Background:Advancing the HIV response in Missouri, an Ending the HIV Epidemic priority state, requires stronger characterization of treatment gaps. Routine cross-sectional reporting may fail to capture important gaps in care that longitudinal methods can reveal. Methods:We characterized clinic engagement and viral suppression among people with Human Immunodeficiency Virus (HIV) aged ≥18 years who were newly linked to clinic in St Louis, Missouri, between 1 January 2015 and 15 March 2020. Using multistate analytic methods that capture change over time, we estimated the prevalence of individuals in 9 mutually exclusive and exhaustive states over 3 years following linkage to clinic. Care states were based on engagement (disengagement ≥90 days late for a scheduled appointment) and viral load status (suppression defined as viral load <200 copies/mL ≤200 days). Results:Overall 1110 patients were newly linked to clinic during the observation period, contributing 2255.4 person-years of follow-up. One year following linkage, 54.8% (95% CI, 51.6%-57.9%) were continuously retained, 15.2% (95% CI, 13.0%-17.7%) were reengaged, and 29.3% (95% CI, 26.6%-32.2%) were disengaged. In addition, 93.0% (95% CI, 90.6%-95.1%) of continuously retained individuals were virally suppressed at 1 year as compared with 81.6% (95% CI, 75.2%-87.7%) of reengaged individuals. Younger individuals and those from historically marginalized communities were more likely to disengage, reengage, and become viremic. Conclusions:Multistate methods revealed a pattern of disengagement from clinic and reengagement, accompanied by elevated risk of viremia during disengagement. Shifting retention efforts from preventing isolated missed visits toward supporting sustained, long-term engagement in care is a key priority.

Background:The dimorphic mycoses (DMs) histoplasmosis, blastomycosis, and coccidioidomycosis are classically thought to be geographically restricted to specific regions of the United States. The current scientific consensus is that these geographic boundaries are expanding, but the extent of this expansion remains uncertain. Methods:This study is a retrospective analysis of >21 million (annually) commercially insured individuals within the United States during 2007-2016. Diagnosis of histoplasmosis, coccidioidomycosis, and blastomycosis were identified using International Classification of Diseases, Ninth/Tenth Revision codes within the Merative MarketScan database. Results:There were 37 513 histoplasmosis, 14 987 coccidioidomycosis, and 2207 blastomycosis diagnoses during 2007-2016 within 387 Metropolitan Statistical Areas. DMs were consistently diagnosed outside their historical hyperendemic regions. Conclusions:New diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were routinely made outside their historically defined regions of endemicity. While exposure to hyperendemic regions remains a risk factor for developing a DM infection, clinicians should consider testing any patient presenting with a compatible clinical syndrome, regardless of their geographic history. Increased suspicion of DM infection will lead to fewer missed or delayed diagnoses, thereby improving patient outcomes.

Infliximab may play an important role in reducing mortality in severe COVID-19, though optimal dosing is unknown. This secondary analysis of the ACTIV-1 IM trial characterized infliximab pharmacokinetics and outcomes in patients hospitalized with severe COVID-19. ACTIV-1 IM included patients admitted with COVID-19 pneumonia who received infliximab in addition to routine care. Infliximab was administered as a single 5-mg/kg intravenous dose. The primary exposure variable was predicted infliximab concentrations over 28 days (AUC0-28). Logistic regression modeling was used to relate AUC0-28 to the primary outcome of 28-day mortality, adjusted for age. The relationship between AUC0-28 and the secondary outcome of time to recovery was evaluated using a Fine-Gray model, adjusted for age, with death as a competing risk. AUC0-28 was higher in patients who did not die versus those who died, with a median (range) of 20,681 mg h/L (8379-60,322) versus 17,392 (9543-43,145), P < .001. A 5000-unit increase in AUC0-28 was associated with decreased mortality (OR 0.62, 95% CI 0.43-0.88, P = .008) and decreased composite safety events (OR 0.57, 95% CI 0.45-0.71, P < .001). Higher AUC0-28 was associated with a greater probability of recovery; an AUC0-28 ≤ 17,400 mg h/L was associated with a 3.45-fold higher (95% CI 2.23-5.34) probability of recovery at Day 28, as was an AUC0-28 >17,400 mg h/L, albeit at a lower rate (1.18-fold higher [95% CI 1.07-1.32]), P < .002 for both. Overall, 113/390 (29.0%) patients did not achieve an optimal predicted infliximab AUC0-28 of at least 17,400 mg h/L, particularly those <100 kg and those with the highest baseline disease severity.

Background: Understanding factors that predict progression to severe COVID-19 is critical. Antibodies targeting SARS-CoV-2 spike protein confer protection, while the N protein of SARS-CoV-2 plays roles in viral replication and immune dysfunction. This study explores the significance of N protein and anti-spike antibodies on disease severity, progression, and mortality. Objectives: To evaluate the relationship between SARS-CoV-2 N protein and anti-spike antibody levels with disease severity, clinical outcomes, and mortality in hospitalized patients with COVID-19. Design: A secondary analysis of serologic data from participants in the ACTIV-1 randomized clinical trial, which evaluated immunomodulators for the treatment of hospitalized patients with COVID-19. Methods: A subanalysis of the ACTIV-1 immune modulator trial was conducted. Samples collected at randomization were tested for N protein levels and anti-spike antibodies. Logistic regression and linear models were employed to examine the association between serological measures and clinical outcomes, including 28-day mortality as well as progression to high-flow nasal cannula (HFNC) and invasive mechanical ventilation (MV). Results: Among the 496 participants with detectable serum N protein, the median was 1143 ng/dL, and levels decreased from 2559 ng/dL in participants randomized at 6 days of symptom onset to 477.6 ng/dL at 11 days. Higher anti-spike antibody levels were seen as the days from symptom onset progressed or disease severity increased. Greater disease severity at randomization was associated with 28-day mortality, prolonged days of oxygenation, ventilation, hospitalization, and risk of new non-invasive ventilation, HFNC, MV, or extracorporeal membrane oxygenation use. N protein levels were associated with a higher risk of new non-invasive ventilation or HFNC use, longer oxygenation duration, and extended hospitalization. Anti-spike antibody serologies were not associated with clinical outcomes. Conclusion: N protein levels could provide insights into COVID-19 disease progression and prognosis. Further research is needed to explore the clinical implications of these findings to optimize patient care and enhance outcomes.

Background:Coronavirus disease 2019 (COVID-19) pneumonia requires considerable healthcare resources. Research Objective:Examine if a single dose of infliximab or abatacept, in addition to remdesivir and steroids, decreased resource utilization among participants hospitalized with COVID-19 pneumonia. Study Design and Methods:Accelerating COVID-19 Therapeutic Interventions and Vaccines Immunomodulator (ACTIV-1 IM) master protocol was a randomized, placebo-controlled trial examining the potential benefit in time to recovery and mortality of immunomodulators infliximab, abatacept, and cenicriviroc. This observational study performs a secondary analysis of the infliximab, abatacept, and common placebo participants to examine resource utilization. Hospital days, intensive care unit days, days with supplemental oxygen, days with high flow nasal cannula or non-invasive ventilation, ventilator days, and days of extracorporeal membrane oxygenation were each examined. Proportional odds models were used to compare days alive and free of resource use over 28 days between infliximab and placebo groups and between abatacept and placebo groups. Results:Infliximab infusion, compared to placebo, was associated with greater odds of being alive and free of all interventions tested. Abatacept use was associated only with greater odds of days alive and free of hospitalization and supplemental oxygen. Interpretation:Infliximab and abatacept use were associated with decreased use of healthcare resources over 28 days compared to placebo, but the absolute differences were small. Clinical trial registration:www.clinicaltrials.gov (NCT04593940).

Importance:The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. Objective:To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments. Design, Setting, and Participants:This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. Exposure:Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). Main Outcomes and Measures:Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. Results:Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. Conclusions and Relevance:In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. Trial Registration:ClinicalTrials.gov Identifier: NCT04593940.

Background: Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens. Methods: Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART. We compared non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48 months' risk and risk differences (RD) of MACE. Results: Among 37 935 ART initiators (median age, 40 years; 23% female; 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months (RD, 0.50; 95% CI, 0.14-0.99), 18 months (RD, 0.53; 95% CI, 0.11-1.06), and 24 months (RD, 0.62; 95% CI, 0.04-1.29) for PI initiators, and at 12 (RD, 0.20; 95% CI, 0.03-0.37) and 18 months (RD, 0.31; 95% CI, 0.06-0.54) for INSTI initiators; the precision of estimates was limited for longer duration of follow-up. Conclusions: Among ART initiators, PI-based and INSTI-based regimens were associated with higher short-term risk of MACE compared to NNRTI-based regimens. The pattern of association between INSTIs and PIs with excess risk of MACE was similar.

Background Coronavirus disease 2019 (COVID-19) pneumonia requires considerable healthcare resources. Research Objective Examine if a single dose of infliximab or abatacept, in addition to remdesivir and steroids, decreased resource utilization among participants hospitalized with COVID-19 pneumonia. Study Design and Methods Accelerating COVID-19 Therapeutic Interventions and Vaccines Immunomodulator (ACTIV-1 IM) master protocol was a randomized, placebo-controlled trial examining the potential benefit in time to recovery and mortality of immunomodulators infliximab, abatacept, and cenicriviroc. This observational study performs a secondary analysis of the infliximab, abatacept, and common placebo participants to examine resource utilization. Hospital days, intensive care unit days, days with supplemental oxygen, days with high flow nasal cannula or non-invasive ventilation, ventilator days, and days of extracorporeal membrane oxygenation were each examined. Proportional odds models were used to compare days alive and free of resource use over 28 days between infliximab and placebo groups and between abatacept and placebo groups. Results Infliximab infusion, compared to placebo, was associated with greater odds of being alive and free of all interventions tested. Abatacept use was associated only with greater odds of days alive and free of hospitalization and supplemental oxygen. Interpretation Infliximab and abatacept use were associated with decreased use of healthcare resources over 28 days compared to placebo, but the absolute differences were small.

Strengthening and expanding interprofessional team-based care is an important component of the Infectious Diseases Society of America's Workforce Development Strategy to expand and promote equitable access to expert infectious diseases (ID) care. This statement defines the roles of care team members and highlights the need for ID curricula and training programs for advanced practice providers to support implementation of ID team-based care.

ImportanceThe pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.ObjectiveTo characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.Design, Setting, and ParticipantsThis study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024.ExposureSingle intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg).Main Outcomes and MeasuresMortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity.ResultsOf the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure.Conclusions and RelevanceIn this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients.Trial RegistrationClinicalTrials.gov Identifier: NCT04593940

A randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the efficacy of infliximab, abatacept, and cenicriviroc in treating patients hospitalized with COVID-19. The patient's clinical status was assessed daily on an 8-point ordinal scale. We evaluated the totality of evidence on the efficacy of the 3 immunomodulators by considering all possible changes in the clinical status of each patient over time. We demonstrated that infliximab accelerated improvement and reduced deterioration of clinical status when added to standard of care. There was also evidence for the benefit of abatacept. There was no evidence for the benefit of cenicriviroc.

COVID-19 disproportionately affects persons with HIV (PWH) in worldwide locations with limited access to SARS-CoV-2 vaccines. PWH exhibit impaired immune responses to some, but not all, vaccines. Lymph node (LN) biopsies from PWH demonstrate abnormal LN structure, including dysregulated germinal center (GC) architecture. It is not clear whether LN dysregulation prevents PWH from mounting Ag-specific GC responses in the draining LN following vaccination. To address this issue, we longitudinally collected blood and draining LN fine needle aspiration samples before and after SARS-CoV-2 vaccination from a prospective, observational cohort of 11 PWH on antiretroviral therapy: 2 who received a two-dose mRNA vaccine series and 9 who received a single dose of the Ad26.COV2.S vaccine. Following vaccination, we observed spike-specific Abs, spike-specific B and T cells in the blood, and spike-specific GC B cell and T follicular helper cell responses in the LN of both mRNA vaccine recipients. We detected spike-specific Abs in the blood of all Ad26.COV2.S recipients, and one of six sampled Ad26.COV2.S recipients developed a detectable spike-specific GC B and T follicular helper cell response in the draining LN. Our data show that PWH can mount Ag-specific GC immune responses in the draining LN following SARS-CoV-2 vaccination. Due to the small and diverse nature of this cohort and the limited number of available controls, we are unable to elucidate all potential factors contributing to the infrequent vaccine-induced GC response observed in the Ad26.COV2.S recipients. Our preliminary findings suggest this is a necessary area of future research.

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This study found clinically significant incidence rates of histoplasmosis in 94% of US states, coccidioidomycosis in 69% of US states, and blastomycosis in 78% of US states. These data suggest expanded geographic distributions of these endemic mycoses. Background The dimorphic mycoses (DMs) of the United States-Histoplasma, Coccidioides, and Blastomyces-commonly known as endemic mycoses of North America (in addition to Paracoccidioides) are increasingly being diagnosed outside their historical areas of endemicity. Despite this trend, the maps outlining their geographic distributions have not been updated in more than half a century using a large, nationwide database containing individual-patient-level data. Methods This was a retrospective analysis of >45 million Medicare fee-for-service beneficiaries from 1 January 2007 through 31 December 2016. Diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were defined by International Classification of Diseases, Ninth/10th Revision, codes. The primary outcome was the incidence of histoplasmosis, coccidioidomycosis, and blastomycosis for each US county. Clinically meaningful thresholds for incidence were defined as 100 cases/100 000 person-years for histoplasmosis and coccidioidomycosis and 50 cases/100 000 person-years for blastomycosis. Results There were 79 749 histoplasmosis, 37 726 coccidioidomycosis, and 6109 blastomycosis diagnoses in unique persons from 2007-2016 across 3143 US counties. Considering all US states plus Washington, DC, 94% (48/51) had >= 1 county above the clinically relevant threshold for histoplasmosis, 69% (35/51) for coccidioidomycosis, and 78% (40/51) for blastomycosis. Conclusions Persons with histoplasmosis, coccidioidomycosis, and blastomycosis are diagnosed in significant numbers outside their historical geographic distributions established >50 years ago. Clinicians should consider DM diagnoses based on compatible clinical syndromes with less emphasis placed on patients' geographic exposure. Increased clinical suspicion leading to a subsequent increase in DM diagnostic testing would likely result in fewer missed diagnoses, fewer diagnostic delays, and improved patient outcomes.

Abstract Background A growing body of evidence suggests potential sex differences in the clinical outcomes of COVID-19. In this study we evaluated whether sex and baseline clinical variables were associated with treatment effect after receipt of immunomodulators vs placebo in a study population derived from ACTIV-1 IM clinical trial. Methods ACTIV-1 IM is a master protocol that evaluated infliximab, abatacept and cenicriviroc in addition to standard of care in adult patients hospitalized with moderate or severe SARS-CoV-2 infection through randomized, double-blind comparisons to shared placebo. We performed a subgroup analysis of the modified intention-to-treat cohort. Primary outcome was association of sex with time-to-recovery at day 28, key secondary outcomes were 28-day mortality and clinical status at day 14. Results A total of 1381 participants were included. There was no difference in treatment effect for primary endpoint of time-to-recovery based on sex for infliximab (RRR 1.14, 95% CI 0.95-1.37 for males and RRR 1.09, 95% CI 0.90-1.34 for females with interaction p=0.77), abatacept (RRR 1.14, 95% CI 0.95–1.37 for males and RRR 1.13, 95% CI 0.91-1.40 for females with interaction p=0.93) or cenicriviroc (RRR 0.99, 95% CI 0.79–1.24 for males, RRR 0.98, 95% CI 0.77-1.24 for females, interaction p=0.93) substudies. There was no difference in treatment effect by sex for secondary outcomes for infliximab and abatacept substudies. The cenicriviroc substudy was terminated early for futility and found no difference in treatment effects based on sex for secondary outcomes either. Conclusion There was no difference in treatment effect for infliximab, abatacept or cenicriviroc among males vs females. This suggests a more complex interplay of pathogen and host factors deserving further research to identify therapeutic targets for COVID-19. Disclosures Radica Alicic, MD, MSc, Boehringer Ingelheim Pharmaceuticals, Inc.: Advisor/Consultant Caryn Morse, MD, Gilead Sciences Inc.: Grant/Research Support|Janssen: Grant/Research Support|Laurent Pharma: Grant/Research Support|Moderna: Grant/Research Support|Ridgeback Bio: Grant/Research Support William G. Powderly, MD, Merck: Advisor/Consultant

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

Background. Prior randomized clinical trials have reported benefit of fluvoxamine >= 200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods. This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation >= 92%. The primary outcome was clinical deterioration within 15 days of randomization, defined as having both (1) shortness of breath (severity >= 4 on a 0-10 scale or requiring hospitalization) and (2) oxygen saturation <92% on room air or need for supplemental oxygen. Results. A total of 547 participants were randomized and met mITT criteria (n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower-than-predicted event rates and declining accrual concurrent with vaccine availability in the United States and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68%; 95% CI, -3.0% to 4.4%; log-rank P =.91). Conclusions. This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates.

Background This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins. Methods We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1368-bed tertiary care academic hospital, in Saint Louis, Missouri, from 1 February 2012 to 30 April 2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6269 control patients that had similar Candida BSI risk-factors. The 90-day all-cause mortality attributable to Candida BSI was calculated using three methods-propensity score matching, matching by inverse weighting of propensity score, and stratified analysis by quintile. Results The 90-day crude mortality was 42.4% (269 patients) for Candida BSI cases and 17.1% (1083 patients) for frequency-matched controls. Following propensity score-matching, the attributable risk difference for 90-day mortality was 28.4% with hazard ratio (HR) of 2.12 (95% confidence interval [CI], 1.98-2.25, P < .001). In the stratified analysis, the risk for mortality at 90 days was highest in patients in the lowest risk quintile to develop Candida BSI (hazard ratio [HR] 3.13 (95% CI, 2.33-4.19). Patients in this lowest risk quintile accounted for 81(61%) of the 130 untreated patients with Candida BSI. Sixty-nine percent of untreated patients (57/83) died versus 35% of (49/127) of treated patients (P < .001). Conclusions Patients with Candida BSI continue to experience high mortality. Mortality attributable to Candida BSI was more pronounced in patients at lowest risk to develop Candida BSI. A higher proportion of these low-risk patients went untreated, experienced higher mortality, and should be the target of aggressive interventions to ensure timely, effective treatment. In the modern era of echinocandins, this study found the crude and attributable mortality of Candidabloodstream infections remain high-42% and 28%, respectively. Patients at the lowest risk of developing infection were found to have the highest attributable mortality.*

Background: The true prevalence of COVID-19 is difficult to estimate due to the absence of random population-based testing. To estimate current and past COVID-19 infection prevalence in a large urban area, we conducted a population-based survey in St. Louis County, Missouri. Methods: The population-based survey of active infection (PCR) and seroprevalence (IgG antibodies) of adults ( & GE;18 years) was conducted through random-digit dialing and targeted sampling of St. Louis County residents with oversampling of Black residents. Infection prevalence of residents was estimated using design-based and raking weighting. Results: Between August 17 and October 24, 2020, 1245 residents completed a survey and underwent PCR testing; 1073 residents completed a survey and underwent PCR and IgG testing or self-reported results. Weighted prevalence estimates of residents with active infection were 1.9% (95% CI, 0.4%-3.3%) and 5.6% were ever infected (95% CI, 3.3%-8.0%). Overall infection hospitalization and fatality ratios were 4.9% and 1.4%, respectively. Conclusions: Through October 2020, the percentage of residents that had ever been infected was relatively low. A markedly higher percentage of Black and other minorities compared to White residents were infected with COVID-19. The St. Louis region remained highly vulnerable to widespread infection in late 2020.(C) 2022 Elsevier Inc. All rights reserved.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41-0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov (NCT04593940).