MoMo30 Binds to SARS-CoV-2 Spike Variants and Blocks Infection by SARS-CoV-2 Pseudovirus.

MoMo30 is an antiviral protein isolated from aqueous extracts of Momordica balsamina L. (Senegalese bitter melon). Previously, we demonstrated MoMo30's antiviral activity against HIV-1. Here, we explore whether MoMo30 has antiviral activity against the COVID-19 virus, SARS-CoV-2. MLV particles pseudotyped with the SARS-CoV-2 Spike glycoprotein and a Luciferase reporter gene (SARS2-PsV) were developed from a three-way co-transfection of HEK293-T17 cells. MoMo30's inhibition of SARS2-PsV infection was measured using a luciferase assay and its cytotoxicity using an XTT assay. Additionally, MoMo30's interactions with the variants and domains of Spike were determined by ELISA. We show that MoMo30 inhibits SARS2-PsV infection. We also report evidence of the direct interaction of MoMo30 and SARS-CoV-2 Spike from WH-1, Alpha, Delta, and Omicron variants. Furthermore, MoMo30 interacts with both the S1 and S2 domains of Spike but not the receptor binding domain (RBD), suggesting that MoMo30 inhibits SARS-CoV-2 infection by inhibiting fusion of the virus and the host cell via interactions with Spike.

The Surgical Management of NCAA Division 1 College Football Injuries Post COVID-19: A Single Institution Retrospective Review.

ABSTRACT: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning.

Modifying Whole Health Services for Successful Telehealth Delivery: Lessons from Veterans Health Administration's Rapid Transition During the COVID-19 Pandemic.

Introduction: The Veterans Health Administration (VHA) is shifting care from a disease-oriented to health-creating approach that aims to provide whole person care. This Whole Health (WH) system combines person-centered care with delivery of WH services (e.g., health coaching, well-being education and skill-building classes, and evidence-based complementary and integrative health therapies), alongside conventional medical services. During the COVID-19 pandemic, WH services were modified for delivery through telehealth (teleWH). This article characterizes modifications to WH services made to maintain continuity during the transition to telehealth formats. Materials and methods: We conducted semistructured qualitative interviews with a purposive sample of 51 providers delivering teleWH services at 10 VHA medical centers. We examined WH service modifications as well as facilitators and barriers to those modifications using rapid coding and directed content analysis. Results: Modifications were driven by (1) preparing for teleWH service delivery and (2) improving teleWH service delivery. To prepare for teleWH services, modifications were prompted by access, readiness, and setting and resources. Modifications to improve the delivery of teleWH services were motivated by engagement, community-building, safety, and content for a teleWH environment. One-on-one teleWH services required the fewest modifications, while more significant modifications were needed for well-being, skill-building, and movement-based groups, and reconfiguration of manual therapies. Discussion: Findings highlighted the need for modifications to ensure that teleWH services are accessible and safe and support interpersonal relationships between patients and providers, as well as in group-based classes. Successfully delivering teleWH services requires proactive preparation that considers access, readiness, and the availability of resources to engage in teleWH services. Tailoring strategies and considering the unique needs of different teleWH services are critical. Conclusions: The COVID-19 pandemic catalyzed teleWH service implementation, utilization, and sustainment. The challenges faced and modifications made during this transition provide lessons learned for other health care systems as they attempt to implement teleWH services.

Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents.

Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies. Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies. Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.

Whole Health coaching to rural Veterans through telehealth: Advantages, gaps, and opportunities.

Background: The Veterans Health Administration (VHA) is one of the largest providers of telehealth in the United States and continues to lead the way in transforming healthcare services. VHA has been implementing its Whole Health (WH) initiative since 2018, a proactive practice empowering patients to take charge of their health and well-being. A key facilitator of the WH initiative is the WH coach who partners with Veterans to achieve their health-related goals. A gap exists in the literature regarding the understanding of WH coaches' use of telehealth to engage rural-residing Veterans. COVID-19 unexpectedly interrupted in-person VHA delivery of care, including WH coaching which primarily relied on in-person delivery and focused less on telehealth. During the pandemic, WH coaches had to adapt and integrate different modalities to engage their Veteran patients. We examined WH coaches' approaches to extending coaching to rural Veterans via technology, emphasizing the advantages of telehealth, existing gaps in telehealth delivery, and opportunities for telehealth as a coaching modality. Methods: This project was implemented as part of a larger mixed methods evaluation regarding WH coaching for rural Veterans; this manuscript presents the findings from the qualitative data from the larger study. The qualitative dataset is comprised of data collected using three different qualitative methods: four focus groups (n = 11; 3-4 participants per group), in-depth individual interviews (n = 9), and open-ended responses from a national web-based survey (n = 140). Focus group, in-depth interview, and open-ended survey data were collected sequentially and separately analyzed following each wave of data collection. Findings from the three analyses were then collaboratively merged, compared, reorganized, and refined by the evaluation team to create final themes. Results: Three final themes that emerged from the merged data were: (1) Advantages of Telehealth; (2) Telehealth Gaps for Rural Veterans, and (3) Strategies for Bridging Telehealth Gaps. Themes explicate telehealth advantages, gaps, and opportunities for rural Veteran WH coaching. Conclusion: Findings highlight that video telehealth alone is not sufficient for meeting the needs of rural Veterans. Digital technologies hold promise for equalizing health access gaps; however, both human factors and broadband infrastructure constraints continue to require WH coaches to use a mix of modalities in working with rural Veterans. To overcome challenges and bridge gaps, WH coaches should be ready to adopt a blended approach that integrates virtual, in-person, and lower-tech options.

Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.1.1.529) variant (ARO) in 6-week-old female BALB/c mice. AdW and AdB were administered intramuscularly or intranasally, while ARW and ARO were administered intramuscularly. Intranasal or intramuscular vaccination with AdB followed by ARO booster exhibited the highest levels of cross-reactive IgG, pseudovirus-neutralising antibody (PNAb) responses, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition rates against different 2019-nCoV variants among all vaccination groups. Moreover, intranasal AdB vaccination followed by ARO induced higher levels of IgA and neutralising antibody responses against live 2019-nCoV than intramuscular AdB vaccination followed by ARO. A single dose of AdB administered intranasally or intramuscularly induced broader cross-NAb responses than AdW. Th1-biased cellular immune response was induced in all vaccination groups. Intramuscular vaccination-only groups exhibited higher levels of Th1 cytokines than intranasal vaccination-only and intranasal vaccination-containing groups. However, no obvious differences were found in the levels of Th2 cytokines between the control and all vaccination groups. Our findings provide a basis for exploring vaccination strategies against different 2019-nCoV variants to achieve high broad-spectrum immune efficacy.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

Sequentially immune-induced antibodies could cross-neutralize SARS-CoV-2 variants.

BACKGROUND: The Omicron (B.1.1.529) SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike protein. Since the vaccine-induced neutralizing antibody targets are the spike protein, this may lead to the possibility of vaccine-induced humoral immunity escape. METHODS: We measured the neutralizing activity in vitro for Omicron and compared this with wild type (WH-09) and Delta variants in human and monkey sera from different types of immunity. The monkey sera samples were collected at 1 and 3 months post three-dose inactivated (PiCoVacc) and recombinant protein (ZF2001) vaccination. Human sera were collected from 1 month post three-dose inactivated vaccination. RESULTS: In inactivated vaccine sera, at 1/3 months post three-dose, geometric mean titers (GMTs) of neutralization antibody (NAb) against the Omicron variant were 4.9/5.2-fold lower than those of the wild type. In recombinant protein vaccine sera, GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild type. In human sera, at 1 month post three-dose inactivated vaccination, GMTs of NAb against Omicron were 3.1-fold lower than those of the wild type. CONCLUSION: This study demonstrated that despite a reduction in neutralization titers, cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination.

Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects.

Introduction: An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methods: The novel N-IgY-pAb and its intranasal spray response against the wild type ("'WH-Human 1") SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray. Results: Seventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121). Discussion and conclusion: We concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and "cocktails" of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.

Return-to-work, disabilities and occupational health in the age of COVID-19.

We have read with great interest the two editorials by Burdorf et al: "The COVID-19 pandemic: one year later - an occupational perspective" (1) and "The COVID-19 (Coronavirus) pandemic: consequences for occupational health" (2). The authors highlight the importance of the societal consequences of the outbreak and changes in the world of work to manage occupational health. The key points identified - such as individual socio-economic factors, psychological effects and occupations with highest risk of contamination - modify return-to-work approaches. It is estimated that around 800 million people of working age worldwide were living with disabilities before the SARS-CoV-2 pandemic. In early January 2021, the cumulative COVID-19 hospitalisation rate reached 207.4/100 000 (18-49-year-olds) and 505.7/100 000 (50-64-year-olds), respectively, in the United States (3). In France, the hospitalisation rate was 411.5/100 000 across all ages (4). A recent cohort study of working-age men who were hospitalised for COVID-19 highlighted the long-term health consequences of such a disease (5). The SARS-CoV-2 pandemic creates new challenges for occupational health, shifting attention away from return-to-work after health problems to resuming work during an outbreak, dealing with lockdown, and taking special account of workers with vulnerabilities (6, 7). We recommend considering three different aspects of occupational medicine during a pandemic. Firstly, for most workers at high-risk of severe COVID-19, the issues of work disability and resuming work had never occurred before the epidemic. Recommendations such as physical and social distancing and wearing a facemask are highly advisable to protect against infection but may not be enough to enable some individuals to resume work. Therefore, decision-making requires individual comprehensive assessments of the underlying medical condition, the SARS-CoV-2 contamination risk associated with either regular work or teleworking, and vaccination opportunities. The second situation concerns workers who have suffered from COVID-19. Preliminary studies suggest that long recovery duration is related to high severity (7), but this is still a matter of debate for patients suffering from "long COVID-19" (5, 8, 9), a condition for which the long-term effects remain unknown. Any long-running recovery must be considered to be a potential sign of long COVID-19. These long-lasting syndromes occur among patients with severe symptoms but have also been reported independently of acute phase severity, hospitalisation and receiving medical oxygen (8, 9). Researchers worldwide are currently investigating such syndromes. Strategies promoting return to work for these workers will need to be implemented and could be similar to programmes developed for other chronic conditions. Moreover, numerous more serious sequelae following critical illness suggest the need for enhanced support by rehabilitation and occupational health specialists. Finally, the consequences of the epidemic must be evaluated over time for people who suffered from functional limitations before COVID-19 as their physical and mental condition may be modified by the epidemic and, specifically, the consequences of lockdown (10). In all of these situations, medical, social, financial and working contexts are key elements. In addition to a medical assessment, the use of scales such as the Work Ability Index (WAI) (11) or the Work Productivity and Activity Impairment (WPAI) (12) can help perform long-term follow-up and provide information about work capacity and workload. It also gives a "back to basics" perspective, urging politicians to move towards a `decent-work-for-all` policy, as advocated by the United Nation`s Sustainable Development Goal (SDG) 8, which the WHO has endorsed (13). References 1. Burdorf A, Porru F, Rugulies R. The COVID-19 pandemic: one year later - an occupational perspective. Scand J Work Environ Health - online first. https://doi.org/10.5271/sjweh.3956 2. Burdorf A, Porru F, Rugulies R. The COVID-19 (Coronavirus) pandemic: consequences for occupational health. Scand J Work Environ Health. 2020;46(3):229-230. https://doi:org/10.5271/sjweh.3893. 3. COVID-19 Hospitalizations [Internet]. Available from: https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html 4. COVID-19 in France, vaccine and allergy management in occupational setting. Descatha A et al. Arch Mal Prof Environ 2021. Accepted for publication. 5. Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021;397(10270):220-32 https://doi.org/10.1016/S0140-6736(20)32656-8 6. Shaw WS, Main CJ, Findley PA, Collie A, Kristman VL, Gross DP. Opening the Workplace After COVID-19: What Lessons Can be Learned from Return-to-Work Research? J Occup Rehabil. 2020;30(3):299-302. https://doi.org/10.1007/s10926-020-09908-9 7. Taylor T, Das R, Mueller K, Pransky G, Christian J, Orford R, et al. Safely Returning America to Work: Part I: General Guidance for Employers. J Occup Environ Med. 2020;62(9):771-9. https://doi.org/10.1097/JOM.0000000000001984 8. Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;324(6):603-5. https://doi.org/10.1001/jama.2020.12603 9. Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020. MMWR Morb Mortal Wkly. 2020;69(30):993-8. https://doi.org/10.15585/mmwr.mm6930e1 10. Chudasama YV, Gillies CL, Zaccardi F, Coles B, Davies MJ, Seidu S, et al. Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals. Diabetes Metab Syndr. 2020;14(5):965-7. https://doi.org/10.1016/j.dsx.2020.06.042 11. Tuomi K. Eleven-year follow-up of aging workers. Scand J Work Environ Health. 1997;23(1):1-71. 12. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics. 1993;4(5):353-65. https://doi.org/10.2165/00019053-199304050-00006 13. Organization WH. Health in the 2030 agenda for sustainable development. Sixty-Ninth World Health Assembly. Document A. 2016, p69.

Natural and human environment interactively drive spread pattern of COVID-19: A city-level modeling study in China.

A novel Coronavirus COVID-19 has caused high morbidity and mortality in China and worldwide. A few studies have explored the impact of climate change or human activity on the disease incidence in China or a city. The integrated study concerning environment impact on the emerging disease is rarely reported. Therefore, based on the two-stage modeling study, we investigate the effect of both natural and human environment on COVID-19 incidence at a city level. Besides, the interactive effect of different factors on COVID-19 incidence is analyzed using Geodetector; the impact of effective factors and interaction terms on COVID-19 is simulated with Geographically Weighted Regression (GWR) models. The results find that mean temperature (MeanT), destination proportion in population flow from Wuhan (WH), migration scale (MS), and WH*MeanT, are generally promoting for COVID-19 incidence before Wuhan's shutdown (T1); the WH and MeanT play a determinant role in the disease spread in T1. The effect of environment on COVID-19 incidence after Wuhan's shutdown (T2) includes more factors (including mean DEM, relative humidity, precipitation (Pre), travel intensity within a city (TC), and their interactive terms) than T1, and their effect shows distinct spatial heterogeneity. Interestingly, the dividing line of positive-negative effect of MeanT and Pre on COVID-19 incidence is 8.5°C and 1 mm, respectively. In T2, WH has weak impact, but the MS has the strongest effect. The COVID-19 incidence in T2 without quarantine is also modeled using the developed GWR model, and the modeled incidence shows an obvious increase for 75.6% cities compared with reported incidence in T2 especially for some mega cities. This evidences national quarantine and traffic control take determinant role in controlling the disease spread. The study indicates that both natural environment and human factors integratedly affect the spread pattern of COVID-19 in China.

Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.

Emerging infectious diseases always pose a threat to humans along with plant and animal life. SARS-CoV2 is the recently emerged viral infection that originated from Wuhan city of the Republic of China in December 2019. Now, it has become a pandemic. Currently, SARS-CoV2 has infected more than 27.74 million people worldwide, and taken 901,928 human lives. It was named first 'WH 1 Human CoV' and later changed to 2019 novel CoV (2019-nCoV). Scientists have established it as a zoonotic viral disease emerged from Chinese horseshoe bats, which do not develop a severe infection. For example, Rhinolophus Chinese horseshoe bats harboring severe acute respiratory syndrome-related coronavirus (SARSr-CoV) or SARSr-Rh-BatCoV appear healthy and clear the virus within 2-4 months period. The article introduces first the concept of EIDs and some past EIDs, which have affected human life. Next section discusses mysteries regarding SARS-CoV2 origin, its evolution, and human transfer. Third section describes COVID-19 clinical symptoms and factors affecting susceptibility or resistance. The fourth section introduces the SARS-CoV2 entry in the host cell, its replication, and the establishment of productive infection. Section five describes the host's immune response associated with asymptomatic, symptomatic, mild to moderate, and severe COVID-19. The subsequent seventh and eighth sections mention the immune status in COVID-19 convalescent patients and re-emergence of COVID-19 in them. Thereafter, the eighth section describes viral strategies to hijack the host antiviral immune response and generate the "cytokine storm". The ninth section describes about transgenic humane ACE2 (hACE2) receptor expressing mice to study immunity, drugs, and vaccines. The article ends with the development of different immunomodulatory and immunotherapeutics strategies, including vaccines waiting for their approval in humans as prophylaxis or treatment measures.

A new coronavirus associated with human respiratory disease in China.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China

Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1-3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.