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In late January 2021, a clinical laboratory notified the Maryland Department of Health (MDH) that the SARS-CoV-2 variant of concern B.1.351 had been identified in a specimen collected from a Maryland resident with COVID-19 (1). The SARS-CoV-2 B.1.351 lineage was first identified in South Africa (2) and might be neutralized less effectively by antibodies produced after vaccination or natural infection with other strains (3-6). To limit SARS-CoV-2 chains of transmission associated with this index patient, MDH used contact tracing to identify the source of infection and any linked infections among other persons. The investigation identified two linked clusters of SARS-CoV-2 infection that included 17 patients. Three additional specimens from these clusters were sequenced; all three had the B.1.351 variant and all sequences were closely related to the sequence from the index patient's specimen. Among the 17 patients identified, none reported recent international travel or contact with international travelers. Two patients, including the index patient, had received the first of a 2-dose COVID-19 vaccination series in the 2 weeks before their likely exposure; one additional patient had a confirmed SARS-CoV-2 infection 5 months before exposure. Two patients were hospitalized with COVID-19, and one died. These first identified linked clusters of B.1.351 infections in the United States with no apparent link to international travel highlight the importance of expanding the scope and volume of genetic surveillance programs to identify variants, completing contact investigations for SARS-CoV-2 infections, and using universal prevention strategies, including vaccination, masking, and physical distancing, to control the spread of variants of concern.

Background Whole genome sequencing (WGS) is increasingly used for pathogen identification and surveillance. Aim We evaluated costs and benefits of routine WGS through case studies at eight reference laboratories in Europe and the Americas which conduct pathogen surveillance for avian influenza (two laboratories), human influenza (one laboratory) and food-borne pathogens (five laboratories). Methods The evaluation focused on the institutional perspective, i.e. the ‘investment case’ for implementing WGS compared with conventional methods, based on costs and benefits during a defined reference period, mostly covering at least part of 2017. A break-even analysis estimated the number of cases of illness (for the example of Salmonella surveillance) that would need to be avoided through WGS in order to ‘break even’ on costs. Results On a per-sample basis, WGS was between 1.2 and 4.3 times more expensive than routine conventional methods. However, WGS brought major benefits for pathogen identification and surveillance, substantially changing laboratory workflows, analytical processes and outbreaks detection and control. Between 0.2% and 1.1% (on average 0.7%) of reported salmonellosis cases would need to be prevented to break even with respect to the additional costs of WGS. Conclusions Even at cost levels documented here, WGS provides a level of additional information that more than balances the additional costs if used effectively. The substantial cost differences for WGS between reference laboratories were due to economies of scale, degree of automation, sequencing technology used and institutional discounts for equipment and consumables, as well as the extent to which sequencers are used at full capacity.

BackgroundThe E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine.MethodsGenetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding.ResultsOf 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68).ConclusionThough more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.SummaryIn viruses sequenced for Maryland’s routine SARS-CoV-2 genomic surveillance, the spike protein amino acid substitution E484K was more prevalent in viruses that infected vaccinated people than in viruses that infected people who were not vaccinated.

Among 9048 people infected with SARS-CoV-2 between January and May 2021 in Maryland, in regression-adjusted analysis, SARS-CoV-2 viruses carrying the spike protein mutation E484K were disproportionately prevalent among persons infected after full vaccination against COVID-19 compared with infected persons who were not fully vaccinated (aOR, 1.96; 95% CI: 1.36–2.83).

Background Historically, United States’ carbapenem-resistant Enterobacterales (CRE) surveillance and mechanism testing focused on three genera: Escherichia, Klebsiella, and Enterobacter (EsKE); however, other genera can harbour mobile carbapenemases associated with CRE spread. Objectives From January through May 2018, we conducted a 10 state evaluation to assess the contribution of less common genera (LCG) to carbapenemase-producing (CP) CRE. Methods State public health laboratories (SPHLs) requested participating clinical laboratories submit all Enterobacterales from all specimen sources during the surveillance period that were resistant to any carbapenem (Morganellaceae required resistance to doripenem, ertapenem, or meropenem) or were CP based on phenotypic or genotypic testing at the clinical laboratory. SPHLs performed species identification, phenotypic carbapenemase production testing, and molecular testing for carbapenemases to identify CP-CRE. Isolates were categorized as CP if they demonstrated phenotypic carbapenemase production and ≥1 carbapenemase gene (blaKPC, blaNDM, blaVIM, blaIMP, or blaOXA-48-like) was detected. Results SPHLs tested 868 CRE isolates, 127 (14.6%) were from eight LCG. Overall, 195 (26.3%) EsKE isolates were CP-CRE, compared with 24 (18.9%) LCG isolates. LCG accounted for 24 (11.0%) of 219 CP-CRE identified. Citrobacter spp. was the most common CP-LCG; the proportion of Citrobacter that were CP (11/42, 26.2%) was similar to the proportion of EsKE that were CP (195/741, 26.3%). Five of 24 (20.8%) CP-LCG had a carbapenemase gene other than blaKPC. Conclusions Participating sites would have missed approximately 1 in 10 CP-CRE if isolate submission had been limited to EsKE genera. Expanding mechanism testing to additional genera could improve detection and prevention efforts.

Background In April 2017, the Maryland Department of Health (MDH) began screening healthcare contacts of confirmed cases of carbapenemase-producing carbapenem-resistant organisms (CP-CROs) to identify potential transmission, per guidance published by the Centers for Disease Control and Prevention. The results of MDH’s CP-CRO colonization screening surveys (CSSs) conducted as of April 1, 2018, are summarized. Methods Rectal swabs were collected on epidemiologically linked CP-CRO contacts and sent to the MDH Laboratories Administration, where the Cepheid Xpert® Carba-R assay was used to detect five carbapenemases: Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron encoded metallo-β-lactamase (VIM), imipenemase (IMP), and oxacillinase-48-like carbapenemase (OXA-48). Identification of CP-CROs in contacts sometimes resulted in additional CSSs to ensure complete case detection. Non-KPC cases were combined for analysis. Results During April 1, 2017–April 1, 2018, MDH received reports of 278 incident cases of confirmed CP-CROs. Of these, 16 (6%) expressed non-KPC carbapenemases. The 7 (3%) cases with healthcare contacts prompting CSSs led to screening of 132 first-round contacts, with additional CP-CROs identified in 13 (10%), all of which had KPC. Of these, 12 (92%) resided in ventilator units of skilled nursing facilities (vSNFs). In the first-round CSS at one vSNF, 64% of screened contacts were positive for KPC, which had not been identified in the index case. Weekly follow-up CP-CRO admission screenings and serial follow-up CSSs at the vSNF resulted in screening of a total of 72 unique patients; 38 (53%) were KPC-positive. Of these 38 cases, 32 (89%) were previously unidentified and were placed on contact precautions if not already on them. Staff were re-trained in infection prevention (IP) techniques, and staff and KPC-positive patients were cohorted. Conclusion Detection of CP-CROs that express non-KPC carbapenemases in Maryland is rare, and transmission of these carbapenemases has not been identified. However, CSSs identified previously unknown cases of KPC, most commonly in vSNFs, demonstrating the utility of CSSs to detect CP-CROs, and resulting in important IP interventions. Disclosures All authors: No reported disclosures.

Our lab has demonstrated age-related coronary microvascular dysfunction can be reversed by aerobic exercise training; however, the mechanisms that underlie age- and exercise training-induced adaptations of the coronary microvasculature remain to be identified. The adipokine, adiponectin, possesses cardioprotective properties, including anti-atherosclerotic and anti-inflammatory effects in the vascular wall, and is known to inhibit vascular smooth muscle (VSM) proliferation in large arteries. Circulating adiponectin declines with age and increases with regular exercise training. Therefore, we hypothesized that alterations in signaling through the adiponectin/AMPKinase axis contribute to age- and exercise training-induced adaptations of the coronary microvasculature, particularly in VSM. Young (4 mos) and old (22 mos) male Fischer 344 rats were randomly assigned to either a sedentary or an exercise training group. Circulating adiponectin levels were measured by ELISA. Coronary arterioles from the left ventricular (LV) free wall were isolated for assessment of contractile function and VSM proliferation, and levels of contractile and proliferative proteins. Circulating adiponectin levels decreased with age and increased after 10 wks of exercise training in both young and old rats. Age impaired contractile responses of coronary arterioles, and increased proliferation of arteriolar VSM. Age reduced levels of AMPKinase and contractile proteins, smooth muscle myosin 1 (SM1) and smooth muscle myosin 2 (SM2), and increased total levels and phosphorylation of ribosomal protein S6 (rpS6), a downstream effector of mammalian target of rapamycin (mTOR). Exercise training reversed age-induced contractile dysfunction and attenuated VSM proliferation in coronary arterioles. Exercise training restored contractile function and reduced proliferation in coronary arterioles from old rats. Exercise training also returned AMPKinase, SM1, rpS6 and phosphorylated rpS6 levels in arterioles of old rats to those found in arterioles of young rats. These data indicate that changes in adiponectin/AMPKinase axis contribute to age- and exercise training-induced alterations of coronary microvascular phenotype and function.