Highlights d A SARS-CoV-2 variant with Spike G614 has replaced D614 as the dominant pandemic form d The consistent increase of G614 at regional levels may indicate a fitness advantage d G614 is associated with lower RT PCR Cts, suggestive of higher viral loads in patients d The G614 variant grows to higher titers as pseudotyped virions

S evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the current rapidly growing outbreak of coronavirus disease (COVID-19), originating from the city of Wuhan, Hubei Province, China (1). Initially, 41 cases of "pneumonia of unknown etiology" were reported to the World Health Organization by the Wuhan Municipal Health Committee at the end of December 2019 (2). On January 8, 2020, the pathogen was identified (1), and human-to-human transmission was reported soon after. By January 21, most provinces of China had reported COVID-19 cases. By March 16, the outbreak had led to >170,000 total confirmed cases and >6,500 deaths globally. In a period of 3 months, an outbreak of apparent idiopathic pneumonia had become the COVID-19 pandemic.Studying dynamics of a newly emerged and rapidly growing infectious disease outbreak, such as COVID-19, is important but challenging because

Despite improved control measures, Ebola remains a serious public health risk in African regions where recurrent outbreaks have been observed since the initial epidemic in 1976. Using epidemic modeling and data from two well-documented Ebola outbreaks (Congo 1995 and Uganda 2000), we estimate the number of secondary cases generated by an index case in the absence of control interventions R0. Our estimate of R0 is 1.83 (SD 0.06) for Congo (1995) and 1.34 (SD 0.03) for Uganda (2000). We model the course of the outbreaks via an SEIR (susceptible-exposed-infectious-removed) epidemic model that includes a smooth transition in the transmission rate after control interventions are put in place. We perform an uncertainty analysis of the basic reproductive number R0 to quantify its sensitivity to other disease-related parameters. We also analyse the sensitivity of the final epidemic size to the time interventions begin and provide a distribution for the final epidemic size. The control measures implemented during these two outbreaks (including education and contact tracing followed by quarantine) reduce the final epidemic size by a factor of 2 relative the final size with a 2-week delay in their implementation.

The SARS-CoV-2 Spike protein acquired a D614G mutation early in the pandemic that confers greater infectivity and is now the globally dominant form. To determine whether D614G might also mediate neutralization-escape that could compromise vaccine efficacy, sera from Spike-immunized mice, nonhuman primates and humans were evaluated for neutralization of pseudoviruses bearing either D614 or G614 spike. In all cases, the G614 pseudovirus was moderately more susceptible to neutralization. The G614 pseudovirus also was more susceptible to neutralization by receptor binding domain (RBD) monoclonal antibodies and convalescent sera from people infected with either form of the virus. Negative stain electron microscopy revealed a higher percentage of the 1-RBD “up” conformation in the G614 spike, suggesting increased epitope exposure as a mechanism of enhanced vulnerability to neutralization. Based on these findings, the D614G mutation is not expected to be an obstacle for current vaccine development.

Highlights d B.1.1.7 is not a neutralization escape variant of concern for COVID-19 vaccines d B.1.1.7 is unlikely to increase the risk of SARS-CoV-2 reinfection d B.1.1.7 escapes a subset of RBD-specific antibodies