Background: Emerging infectious disease have brought a huge impact on human society in recent years. The outbreak of Zika virus (ZIKV) in the Americas resulted in a large number of babies born with microcephaly. More seriously, the Coronavirus Disease 2019 (COVID-19) caused the global spreads and immeasurable damages. Thus, the monitoring of highly pathogenic virus is of significance to the prevention and control of emerging infectious disease.ResultsHerein, a dendritic polymer probe-amplified ECL-scan imaging system was constructed to realize trace analysis of viral emerging infectious disease. Dendritic polymer probe was employed as the efficient signal giving-out component that could generate amplified electrochemiluminescence (ECL) signal on the integrated chip. And the signal was detected by a single-photon level charge coupled device-based ECL-scan imaging system. With this strategy,the ZIKV in the complex system of blood, urine and saliva were detected. The results indicated that high sensitivity of 50 copies and superior specificity were achieved. Furthermore, this strategy realized highly sensitive detection (10 copies) of S and N protein gene sequence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov2) and spiked pseudovirus samples.ConclusionsThus, the dendritic polymer probe-amplified ECL-scan imaging system suitably met the strict clinical-requirements for trace analysis of emerging virus, and thus has the potential to serve as a paradigm for monitoring of emerging infectious disease.

ABSTRACT All coronaviruses (CoVs) contain a macrodomain, also termed Mac1, in non-structural protein 3 (nsp3) which binds and hydrolyzes ADP-ribose covalently attached to proteins. Despite several reports demonstrating that Mac1 is a prominent virulence factor, there is still a limited understanding of its cellular roles during infection. Currently, most of the information regarding the role of CoV Mac1 during infection is based on a single point mutant of a highly conserved asparagine-to-alanine mutation, which is known to largely eliminate Mac1 ADP-ribosylhydrolase activity. To determine if Mac1 ADP-ribose binding separately contributes to CoV replication, we compared the replication of a murine hepatitis virus (MHV) Mac1 mutant predicted to dramatically reduce ADP-ribose binding, D1329A, to the previously mentioned asparagine mutant, N1347A. D1329A and N1347A both replicated poorly in bone-marrow derived macrophages (BMDMs), were inhibited by PARP enzymes, and were highly attenuated in vivo . However, D1329A was significantly more attenuated than N1347A in all cell lines tested that were susceptible to MHV infection. In addition, D1329A retained some ability to block IFN-β transcript accumulation compared to N1347A, indicating that these two mutants impacted distinct Mac1 functions. Mac1 mutants predicted to eliminate both binding and hydrolysis activities were unrecoverable, suggesting that the combined activities of Mac1 may be essential for MHV replication. We conclude that Mac1 has multiple roles in promoting the replication of MHV, and that these results provide further evidence that Mac1 could be a prominent target for anti-CoV therapeutics. IMPORTANCE In the wake of the COVID-19 epidemic, there has been a surge to better understand how CoVs replicate, and to identify potential therapeutic targets that could mitigate disease caused by SARS-CoV-2 and other prominent CoVs. The highly conserved macrodomain, also termed Mac1, is a small domain within non-structural protein 3. It has received significant attention as a potential drug target as previous studies demonstrated that it is essential for CoV pathogenesis in multiple animal models of infection. However, the various roles and functions of Mac1 during infection remain largely unknown. Here, utilizing recombinant Mac1 mutant viruses, we have determined that different biochemical functions of Mac1 have distinct roles in the replication of MHV, a model CoV. These results indicate that Mac1 is more important for CoV replication than previously appreciated, and could help guide the development of inhibitory compounds that target unique regions of this protein domain.

Background: The outbreak of COVID-19has led to a high demand for finding effective antiviral agents. Preliminary experiments showed that Umifenovir could inhibit coronavirus replication in vivo. There is limited data on the clinical efficacy of COVID-19-infected pneumonia. Therefore, we aimed to evaluate this medication based on clinical findings. Methods: : The present study was designed as a clinical trial to investigate the advantages and disadvantages of this medicine compared to empirical treatment. For this purpose, multi-stage sampling was considered. 56 people who have mild to moderate symptoms without signs of sever pneumonia , were selected by accidental non-random sampling method. This sample size was subsequently divided into two groups (group A threated with hydroxycloroquine and group B who threated with combination hydroxycloroquine and Umifenovir) by randomized block sampling (1:1). During the study, three patients left the case group. Their clinical sighns and symptoms were evaluated on 3 th and 7 th and 14 th days after oncet illness while taking these medicines in the disease course. The SPSS software was used for data analysis and the significance level was considered to be P<0.05. Results: : On the seventh days after visit patients , there were statistically significant differences in recuperation dry cough(p = 0.001), weakness(p = 0.004), gastrointestinal symptoms(p = 0.043) and shortness of breath (p = 0.001) between the two groups, so that in patients who under orescription combination HCQ and Umifenovir group had a faster recovery.Generally during illness , there were statistically significantly faster melioratation myalgia(p = 0.03), gastrointestinal symptoms(p = 0.047), and weakness(p = 0.007)in patients who threated with both HCQ and Umifenovir . Conclusion: Evaluation clinical findings in mild to moderate COVID-19 patients symptoms and sighns recuperation faster in group who under orescription combination HCQ and Umifenovir .regimen. In other words, adding Umifenovir to the empirical treatment accelerated the recovery process of patients’ clinical symptoms. Registration: IR.TUMS.VCR.REC.1399.204, 04.13.2020 , http://ethics.research.ac.ir/IR.TUMS.VCR.REC.1399.204

SUMMARY The rapid spreading of the newly emerged SARS-CoV-2 variant, B.1.1.7, highlighted the requirements to better understand adaptive immune responses to this virus. Since CD8 + T cell responses play an important role in disease resolution and modulation in COVID-19 patients, it is essential to address whether these newly emerged mutations would result in altered immune responses. Here we evaluated the immune properties of the HLA-A2 restricted CD8 + T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8 + T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8 + T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induced the activation and cytotoxicity of CD8 + T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8 + T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab 1707-1716 and I2230T mutation in ORF1ab 2230-2238 . Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8 + T cell responses elicited by infection of mutated strains or vaccination. Graphical Abstract

Low- and middle-income countries (LMICs) face significant challenges in the control of COVID-19, given limited resources, especially for inpatient care. In a parallel effort to that for vaccines, the identification of therapeutics that have near-term potential to be available and easily administered is critical. Using the United States, European Union, and World Health Organization clinical trial registries, we reviewed COVID-19 therapeutic agents currently under investigation. The search was limited to oral or potentially oral agents, with at least a putative anti-SARS-CoV-2 virus mechanism, and with at least 3 registered trials. We describe the available evidence regarding agents that met these criteria and additionally discuss the need for additional investment by the global scientific community in large well-coordinated trials of accessible agents and their combinations in LMICs. The search yielded 636, 175, and 930 trials, in the US, EU, and WHO trial registers, respectively. These trials covered 17 oral or potentially oral repurposed agents that are currently used as antimicrobials and immunomodulatory therapeutics and therefore have established safety. The available evidence regarding proposed mechanism of actions, clinical efficacy, and potential limitations is summarized. We also identified the need for large well-coordinated trials of accessible agents and their combinations in LMICs. Several repurposed agents have potential to be safe, available, and easily administrable to treat COVID-19. To prevent COVID-19 from becoming a neglected tropical disease, there is critical need for rapid and coordinated effort in their evaluation and the deployment of those found to be efficacious.

Repurposing drugs as treatments for COVID-19 has drawn much attention. A common strategy has been to screen for established drugs, typically developed for other indications, that are antiviral in cells or organisms. Intriguingly, most of the drugs that have emerged from these campaigns, though diverse in structure, share a common physical property: cationic amphiphilicity. Provoked by the similarity of these repurposed drugs to those inducing phospholipidosis, a well-known drug side effect, we investigated phospholipidosis as a mechanism for antiviral activity. We tested 23 cationic amphiphilic drugs—including those from phenotypic screens and others that we ourselves had found—for induction of phospholipidosis in cell culture. We found that most of the repurposed drugs, which included hydroxychloroquine, azithromycin, amiodarone, and four others that have already progressed to clinical trials, induced phospholipidosis in the same concentration range as their antiviral activity; indeed, there was a strong monotonic correlation between antiviral efficacy and the magnitude of the phospholipidosis. Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis depends on the gross physical properties of drugs, and does not reflect specific target-based activities, rather it may be considered a confound in early drug discovery. Understanding its role in infection, and detecting its effects rapidly, will allow the community to better distinguish between drugs and lead compounds that more directly impact COVID-19 from the large proportion of molecules that manifest this confounding effect, saving much time, effort and cost. One Sentence Summary Drug-induced phospholipidosis is a single mechanism that may explain the in vitro efficacy of a wide-variety of therapeutics repurposed for COVID-19.

Convalescent plasma has been used worldwide to treat patients hospitalized with COVID-19 and prevent disease progression. Despite global usage uncertainty remains regarding plasma efficacy as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a systematic literature review and used a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan-Meier survival plots. Qualitative inspection of all available Kaplan-Meier survival data and an aggregate Kaplan- Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented at the immediate onset of future infectious disease outbreaks.

Summary Paragraph We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone 1 , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications 2 , as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry 3 . We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone also potently suppresses SARS-CoV-2 replication post-entry and is 1,000-fold more potent than Remdesivir 4 . Inhibition of HS biosynthesis and SARS-CoV-2 infection depends on specific inhibition of PRS, possibly due to translational suppression of proline-rich proteins. We find that pp1a and pp1ab polyproteins of SARS-CoV-2, as well as several HS proteoglycans, are proline-rich, which may make them particularly vulnerable to halofuginone’s translational suppression. Halofuginone is orally bioavailable, has been evaluated in a phase I clinical trial in humans and distributes to SARS-CoV-2 target organs, including the lung, making it a near-term clinical trial candidate for the treatment of COVID-19.

he COVID-19 pandemic calls for a collective response at the global and regional level. Otherwise, some nations may be left behind and the potential for the contagion to return remains high. As advanced regional blocs, the EU and ASEAN have a major responsibility to their members for coordinating health protection measures and access to vaccines, maintaining the mobility of people and goods, and supporting their economy. The pandemic is therefore a test for regions. They must demonstrate that they are at least making national measures more effective. This paper seeks to determine whether the EU and ASEAN have passed the COVID- 19 test. It does so by analysing their responses in 2020 when the countries were hit by the first wave of contagion. The first section of the paper considers their attitude and action when the initial cases appeared in Europe and Southeast Asia in the early part of 2020. While the second section focuses on vaccines and the policies adopted in each region. The paper concludes that overall, the responses of the two regions to their COVID-19 test were late and insufficient.

Many patients with SARS-CoV-2 infection develop neurological signs and symptoms, though, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological, and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical center. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit (ICU). Hospital-associated complications were common, including 8 (20%) with deep vein thrombosis/pulmonary embolism (DVT/PE), 7 (17%) patients with acute kidney injury requiring dialysis, and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 hours of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischemic changes in all brains, both global and focal; large and small infarcts, many of which appeared hemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, though none had evidence of vasculitis. Eighteen (44%) contained pathologies of neurodegenerative diseases, not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR (qRT-PCR), RNAscope, and immunocytochemistry with primers, probes, and antibodies directed against the spike and nucleocapsid regions. qRT-PCR revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in nasal epithelia. RNAscope and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in COVID-19 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischemia. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19, might contribute to chronic neurological problems.

ABSTRACT Hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma (CP) are under evaluation in several clinical trials of hospitalized COVID-19 patients. Here we explored the antibody epitope repertoire, antibody binding and virus neutralizing capacity of six hCoV-2IG batches as well as nine convalescent plasma (CP) lots against SARS-CoV-2 and emerging variants of concern (VOC). The Gene-Fragment Phage display library spanning the SARS-CoV-2 spike demonstrated broad recognition of multiple antigenic sites spanning the entire spike including NTD, RBD, S1/S2 cleavage site, S2-fusion peptide and S2-heptad repeat regions. Antibody binding to the immunodominant epitopes was higher for hCoV-2IG than CP, with predominant binding to the fusion peptide. In the pseudovirus neutralization assay (PsVNA) and in the wild-type SARS-CoV-2 PRNT assay, hCoV-2IG lots showed higher titers against the WA-1 strain compared with CP. Neutralization of SARS-CoV-2 VOCs from around the globe were reduced to different levels by hCoV-2IG lots. The most significant loss of neutralizing activity was seen against the B.1.351 (9-fold) followed by P.1 (3.5-fold), with minimal loss of activity against the B.1.17 and B.1.429 (≤2-fold). Again, the CP showed more pronounced loss of cross-neutralization against the VOCs compared with hCoV-2IG. Significant reduction of hCoV-2IG binding was observed to the RBD-E484K followed by RBD-N501Y and minimal loss of binding to RBD-K417N compared with unmutated RBD. This study suggests that post-exposure treatment with hCoV-2IG is preferable to CP. In countries with co-circulating SARS-CoV-2 variants, identifying the infecting virus strain could inform optimal treatments, but would likely require administration of higher volumes or repeated infusions of hCOV-2IG or CP, in patients infected with the emerging SARS-CoV-2 variants.

A recent outbreak of a new strain of Coronavirus (SARS-CoV-2) has become a global health burden, which has resulted in deaths. No proven drug has been found to effectively cure this fast-spreading infection, hence the need to explore old drugs with the known profile in tackling this pandemic. Computer-aided drug design approach involving virtual screening was used to obtain the binding scores and inhibiting efficiencies of previously known antibiotics against SARS-CoV-2 main protease (M pro ). In silico pre-clinical studies which include Drug-likeness, Bioactivity, and ADMET profiling were done using Molinspiration online tool and ADMET SAR2 webserver respectively, and the results were compared with those of drugs currently involved in clinical trials in the ongoing pandemic. Although antibiotics have been speculated to be of no use in the treatment of viral infections, literature has emerged lately to reveal antiviral potential and immune-boosting ability of antibiotics. This study identified Tarivid and Ciprofloxacin with binding affinities of -8.3 and − 8.1 kcal/mol, respectively as significant inhibitors of SARS-CoV-2 (M pro ) with better pharmacokinetics, drug-likeness and oral bioavailabity, bioactivity properties, ADMET properties and inhibitory strength compared to Remdesivir (-7.6 kcal/mol) and Azithromycin (-6.3 kcal/mol). These observations will provide insight for further research (clinical trial) in the cure and management of COVID-19.

SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified twelve potentially functional structural elements within the SARS-CoV-2 genome, observed that identical sequences can fold into divergent structures on different subgenomic RNAs, and that WT and Δ382 virus genomes can fold differently. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host RNAs. SARS-CoV-2 binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2’-O-methylated. 2’-O-methylation sites in the virus genome are enriched in the untranslated regions and are associated with increased pair-wise interactions. SARS-CoV-2 infection results in a global decrease of 2’-O-methylation sites on host mRNAs, suggesting that binding to snoRNAs could be a pro-viral mechanism to sequester methylation machinery from host RNAs towards the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, cellular factors important during infection and provide a platform for targeted therapy.

The words we use to talk about the current epidemiological crisis on social media can inform us on how we are conceptualizing the pandemic and how we are reacting to its development. This paper provides an extensive explorative analysis of how the discourse about Covid-19 reported on Twitter changes through time, focusing on the first wave of this pandemic. Based on an extensive corpus of tweets (produced between 20th March and 1st July 2020) first we show how the topics associated with the development of the pandemic changed through time, using topic modeling. Second, we show how the sentiment polarity of the language used in the tweets changed from a relatively positive valence during the first lockdown, toward a more negative valence in correspondence with the reopening. Third we show how the average subjectivity of the tweets increased linearly and fourth, how the popular and frequently used figurative frame of WAR changed when real riots and fights entered the discourse.

When the first suspected human-to-human transmission of the novel coronavirus was reported in January 2020, the United States had in place an elaborate set of pandemic disaster and response plans that spanned hundreds of pages. The George W. Bush administration spearheaded national pandemic planning in 2005 as part of the post-September 11 efforts to modernize the country’s disaster response capabilities. Subsequent administrations revisited and revised the various pandemic plans, including the Trump administration as recently as 2017 and 2018. Despite these detailed plans, the Trump administration was slow to respond to the emerging public health crisis or implement any of the prescribed protocols. Federal officials lost valuable time as they downplayed the risk posed by COVID-19 and repeatedly assured the American people that the virus would simply “go away.” By March 2020, a frightening spike in cases in the Northeast made the pandemic impossible to ignore. President Trump and other administration officials shifted tactics and began to characterize COVID-19 as the quintessential “black swan” – a threat that no one could have foreseen. President Trump repeatedly told the American people that “no one could have predicted something like this” even though official federal policy suggested a very different story. Far from being a black swan, the COVID-19 pandemic was widely anticipated and, according to many epidemiologists, inevitable. This article argues that our botched federal response was not so much a failure of policy per se, but rather a failure of political will. The federal government had a robust pandemic policy in place; it simply chose not to follow it. This failure of political will illustrates the dangers that arise when public health measures are politicized and weaponized for partisan advantage and demands strong interventions to ensure federal accountability and transparency. The first section of this article outlines the evolution of our national pandemic plans within the broader context of disaster and response planning. The second section explains the pandemic staging framework that is used to organize and coordinate decision making within a pandemic. The third section charts the federal response during the crucial first three months of the public health crisis, specifically identifying instances where the federal government failed to follow its own clearly articulated pandemic policy. The final section outlines some lessons learned from the pandemic and proposes reforms to insulate public health measures from partisan wrangling and keep our federal government faithful to its foremost obligation, namely to promote the general welfare

Development of effective vaccines against Coronavirus Disease 2019 (COVID-19) is a global imperative. Rapid immunization of the world human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and many different vaccine approaches are being pursued to meet this task. Engineered filamentous bacteriophage (phage) have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the design, development, and initial evaluation of targeted phage-based vaccination approaches against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) by using dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. Towards a unique phage- and AAVP-based dual-display candidate approach, we first performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein for display on the recombinant major capsid coat protein pVIII. Targeted phage particles carrying one of these epitopes induced a strong and specific humoral response. In an initial experimental approach, when these targeted phage particles were further genetically engineered to simultaneously display a ligand peptide (CAKSMGDIVC) on the minor capsid protein pIII, which enables receptor-mediated transport of phage particles from the lung epithelium into the systemic circulation (termed “dual-display”), they enhanced a systemic and specific spike (S) protein-specific antibody response upon aerosolization into the lungs of mice. In a second line of investigation, we engineered targeted AAVP particles to deliver the entire S protein gene under the control of a constitutive cytomegalovirus (CMV) promoter, which induced tissue-specific transgene expression stimulating a systemic S protein-specific antibody response. As proof-of-concept preclinical experiments, we show that targeted phage- and AAVP-based particles serve as robust yet versatile enabling platforms for ligand-directed immunization and promptly yield COVID-19 vaccine prototypes for further translational development. Significance The ongoing COVID-19 global pandemic has accounted for over 2.5 million deaths and an unprecedented impact on the health of mankind worldwide. Over the past several months, while a few COVID-19 vaccines have received Emergency Use Authorization and are currently being administered to the entire human population, the demand for prompt global immunization has created enormous logistical challenges--including but not limited to supply, access, and distribution--that justify and reinforce the research for additional strategic alternatives. Phage are viruses that only infect bacteria and have been safely administered to humans as antibiotics for decades. As experimental proof-of-concept, we demonstrated that aerosol pulmonary vaccination with lung-targeted phage particles that display short epitopes of the S protein on the capsid as well as preclinical vaccination with targeted AAVP particles carrying the S protein gene elicit a systemic and specific immune response against SARS-CoV-2 in immunocompetent mice. Given that targeted phage- and AAVP-based viral particles are sturdy yet simple to genetically engineer, cost-effective for rapid large-scale production in clinical grade, and relatively stable at room temperature, such unique attributes might perhaps become additional tools towards COVID-19 vaccine design and development for immediate and future unmet needs.

During the recent Coronavirus disease 2019 (COVID-19) outbreak, the microblogging service Twitter has been widely used to share opinions and reactions to events. Italy was one of the first European countries to be severely affected by the outbreak and to establish lockdown and stay-at-home orders, potentially leading to country reputation damage. We resort to sentiment analysis to investigate changes in opinions about Italy reported on Twitter before and after the COVID-19 outbreak. Using different lexicons-based methods, we find a breakpoint corresponding to the date of the first established case of COVID-19 in Italy that causes a relevant change in sentiment scores used as proxy of the country reputation. Next, we demonstrate that sentiment scores about Italy are strongly associated with the levels of the FTSE-MIB index, the Italian Stock Exchange main index, as they serve as early detection signals of changes in the values of FTSE-MIB. Finally, we make a content-based classification of tweets into positive and negative and use two machine learning classifiers to validate the assigned polarity of tweets posted before and after the outbreak.

Nonlinear dynamics perspective is an interesting approach to describe COVID-19 epidemics, providing information to support strategic decisions. This paper proposes a dynamical map to describe COVID-19 epidemics based on the classical susceptible-exposed-infected-recovered (SEIR) differential model, incorporating vaccinated population. On this basis, the novel map represents COVID-19 discrete-time dynamics by adopting three populations: infected, cumulative infected and vaccinated. The map promotes a dynamical description based on algebraic equations with a reduced number of variables and, due to its simplicity, it is easier to perform parameter adjustments. In addition, the map description allows analytical calculations of useful information to evaluate the epidemic scenario, being important to support strategic decisions. In this regard, it should be pointed out the estimation of the number death cases, infectious rate and the herd immunization point. Numerical simulations show the model capability to describe COVID-19 dynamics, capturing the main features of the epidemic evolution. Reported data from Germany, Italy and Brazil are of concern showing the map ability to describe different scenario patterns that include multi-wave and plateaus behaviors. The effect of vaccination is analyzed considering different campaign strategies, showing its importance to control the epidemics.

Flaviviruses , including Zika virus (ZIKV), are a significant global health concern, yet no licensed antivirals exist to treat disease. The small Membrane (M) protein plays well-defined roles during viral egress and remains within virion membranes following release and maturation. However, it is unclear whether M plays a functional role in this setting. Here, we show that M forms oligomeric membrane-permeabilising channels in vitro , with increased activity at acidic pH and sensitivity to the prototypic channel-blocker, rimantadine. Accordingly, rimantadine blocked an early stage of ZIKV cell culture infection. Structure-based channel models, comprising hexameric arrangements of two trans -membrane domain protomers were shown to comprise more stable assemblages than other oligomers using molecular dynamics (MD) simulations. Models contained a predicted lumenal rimantadine binding site, as well as a second druggable target region on the membrane-exposed periphery. In silico screening enriched for repurposed drugs/compounds predicted to bind to either one site or the other. Hits displayed superior potency in vitro and in cell culture compared with rimantadine, with efficacy demonstrably linked to virion-resident channels. Finally, rimantadine effectively blocked ZIKV viraemia in preclinical models, supporting that M constitutes a physiologically relevant target. This could be explored by repurposing rimantadine, or development of new M-targeted-therapies.

Background: The objective of the study was to understand how pregnant women learned about Zika infection and to identify what sources of information were likely to influence them during their pregnancy.MethodsWe conducted 13 semi-structed interviews in English and Spanish with women receiving prenatal care who were tested for Zika virus infection. We analyzed the qualitative data using grounded theory.ResultsPregnant women in the Bronx learned about Zika from family, television, the internet and their doctor. Informational sources played different roles. Television, specifically Spanish language networks, was often the initial source of information. Women searched the internet for additional information about Zika. Later, they engaged in further discussions with their healthcare providers.ConclusionsTelevision played an important role in providing awareness about Zika to pregnant women in the Bronx, but that information was incomplete. The internet and healthcare providers were sources of more complete information and are likely the most influential. Efforts to educate pregnant women about emerging infectious diseases will benefit from using a variety of approaches including television messages that promote public awareness followed up by reliable information via the internet and healthcare providers.

ABSTRACT Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.

Background: The current outbreak of COVID-19 is a major pandemic that has adversely affected the world economies, societies and also an increase in health burdens within a short time. South Africa has the highest number of confirmed COVID-19 cases in Africa and is the fourteenth most affected country in the world. Understanding the country’s COVID-19 infection rate will help in preventing the spread of the disease. Method: We propose to estimate both the the positive testing rate and the rate at which the positive testing rate changes over time using a flexible semi-parametric model. We used publicly available data collected from March 5th to September 2nd 2020. Results: : We found that the positive testing rate was declining from early March when the disease was first observed until early May. In the month of July 2020, the infection reached its peak then its started to decrease again. Conclusion: The observed increase in the positive testing rates between May and July 2020 could imply that the testing algorithm was effective; however its effectiveness declined after the end of July 2020, which coincided with the end of winter season in the country.

ABSTRACT The nasal-mucosa constitutes the primary entry site for respiratory viruses including SARS-CoV-2. While the imbalanced innate immune response of end-stage COVID-19 has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo , coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local-mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with rapid increase in tissue-associated viral sub-genomic mRNA, and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon stimulated genes, cytokines and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tract, that are distinct to SARS-CoV-2. The studies shed light on the role of the nasal-mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV-2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19. IMPORTANCE In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal-mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues, infected in parallel with SARS-CoV-2 and influenza virus, we have revealed distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal-mucosal infection model can be employed to assess the impact of viral evolutionary changes, and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.

In this manuscript we describe the engineering of a biomarker for the diagnosis and prognosis of Zika-associated neurological disease. Although the causal association between congenital Zika virus (ZIKV) infection and neurological manifestations has been well documented in the recent years, biomarkers for proper diagnostic and disease outcome still remain to be defined. Combining high-density peptide array and multivariate analysis, we have identified an ZIKV epitope that is associated to a lack of IgG antibody response in patients with severe neurological symptoms. An engineered chimera was developed to discriminate between mild and severe clinical forms of the disease.

Suppression of the first wave of COVID-19 in Japan is assumedly attributable to people’s increased risk perception by acquiring information from the government and media reports. In this study, going out in public amidst the spread of COVID-19 infections was investigated by examining new polymerase chain reaction (PCR) positive cases of COVID-19 and its relationship to four indicators of people going out in public (the people flow, the index of web searches for going outside, the number of times people browse restaurants, and the number of hotel guests), from the Regional Economic and Social Analysis System (V-RESAS). Two waves of COVID-19 infections were examined with cross-correlation analysis. In the first wave, all four indicators of going out reacted oppositely with the change in new PCR positive cases, showing a lag period of –1 to +6 weeks. In the second wave, the same relationship was only observed for the index of web searches for going outside. These results suggest that going out in public could not be described by new PCR positive cases alone in the second wave, even though they could explain people going out to some extent in the first wave.