New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV-2 pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID-19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.
By conducting a retrospective, cross-sectional analysis of SARS-CoV-2 seroprevalence in a sentinel group (enriched for SARS-CoV-2 infections) and a screening group (representative of the general population) using >5,000 plasma samples from patients at Mount Sinai Hospital in New York City (NYC), we identified seropositive samples as early as in the week ending February 23, 2020. A stark increase in seropositivity in the sentinel group started the week ending March 22 and in the screening group in the week ending March 29. By the week ending April 19, the seroprevalence in the screening group reached 19.3%, which is well below the estimated 67% needed to achieve community immunity to SARS-CoV-2. These data potentially suggest an earlier than previously documented introduction of SARS-CoV-2 into the NYC metropolitan area.
As severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infections continue, there is a substantial need for cost‐effective and large‐scale testing that utilizes specimens that can be readily collected from both symptomatic and asymptomatic individuals in various community settings. Although multiple diagnostic methods utilize nasopharyngeal specimens, saliva specimens represent an attractive alternative as they can rapidly and safely be collected from different populations. While saliva has been described as an acceptable clinical matrix for the detection of SARS‐CoV‐2, evaluations of analytic performance across platforms for this specimen type are limited. Here, we used a novel sensitive RT‐PCR/MALDI‐TOF mass spectrometry‐based assay (Agena MassARRAY®) to detect SARS‐CoV‐2 in saliva specimens. The platform demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of the platform and determined the limit of detection of the assay to be 1562.5 copies/ml. Furthermore, across the five individual target components of this assay, there was a range in analytic sensitivities for each target with the N2 target being the most sensitive. Overall, this system also demonstrated comparable performance when compared to the detection of SARS‐CoV‐2 RNA in saliva by the cobas® 6800/8800 SARS‐CoV‐2 real‐time RT‐PCR Test (Roche). Together, we demonstrate that saliva represents an appropriate matrix for SARS‐CoV‐2 detection on the novel Agena system as well as on a conventional real‐time RT‐PCR assay. We conclude that the MassARRAY® system is a sensitive and reliable platform for SARS‐CoV‐2 detection in saliva, offering scalable throughput in a large variety of clinical laboratory settings.
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