RESUMEN
The emergence of SARS-CoV-2 variants of concern has prompted the need for near real-time genomic surveillance to inform public health interventions. In response to this need, the global scientific community, through unprecedented effort, has sequenced and shared over 10 million genomes through GISAID, as of May 2022. This extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info, a platform that currently tracks over 40 million combinations of PANGO lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials, and the general public. We describe the interpretable and opinionated visualizations in the variant and location focussed reports available in our web application, the pipelines that enable the scalable ingestion of heterogeneous sources of SARS-CoV-2 variant data, and the server infrastructure that enables widespread data dissemination via a high performance API that can be accessed using an R package. We present a case study that illustrates how outbreak.info can be used for genomic surveillance and as a hypothesis generation tool to understand the ongoing pandemic at varying geographic and temporal scales. With an emphasis on scalability, interactivity, interpretability, and reusability, outbreak.info provides a template to enable genomic surveillance at a global and localized scale.
RESUMEN
Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness. One-Sentence SummarySocioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.
RESUMEN
The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.
RESUMEN
In vitro antibody selection against pathogens from naive combinatorial libraries can yield various classes of antigen-specific binders that are distinct from those evolved from natural infection1-4. Also, rapid neutralizing antibody discovery can be made possible by a strategy that selects for those interfering with pathogen and host interaction5. Here we report the discovery of antibodies that neutralize SARS-CoV-2, the virus responsible for the COVID-19 pandemic, from a highly diverse naive human Fab library. Lead antibody 5A6 blocks the receptor binding domain (RBD) of the viral spike from binding to the host receptor angiotensin converting enzyme 2 (ACE2), neutralizes SARS-CoV-2 infection of Vero E6 cells, and reduces viral replication in reconstituted human nasal and bronchial epithelium models. 5A6 has a high occupancy on the viral surface and exerts its neutralization activity via a bivalent binding mode to the tip of two neighbouring RBDs at the ACE2 interaction interface, one in the "up" and the other in the "down" position, explaining its superior neutralization capacity. Furthermore, 5A6 is insensitive to several spike mutations identified in clinical isolates, including the D614G mutant that has become dominant worldwide. Our results suggest that 5A6 could be an effective prophylactic and therapeutic treatment of COVID-19.
RESUMEN
The emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV, the etiological agent that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike (S) glycoprotein of SARS-CoV in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV fragment were able to recognise the S protein of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19.
