hit the pause button on their economies and their citizens’ lives, stopping sports events, religious services, and other social gatherings School closures in 188 countries affect more than 1 5 billion students Borders are closed and businesses shuttered While some countries are still seeing daily case numbers increase, others—first in Asia but increasingly in Europe—have managed to bend the curve, slowing the transmission of COVID-19


title: Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2

text: During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.


title: Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients

text: Objective To assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients. Design Since February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. Results GI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-... days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms. Conclusions GI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.