Physical Function Does Not Predict Care Assessment Need Score in Older Veterans

Objective: The Veterans Health Administration’s Care Assessment Need (CAN) score is a statistical model, aimed to predict high-risk patients. We were interested in determining if a relationship existed between physical function and CAN scores. Method: Seventy-four older (71 ± 1 years) male Veterans underwent assessment of CAN score and subjective (Short Form–36 [SF-36]) and objective (self-selected walking speed, four square step test, short physical performance battery) assessment of physical function. Results: Approximately 25% of participants self-reported limitations performing lower intensity activities, while 70% to 90% reported limitations with more strenuous activities. When compared with cut points indicative of functional limitations, 35% to 65% of participants had limitations for each of the objective measures. Any measure of subjective or objective physical function did not predict CAN score. Conclusion: These data indicate that the addition of a physical function assessment may complement the CAN score in the identification of high-risk patients. </jats:p

In Vitro Study Comparing SARS-CoV-2 Ancestral and Omicron Lineages Sequence &amp; Neutralization Differences

Introduction: COVID-19 remains a worldwide public health concern. SARS-CoV-2 binds to cells via its spike (S) protein, which has undergone significant evolution since its emergence. New SARS-CoV-2 variants can differentially escape antibody neutralization. In 2022 the Omicron variant BA.2 emerged and its diversity expanded to include BA.4 and BA.5 later that same year. During this time, the XBB lineage also emerged, as a recombination event between two BA.2 subvariants, with XBB.1.5 becoming the predominant circulating Omicron sub lineage. BA.2.86.1 independently arose through the evolution of BA.2, from which JN.1 evolved in 2023; JN.1 was the predominant circulating variant as of April 2024. This study compared sequence changes in the spike protein of SARS-CoV-2 between ancestral WA1/2020 and Omicron lineages and evaluated the impact of those sequence differences on neutralization. Methods: Human sera were obtained from adult participants aged ≥ 18 years who received either the BA.4/BA.5 bivalent vaccine or the XBB.1.5 monovalent vaccine. Serum samples selected for analysis were collected the day of vaccination, and 12-56 days after last vaccination from participants who had no prior diagnosis of infection with SARS-CoV-2 based on self-reporting or negative anti-nucleocapsid antibodies detected in the serum samples. In vitro neutralization activity of paired pre- and post- SARS-CoV-2 vaccination sera pools were tested using a focus reduction neutralization test (FRNT) against ancestral strain USA-WA1/2020, and Omicron variants XBB.1.5, JD.1.1.1, BA.2.86 and JN.1. Results: Compared to variants that circulated before JN.1, phylogenetic analysis of JN.1 variants revealed a higher proportion of spike mutations R346T and F456L. Compared to vaccination with the bivalent BA.4/BA.5 vaccine, vaccination with the XBB.1.5 monovalent vaccine resulted in greater neutralizing antibody titers against JD.1.1.1, BA.2.86, and JN.1 in vitro than vaccination with the bivalent BA.4/BA.5 vaccine. The monovalent booster also increased serum antibody neutralization of XBB.1.5, and bivalent vaccine increased neutralization of the ancestral strain. Discussion: This study suggests that sequence changes in the spike protein of SARS-CoV-2 result in changes in neutralization of SARS-CoV-2 Omicron variants and that broader neutralizing antibody responses against emerging Omicron variants of different parentage may be achieved with updated vaccine formulations. Ongoing monitoring of the correlation between genotypic characterization and phenotypic characterization via neutralization of SARS-CoV-2 infection as this virus continues to evolve is important. Conclusion: SARS-CoV-2 remains prevalent worldwide with ongoing spike protein evolution underscoring the need for continued monitoring of SARS-CoV-2 variant proportions and assessment of vaccine-induced neutralization of emerging variants. These data can inform interpretation of vaccine effectiveness and decisions about COVID-19 vaccine composition

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as JN lineages ), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, 18 October 2023-9 March 2024

Background Assessing variant-specific coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages.Methods We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 US states admitted 18 October 2023-9 March 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression.Results A total of 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4580 control patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% confidence interval [CI], 36.1-67.1%) against XBB lineage hospitalization and 32.7% (95% CI, 1.9-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR], .80; 95% CI, .46-1.38) and IMV or death (aOR, .69; 95% CI, .34-1.40) were not significantly different among JN compared with XBB lineage hospitalizations.Conclusions Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB. Analysis of data from a US inpatient surveillance network showed that updated 2023-2024 COVID-19 vaccination provided protection against hospitalization for SARS-CoV-2 XBB and JN lineages. Clinical severity of JN lineage hospitalizations was not increased relative to XBB lineage hospitalizations