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Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.

Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.

A novel series of metal(II) complexes (1-5) [M

Coronavirus disease 2019 (COVID-19) has gained prominence as a global pandemic. Studies have suggested that systemic alterations persist in a considerable proportion of COVID-19 patients after hospital discharge. We used proteomic and metabolomic approaches to analyze plasma samples obtained from 30 healthy subjects and 54 COVID-19 survivors 6 months after discharge from the hospital, including 30 non-severe and 24 severe patients. Through this analysis, we identified 1019 proteins and 1091 metabolites. The differentially expressed proteins and metabolites were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Among the patients evaluated, 41% of COVID-19 survivors reported at least one clinical symptom and 26.5% showed lung imaging abnormalities at 6 months after discharge. Plasma proteomics and metabolomics analysis showed that COVID-19 survivors differed from healthy control subjects in terms of the extracellular matrix, immune response, and hemostasis pathways. COVID-19 survivors also exhibited abnormal lipid metabolism, disordered immune response, and changes in pulmonary fibrosis-related proteins. COVID-19 survivors show persistent proteomic and metabolomic abnormalities 6 months after discharge from the hospital. Hence, the recovery period for COVID-19 survivors may be longer.

Bats are natural reservoirs for both

Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

Diverse coronavirus (CoV) strains can infect both humans and animals and produce various diseases. CoVs have caused three epidemics and pandemics in the last two decades, and caused a severe impact on public health and the global economy. Therefore, it is of utmost importance to understand the emergence and evolution of endemic and emerging CoV diversity in humans and animals. For diverse bird species, the Infectious Bronchitis Virus is a significant one, whereas feline enteric and canine coronavirus, recombined to produce feline infectious peritonitis virus, infects wild cats. Bovine and canine CoVs have ancestral relationships, while porcine CoVs, especially SADS-CoV, can cross species barriers. Bats are considered as the natural host of diverse strains of alpha and beta coronaviruses. Though MERS-CoV is significant for both camels and humans, humans are nonetheless affected more severely. MERS-CoV cases have been reported mainly in the Arabic peninsula since 2012. To date, seven CoV strains have infected humans, all descended from animals. The severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) are presumed to be originated in Rhinolopoid bats that severely infect humans with spillover to multiple domestic and wild animals. Emerging alpha and delta variants of SARS-CoV-2 were detected in pets and wild animals. Still, the intermediate hosts and all susceptible animal species remain unknown. SARS-CoV-2 might not be the last CoV to cross the species barrier. Hence, we recommend developing a universal CoV vaccine for humans so that any future outbreak can be prevented effectively. Furthermore, a One Health approach coronavirus surveillance should be implemented at human-animal interfaces to detect novel coronaviruses before emerging to humans and to prevent future epidemics and pandemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic of the Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at 'Extra-viral' Spike (S) protein as vaccine vehicles, but there are concerns regarding ‘viral immune escape’ since multiple mutations may enable the mutated virus strains to escape from immunity against S protein. The ‘Intra-viral’ Nucleocapsid (N-protein) is relatively conserved among mutant strains of coronaviruses during spread and evolution. Herein, we demonstrate novel vaccine candidates against SARS-CoV-2 by using the whole conserved N-protein or its fragment/peptides. Using ELISA assay, we showed that high titers of specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting that N-protein is an excellent immunogen to stimulate host immune system and robust B-cell activation. We synthesized three peptides located at the conserved regions of N-protein among CoVs. One peptide showed as a good immunogen for vaccination as well. Cytokine arrays on post-vaccination mouse sera showed progressive up-regulation of various cytokines such as IFN-γ and CCL5, suggesting that TH1 associated responses are also stimulated. Furthermore, vaccinated mice exhibited an elevated memory T cells population. Here, we propose an unconventional vaccine strategy targeting the conserved N-protein as an alternative vaccine target for coronaviruses. Moreover, we generated a mouse monoclonal antibody specifically against an epitope shared between SARS-CoV and SARS-CoV-2, and we are currently developing the First-in-Class humanized anti-N-protein antibody to potentially treat patients infected by various CoVs in the future.

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.

The SARS-CoV-2 pandemic prompts evaluation of recombination in human coronavirus (hCoV) evolution. We undertook recombination analyses of 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV genome sequences using the RDP4 software. We found moderate evidence for 8 SARS-CoV-2 recombination events, two of which involved the spike gene, and low evidence for one SARS-CoV-1 recombination event. Within MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, we noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively. There was propensity for recombination breakpoints in the non-ORF1 region of the genome containing structural genes, and recombination severely skewed the temporal structure of these data, especially for NL63 and OC43. Bayesian time-scaled analyses on recombinant-free data indicated the sampled diversity of seasonal CoVs emerged in the last 70 years, with 229E displaying continuous lineage replacements. These findings emphasize the importance of genomic based surveillance to detect recombination in SARS-CoV-2, particularly if recombination may lead to immune evasion.

Summary Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy. (Funded by the Singapore National Research Foundation and National Medical Research Council.)

We compared the electrostatic properties of the spike proteins (S-proteins) of three coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2, and their interactions with photosensitizers (PSs), octacationic octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) and monocationic methylene blue (MB). We found a major common PS binding site at the connection of the S-protein stalk and head. The molecules of Zn-PcChol8+ and MB also form electrostatic encounter complexes with large area of negative electrostatic potential at the head of the S-protein of SARS-CoV-2, between fusion protein and heptad repeat 1 domain. The top of the SARS-CoV spike head demonstrates a notable area of electrostatic contacts with Zn-PcChol8+ and MB that corresponds to the N-terminal domain. The S-protein protomers of SARS-CoV-2 in “open” and “closed” conformations demonstrate different ability to attract PS molecules. In contrast with Zn-PcChol8+, MB possesses the ability to penetrate inside the pocket formed as a result of SARS-CoV-2 receptor binding domain transition into the “open” state. The existence of binding site for cationic PSs common to the S-proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV creates prospects for the wide use of this type of PSs to combat the spread of coronaviruses.

Within the last 2 decades, severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks; yet, for reasons not fully understood, the coronavirus disease 2019 pandemic caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1, despite striking similarities between these two viruses. The SARS-CoV-1 and SARS-CoV-2 spike proteins, both of which bind to host cell angiotensin-converting enzyme 2, have been implied to be a potential source of their differential transmissibility. However, the mechanistic details of prefusion spike protein binding to angiotensin-converting enzyme 2 remain elusive at the molecular level. Here, we performed an extensive set of equilibrium and nonequilibrium microsecond-level all-atom molecular dynamics simulations of SARS-CoV-1 and SARS-CoV-2 prefusion spike proteins to determine their differential dynamic behavior. Our results indicate that the active form of the SARS-CoV-2 spike protein is more stable than that of SARS-CoV-1 and the energy barrier associated with the activation is higher in SARS-CoV-2. These results suggest that not only the receptor-binding domain but also other domains such as the N-terminal domain could play a crucial role in the differential binding behavior of SARS-CoV-1 and SARS-CoV-2 spike proteins.

Recent outbreaks of zoonotic coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have caused tremendous casualties and great economic shock. Although some repurposed drugs have shown potential therapeutic efficacy in clinical trials, specific therapeutic agents targeting coronaviruses have not yet been developed. During coronavirus replication, a replicase gene cluster, including RNA-dependent RNA polymerase (RdRp), is alternatively translated via a process called -1 programmed ribosomal frameshift (−1 PRF) by an RNA pseudoknot structure encoded in viral RNAs. The coronavirus frameshifting has been identified previously as a target for antiviral therapy. In this study, the frameshifting efficiencies of MERS-CoV, SARS-CoV and SARS-CoV-2 were determined using an in vitro −1 PRF assay system. Our group has searched approximately 9689 small molecules to identify potential −1 PRF inhibitors. Herein, we found that a novel compound, 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline (KCB261770), inhibits the frameshifting of MERS-CoV and effectively suppresses viral propagation in MERS-CoV-infected cells. The inhibitory effects of 87 derivatives of furo[2,3-b]quinolines were also examined showing less prominent inhibitory effect when compared to compound KCB261770. We demonstrated that KCB261770 inhibits the frameshifting without suppressing cap-dependent translation. Furthermore, this compound was able to inhibit the frameshifting, to some extent, of SARS-CoV and SARS-CoV-2. Therefore, the novel compound 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline may serve as a promising drug candidate to interfere with pan-coronavirus frameshifting.

The COVID-19 pandemic is caused by SARS-CoV-2, a novel zoonotic coronavirus. Emerging evidence indicates that preexisting humoral immunity against other seasonal human coronaviruses (HCoVs) plays a critical role in the specific antibody response to SARS-CoV-2. However, current work to assess the effects of preexisting and cross-reactive anti-HCoVs antibodies has been limited. To address this issue, we have adapted our previously reported multiplex assay to simultaneously and quantitatively measure anti-HCoV antibodies. The full mPlex-CoV panel covers the spike (S) and nucleocapsid (N) proteins of three highly pathogenic HCoVs (SARS-CoV-1, SARS-CoV-2, MERS) and four human seasonal strains (OC43, HKU1, NL63, 229E). Combining this assay with volumetric absorptive microsampling (VAMS), we measured the anti-HCoV IgG, IgA, and IgM antibodies in fingerstick blood samples. The results demonstrate that the mPlex-CoV assay has high specificity and sensitivity. It can detect strain-specific anti-HCoV antibodies down to 0.1 ng/ml with 4 log assay range and with low intra- and inter-assay coefficients of variation (%CV). We also estimate multiple strain HCoVs IgG, IgA and IgM concentration in VAMS samples in three categories of subjects: pre-COVID-19 (n=21), post-COVID-19 convalescents (n=19), and COVID-19 vaccine recipients (n=14). Using metric multidimensional scaling (MDS) analysis, HCoVs IgG concentrations in fingerstick blood samples were well separated between the pre-COVID-19, post-COVID-19 convalescents, and COVID-19 vaccine recipients. In addition, we demonstrate how multi-dimensional scaling analysis can be used to visualize IgG mediated antibody immunity against multiple human coronaviruses. We conclude that the combination of VAMS and the mPlex-Cov assay is well suited to performing remote study sample collection under pandemic conditions to monitor HCoVs antibody responses in population studies.

The source of the COVID-19 pandemic is unknown, but the natural host of the progenitor sarbecovirus is thought to be Asian horseshoe (rhinolophid) bats. We identified and sequenced a novel sarbecovirus (RhGB01) from a British horseshoe bat, at the western extreme of the rhinolophid range. Our results extend both the geographic and species ranges of sarbecoviruses and suggest their presence throughout the horseshoe bat distribution. Within the spike protein receptor binding domain, but excluding the receptor binding motif, RhGB01 has a 77% (SARS-CoV-2) and 81% (SARS-CoV) amino acid homology. While apparently lacking hACE2 binding ability, and hence unlikely to be zoonotic without mutation, RhGB01 presents opportunity for SARS-CoV-2 and other sarbecovirus homologous recombination. Our findings highlight that the natural distribution of sarbecoviruses and opportunities for recombination through intermediate host co-infection are underestimated. Preventing transmission of SARS-CoV-2 to bats is critical with the current global mass vaccination campaign against this virus.

Pulmonary fibrosis is the end stage of a broad range of heterogeneous interstitial lung diseases and more than 200 factors contribute to it. In recent years, the relationship between virus infection and pulmonary fibrosis is getting more and more attention, especially after the outbreak of SARS-CoV-2 in 2019, however, the mechanisms underlying the virus-induced pulmonary fibrosis are not fully understood. Here, we review the relationship between pulmonary fibrosis and several viruses such as Human T-cell leukemia virus (HTLV), Human immunodeficiency virus (HIV), Cytomegalovirus (CMV), Epstein–Barr virus (EBV), Murine γ-herpesvirus 68 (MHV-68), Influenza virus, Avian influenza virus, Middle East Respiratory Syndrome (MERS)-CoV, Severe acute respiratory syndrome (SARS)-CoV and SARS-CoV-2 as well as the mechanisms underlying the virus infection induced pulmonary fibrosis. This may shed new light on the potential targets for anti-fibrotic therapy to treat pulmonary fibrosis induced by viruses including SARS-CoV-2.

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses

Introduction: Seven coronavirus species have been identified that can infect humans. While human coronavirus infections had been historically associated with only mild respiratory symptoms similar to the common cold, three coronaviruses identified since 2003, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, cause life-threatening severe respiratory syndromes. The coronavirus disease 2019 (COVID-19) caused by the highly transmissible SARS-CoV-2 has triggered a worldwide health emergency. Due to the lack of effective drugs and vaccination, rapid and reliable detection is of vital importance to control coronavirus epidemics/pandemics.Area covered: A literature search was performed in Pubmed covering the detections and diagnostics of SARS, MERS and SARS-CoV-2. This review summarized the current knowledge of established and emerging methods for coronavirus detection. The characteristics of different diagnostic approaches were described, and the strengths and weaknesses of each method were analyzed and compared. In addition, future trends in the field of coronavirus detection were also discussed.Expert opinion: Nucleic acid-based RT-PCR is the current golden-standard of coronavirus detection, while immunoassays provide history of coronavirus infection besides diagnostic information. Integrated high-throughput system holds the great potential and is the trend of future detection and diagnosis of virus infection.

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

BackgroundSevere Acute Respiratory Syndrome (SARS) corona virus (CoV) infections are a serious public health threat because of their pandemic-causing potential. This work is the first to analyze mRNA expression data from SARS infections through meta-analysis of gene signatures, possibly identifying therapeutic targets associated with major SARS infections.MethodsThis work defines 37 gene signatures representing SARS-CoV, Middle East Respiratory Syndrome (MERS)-CoV, and SARS-CoV2 infections in human lung cultures and/or mouse lung cultures or samples and compares them through Gene Set Enrichment Analysis (GSEA). To do this, positive and negative infectious clone SARS (icSARS) gene panels are defined from GSEA-identified leading-edge genes between two icSARS-CoV derived signatures, both from human cultures. GSEA then is used to assess enrichment and identify leading-edge icSARS panel genes between icSARS gene panels and 27 other SARS-CoV gene signatures. The meta-analysis is expanded to include five MERS-CoV and three SARS-CoV2 gene signatures. Genes associated with SARS infection are predicted by examining the intersecting membership of GSEA-identified leading-edges across gene signatures.ResultsSignificant enrichment (GSEA pConclusionThe GSEA-based meta-analysis approach used here identifies genes with and without reported associations with SARS-CoV infections, highlighting this approach’s predictability and usefulness in identifying genes that have potential as therapeutic targets to preclude or overcome SARS infections.

A COVID-19 diagnosis is usually based on PCR detection of viral RNA in airway specimens in a patient with typical clinical fea-tures. Histological features of the COVID-19 lung disease are reported from autopsies. Transbronchial cryobiopsy (TBCB) is an evolving technique usually performed in the diagnosis of interstitial lung disease. We report a TBCB in a 76-year-old female patient who had repeatedly tested negative for SARS-CoV-2 infection. The pathological examination revealed the presence of interstitial pneumonia with lymphocytic infiltration. The qRT-PCR against SARS-CoV-2 from a pharyngeal swab was positive after performing the TBCB.

Last December 2019, a new virus, named novel Coronavirus (COVID-2019) causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID-2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID-2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast-unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab non structural protein 2 (nsp2) and nsp3 was tested by TMHMM, MEMSAT, and MEMPACK tools. Three-dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (P .05). Position 723 in the COVID-2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (P .05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared with severe acute respiratory syndrome (SARS) and Bat SARS-like CoV. The stabilizing mutation falling in the endosome-associated-protein-like domain of the nsp2 protein could account for COVID-2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID-2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen.

Data sources This review included 13 clinical studies (observational or clinical trial) which reported results of studies of the 2019 novel coronavirus (2019-nCoV). The other 62 referenced papers were of different types (eg, reviews, WHO protocols, letter to editor etc). Study selection The study selected trials, reviews, and in-vitro research assessing the critical aspects of saliva as an easily accessible and early-stage diagnostic source, and also an entry route for 2019-nCoV. Most of the clinical studies were descriptive case series of patients who had contracted 2019-nCoV in China. These were mainly studies designed to compare saliva samples with throat swabs, with regard to the presence of 2019-nCoV RNA. Another aspect of the included studies was the susceptibility of oral tissues to 2019-nCoV due to the expression of angiotensin-converting enzyme II (ACE2) as a receptor for the 2019-nCoV. Some review studies and clinical infection control protocols were also included to discuss the transmission patterns of 2019-nCoV from the oral cavity. Studies were not restricted to English language and they were not all full-text papers. Data extraction and synthesis A narrative synthesis of the results was conducted using distinct headings and subheadings, defined by the authors based on relevancy to the consensus about the importance of saliva with reference to 2019-nCoV. Results There was an inherent heterogeneity among the included clinical studies concerning their designs, sampling techniques, and the results about the diagnostic value of saliva. The percentage of coronavirus disease of 2019 (COVID-19) patients with positive 2019-nCoV RNA varied from 12.9% to 91.67% among these studies. Regarding the possibility of direct virus invasion into the oral tissues, the results suggested that ACE2+ cells in salivary glands could possibly be the target cells of 2019-nCoV and theoretically could generate infectious saliva in a sustained way. Furin was suggested as another protein which makes the tongue more vulnerable to 2019-nCoV, especially in conditions inducing its upregulation (for example, squamous cell carcinoma). According to the comparisons between 2019-nCoV and SARS-CoV, saliva could be considered of diagnostic value via the early detection of viral RNA for both of the viruses. Whilst the viral peak was shown to be at onset of symptoms for 2019-nCoV, it can linger up to the tenth day after the appearance of symptoms for SARS-CoV. Finally, this paper warns about airborne transmission, particularly for close contacts. Conclusions Saliva can be proposed as an easily accessible diagnostic source although further clinical studies are required. Given the presence of viral RNA in saliva in the early stages of COVID-19, the recommendations to wear masks to prevent the rapid transmission of infectious droplets into the air, and keep a safe distance from other people are clearly based in evidence.

We profiled the serological responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and spike (S) glycoprotein. The majority of the patients developed robust antibody responses between 17 and 23 days after illness onset. Delayed, but stronger antibody responses were observed in critical patients.

This report presents a novel approach to estimate the total number of COVID-19 cases in the United States, including undocumented infections, by combining the Centers for Disease Control and Prevention’s influenza-like illness surveillance data with aggregated prescription data. We estimated that the cumulative number of COVID-19 cases in the United States by 4 April 2020 was > 2.5 million.

The viruses causing the SARS outbreak of 2002-2003 and current COVID-19 pandemic are related betacoronaviruses. What insights were learned from SARS that can inform SARS-CoV-2 vaccine development? Focusing on important lessons from SARS vaccine development and two SARS vaccines evaluated in humans may guide SARS-CoV-2 vaccine design, testing, and implementation.

In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.