Annals of Internal Medicine

An essential precondition for successful "herd immunity" strategies for the control of SARS-CoV-2 is that reinfection with the virus be relatively rare. Some infection control, prioritization, and testing strategies for SARS-CoV-2 were designed on the premise of rare re-infection. The U.S. Veterans Health Administration (VHA) includes 171 medical centers and 1,112 outpatient sites of care, with widespread SARS-CoV-2 test availability. We used the VHAs unified, longitudinal electronic health record to measure the frequency of re-infection with SARS-CoV-2 at least 90 days after initial diagnosis We identified 308,051 initial cases of SARS-CoV-2 infection diagnosed in VHA between March 2020 and January 2022; 58,456 (19.0%) were associated with VHA hospitalizations. A second PCR-positive test occurred in 9,203 patients in VA at least 90-days after their first positive test in VHA; 1,562 (17.0%) were associated with VHA hospitalizations. An additional 189 cases were identified as PCR-positive a third time at least 90-days after their second PCR-positive infection in VHA; 49 (25.9%) were associated with VHA hospitalizations. The absolute number of re-infections increased from less than 500 per month through November 2021, to over 4,000 per month in January 2022.

ObjectiveTo estimate the effectiveness of 2-dose and 3-dose mRNA vaccination (BNT162b2 and mRNA-1273) against general SARS-CoV-2 infection (asymptomatic or symptomatic) caused by the omicron variant. DesignPropensity-score matched retrospective Cohort Study. SettingLarge public university undergoing weekly Covid-19 testing in South Carolina, USA. ParticipantsPopulation consists of 24,145 university students and employees undergoing weekly Covid-19 testing between January 3rd and January 31st, 2022. The analytic sample was constructed via propensity score matching on vaccination status: Unvaccinated, completion of 2-dose mRNA series within previous 5 months, and receipt of mRNA booster dose within previous 5 months. The resulting analytic sample consists of 1,944 university students and 658 university employees. InterventionVaccination with a two dose or 3 dose regimen of the BNT162b2 or mRNA-1273 vaccine. ResultsBooster protection against any SARS-CoV-2 infection was 66.4% among employees (95% CI: 46.1-79.0%; P<.001) and 45.4% among students (95% CI: 30.0-57.4%; P<.001). Compared to the 2-dose mRNA series, estimated increase in protection from the booster dose was 40.8% among employees (P=.024) and 37.7% among students (P=.001). We did not have enough evidence to conclude a statistically significant protective effect of the 2-dose mRNA vaccination series, nor did we have enough evidence to conclude that protection waned in the 5-month period after receipt of the 2nd or 3rd mRNA dose. Furthermore, we did not find evidence that protection varied by manufacturer. ConclusionsCovid-19 mRNA booster doses offer moderate protection against any SARS-CoV-2 infection caused by the omicron variant and provide a substantial increase in protection relative to the 2-dose mRNA vaccination series.

Background: Phase I/II clinical trials have explored whole-lung low-dose radiotherapy (LD-RT) as a potential treatment for patients with COVID-19-related acute respiratory distress syndrome (ARDS). Initial findings require reproduction. Concomitant LD-RT administration with existing therapies requires safety evaluation. Methods: Patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesevir were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared to controls blindly matched by age, comorbidity, and disease severity. Eligible patients were hospitalized, SARS-CoV-2 positive, had radiographic consolidations, and required supplemental oxygen. Endpoints included safety, clinical recovery, intubation, radiographic changes, and biomarker response. Findings: 20 patients received whole-lung LD-RT between Jun 11 and Dec 7, 2020 and were compared to controls. Freedom from intubation improved from 68% in controls to 86% following LD-RT (p=0.09) as did C-reactive protein (CRP) (p=0.02) and creatine kinase (CK) (p&lt;0.01) levels, consistent with prior report. Eighty percent of LD-RT patients experienced rapid decline in CRP within 3 days and were classified as LD-RT responders. Intubation-free survival (100% vs 66%, p=0.01) and oxygenation loads were lower in LD-RT responders compared to matched controls: 32% lower per individual (p=0.03) and 56% lower for the cohort (p=0.06). No patient whose CRP declined following LD-RT died or required intubation, whereas all LD-RT non-responders died. Observed reduction of prolonged recoveries and hospitalization times did not reach significance. Radiographic changes were equivalent. Interpretation: A cohort of patients with COVID-19-related ARDS treated with LD-RT demonstrated superior freedom from intubation compared to matched controls, especially LD-RT responders (p=0.01). LD-RT appears safe to deliver with concurrent drugs. LD-RT lowered CRP and CK biomarkers. CRP response predicted favorable outcome. Optimal timing for LD-RT after oxygen dependence but before intubation may extinguish immunopathology prior to systemic spread. Confirmatory clinical trials are warranted.

BackgroundSafety of whole-lung low-dose radiation therapy (LD-RT) for COVID-19 pneumonia has been established in two phase I trials. By focally dampening pulmonary cytokine hyperactivation, LD-RT may improve outcomes in hospitalized and oxygen-dependent COVID-19 patients. MethodsPatients with COVID-19 pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or at least until hospital discharge, and compared to an age- and comorbidity-matched control cohort. COVID-19-positive patients eligible for this protocol were hospitalized, had radiographic consolidations, and required supplemental oxygen. Efficacy endpoints were time to clinical recovery, radiographic improvement, and serologic responses. ResultsTen patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared to ten matched control patients, of whom six received COVID-directed therapy. Median time to clinical recovery was 12 days for the control cohort vs 3 days for LD-RT (HR 2.9, p=0.05). Median time to hospital discharge (20 and 12 days, p=0.19), and intubation rates (40% and 10%, p=0.12) were shorter for the LD-RT cohort. The LD-RT cohort had faster radiographic improvement (p=0.03), even among patients with high COVID burden. Serologic recovery in specific hematologic, cardiac, hepatic, clotting, and inflammatory markers occurred more rapidly following LD-RT than among matched controls. ConclusionsStrong efficacy signals, including a 3-fold risk reduction in time to clinical improvement, were observed following LD-RT compared to matched patients receiving COVID-directed therapy for COVID-19 pneumonia. Given the global availability of radiation accelerators, ongoing international efforts to investigate the optimal role of LD-RT in COVID-19 pneumonia are justified. Clinical Trial RegistrationNCT04366791.

BackgroundIt has been suggested that many of those who died from COVID-19 were older, had more comorbidities, and would have died within a short period anyway. We estimated the number and percent of excess deaths due to COVID-19 In April 2020 in the United States, New York City, and Michigan. MethodsFor each locale we calculated attributable fractions in the exposed comparing observed COVID-19 deaths and expected deaths. In addition, we estimated the number of months it would take for the excess deaths to occur without the virus and the proportions of the populations that were infected leading to the April deaths. We compared the excess deaths from the attributable fraction method to those obtained by comparing weekly deaths in 2019 and 2020. ResultsUsing an assumed infection fatality rate of 1%, the percentages of excess deaths were 95%, 97%, and 95% in the US, NYC, and MI equivalent to 54,560; 14,951; and 3,338 deaths, respectively. Absent the virus these deaths would have occurred over 21.0, 29.2, and 18.4 months in the respective locations. An estimated 1.7% of the US population was infected between March 13 and April 10, 2020. Nearly 19% were infected in NYC. ConclusionsOver 75% of COVID-19 deaths in April 2020 were excess deaths meaning they would not have occurred in April without SARS-CoV-2 but would have been spread out over the ensuing 18 to 29 months. Confirmed cases in the US under-report the actual number of infections by at least an order of magnitude. Excess death numbers calculated using the attributable fraction in the exposed are similar to those obtained from weekly mortality reports.

BackgroundUniversity campuses present an ideal environment for viral spread and are therefore at extreme risk of serving as a hotbed for a COVID-19 outbreak. While active surveillance throughout the semester such as widespread testing, contact tracing, and case isolation, may assist in detecting and preventing early outbreaks, these strategies will not be sufficient should a larger outbreak occur. It is therefore necessary to limit the initial number of active cases at the start of the semester. We examine the impact of pre-semester NAT testing on disease spread in a university setting. MethodsWe implement simple dynamic transmission models of SARS-CoV-2 infection to explore the effects of pre-semester testing strategies on the number of active infections and occupied isolation beds throughout the semester. We assume an infectious period of 3 days and vary R0 to represent the effectiveness of disease mitigation strategies throughout the semester. We assume the prevalence of active cases at the beginning of the semester is 5%. The sensitivity of the NAT test is set at 90%. ResultsIf no pre-semester screening is mandated, the peak number of active infections occurs in under 10 days and the size of the peak is substantial, ranging from 5,000 active infections when effective mitigation strategies (R0 = 1.25) are implemented to over 15,000 active infections for less effective strategies (R0 = 3). When one NAT test is mandated within one week of campus arrival, effective (R0 = 1.25) and less effective (R0 = 3) mitigation strategies delay the onset of the peak to 40 days and 17 days, respectively, and result in peak size ranging from 1,000 to over 15,000 active infections. When two NAT tests are mandated, effective (R0 = 1.25) and less effective (R0 = 3) mitigation strategies delay the onset of the peak through the end of fall semester and 20 days, respectively, and result in peak size ranging from less than 1,000 to over 15,000 active infections. If maximum occupancy of isolation beds is set to 2% of the student population, then isolation beds would only be available for a range of 1 in 2 confirmed cases (R0 = 1.25) to 1 in 40 confirmed cases (R0 = 3) before maximum occupancy is reached. ConclusionEven with highly effective mitigation strategies throughout the semester, inadequate pre-semester testing will lead to early and large surges of the disease and result in universities quickly reaching their isolation bed capacity. We therefore recommend NAT testing within one week of campus return. While this strategy is sufficient for delaying the timing of the outbreak, pre-semester testing would need to be implemented in conjunction with effective mitigation strategies to reduce the outbreak size.

Background In the United States, streamlining the kidney transplantation (KT) evaluation process may reduce disparities and barriers to KT access. Prior work showed that the Kidney Transplant Fast Track (KTFT) program shortened this process and reduced racial disparities in waitlisting and overall KT. However, within a setting where evaluation-related structural barriers have been addressed, a comprehensive longitudinal evaluation incorporating sociocultural factors (e.g., medical mistrust, healthcare-related discrimination/racism) alongside race/ethnicity as prespecified predictors across multiple KT milestones, including KT type (living [LDKT] and deceased donor KT [DDKT]), has not been performed. MethodsIn this secondary analysis, data came from the KTFT study, a prospective KT candidate cohort. Participants were recruited before KT evaluation start (05/2015-06/2018), coinciding with baseline measure collection, then followed via medical record through 08/2022. We used hierarchically-adjusted Fine-Gray proportional hazards models in this exploratory analysis. ResultsAmong 1108 KT candidates (243 Black, 783 White, 82 Other), medical mistrust was associated with lower cumulative incidence of waitlisting, but no other sociocultural factors were associated with outcomes. Racial and ethnic differences emerged for KT type: Black participants had a greater cumulative incidence of DDKT, and participants categorized as Other race/ethnicity had a lower cumulative incidence of LDKT, relative to White participants. Conclusions Although KTFT reduced racial/ethnic disparities in waitlisting and overall KT receipt, we identified racial/ethnic differences in LDKT and DDKT. Medical mistrust was a significant barrier to waitlisting. Findings suggest that even when the KT evaluation process is streamlined, sociocultural factors and race/ethnicity may influence KT outcomes.

Organ procurement in the US has received attention from government officials and policymakers the last two years, culminating in CMS releasing an updated Final Rule related to organ donation this year. This regulatory change revises how organ procurement organizations (OPOs), the federal contractors tasked with managing deceased donation, are evaluated and certified/de-certified. We used 2019 data and the CMS methodology to calculate race-stratified donation data among racial/ethnic minorities across the 57 OPOs. We found that the variability in donation rates across the 57 OPOs are greater among minority populations than non-Hispanic white potential donors. Among Tier 3 OPOs, there are: a) some with low donation rates across all racial/ethnic groups; b) some with low donation rates among only certain groups, and c) some where donation rates are lowest among non-Hispanic white patients. Among low-performing OPOs, these race/ethnicity-stratified data show that under-performance in certain areas is not due to the population demographics, and identifies areas for targeted interventions to increase donation and avoid decertification

Viral infections remain a cause of substantial morbidity and mortality in allogeneic hematopoietic cell transplant (aHCT) recipients. While antiviral prophylaxis has dramatically reduced the risk of herpes simplex virus (HSV) disease, the relationship between HSV serostatus and major post-transplant complications in the context of HSV prophylaxis is unknown. We evaluated the association between HSV serostatus and survival among adults who received a first aHCT at the Fred Hutchinson Cancer Center between 2002 and 2022. Patients were screened for HSV-1 and HSV-2 by Western blot (WB) prior to transplant. We fit Cox proportional hazards models for mortality up to one year post-transplant, comparing HSV seropositive to seronegative patients. Models were adjusted for age, sex, cytomegalovirus (CMV) serostatus, conditioning regimen, disease risk, graft type and HLA matching, year of transplant and acute graft-versus host disease. A total of 4,016 aHCT recipients were included in this analysis. The cumulative all-cause 1-year mortality was 29.8%. For HSV-1, the adjusted hazard ratio (aHR) for all-cause mortality comparing seropositive to seronegative individuals was 1.20 (95% CI: 1.06-1.36). The aHRs for relapse, non-relapse mortality (NRM) and relapse-related mortality (RRM) were 1.46 (1.24-1.71), 1.04 (0.89-1.21), and 1.75 (1.40-2.19), respectively. For HSV-2, the aHRs for all-cause mortality, relapse, NRM, and RRM were 1.03 (0.93-1.14), 1.16 (1.03-1.31), 0.99 (0.87-1.13), and 1.13 (0.97-1.33), respectively. Despite universal antiviral prophylaxis, HSV-1 seropositivity was associated with higher mortality in the year after transplant, driven by RRM. Further studies are needed to confirm the association and understand the potential mechanisms underlying this relationship.

From 2019 to 2021, U.S. life expectancy at birth fell by roughly 2.45 years to the lowest level since 1996. Although life expectancy rose in 2022 and 2023, it did not fully return to its 2019 level. Now that 2024 death reports have stabilized, I constructed abridged life tables for 2019- 2024 using CDC WONDER Multiple Cause of Death mortality data and Census Bureau Vintage population estimates to assess recent trends. This is an update of a report posted on June 2, 2025. In 2024, life expectancy at birth climbed by nearly 0.6 years over 2023 to 79.12 years, while life expectancy at age 65 increased by approximately 0.2 years to 19.87 years. These 2024 gains have almost offset the declines experienced during the COVID-19 pandemic. However, US mortality continues to exceed that in other high-income countries.

BackgroundLittle is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in this population, particularly after the emergence of the Omicron variant. ObjectiveTo determine the effectiveness of tixagevimab/cilgavimab for prevention of SARS-CoV-2 infection and severe disease among immunocompromised patients. DesignRetrospective cohort study with propensity matching and difference-in-difference analyses. SettingU.S. Department of Veterans Affairs (VA) healthcare system. ParticipantsVeterans age [&ge;]18 years as of January 1, 2022, receiving VA healthcare. We compared a cohort of 1,848 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to matched controls selected from 251,756 patients who were on immunocompromised or otherwise at high risk for COVID-19. Patients were followed through April 30, 2022, or until death, whichever occurred earlier. Main OutcomesComposite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used cox proportional hazards modelling to estimate the hazard ratios (HR) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. ResultsMost (69%) tixagevimab/cilgavimab recipients were [&ge;]65 years old, 92% were identified as immunocompromised in electronic data, and 73% had [&ge;]3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to propensity-matched controls, tixagevimab/cilgavimab-treated patients had a lower incidence of the composite COVID-19 outcome (17/1733 [1.0%] vs 206/6354 [3.2%]; HR 0.31; 95%CI, 0.18-0.53), and individually SARS-CoV-2 infection (HR 0.34; 95%CI, 0.13-0.87), COVID-19 hospitalization (HR 0.13; 95%CI, 0.02-0.99), and all-cause mortality (HR 0.36; 95%CI, 0.18-0.73). LimitationsConfounding by indication and immortal time bias. ConclusionsUsing national real-world data from predominantly vaccinated, immunocompromised Veterans, administration of tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection, COVID-19 hospitalization, and all-cause mortality during the Omicron surge.

IntroductionVaccine mandates have been used to minimize the duty days lost and deaths attributable to infectious disease among active duty Service members (ADSMs). In response to the global COVID-19 pandemic, in August 2021, the United States Department of Defense issued a COVID-19 vaccine mandate for all ADSMs. This study aimed to investigate COVID-19 vaccine uptake among the ADSM population, as well as factors associated with timing of COVID-19 vaccine receipt. MethodsThis study included ADSMs on active duty between 1/1/2020-6/30/2022. Univariate analyses investigated associations between demographic factors (age, sex, race, ethnicity, branch of service, rank, state of residence) and COVID-19 diagnosis with the following outcomes: 1) time to primary series initiation in relation to the DoD vaccine mandate, 2) time between doses of the two-dose primary series, and 3) time between booster eligibility and receipt ResultsA total of 1,799,466 ADSMs were included, with 90% receiving [&ge;]1 COVID-19 vaccine dose during the study period and 77% initiating the primary series prior to the mandate. Over 80% of ADSMs received a complete primary series, with 96% of those adhering to the recommended regimen. History of COVID-19 diagnosis was associated with later receipt of all doses. ConclusionsCOVID-19 vaccine uptake was high among all ADSMs, with the majority initiating the primary series before the mandate. The high vaccine uptake among ADSMs shown here may be used as a guide to both military and civilian pandemic policy and outreach efforts related to enhanced vaccine uptake.

Incomplete information on HLA allele typing is a persistent problem when analyzing the role of Human Leukocyte Antigen (HLA) in transplantation. To refine the predictions possible with partial knowledge of HLA typing, some researchers use HaploStats statistics on the frequencies of haplotypes within specified ethnic/national populations to impute complete HLA allele typing. We evaluated methods that use imputation to predict patient outcomes after organ transplantation, with focus on prediction of graft survival conditional on typing information of the donor and recipient. Logical arguments show that imputation yields no predictive power when predictions are conditioned on all observed HLA typing data. Computational experiments indicate that imputation does not have predictive power when applied to risk-assessment models that make predictions conditional on only part of the observable HLA data. We therefore caution against reliance on imputation to overcome incomplete measurement. We encourage high-resolution typing of HLA antigens to improve prediction of transplant outcomes and matching of donors with recipients. Similar considerations should likely apply in other clinical settings.

BackgroundGiven the limited supply of two COVID-19 vaccines, it will be important to choose which risk groups to prioritize for vaccination in order to get the most health benefits from that supply. MethodIn order to help decide how to get the maximum health yield from this limited supply, we implemented a logistic regression model to predict COVID-19 death risk by age, race, and sex and did the same to predict COVID-19 case risk. ResultsOur predictive model ranked all demographic groups by COVID-19 death risk. It was highly concentrated in some demographic groups, e.g. 85+ year old Black, Non-Hispanic patients suffered 1,953 deaths per 100,000. If we vaccinated the 17 demographic groups at highest COVID-19 death ranked by our logistic model, it would require only 3.7% of the vaccine supply needed to vaccinate all the United States, and yet prevent 47% of COVID-19 deaths. Nursing home residents had a higher COVID-19 death risk at 5,200 deaths/100,000, more than our highest demographic risk group. Risk of prison residents and health care workers (HCW) were lower than that of our demographic groups with the highest risks. We saw much less concentration of COVID-19 case risk in any demographic groups compared to the high concentration of COVID-19 death in some such groups. We should prioritize vaccinations with the goal of reducing deaths, not cases, while the vaccine supply is low. ConclusionSARS-CoV-2 vaccines protect against severe COVID-19 infection and thus against COVID-19 death per vaccine studies. Allocating at least some of the early vaccine supplies to high risk demographic groups could maximize lives saved. Our model, and the risk estimate it produced, could help states define their vaccine allocation rules.

More than 4,000 colleges and universities in the U.S. are scheduled to start a new semester in August or September, 2021. Many colleges require Covid-19 vaccination, as well as some combination of face coverings or diagnostic testing, while others do not (in some cases due to governance structure). Large state universities may especially have limitations and are not requiring vaccination, testing, or indoor face coverings, nor offering hybrid classes (to promote physical distancing). Group living quarters or classrooms with densely packed students are among the riskiest settings for infectious disease spread.

BackgroundAllogeneic hematopoietic cell transplantation (HCT) can be complicated by the development of organ toxicity and infection necessitating intensive care. Risk factors for intensive care admission are unclear due to heterogeneity across centers, and long-term outcome data after intensive care are sparse due to a historical paucity of survivors. MethodsThe Center for International Blood and Marrow Transplant Research (CIBMTR) was queried to identify patients age [&le;]21 years who underwent a 1st allogeneic HCT between 2008-2014 in the United States or Canada. Records were cross-referenced with the Virtual Pediatric Systems pediatric ICU database to identify intensive care admissions. CIBMTR follow-up data were collected through the year 2020. ResultsWe identified 6,995 pediatric HCT patients from 69 HCT centers, of whom 1,067 required post-HCT intensive care. The cumulative incidence of PICU admission was 8.3% at day +100, 12.8% at 1 year, and 15.3% at 5 years post HCT. PICU admission was linked to younger age, lower median zip code income, Black or multiracial background, pre-transplant organ toxicity, pre-transplant CMV seropositivity, use of umbilical cord blood and/or HLA-mismatched allografts, and the development of post-HCT graft-versus-host disease or malignancy relapse. Among PICU patients, survival to ICU discharge was 85.7% but more than half of ICU survivors were readmitted to a PICU during the study interval. Overall survival from the time of 1st PICU admission was 52.5% at 1 year and 42.6% at 5 years. Long-term post-ICU survival was worse among patients with malignant disease (particularly if relapsed), as well as those with poor pre-transplant organ function and alloreactivity risk-factors. In a landmark analysis of all 1-year HCT survivors, those who required intensive care in the first year had 10% lower survival at 5 years (77.1% vs. 87.0%, p<0.001) and developed new dialysis-dependent renal failure at a greater rate (p<0.001). ConclusionsIntensive care management is common in pediatric HCT patients. Survival to ICU discharge is high, but ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in many patients. Together, these data suggest an ongoing burden of toxicity in pediatric HCT patients that continues to limit long-term survival.

IntroductionSince March of 2020, over 210 million SARS-CoV-2 cases have been reported and roughly five billion doses of a SARS-CoV-2 vaccine have been delivered. The rise of the more infectious delta variant has recently indicated the value of reinstating previously relaxed non-pharmacological and test-driven preventative measures. These efforts have been met with resistance, due, in part, to a lack of site-specific quantitative evidence which can justify their value. As vaccination rates continue to increase, a gap in knowledge exists regarding appropriate thresholds for escalation and de-escalation of COVID-19 preventative measures. MethodsWe conducted a series of simulation experiments, trialing the spread of SARS-CoV-2 virus in a hypothesized working environment that is subject to COVID-19 infections from the surrounding community. We established cohorts of individuals who would, in simulation, work together for a set period of time. With these cohorts, we tested the rates of workplace and community acquired infections based on applied isolation strategies, community infection rates (CIR), scales of testing, non-pharmaceutical interventions, variant predominances and testing strategies, vaccination coverages, and vaccination efficacies of the members included. Permuting through each combination of these variables, we estimated expected case counts for 33,462 unique workplace scenarios. ResultsWhen the CIR is 5 new confirmed cases per 100,000 or fewer, and at 50% of the workforce is vaccinated with a 95% efficacious vaccine, then testing daily with an antigen-based or PCR based test in only unvaccinated workers will result in less than one infection through 4,800 person weeks. When the community infection rate per 100,000 persons is less than or equal to 60, and the vaccination coverage of the workforce is 100% with 95% vaccine efficacy then no masking or routine testing + isolation strategies are needed to prevent workplace acquired infections regardless of variant predominance. Identifying and isolating workers with antigen-based SARS-CoV-2 testing methods results in the same or fewer workplace acquired infections than testing with polymerase chain reaction (PCR) methods. ConclusionsSpecific scenarios exist in which preventative measures taken to prevent SARS-CoV-2 spread, including masking, and testing plus isolation strategies can safely be relaxed. Further, efficacious testing with quarantine strategies exist for implementation in only unvaccinated cohorts in a workplace. Due to shorter turnaround time, antigen-based testing with lower sensitivity is more effective than PCR testing with higher sensitivities in comparable testing strategies. The general reference interactive heatmap we provide can be used for site specific, immediate, parameter-based case count predictions to inform appropriate institutional policy making.

ImportanceActive monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. ObjectiveTo conduct near real-time monitoring of health outcomes following COVID-19 vaccination in the United States (US) pediatric population aged 6 months to 17 years. DesignWe evaluated 21 pre-specified health outcomes; 15 were sequentially tested through near real-time surveillance, and 6 were monitored descriptively within a cohort of vaccinated children. We tested for increased rate of each outcome following vaccination compared to a historical comparator cohort. SettingThis population-based study was conducted under the US Food and Drug Administration public health surveillance mandate using three commercial claims databases. ParticipantsChildren aged 6 months to 17 years were included if they received a monovalent COVID-19 vaccine dose before early 2023 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination dose. ExposureExposure was defined as receipt of a monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose. The primary analysis evaluated dose 1 and dose 2 combined, and secondary analyses evaluated each dose separately. Follow-up time was censored at death, disenrollment, end of risk window, end of study period, or a subsequent dose administration. Main OutcomesTwenty-one prespecified health outcomes. ResultsThe study included 4,102,016 enrollees aged 6 months to17 years. Thirteen of 15 outcomes sequentially tested did not meet the threshold for a statistical signal. In the primary analysis, myocarditis or pericarditis signals were detected following BNT162b2 vaccine in children aged 12-17 years old and seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates. Conclusions and RelevanceOf the two signaled outcomes, the myocarditis or pericarditis signals are consistent with previously published reports. The new signal detected for seizures/convulsions among younger children should be further investigated in a robust epidemiological study with better confounding adjustment.

ImportanceDonor hospitals in the United States are assigned to a designated organ procurement organization (OPO) responsible for managing deceased donors in the designated donation service area (DSA). Donor hospitals can apply for waivers to work with a different OPO with appropriate justification, and beginning with the 2026 OPO certification cycle, the highest-performing OPOs can bid to work with donor hospitals managed by intermediate- and low-performing OPOs. ObjectiveWe sought to evaluate the impact of donor hospital waivers on organ donation activity. DesignRetrospective cohort study. SettingWe evaluated Organ Procurement and Transplantation Network (OPTN) data from two OPOs (Donor Network West and Honor Bridge), each with a donor hospital (Renown Regional Medical Center and North Carolina Baptist Hospital) in its DSA granted a waiver to work with a different OPO beginning in April 2025. Main OutcomeWe assessed changes in the number of organ donors and organs transplanted pre- and post-granting of a waiver using a difference-in-differences approach based on multilevel mixed-effects models. ResultsAfter switching OPO affiliations, these two donor hospitals had marked and statistically significant increases in the number of donors recovered and organs transplanted, despite stable numbers of reported deaths at each hospital. In multivariable models, switching OPO affiliations was associated with a statistically significant increase in donors recovered and organs transplanted. Conclusion: With eight months of post-waiver data, donor hospitals with granted waivers had significant increases in donation activity driven by improved donor conversion rather than changes in referral patterns or organ yield per donor. Although longer-term data are needed to confirm these findings, CMS and the organ transplant community should feel confident that changing donor hospital-OPO affiliations will not negatively impact donation and may lead to significant increases in donation. These data also counter unfounded concerns that the continued granting of waivers and realignments of donor hospital-OPO affiliations during the 2026 recertification cycle will lead to a collapse of the system of organ donation. KEY POINTSO_ST_ABSQuestionC_ST_ABSDo donor hospitals who request a waiver to change OPO affiliations have changes in organ donation rates? FindingsUsing a difference-in-difference approach, the two donor hospitals who changed OPO affiliations had a significant increase in organ donors and organs transplanted after being granted a waiver. MeaningDonor hospitals that change OPO affiliations have an immediate increase in organ donation activity.

From 2019 to 2021 life expectancy at birth in the United States (US) declined by approximately 2.45 years to values not seen since 1996. Complete life tables for 2019 to 2022 were constructed for the total US population, females, and males using mortality data from the CDC WONDER Multiple Cause of Death database and Census Bureau Vintage population estimates. Life expectancy at birth increased by 1.07 years between 2021 and 2022. Nearly 40% of lost life expectancy years at birth were regained in 2022.