Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Social determinants of adult COVID-19 vaccine acceptance and uptake in a Brazilian urban informal community: a longitudinal time-to-event study.

Residents of informal urban settlements have a high risk of COVID-19 exposure and have less access to medical care, making vaccine-driven prevention critical in this vulnerable population. Despite robust vaccination campaigns in Brazil, vaccine uptake and timing continue to be influenced by social factors and contribute to health disparities. To address this, we conducted a sequential survey in a cohort of 717 adults in an urban favela in Salvador, Brazil where participants were interviewed in 2020, before vaccines were rolled out, and in 2022, after primary and booster dose distribution. We collected data on demographics, social characteristics, and COVID-19 vaccination status and intent. Primary series uptake was high (91.10% for 1 st dose and 94.74% for 2 nd dose among eligible); however, booster uptake was lower (63.51% of eligible population) at the time of the second interview, suggesting a decreasing interest in vaccination. To account for both vaccine refusal and delays, we conducted a Cox time-to-event analysis of dose uptake using sequential independent outcomes. Exposure times were determined by dose eligibility date to account for age and comorbidities. Intent to vaccinate in 2020 (hazard ratio [HR]: 1.54, CI: [1.05, 1.98]) and age (HR: 1.27, CI: [1.01, 2.08]) were associated with higher vaccination rates for the 1 st dose. Males were less likely to receive the 1 st dose (HR: 0.61, CI: [0.35, 0.83]), and, compared to catholics, 2 nd dose uptake was lower for those identifying with Pentecostalism (HR: 0.49, CI: [0.37, 0.66]) and without a religion (HR: 0.49, CI: [0.37, 0.66]), with the latter association disappearing after controlling by age. Risk perception was associated with 2 nd dose uptake (HR: 1.15, CI: [1.08, 1.26]). The role of sex and religion in vaccination behavior highlights the need for targeted outreach and interfacing with local organizations. The data offers lessons to build a long-term COVID-19 vaccination strategy beyond availability.

Evidence of leaky protection following COVID-19 vaccination and SARS-CoV-2 infection in an incarcerated population.

Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent ("leaky") protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25-0.54]; 0.57 [0.42-0.78]; 0.24 [0.15-0.39]; respectively) and with cellblock exposures (0.61 [0.49-0.75]; 0.69 [0.58-0.83]; 0.41 [0.31-0.55]; respectively) but not with cell exposures (0.89 [0.58-1.35]; 0.96 [0.64-1.46]; 0.80 [0.46-1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.

Covid-19 vaccine acceptance among individuals incarcerated in Connecticut state jails.

BACKGROUND: Vaccine hesitancy is common among incarcerated populations and, despite vaccination programs, vaccine acceptance within residents remains low, especially within jails. With the goal of assessing the Connecticut DOC's COVID-19 vaccine program within jails we examined if residents of DOC operated jails were more likely to become vaccinated following incarceration than in the community. Specifically, we conducted a retrospective cohort analysis among people who spent at least one night in a DOC-operated jail between February 2 and November 8, 2021, and were eligible for vaccination at the time of incarceration (intake). We compared the vaccination rates before and after incarceration using an age-adjusted survival analysis with a time-varying exposure of incarceration and an outcome of vaccination. RESULTS: During the study period, 3,716 people spent at least one night in jail and were eligible for vaccination at intake. Of these residents, 136 were vaccinated prior to incarceration, 2,265 had a recorded vaccine offer, and 479 were vaccinated while incarcerated. The age-adjusted hazard of vaccination following incarceration was significantly higher than prior to incarceration (12.5; 95% Confidence Intervals: 10.2-15.3). CONCLUSIONS: We found that residents were more likely to become vaccinated in jail than in the community. Though these findings highlight the utility of vaccination programs within jails, the low level of vaccination in this population speaks to the need for additional program development within jails and the community.

Testing Frequency Matters: An Evaluation of the Diagnostic Performance of a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Rapid Antigen Test in US Correctional Facilities.

BACKGROUND: The Centers for Disease Control and Prevention recommends serial rapid antigen assay collection within congregate facilities. Although modeling and observational studies from communities and long-term care facilities have shown serial collection provides adequate sensitivity and specificity, the accuracy within correctional facilities remains unknown. METHODS: Using Connecticut Department of Correction data from 21 November 2020 to 15 June 2021, we estimated the accuracy of a rapid assay, BinaxNOW (Abbott), under 3 collection strategies: single test collection and serial collection of 2 and 3 tests separated by 1-4 days. The sensitivity and specificity of the first (including single), second, and third serially collected BinaxNOW tests were estimated relative to RT-PCRs collected ≤1 day of the BinaxNOW test. The accuracy metrics of the testing strategies were then estimated as the sum (sensitivity) and product (specificity) of tests in each strategy. RESULTS: Of the 13 112 residents who contributed ≥1 BinaxNOW test during the study period, 3825 contributed ≥1 RT-PCR paired BinaxNOW test. In relation to RT-PCR, the 3-rapid-antigen-test strategy had a sensitivity of 95.9% (95% CI: 93.6-97.5%) and specificity of 98.3% (95% CI: 96.7-99.1%). The sensitivities of the 2- and 1-rapid-antigen-test strategies were 88.8% and 66.8%, and the specificities were 98.5% and 99.4%, respectively. The sensitivity was higher among symptomatic residents and when RT-PCRs were collected before BinaxNOW tests. CONCLUSIONS: We found serial antigen test collection resulted in high diagnostic accuracy. These findings support serial collection for outbreak investigation, screening, and when rapid detection is required (such as intakes or transfers).

Use of Whole-Genome Sequencing to Estimate the Contribution of Immune Evasion and Waning Immunity on Decreasing COVID-19 Vaccine Effectiveness.

BACKGROUND: The impact variant-specific immune evasion and waning protection have on declining coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) remains unclear. Using whole-genome sequencing (WGS), we examined the contribution these factors had on the decline that followed the introduction of the Delta variant. Furthermore, we evaluated calendar-period-based classification as a WGS alternative. METHODS: We conducted a test-negative case-control study among people tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 April and 24 August 2021. Variants were classified using WGS and calendar period. RESULTS: We included 2029 cases (positive, sequenced samples) and 343 727 controls (negative tests). VE 14-89 days after second dose was significantly higher against Alpha (84.4%; 95% confidence interval [CI], 75.6%-90.0%) than Delta infection (68.9%; 95% CI, 58.0%-77.1%). The odds of Delta infection were significantly higher 90-149 than 14-89 days after second dose (P value = .003). Calendar-period-classified VE estimates approximated WGS-classified estimates; however, calendar-period-based classification was subject to misclassification (35% Alpha, 4% Delta). CONCLUSIONS: Both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While calendar-period-classified VE estimates mirrored WGS-classified estimates, our analysis highlights the need for WGS when variants are cocirculating and misclassification is likely.

Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case-control analysis.

BACKGROUND: The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. METHODS AND FINDINGS: We conducted a test-negative case-control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study's limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. CONCLUSIONS: In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.

Effectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil.

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6-11.5) and 56.8% (95% CI, 56.3-57.3) in the period 8-59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9-80.7) and 86.0% (95% CI, 84.5-87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study.

OBJECTIVE: To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in São Paulo State, Brazil. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo State, Brazil. PARTICIPANTS: Adults aged ≥18 years who were residents of São Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test. MAIN OUTCOME MEASURES: RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness. RESULTS: From 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards. CONCLUSIONS: Significant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.

Effectiveness of CoronaVac, ChAdOx1 nCoV-19, BNT162b2, and Ad26.COV2.S among individuals with previous SARS-CoV-2 infection in Brazil: a test-negative, case-control study.

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1-42·6) for CoronaVac, 56·0% (51·4-60·2) for ChAdOx1 nCoV-19, 44·0% (31·5-54·2) for Ad26.COV2.S, and 64·8% (54·9-72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3-85·8) for CoronaVac, 89·9% (83·5-93·8) for ChAdOx1 nCoV-19, 57·7% (-2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3-97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.

Are hematopoietic cell transplant recipients with Gram-negative bacteremia spending more time outpatient while on intravenous antibiotics? Addressing trends over 10 years at a single center.

INTRODUCTION: The increasing proportion of outpatient allogeneic hematopoietic cell transplants (HCTs) coupled with increased access of once-daily broad-spectrum antibiotics and evidence that outpatient antibiotic treatment may be safer and less costly than inpatient treatment, suggest that allogeneic HCT recipients with Gram-negative rod bacteremia (GNRBs) are increasingly being treated in ambulatory care settings. METHODS: Using data from the first GNRB event that occurred within the first 100 days posttransplantation among allogeneic HCT recipients transplanted at a single center between 2007 and 2016, we estimated the temporal trends in GNRB incidence and treatment management of GNRBs and identified if patient or infection characteristics impacted observed trends. RESULTS: A total of 11% (238/2165) of the observed allogeneic HCT recipients experienced ≥1 GNRB with available resistance data and contributed antibiotic treatment time. Patients, on average, received 55.1% of their antibiotic treatment in an outpatient setting and we observed a significant decline in the proportion of treatment time spent outpatient (crude: -3.3% [95% confidence interval: -5.0, -1.6%]). We observed similar declines in the proportion of treatment time spent outpatient among patients with similar GNRB and pretransplant complexity factors but not among patients with similar posttransplant complications (p value: .165). CONCLUSION: These results suggest that, despite increased availability of outpatient suitable treatment options, allogeneic HCT recipients with GNRBs received less treatment in outpatient settings. However, among patients with similar posttransplant complications, the lack of significant decline suggests that treatment location decisions remained consistent for patients with similar posttransplant complications. These findings suggest the need for additional interventions targeting outpatient antibiotic treatment among allogeneic HCT recipients with GNRBs.

Limits of the Glasgow Coma Scale When Assessing for Sepsis in Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: The well-documented association between acute mental status changes and sepsis development and progression makes acute mental status an attractive factor for sepsis screening tools. However, the usefulness of acute mental status within these criteria is limited to the frequency and accuracy of its capture. The Glasgow Coma Scale (GCS) score-the acute mental status indicator in many clinical sepsis criteria-is infrequently captured among allogeneic hematopoietic cell transplant recipients with suspected infections, and its ability to serve as an indicator of acute mental status among this high-risk population is unknown. OBJECTIVE: We evaluated the GCS score as an indicator of acute mental status during the 24 hours after suspected infection onset among allogeneic hematopoietic cell transplant recipients. METHODS: Using data from the first 100 days posttransplant for patients transplanted at a single center between September 2010 and July 2017, we evaluated the GCS score as an indicator of documented acute mental status during the 24 hours after suspected infection onset. From all inpatients with suspected infections, we randomly selected a cohort based on previously published estimates of GCS score frequency among hematopoietic cell transplant recipients with suspected infections and performed chart review to ascertain documentation of clinical acute mental status within the 24 hours after suspected infection onset. RESULTS: A total of 773 patients had ≥1 suspected infections and experienced 1,655 suspected infections during follow-up-625 of which had an accompanying GCS score. Among the randomly selected cohort of 100 persons with suspected infection, 28 were accompanied with documented acute mental status, including 18 without a recorded GCS. In relation to documented acute mental status, the GCS had moderate to high sensitivity and high specificity. DISCUSSION: These data indicate that, among allogeneic hematopoietic cell transplant recipients with suspected infections, the GCS scores are infrequently collected and have a moderate sensitivity. If sepsis screening tools inclusive of acute mental status changes are to be used, nursing teams need to increase measurement of GCS scores among high sepsis risk patients or identify a standard alternative indicator.

Development and Validation of a Machine Learning Model to Estimate Bacterial Sepsis Among Immunocompromised Recipients of Stem Cell Transplant.

Importance: Sepsis disproportionately affects recipients of allogeneic hematopoietic cell transplant (allo-HCT), and timely detection is crucial. However, the atypical presentation of sepsis within this population makes detection challenging, and existing clinical sepsis tools have limited prognostic value among this high-risk population. Objective: To develop a full risk factor (demographic, transplant, clinical, and laboratory factors) and clinical factor-specific automated bacterial sepsis decision support tool for recipients of allo-HCT with potential bloodstream infections (PBIs). Design, Setting, and Participants: This prognostic study used data from adult recipients of allo-HCT transplanted at the Fred Hutchinson Cancer Research Center, Seattle, Washington, between June 2010 and June 2019 randomly divided into 70% modeling and 30% validation data sets. Tools were developed using the area under the curve (AUC) optimized SuperLearner, and their performance was compared with existing clinical sepsis tools: National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), and Systemic Inflammatory Response Syndrome (SIRS), using the validation data set. Data were analyzed between January and October of 2020. Main Outcomes and Measures: The primary outcome was high-sepsis risk bacteremia (culture confirmed gram-negative species, Staphylococcus aureus, or Streptococcus spp bacteremia), and the secondary outcomes were 10- and 28-day mortality. Tool discrimination and calibration were examined using accuracy metrics and expected vs observed probabilities. Results: Between June 2010 and June 2019, 1943 recipients of allo-HCT received their first transplant, and 1594 recipients (median [interquartile range] age at transplant, 54 [43-63] years; 911 [57.2%] men; 1242 individuals [77.9%] identifying as White) experienced at least 1 PBI. Of 8131 observed PBIs, 238 (2.9%) were high-sepsis risk bacteremia. Compared with high-sepsis risk bacteremia, the full decision support tool had the highest AUC (0.85; 95% CI, 0.81-0.89), followed by the clinical factor-specific tool (0.72; 95% CI, 0.66-0.78). SIRS had the highest AUC of existing tools (0.64; 95% CI, 0.57-0.71). The full decision support tool had the highest AUCs for PBIs identified in inpatient (0.82; 95% CI, 0.76-0.89) and outpatient (0.82; 95% CI, 0.75-0.89) settings and for 10-day (0.85; 95% CI, 0.79-0.91) and 28-day (0.80; 95% CI, 0.75-0.84) mortality. Conclusions and Relevance: These findings suggest that compared with existing tools and the clinical factor-specific tool, the full decision support tool had superior prognostic accuracy for the primary (high-sepsis risk bacteremia) and secondary (short-term mortality) outcomes in inpatient and outpatient settings. If used at the time of culture collection, the full decision support tool may inform more timely sepsis detection among recipients of allo-HCT.

Change in COVID-19 risk over time following vaccination with CoronaVac: A testnegative case-control study.

OBJECTIVE: To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech) in São Paulo state, Brazil. DESIGN: Test negative case-control study. SETTING: Community testing for covid-19 in São Paulo state, Brazil. PARTICIPANTS: Adults aged 18-120 years who were residents of São Paulo state, without a previous laboratory-confirmed covid-19 infection, who received only two doses of CoronaVac, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 30 September 2021. MAIN OUTCOME MEASURES: RT-PCR-confirmed symptomatic covid-19 and associated hospital admissions and deaths. Cases were pair-matched to test-negative controls by age (in 5-year bands), municipality of residence, healthcare worker (HCW) status, and date of RT-PCR test (±3 days). Conditional logistic regression was adjusted for sex, number of covid-19-associated comorbidities, race, and previous acute respiratory infection. RESULTS: From 137,820 eligible individuals, 37,929 cases with symptomatic covid-19 and 25,756 test-negative controls with covid-19 symptoms were formed into 37,929 matched pairs. Adjusted odds ratios of symptomatic covid-19 increased with time since series completion, and this increase was greater in younger individuals, and among HCWs compared to non-HCWs. Adjusted odds ratios of covid-19 hospitalisation or death were significantly increased from 98 days since series completion, compared to individuals vaccinated 14-41 days previously: 1.40 (95% confidence interval 1.09 to 1.79) from 98-125 days, 1.55 (1.16 to 2.07) from 126-153 days, 1.56 (1.12 to 2.18) from 154-181 days, and 2.12 (1.39-3.22) from 182 days. CONCLUSIONS: In the general population of São Paulo state, Brazil, an increase in odds of moderate and severe covid-19 outcomes was observed over time following primary series completion with CoronaVac.

Predictive Value of 3 Clinical Criteria for Sepsis (Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and National Early Warning Score) With Respect to Short-term Mortality in Allogeneic Hematopoietic Cell Transplant Recipients With Suspected Infections.

BACKGROUND: Sepsis disproportionately affects allogeneic hematopoietic cell transplant (HCT) recipients and is challenging to define. Clinical criteria that predict mortality and intensive care unit end-points in patients with suspected infections (SIs) are used in sepsis definitions, but their predictive value among immunocompromised populations is largely unknown. Here, we evaluate 3 criteria among allogeneic HCT recipients with SIs. METHODS: We evaluated Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) in relation to short-term mortality among recipients transplanted between September 2010 and July 2017. We used cut-points of ≥ 2 for qSOFA/SIRS and ≥ 7 for NEWS and restricted to first SI per hospital encounter during patients' first 100 days posttransplant. RESULTS: Of the 880 recipients who experienced ≥ 1 SI, 58 (6.6%) died within 28 days and 22 (2.5%) within 10 days of an SI. In relation to 10-day mortality, SIRS was the most sensitive (91.3% [95% confidence interval {CI}, 72.0%-98.9%]) but least specific (35.0% [95% CI, 32.6%-37.5%]), whereas qSOFA was the most specific (90.5% [95% CI, 88.9%-91.9%]) but least sensitive (47.8% [95% CI, 26.8%-69.4%]). NEWS was moderately sensitive (78.3% [95% CI, 56.3%-92.5%]) and specific (70.2% [95% CI, 67.8%-72.4%]). CONCLUSIONS: NEWS outperformed qSOFA and SIRS, but each criterion had low to moderate predictive accuracy, and the magnitude of the known limitations of qSOFA and SIRS was at least as large as in the general population. Our data suggest that population-specific criteria are needed for immunocompromised patients.

A Targeted Screening Program for Latent Tuberculosis Infection Among Hematopoietic Cell Transplant Recipients.

BACKGROUND: US hematopoietic cell transplantation (HCT) recipients have a low prevalence of latent tuberculosis infection (LTBI), but if latently infected they are at risk for progression to active tuberculosis. At our center, all HCT recipients underwent LTBI testing pretransplant by tuberculin skin testing (TST) until 2013 when we implemented a targeted screening program. Our objective was to assess the utility of our screening program that incorporated a pretransplant LTBI questionnaire to target TST and QuantiFERON TB Gold (QFT) testing. METHODS: We performed a retrospective cohort study of HCT recipients undergoing first transplant from 2014 to 2016. Patients with positive, indeterminate, and a subset with negative QFT results underwent electronic medical record (EMR) review to assess TST results and risk factors for LTBI. RESULTS: Among 1290 eligible recipients, 457 (35%) had at least 1 risk factor for LTBI on the pretransplant questionnaire; nonwhites were more likely to undergo LTBI testing (P < .0001). Overall, 16 of 1290 (1.2%) had at least 1 positive LTBI test. Of those screened by QFT, 14 of 457 (3%) were positive and 52 (11%) were indeterminate. Among those undergoing EMR review, 123 of 267 (46%) had TST records; 4 of 123 (3%) positive by both TST and QFT, and 2 (2%) by TST alone. Two or more risk factors were reported among the majority of LTBI-positive patients (15 of 16 [94%]). All patients with at least 1 positive test for LTBI (n = 16) were evaluated, and 11 of 16 (69%) were recommended to receive treatment. CONCLUSIONS: Incorporating a pretransplant LTBI questionnaire allowed for an approximate 65% reduction in LTBI testing when compared with universal testing among this low prevalence population.