ABSTRACT
Background: Infections with SARS-CoV- 2 cause the coronavirus disease 2019 (COVID-19) pandemic. Alterations in immune cells of COVID-19 patients may predict the subsequent severity of disease. The changes in composition of immune cells in COVID-19 patients include lymphopenia, lower neutrophil to lymphocyte-ratios and an eosinopenia in about 50 to 80% of hospitalized patients. Eosinophils and neutrophils can interact with T cells via immune checkpoints receptors such as programmed death (PD)-1 on T cells and its counterpart PD-ligand 1 (PD-L1) on eosinophils or neutrophils. There are only limited studies on PD-1 and PD-L1 expressions in viral infections, we aimed to elucidate the interplay of T cells and other peripheral cells by analysing the immune checkpoints PD-1 and PD-L1 in expression during COVID-19. Method(s): Using flow cytometry, we have now analysed the immune checkpoint receptor expressions on whole blood cells from a total of 38 COVID-19 patients. The patient cohort comprises all ages and both sexes with the disease severity ranging from mild, moderate to severe, with ~10% mortality. We have further been investigating 21 biomarkers (G-CSF, GM-CSF, IFN-gamma, TGF-beta1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-23, IL-33, IP-10, MCP-1, MIP-1beta, TNF-alpha, and YKL-40) in plasma on a cohort of 76 COVID-19 patients using the MesoScale Multiplex Assay platform, with 48 healthy controls. Result(s): PD-L1 expression on eosinophils was significantly lower in COVID-19 patients in initial stages of infection, relative to healthy controls. There was an inverse relationship between disease progression and the expression of PD-1 on CD8+ T cells. These data suggests that analysis of PD-L1- PD1 cell networks in immune cells of EDTA blood of COVID-19 patients can predict disease outcomes. While most detectable biomarkers are strongly increased in COVID samples overall compared to healthy controls, the more severe the disease the higher the blood biomarker concentration. Conclusion(s): Taken together, the analysis of PD-L1- PD1 cell networks in immune cells together with plasma biomarkers of COVID-19 patients can predict disease outcomes.
ABSTRACT
Background. The COVID pandemic shifted antimicrobial stewardship resources at community hospitals. One reason for this shift was new COVID treatments, the first of which was remdesivir, which received initial emergency use authorization (EUA) for the treatment of COVID-19 in May 2020. The UNC Health Southeastern (UNC SEH) pharmacy director stewarded remdesivir by reviewing patients to ensure they met emergency use authorization (EUA) and guideline-based appropriateness criteria. The infectious diseases physician resolved any disputes regarding patient candidacy for remdesivir. The goal of remdesivir stewardship was to optimize care;however, the shift in workflow presented an unrecognized opportunity for stewards to reduce remdesivir costs. Methods. The percentage of COVID patient admissions receiving remdesivir at UNC SEH for calendar years 2020 and 2021 was benchmarked against 32 community hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) (Figure 1). UNC SEH purchasing data were used to calculate remdesivir expenditures for 2020 and 2021. Next, the anticipated cost if the hospital had prescribed remdesivir to the same percentage of admissions as the DASON mean was calculated. The difference was calculated to determine the cost avoidance achieved by having below average use of remdesivir (Table 1). Results. At UNC SEH, 28.1% of COVID admissions received remdesivir in 2020 and annual remdesivir expenditures were $693,680. In 2021, 47.45% of COVID-19 admissions received remdesivir and drug expenditures were $1,248,000. The DASON mean % of COVID admissions receiving remdesivir in 2020 was 44.08% and 60.07% in 2021. A total cost avoidance of $726,407 was calculated based on the hospital's below-benchmark use of remdesivir (Table 1). Conclusion. UNC SEH achieved significant cost-savings in 2020 and 2021 due to active remdesivir stewardship. The team created a patient-centered model that focused on using drugs for the right patients and the organization realized cost-savings while ensuring that patients received therapy in accordance with remdesivir EUAs and published guidelines.
ABSTRACT
Background. COVID-19 shifted antibiotic stewardship program resources and changed antibiotic use (AU). Shifts in patient populations with COVID surges, including pauses to surgical procedures, and dynamic practice changes makes temporal associations difficult to interpret. Our analysis aimed to address the impact of COVID on AU after adjusting for other practice shifts. Methods. We performed a longitudinal analysis of AU data from 30 Southeast US hospitals. Three pandemic phases (1: 3/20-6/20;2: 7/20-10/20;3: 11/20-2/21) were compared to baseline (1/2018-1/2020). AU (days of therapy (DOT)/1000 patient days (PD)) was collected for all antimicrobial agents and specific subgroups: broad spectrum (NHSN group for hospital-onset infections), CAP (ceftriaxone, azithromycin, levofloxacin, moxifloxacin, and doxycycline), and antifungal. Monthly COVID burden was defined as all PD attributed to a COVID admission. We fit negative binomial GEE models to AU including phase and interaction terms between COVID burden and phase to test the hypothesis that AU changes during the phases were related to COVID burden. Models included adjustment for Charlson comorbidity, surgical volume, time since 12/2017 and seasonality. Results. Observed AU rates by subgroup varied over time;peaks were observed for different subgroups during distinct pandemic phases (Figure). Compared to baseline, we observed a significant increase in overall, broad spectrum, and CAP groups during phase 1 (Table). In phase 2, overall and CAP AU was significantly higher than baseline, but in phase 3, AU was similar to baseline. These phase changes were separate from effects of COVID burden, except in phase 1 where we observed significant effects on antifungal (increased) and CAP (decreased) AU (Table). Conclusion. Changes in hospital AU observed during early phases of the COVID pandemic appeared unrelated to COVID burden and may have been due to indirect pandemic effects (e.g., case mix, healthcare resource shifts). By pandemic phase 3, these disruptive effects were not as apparent, potentially related to shifts in non-COVID patient populations or ASP resources, availability of COVID treatments, or increased learning, diagnostic certainty, and provider comfort with avoiding antibacterials in patients with suspected COVID over time. (Figure Presented).
ABSTRACT
Background: Older Nursing Home Residents (NHRs) are at greatest risk of morbidity and mortality from SARS-CoV-2, particularly in the context of both waning vaccine efficacy and the emergence of Variants-of-Concern (VOCs). However, the determinants of long-term vaccine-induced protective antibody responses are yet to be determined in this group. Methods: NH-COVAIR recruited older NHRs for comprehensive clinical and frailty (NH-FRAIL) assessment. Blood samples were obtained pre-vaccination, at 6-weeks and 6-months following primary vaccination and 6-months following booster vaccination. Antibody titres were measured using both an electrochemiluminescence assay and a custom bead-based array (Luminex™) to measure antibody titre and avidity for Wuhan strain/major VOC antigens. Stepwise adjusted linear regression (log-transformed) assessed longitudinal determinants of vaccine-induced antibody responses. Results: Of 86 participants (81.1 ± 10.8 years;65% female), just under half (45.4%) had evidence of previous SARS-CoV-2 infection. All NHRs mounted a significant antibody-response to vaccination at 5 weeks followed by a significant decrease in antibody titre by 6 months. Previous SARS-CoV-2 infection was the strongest predictor of antibody waning at all timepoints (β: 3.59;2.89, 4.28;P < 0.001 for 6-months). Independent of infection history, both age (β: –0.05;–0.08, –0.02;p<0.001) and frailty (β: –0.22;–0.33, –0.11;p<0.001) were associated with faster antibody waning at 6-months. Cross-reactivity and avidity were significantly lower for Beta (B.1.351) and Gamma (P.1) VOC strains (all p<0.001). Additionally, there was faster antibody waning and significantly reduced antibody avidity to Beta and Gamma VOCs in SARS-CoV-2 naïve NHRs. Conclusion: Older NHRs are capable of mounting protective antibody responses to SARS-CoV-2 vaccination. Responses were more durable, with a greater cross-reactivity to and avidity for VOCs in those with previous SARS-CoV-2 infection. Increasing age and greater frailty in NHRs was associated with faster antibody waning. Our findings support ongoing serological surveillance and use of additional vaccine doses in older NHRs, particularly in those without previous SARS-CoV-2 exposure.
ABSTRACT
Introduction Older nursing home residents are the population at greatest risk of morbidity and mortality from SARS-CoV-2 infection. No studies have examined the determinants of long-term antibody responses post-vaccination in this group. Method Longitudinal cohort study in residents of 5 nursing homes assessed prior to vaccination and at both 5-weeks and 6-months post SARS-CoV2 vaccine (BNT162b2). Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty (NH-FRAIL) and SARS-CoV-2 infection history. Serum Nucleocapsid and Anti-Spike Receptor Binding Domain (RBD) antibodies were analysed at all timepoints and an in vitro Angiotensin Converting Enzyme (ACE2) Receptor-Spike RBD neutralisation assay used to assess serum neutralisation capacity. Results Of 86 participants (81.1 ± 10.8 years;65% female), just-under half (45.4%;39/86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5-weeks and a significant decline in this response by 6-months. SARS-CoV-2 infection history was the strongest predictor of antibody titre (log-transformed) at both 5-weeks (β: 3.00;95% CI [Confidence Interval]: 2.32, 3.70;p < 0.001) and 6-months (β: 3.59;95% CI: 2.89, 4.28;p < 0.001). Independent of SARS-CoV-2 infection history, both age in years (β: -0.05;95% CI: −0.08, −0.02;p < 0.001) and frailty (β: -0.22;95% CI: −0.33, −0.11;p < 0.001) were associated with a lower antibody titre at 6-months. Antibody titres at both 5-weeks and 6-months significantly correlated with in vitro neutralisation capacity. Conclusion and Implications In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titres at 6-months, whilst age and frailty were independently associated with lower titres at 6-months. Antibody titres significantly correlated with in vitro neutralisation capacity. Whilst older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titres, SARS-CoV-2 infection and clinical outcomes remains to be fully elucidated in this cohort.
ABSTRACT
Background. The COVID-19 pandemic placed a strain on inpatient clinical and hospital programs due to increased patient volume and rapidly evolving data on best COVID-19 management strategies. However, the impact of the pandemic on ASPs has not been well described. Methods. We performed a cross-sectional electronic survey of stewardship pharmacy and physician leaders in 37 hospitals within the Duke Antimicrobial Stewardship Outreach Network (DASON) (community) and Duke/UNC Health systems (academic) in April-May 2021. The survey included 60 questions related to staffing changes, use of COVID-targeted therapies, related restrictions, and medication shortages. Results. Twenty-seven facilities responded (response rate of 73%). Pharmacy personnel was reduced in 17 (63%) facilities by an average of 16%. Impacted pharmacy personnel included the stewardship lead in 15/17 (88.2%) hospitals. Converting to remote work was rare and only reported in academic institutions (n=2, 7.4%). ASP personnel were reassigned to non-stewardship duties in 12 (44%) hospitals with only half returning to routine ASP work as of May 2021. Respondents estimated that 62% of routine ASP activities were diverted during the time of the pandemic. Non-traditional, pandemic-related ASP activities included managing multiple drug shortages, of which ventilator support medications (91%) were most common affecting patient care at 52% of facilities. Steroid and hydroxychloroquine shortages were less frequent (44% and 22%, respectively). Despite staff reductions, pharmacists often served as primary contact for remdesivir approvals either using a criteria-based checklist at dispensing or as part of a dedicated phone approval team (Figure). Most (77%) hospitals used a criteria-based pharmacist review strategy after remdesivir FDA approval. Restriction processes for other COVID-19 therapies such as tocilizumab, hydroxychloroquine, and ivermectin were reported in 64% of hospitals. Proportion of facilities implementing specific remdesivir allocation strategies from the time of the first US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) through FDA approval Conclusion. Pandemic response diverted routine ASP work and has not yet returned to baseline. Despite the reduction in pharmacy personnel due to the pandemic, the ASP pharmacy lead took on a novel and critical stewardship role throughout the pandemic exemplified by their involvement in novel treatment allocation for COVID patients.