No abstract

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.

T he prototypical vaccine used in postexposure settings was developed over a century ago for use following exposure to a potentially rabid animal (9, 14). Postexposure vaccination remains the worldwide standard for the prevention of rabies infections of humans. Despite the long history of rabies vaccine use as a postexposure treatment and the facts that over two-thirds of the world population live in regions where rabies is endemic and that over 55,000 people die every year due to RV infections, little information is available regarding the development of effective B cell responses early postvaccination, which may influence the outcome of postexposure vaccine efficacy. Current vaccines for human use are based on inactivated RV strains. Therefore, vaccineinduced protection against RV has long been described as being dependent solely on CD4 ϩ T cell help for the induction of protective antibody responses (9). These observations are supported by experiments carried out in RV-vaccinated nude mice that did not develop anti-RV antibody responses and were not protected against pathogenic challenge in preexposure settings (29). Similarly, Mifune et al. (16) showed that vaccinated athymic nude mice did not produce anti-RV antibodies in postexposure experiments. Furthermore, neutralizing antibodies directed against RV antigens were shown to be produced only with the assistance of Thelper cells (1). Finally, T cell depletion studies further showed the importance of CD4 ϩ T cells in generating neutralizing, protective antibodies in mice after RV infection (21). Together, these experiments showed that current inactivated RV-based vaccines rely on T cell help for the elicitation of effective antibody responses associated with protection against pathogenic challenge.Vaccine-induced immunity is a complex process involving innate and adaptive immune responses. During the development of typical vaccine-induced immunity, antigen-primed T cells migrate to the T and B cell borders of secondary lymphoid organs, where they interact with their cognate antigen-specific B cells. After activation, B cells differentiate into early, short-lived extrafollicular plasma cells, germinal center (GC) B cells, or early unswitched memory B cells that can recirculate (7). Within GCs, B cells differentiate into memory B cells or long-lived plasma cells that secrete high-affinity, postswitched antibodies. In most cases, fully formed GC-derived memory B cells and plasma cells can take from days to weeks to develop. From a traditional vaccination standpoint, this lag time between vaccination and GC B cell development is required and usually acceptable, since GC B cells are critical for long-term B cell responses to protect against future exposure to the pathogen. However, vaccines are also used in postexposure settings after exposure to pathogens, such as for RV. Since the lag time between vaccination and the generation of effective GC B cell responses might be too long, administration of postexposure vaccines for the prevention of rabies infection may...

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.

No abstract