Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data.

OBJECTIVES: To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans. DESIGN: Test-negative case-control study of SARS-CoV-2 mRNA vaccine effectiveness. SETTING: Veterans Health Administration (VHA) medical centers. PARTICIPANTS: Veterans 19 years and older who had at least one COVID-19/Flu like symptoms and received a SARS-CoV-2 PCR or antigen test at VHA medical centers between July 25 to September 30, 2021. INTERVENTION: mRNA vaccination. MEASUREMENTS: New SARS-CoV-2 infection. Vaccine effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls, where cases were patients who had a COVID-19 test and tested positive for SARS-CoV-2, and controls were those who tested negative. Frailty was measured using the VA frailty index, categorized as robust (0-<0.1), pre-frail (≥0.1-<0.21) and frail (≥0.21). RESULTS: A total of 58,604 patients (age:58.9±17.0, median:61, IQR:45-72; 87.5%men; 68.1%white; 1.3%African American, 8.3%Hispanic) were included in the study. Of these, 27,733 (47.3%) were robust, 16,276 (27.8%) were prefrail, and 14,595 (24.9%) were frail. mRNA vaccine effectiveness against the Delta variant symptomatic infection was lower in patients with frailty, 62.8 %(95%CI:59.8-65.7), versus prefrail 73.9%(95%CI:72.0-75.7), and robust, 77.0 %(95%CI:75.7-78.3). CONCLUSIONS: This test-negative case control study showed that mRNA vaccine effectiveness against infection declined in veterans with frailty. Frailty status is a factor to consider when designing, developing, and evaluating COVID-19 vaccines.

Association between a Frailty Index from Common Laboratory Values and Vital Signs (FI-LAB) and Hospital and Post-Hospital Outcomes in Veterans with COVID-19 Infection.

OBJECTIVES: Determine the association of higher FI-LAB scores, derived from common laboratory values and vital signs, with hospital and post-hospital outcomes in Veterans hospitalized with COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter, cohort study of 7 Veterans Health Administration (VHA) medical centers in Florida and Puerto Rico. Patients aged 18 years and older hospitalized with COVID-19 and followed for up to 1 year post discharge or until death. Clinical Frailty Measure: FI-LAB. MAIN OUTCOMES AND MEASURES: Hospital and post-hospital outcomes. RESULTS: Of the 671 eligible patients, 615 (91.5%) patients were included (mean [SD] age, 66.1 [14.8] years; 577 men [93.8%]; median stay, 8 days [IQR:3-15]. There were sixty-one in-hospital deaths. Veterans in the moderate and high FI-LAB groups had a higher proportion of inpatient mortality (13.3% and 20.6%, respectively) than the low group (4.1%), p <0.001. Moderate and high FI-LAB scores were associated with greater inpatient mortality when compared to the low group, OR:3.22 (95%CI:1.59-6.54), p=.001 and 6.05 (95%CI:2.48-14.74), p<0.001, respectively. Compared with low FI-LAB scores, moderate and high scores were also associated with prolonged length of stay, intensive care unit (ICU) admission, and transfer. CONCLUSIONS AND RELEVANCE: In this study of patients admitted to 7 VHA Hospitals during the first surge of the pandemic, higher FI-LAB scores were associated with higher in-hospital mortality and other in-hospital outcomes; FI-LAB can serve as a validated, rapid, feasible, and objective frailty tool in hospitalized adults with COVID-19 that can aid clinical care.

Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data

Objectives To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans. Design Test-negative case-control study of SARS-CoV-2 mRNA vaccine effectiveness. Setting Veterans Health Administration (VHA) medical centers. Participants Veterans 19 years and older who had at least one COVID-19/Flu like symptoms and received a SARS-CoV-2 PCR or antigen test at VHA medical centers between July 25 to September 30, 2021. Intervention mRNA vaccination. Measurements New SARS-CoV-2 infection. Vaccine effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls, where cases were patients who had a COVID-19 test and tested positive for SARS-CoV-2, and controls were those who tested negative. Frailty was measured using the VA frailty index, categorized as robust (0–<0.1), pre-frail (≥0.1–<0.21) and frail (≥0.21). Results A total of 58,604 patients (age:58.9±17.0, median:61, IQR:45–72;87.5%men;68.1%white;1.3%African American, 8.3%Hispanic) were included in the study. Of these, 27,733 (47.3%) were robust, 16,276 (27.8%) were prefrail, and 14,595 (24.9%) were frail. mRNA vaccine effectiveness against the Delta variant symptomatic infection was lower in patients with frailty, 62.8 %(95%CI:59.8–65.7), versus prefrail 73.9%(95%CI:72.0–75.7), and robust, 77.0 %(95%CI:75.7–78.3). Conclusions This test-negative case control study showed that mRNA vaccine effectiveness against infection declined in veterans with frailty. Frailty status is a factor to consider when designing, developing, and evaluating COVID-19 vaccines. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12603-023-1885-1 and is accessible for authorized users.

Association between a Frailty Index from Common Laboratory Values and Vital Signs (FI-LAB) and Hospital and Post-Hospital Outcomes in Veterans with COVID-19 Infection

Objectives Determine the association of higher FI-LAB scores, derived from common laboratory values and vital signs, with hospital and post-hospital outcomes in Veterans hospitalized with COVID-19 infection. Design, Setting, and Participants A retrospective, multicenter, cohort study of 7 Veterans Health Administration (VHA) medical centers in Florida and Puerto Rico. Patients aged 18 years and older hospitalized with COVID-19 and followed for up to 1 year post discharge or until death. Clinical Frailty Measure: FI-LAB. Main Outcomes and Measures Hospital and post-hospital outcomes. Results Of the 671 eligible patients, 615 (91.5%) patients were included (mean [SD] age, 66.1 [14.8] years;577 men [93.8%];median stay, 8 days [IQR:3-15]. There were sixty-one in-hospital deaths. Veterans in the moderate and high FI-LAB groups had a higher proportion of inpatient mortality (13.3% and 20.6%, respectively) than the low group (4.1%), p <0.001. Moderate and high FI-LAB scores were associated with greater inpatient mortality when compared to the low group, OR:3.22 (95%CI:1.59-6.54), p=.001 and 6.05 (95%CI:2.48-14.74), p<0.001, respectively. Compared with low FI-LAB scores, moderate and high scores were also associated with prolonged length of stay, intensive care unit (ICU) admission, and transfer. Conclusions and Relevance In this study of patients admitted to 7 VHA Hospitals during the first surge of the pandemic, higher FI-LAB scores were associated with higher in-hospital mortality and other in-hospital outcomes;FI-LAB can serve as a validated, rapid, feasible, and objective frailty tool in hospitalized adults with COVID-19 that can aid clinical care. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12603-023-1886-0 and is accessible for authorized users.

The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty.

BACKGROUND: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 ("mild") or 6 ("moderate"), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

Resuscitation status changes in hospitalized older veterans with frailty and COVID-19 infection

Background: COVID-19 infection in older adults may cause serious clinical complications requiring hospitalization. Frailty is a clinical syndrome characterized by a loss of physiologic reserve that increases the risk for poor health outcomes. Identification of frailty status during hospitalization my influence clinicians, patients and surrogates' resuscitation decisions. The study aim was to determine whether frailty changes resuscitation decisions (code) in hospitalized older veterans with COVID 19 infection. Methods: Retrospective case series of Veterans ≥65 years old, hospitalized with COVID-19 infection at 7 VA centers in Florida from March-August 2020. We used a 31-item VA Frailty index (VA-FI) to determine frailty status on admission based on clinical variables found in the medical records. The VA-FI categorized veterans in two groups: non- frail (FI<.21) and frail (FI≥.21). Information on changes in code status upon admission and during hospitalization were obtained from in-depth chart audits. After adjusting for age, gender, race, and ethnicity, we performed a binomial logistic regression by calculating Odds ratios (OR) with 95% confidence intervals (CI) with frailty status as the independent variable and change in code status from FC to DNR/DNI as the dependent variable. Results: 400 Older Veterans were hospitalized, mean age 76.30 (SD=8.26) years, 64.75% Caucasian (n=259), 85.25% non-Hispanic (n=341), and 97.25% (n=389) male. On hospital admission, 73.50% (n=294) were full code (FC), 25.50% (n=102) had do not resuscitate/ do not intubate (DNR/DNI) status and 1.00% (n=4) had DNR/OK to intubate order. During the course of the hospital stay, 18 Veterans changed code status from FC to DNR/DNI (Non-frail n=4, 13.33%, frail n=14, 46.67%) and 12 changed from DNR/DNI to FC (Non-frail n=5, 16.67%, frail n=7, 23.33%). Frailty status was not associated with the decision to change code status from FC to DNR (OR:1.65 95%CI .226-12.092, p=0.620). Conclusion: In older Veterans hospitalized with COVID-19 infection frailty status was not associated with changes in code status from full code to DNR/DNI. Future studies are needed to confirm these preliminary findings in larger and more diverse populations.

Association between a frailty index of laboratory values (FI-LAB) and inpatient mortality in veterans hospitalized with COVID-19

Background: Frailty is a syndrome characterized by vulnerability to stressors resulting from multisystemic loss of physiological reserve associated with poor clinical outcomes. Recent studies have shown worse outcomes and higher mortality rate in older adults with COVID 19 infection. The risk for mortality may be even higher in hospitalized older adults with coexistent frailty and COVID 19 infection. The FI-LAB is a validated, objective measure of frailty in acute care settings which is based on laboratory values and vital signs. The study aim was to assess the FI-LAB score as a predictor of inpatient mortality in Veterans admitted with COVID-19 Infection. Methods: Retrospective cohort study conducted in a population of veterans admitted with COVID-19 infection to 7 VISN 8 acute care facilities across Florida. We calculated the 31-item FI-LAB using laboratory values and vital signs upon admission. Veterans were categorized as low (<0.25), moderate (0.25-0.40), and high (>0.40) based on FI-LAB scores. Differences in inpatient mortality among the 3 FI-LAB groups were determined using a Cox regression model, adjusted for age, BMI, gender, race, and ethnicity. Results: 700 patients were hospitalized, mean age 66.03 (range:22-103, SD=14.86) years, Caucasian 58.14% (n=407), non-Hispanic 81.71% (n=572), and 93.86% (n=657) male. According to the FI-LAB, 47.42% (n=332), 43.85% (n=307), and 8.71% (n=61) were in the low, moderate and high groups, respectively. There were 53 total inpatient deaths (<65, n=6, 11.32% and ≥65 years, n=47, 88.68%): FI-LAB low 10 (3.01%), moderate 3 (10.09%), high 12 (19.67%), p<.0005. The median follow up was 5 days (IQR=12). As compared with the low FI-LAB group, Veterans in the moderate and high groups had higher mortality risk, adjusted hazard ratio (HR)=2.87 (95%CI:1.36-6.06), p=0.006 and HR=5.23 (95%CI:2.10-13.06), respectively, p<.005. Conclusions: Moderate and higher FI-LAB groups were associated with higher inpatient mortality than the low category. Most deaths were among older adults. The FI-LAB may identify patients at higher mortality risk and assist clinicians in the development of early strategies to reduce mortality in hospitalized older patients with frailty and COVID 19 infection.

Erratum to: Screening for and Managing the Person with Frailty in Primary Care: ICFSR Consensus Guidelines (The journal of nutrition, health & aging, (2020), 10.1007/s12603-020-1492-3)

The authors apologize for a typing error that occurred in the September 2020 article that changes the meaning of a sentence. Correction: Page 921, right column, 2nd paragraph, line 8, change «match» to «watch» so it reads, «Primary care providers should watch for frailty development due to physical inactivity during the COVID-19 pandemic (47).» In addition, the author listed as “C. Won Won” wishes to be known as “C.W. Won.” © 2020, The Journal of Nutrition, Health & Aging.