Search

ImportancemRNA COVID-19 vaccines require two primary doses. The optimal timing of second dose administration with respect to vaccine effectiveness of the primary series has not been thoroughly evaluated and has implications for vaccination strategies.ObjectiveTo assess whether the effectiveness of mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) against SARS-CoV-2 infection differs by varying intervals between the first and second doses of the primary series among the general population.DesignWe employed a trial emulation approach (clone-censor weight analysis) to estimate the risk of SARS-CoV-2 infection after the first dose administration under the scenario where the total study population had followed each of the following interdose intervals: recommended by the Food and Drug Administration (FDA) (17-25 days for Pfizer-BioNTech; 24-32 days for Moderna), late-but-allowable (26-42 days for Pfizer-BioNTech; 33-49 days for Moderna), and late (≥43 days for Pfizer-BioNTech; ≥50 days for Moderna).SettingGeorgia, USA.ParticipantsIndividuals who received ≥1 dose of mRNA COVID-19 vaccines in Georgia between December 13, 2020 and March 16, 2022.ExposureDosing protocols based on the timing of the second dose administration.Main Outcomes and MeasuresSARS-CoV-2 infection was defined as a positive result by a real-time reverse transcriptase PCR or antigen test. The follow-up period began the day after the first dose administration and ended at the earliest of SARS-CoV-2 infection, protocol nonadherence, or end of study.ResultsIn the short-term, the cumulative risk of SARS-CoV-2 infection was lowest under the FDA-recommended protocol (risk ratio (RR) on Day 50 after the first dose administration compared to the FDA-recommended protocol: 1.08 [95% confidence interval 1.07-1.10] under the late-but-allowable and 1.14 [1.12-1.16] under the late protocol). Longer-term, the late-but-allowable protocol resulted in the lowest risk (RR on Day 120: 0.83 [0.82-0.84] for the late-but-allowable and 1.10 [1.08-1.12] for the late protocol). The late protocol consistently yielded the highest risk among all protocols.Conclusions and RelevanceDelaying the timing of the second dose administration by a week may provide stronger protection against SARS-CoV-2 infection, but a longer delay would increase the risk of infection.KEY POINTSQuestionDoes the effectiveness of mRNA COVID-19 vaccines differ by intervals between the first and second doses of the primary series?FindingsThis study of >6 million mRNA COVID-19 vaccine recipients in Georgia, US used a trial emulation approach to compare the risk of SARS-CoV-2 infection under three protocols based on the timing of the second dose (“recommended,” “late-but-allowable,” and “late”). The late-but-allowable protocol led to the lowest cumulative risk in a long term.MeaningDelaying the receipt of the second dose by a week may decrease the risk of SARS-CoV-2 infection, but a longer delay would increase the risk.

In the effort to control SARS-CoV-2 transmission, public health agencies in the United States and globally are aiming to increase population immunity. Immunity through vaccination and acquired following recovery from natural infection are the two means to building up population immunity, with vaccination representing the safe pathway. However, measuring the contribution to population immunity from vaccination or natural infection is non-trivial. Historical COVID-19 case counts and vaccine coverage are necessary information but are not sufficient to approximate population immunity. Here, we consider the nuances of measuring each and propose an analytical framework for integrating the necessary data on cumulative vaccinations and natural infections at the state and national level. To guide vaccine roll-out and other aspects of control over the coming months, we recommend analytics that combine vaccine coverage with local (e.g. county-level) history of case reports and adjustment for waning antibodies to establish local estimates of population immunity. To do so, the strategic use of minimally-biased serology surveys integrated with vaccine administration data can improve estimates of the aggregate level of immunity to guide data-driven decisions to re-open safely and prioritize vaccination efforts.

Background Reported coronavirus disease 2019 (COVID-19) cases underestimate true severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Data on all infections, including asymptomatic infections, are needed. To minimize biases in estimates from reported cases and seroprevalence surveys, we conducted a household-based probability survey and estimated cumulative incidence of SARS-CoV-2 infections adjusted for antibody waning. Methods From August to December 2020, we mailed specimen collection kits (nasal swabs and blood spots) to a random sample of Georgia addresses. One household adult completed a survey and returned specimens for virus and antibody testing. We estimated cumulative incidence of SARS-CoV-2 infections adjusted for waning antibodies, reported fraction, and infection fatality ratio (IFR). Differences in seropositivity among demographic, geographic, and clinical subgroups were explored with weighted prevalence ratios (PR). Results Among 1370 participants, adjusted cumulative incidence of SARS-CoV-2 was 16.1% (95% credible interval [CrI], 13.5%–19.2%) as of 16 November 2020. The reported fraction was 26.6% and IFR was 0.78%. Non-Hispanic black (PR, 2.03; 95% confidence interval [CI], 1.0–4.1) and Hispanic adults (PR, 1.98; 95% CI, .74–5.31) were more likely than non-Hispanic white adults to be seropositive. Conclusions As of mid-November 2020, 1 in 6 adults in Georgia had been infected with SARS-CoV-2. The COVID-19 epidemic in Georgia is likely substantially underestimated by reported cases., Using data from a probability survey of households in Georgia, United States we estimated that 1.3 million adults aged ≥18 years experienced SARS-CoV-2 infections by 16 November 2020, of whom 1 in 4 were reported and of whom 0.78% died.

Background Immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be induced by natural infection or vaccination or both. Interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. Methods We used regression models to evaluate whether the impact of coronavirus disease 2019 (COVID-19) vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for 3 evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy for the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. Results COVID-19 mortality decreased as coverage of ≥1 dose increased among people ≥65 years of age, and this effect did not vary by seroprevalence or proportion of the total population ever infected. Seroprevalence and proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. Conclusions COVID-19 vaccination was associated with a sustained reduction in mortality at state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity.

Supplemental Digital Content is available in the text., Background: Serology tests can identify previous infections and facilitate estimation of the number of total infections. However, immunoglobulins targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to wane below the detectable level of serologic assays (which is not necessarily equivalent to the duration of protective immunity). We estimate the cumulative incidence of SARS-CoV-2 infection from serology studies, accounting for expected levels of antibody acquisition (seroconversion) and waning (seroreversion), and apply this framework using data from New York City and Connecticut. Methods: We estimated time from seroconversion to seroreversion and infection fatality ratio (IFR) using mortality data from March to October 2020 and population-level cross-sectional seroprevalence data from April to August 2020 in New York City and Connecticut. We then estimated the daily seroprevalence and cumulative incidence of SARS-CoV-2 infection. Results: The estimated average time from seroconversion to seroreversion was 3–4 months. The estimated IFR was 1.1% (95% credible interval, 1.0%, 1.2%) in New York City and 1.4% (1.1, 1.7%) in Connecticut. The estimated daily seroprevalence declined after a peak in the spring. The estimated cumulative incidence reached 26.8% (24.2%, 29.7%) at the end of September in New York City and 8.8% (7.1%, 11.3%) in Connecticut, higher than maximum seroprevalence measures (22.1% and 6.1%), respectively. Conclusions: The cumulative incidence of SARS-CoV-2 infection is underestimated using cross-sectional serology data without adjustment for waning antibodies. Our approach can help quantify the magnitude of underestimation and adjust estimates for waning antibodies.

Supplemental Digital Content is available in the text., Background: The synthetic control method evaluates the impact of vaccines while adjusting for a set of control time series representing diseases that are unaffected by the vaccine. However, noise in control time series, particularly in areas with small counts, can obscure the association with the outcome, preventing proper adjustments. To overcome this issue, we investigated the use of temporal and spatial aggregation methods to smooth the controls and allow for adjustment of underlying trends. Methods: We evaluated the impact of pneumococcal conjugate vaccine on all-cause pneumonia hospitalizations among adults ≥80 years of age in 25 states in Brazil from 2005 to 2015. Pneumonia hospitalizations in this group indicated a strong increasing secular trend over time that may influence estimation of the vaccine impact. First, we aggregated control time series separately by time or space before incorporation into the synthetic control model. Next, we developed distributed lags models (DLMs) to automatically determine what level of aggregation was most appropriate for each control. Results: The aggregation of control time series enabled the synthetic control model to identify stronger associations between outcome and controls. As a result, the aggregation models and DLMs succeeded in adjusting for long-term trends even in smaller states with sparse data, leading to more reliable estimates of vaccine impact. Conclusions: When synthetic control struggles to identify important prevaccine associations due to noise in control time series, users can aggregate controls over time or space to generate more robust estimates of the vaccine impact. DLMs automate this process without requiring prespecification of the aggregation level.

Background Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children, The introduction of pneumococcal conjugate vaccines is associated with substantial declines in childhood pneumonia mortality. Approximately 4500 pneumonia deaths were estimated to have been averted among children aged 2–59 months across 10 Latin America and Caribbean countries since vaccine introduction.

Social distancing measures are effective in reducing overall community transmission but much remains unknown about how they have impacted finer-scale dynamics. In particular, much is unknown about how changes of contact patterns and other behaviors including adherence to social distancing, induced by these measures, may have impacted finer-scale transmission dynamics among different age groups. In this paper, we build a stochastic age-specific transmission model to systematically characterize the degree and variation of age-specific transmission dynamics, before and after lifting the lockdown in Georgia, USA. We perform Bayesian (missing-) data-augmentation model inference, leveraging reported age-specific case, seroprevalence and mortality data. We estimate that community-level transmissibility was reduced to 41.2% with 95% CI [39%, 43.8%] of the pre-lockdown level in about a week of the announcement of the shelter-in-place order. Although it subsequently increased after the lockdown was lifted, it only bounced back to 62% [58%, 67.2%] of the pre-lockdown level after about a month. We also find that during the lockdown susceptibility to infection increases with age. Specifically, relative to the oldest age group (>65+), susceptibility for the youngest age group (0-17 years) is 0.13 [0.09, 0.18], and it increases to 0.53 [0.49, 0.59] for 18-44 and 0.75 [0.68, 0.82] for 45- 64. More importantly, our results reveal clear changes of age-specific susceptibility (defined as average risk of getting infected during an infectious contact incorporating age-dependent behavioral factors) after the lockdown was lifted, with a trend largely consistent with reported age-specific adherence levels to social distancing and preventive measures. Specifically, the older groups (>45) (with the highest levels of adherence) appear to have the most significant reductions of susceptibility (e.g., post-lockdown susceptibility reduced to 31.6% [29.3%, 34%] of the estimate before lifting the lockdown for the 65+ group). Finally, we find heterogeneity in case reporting rates among different age groups, with the lowest rate occurring among the 0-18 group (9.7% [6.4%, 19%]). Our results provide a more fundamental understanding of the impacts of stringent lockdown measures, and finer evidence that other social distancing and preventive measures may be effective in reducing SARS-CoV-2 transmission. These results may be exploited to guide more effective implementations of these measures in many current settings (with low vaccination rate globally and emerging variants) and in future potential outbreaks of novel pathogens.

The response to the COVID-19 pandemic in the U.S prompted abrupt and dramatic changes to social contact patterns. Monitoring changing social behavior is essential to provide reliable input data for mechanistic models of infectious disease, which have been increasingly used to support public health policy to mitigate the impacts of the pandemic. While some studies have reported on changing contact patterns throughout the pandemic., few have reported on differences in contact patterns among key demographic groups and none have reported nationally representative estimates. We conducted a national probability survey of US households and collected information on social contact patterns during two time periods: August-December 2020 (before widespread vaccine availability) and March-April 2021 (during national vaccine rollout). Overall, contact rates in Spring 2021 were similar to those in Fall 2020, with most contacts reported at work. Persons identifying as non-White, non-Black, non-Asian, and non-Hispanic reported high numbers of contacts relative to other racial and ethnic groups. Contact rates were highest in those reporting occupations in retail, hospitality and food service, and transportation. Those testing positive for SARS-CoV-2 antibodies reported a higher number of daily contacts than those who were seronegative. Our findings provide evidence for differences in social behavior among demographic groups, highlighting the profound disparities that have become the hallmark of the COVID-19 pandemic.

Background Reported coronavirus disease 2019 (COVID-19) cases underestimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We conducted a national probability survey of US households to estimate cumulative incidence adjusted for antibody waning. Methods From August–December 2020 a random sample of US addresses were mailed a survey and self-collected nasal swabs and dried blood spot cards. One adult household member completed the survey and mail specimens for viral detection and total (immunoglobulin [Ig] A, IgM, IgG) nucleocapsid antibody by a commercial, emergency use authorization–approved antigen capture assay. We estimated cumulative incidence of SARS-CoV-2 adjusted for waning antibodies and calculated reported fraction (RF) and infection fatality ratio (IFR). Differences in seropositivity among demographic, geographic, and clinical subgroups were explored. Results Among 39 500 sampled households, 4654 respondents provided responses. Cumulative incidence adjusted for waning was 11.9% (95% credible interval [CrI], 10.5%–13.5%) as of 30 October 2020. We estimated 30 332 842 (CrI, 26 703 753–34 335 338) total infections in the US adult population by 30 October 2020. RF was 22.3% and IFR was 0.85% among adults. Black non-Hispanics (Prevalence ratio (PR) 2.2) and Hispanics (PR, 3.1) were more likely than White non-Hispanics to be seropositive. Conclusions One in 8 US adults had been infected with SARS-CoV-2 by October 2020; however, few had been accounted for in public health reporting. The COVID-19 pandemic is likely substantially underestimated by reported cases. Disparities in COVID-19 by race observed among reported cases cannot be attributed to differential diagnosis or reporting of infections in population subgroups., One in 8 US adults had been infected with severe acute respiratory syndrome coronavirus 2 by late October 2020; however, few had been accounted for in public health reporting. The scope of the coronavirus disease 2019 pandemic is likely substantially underestimated by reported cases. We conducted a national probability survey of US households to estimate the cumulative incidence adjusted for antibody waning.

Background California has reported the largest number of coronavirus disease 2019 (COVID-19) cases of any US state, with more than 3.5 million confirmed as of March 2021. However, the full breadth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in California is unknown as reported cases only represent a fraction of all infections. Methods We conducted a population-based serosurvey, utilizing mailed, home-based SARS-CoV-2 antibody testing along with a demographic and behavioral survey. We weighted data from a random sample to represent the adult California population and estimated period seroprevalence overall and by participant characteristics. Seroprevalence estimates were adjusted for waning antibodies to produce statewide estimates of cumulative incidence, the infection fatality ratio (IFR), and the reported fraction. Results California’s SARS-CoV-2 weighted seroprevalence during August–December 2020 was 4.6% (95% CI, 2.8%–7.4%). Estimated cumulative incidence as of November 2, 2020, was 8.7% (95% CrI, 6.4%–11.5%), indicating that 2 660 441 adults (95% CrI, 1 959 218–3 532 380) had been infected. The estimated IFR was 0.8% (95% CrI, 0.6%–1.0%), and the estimated percentage of infections reported to the California Department of Public Health was 31%. Disparately high risk for infection was observed among persons of Hispanic/Latinx ethnicity and people with no health insurance and who reported working outside the home. Conclusions We present the first statewide SARS-CoV-2 cumulative incidence estimate among adults in California. As of November 2020, ~1 in 3 SARS-CoV-2 infections in California adults had been identified by public health surveillance. When accounting for unreported SARS-CoV-2 infections, disparities by race/ethnicity seen in case-based surveillance persist., A population-based serosurvey conducted in California found approximately one in three SARS-CoV-2 infections had been reported by November 2020. Disparities in seroprevalence by race/ethnicity and social determinants of health were consistent with those seen among PCR-confirmed cases.

OBJECTIVES: Open-distal anastomosis is the preferred technique over clamp-on technique for surgical repair of acute type A aortic dissection (ATAAD). The aim of this study was to define how outcomes of ATAAD were affected by the use of either technique.METHODS: Nordic Consortium for Acute Type A Aortic Dissection includes 8 academic cardiothoracic hospitals in 4 Nordic countries. The cohort consisted of 1134 patients, 153 clamp-on and 981 open-distal, from 2005 to 2014.RESULTS: Patients who underwent operation with the clamp-on were younger, more frequently had coronary artery disease, bicuspid aortic valve, hypotension/shock or syncope, and a greater PennClass than open-distal patients. Postoperative cerebral vascular accident occurred less frequently in clamp-on (14/153, 10%) compared with the open-distal group (190/981, 20%). Clamp-on had greater 30-day mortality (39/153, 25%) than the open-distal group (158/981, 16%), and 5-year survival was also worse in clamp-on (61.8% ± 4.4%) compared with the open-distal group (73.0% ± 1.6%). The open-distal technique was used more frequently in greater-volume hospitals but was not independently associated with 30-day mortality. Preoperative condition was an independent risk factor whereas hospital volume and later year of operation were beneficial in regard to short-term outcome. Open-distal was independently associated with improved mid-term survival.CONCLUSIONS: Patients who underwent operation with the clamp-on were sicker on presentation and had worse short- and mid-term survival compared with the open-distal group. Patients in the open-distal group had greater rates of cerebrovascular complications. The results support the routine use of open-distal anastomosis as the primary operative strategy for ATAAD, although clamp-on can be performed successfully in select cases.

The proportional incidence of intravenous drug use (IVDU)-associated infective endocarditis (IE) cases requiring surgery has increased significantly, mirroring the national opioid crisis. Recidivism is common but its impact on postoperative outcomes is unclear. We aimed to evaluate short- and mid-term postoperative outcomes associated with recidivism in this population. We retrospectively reviewed 180 consecutive patients (54 IVDU and 126 non-IVDU) surgically treated for IE from 2011 to 2016. The institutional database was linked to the Connecticut Department of Public Health Death Index to capture statewide long-term mortality and causes of death. Regression models were fitted to evaluate the association between IVDU status and perioperative adverse events, mid-term survival, and causes of death. IVDU patients were younger and had fewer comorbidities. Diabetes, hypertension, peripheral vascular disease, and previous coronary artery bypass graft were less frequently present in IVDU patients compared to non-IVDU patients (P

BackgroundReported COVID-19 cases underestimate the true number of SARS-CoV-2 infections. Data on all infections, including asymptomatic infection, are needed to guide state testing and prevention programs. To minimize biases in estimates from seroprevalence surveys and reported cases, we conducted a state-wide probability survey of Georgia households and estimated cumulative incidence of SARS-CoV-2 infections adjusted for antibody waning.MethodsFrom August to December 2020, we mailed kits to self-collect specimens (nasal swabs and blood spots) to a random sample of Georgia addresses. One randomly-selected adult household member completed a survey and returned specimens for virus and antibody testing. We estimated cumulative incidence of SARS-CoV-2 infections adjusted for waning antibodies, reported fraction, and infection fatality ratio (IFR). Differences in seropositivity among demographic, geographic and clinical subgroups were explored with weighted prevalence ratios (PR).ResultsAmong 1,370 Georgia adult participants, adjusted cumulative incidence of SARS-CoV-2 was 16.1% (95% credible interval (CrI): 13.5-19.2%) as of November 16, 2020. The reported fraction was 26.6% and IFR was 0.78%. Non-Hispanic Black (PR: 2.03, CI 1.0, 4.1) and Hispanic adults (PR: 1.98, CI 0.74, 5.31) were more likely than non-Hispanic White adults to be seropositive. Seropositivity in metropolitan Atlanta’s Fulton and DeKalb counties was similar to seropositivity elsewhere in Georgia (7.8% vs. 8.8%).ConclusionsAs of mid-November 2020, one in 6 adults in Georgia had been infected with SARS-CoV-2. The scope of the COVID-19 epidemic in Georgia is likely substantially underestimated by reported cases.Main pointUsing data from a probability survey of households in Georgia, USA, we estimated that 1.3 million adults aged ≥18 years experienced SARS-CoV-2 infections by November 16, 2020, of whom 1 in 4 were reported and of whom 0.78% died.

Background Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions. Methods and findings We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged, Jackie Kleynhans and colleagues investigate whether introduction of the pneumococcal conjugate vaccine may have reduced all-cause pneumonia mortality in South Africa., Author summary Why was this study done? The bacterium, Streptococcus pneumoniae, causes a third of childhood pneumonia deaths in sub-Saharan Africa. The pneumococcal conjugate vaccine (PCV) has been used in South Africa since 2009 and has been found to be effective in reducing vaccine-serotype invasive pneumococcal disease. The effect of PCV on pneumonia mortality has not been assessed in South Africa, or on national scale in Africa. We wanted to estimate the impact of this vaccine on all-cause pneumonia mortality in South Africa. What did the researches do and find? We performed an ecological modelling study using national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality. Due to multiple other changes in South Africa at the time, pneumonia mortality was already decreasing before PCV was introduced. Therefore, we needed to control for these changes while measuring the impact of PCV on pneumonia mortality. We did this by creating a synthetic control from multiple other causes of deaths and compared the number of pneumonia deaths after PCV introduction to this synthetic control. We estimated that pneumonia mortality reduced between 23% and 33% in children younger than 19 years, with an estimated 18,000 deaths prevented between 2009 and 2016. What do these findings mean? PCV has contributed in reducing childhood pneumonia mortality in South Africa. Vaccination of children with PCV should continue globally and should be expanded to all African countries.

Background Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. Methods Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014–June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into 1 episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting–specific incidence estimates were calculated using age-stratified bootstrapping. Results The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged < 5 years (20.4 episodes per 1000 PY), followed by adults aged ≥ 65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY; astrovirus: 1.3 per 1000 PY; rotavirus: 0.5 per 1000 PY). Conclusions Viral enteropathogens, particularly norovirus, are important contributors to MAAGE, especially among children < 5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.

Summary The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance., Graphical Abstract, Highlights • Connecticut’s COVID-19 outbreak resulted from multiple domestic virus introductions • SARS-CoV-2 genomic data indicate that coast-to-coast spread occurred in the United States • Risk of introduction by domestic air travel exceeded international travel in March • Restrictions on international travel did not significantly alter risk estimates, Using genomics and air travel information, the spread of SARS-CoV-2 in the United States from coast to coast is shown to be more a consequence of domestic introductions than of international travel.

Using the national Society of Thoracic Surgeons Adult Cardiac Surgery Database data for thoracic aortic surgical procedures for aortic aneurysm, this study aimed to (1) characterize patients' risk profiles and outcomes, (2) evaluate center volume-outcome relationships across US centers, and (3) identify risk factors for operative mortality.Between 2011 and 2016, 53,559 operations for ascending aortic aneurysm performed across 1,045 centers in the United States were identified. Logistic regression related baseline characteristics and comorbidities to operative mortality. Ten-fold cross-validation was performed to estimate sensitivity and specificity across a range of the discrimination threshold. Centers were stratified into five strata by average annual case volume. Predicted probability of operative mortality was calculated from the model and was used to evaluate patients' risk profiles across the volume strata.Operative mortality occurred in 3.2% of all cases and in 2.2% of elective cases. Only 24 (2.3%) centers performed ≥50 cases annually, whereas 609 (58.3%) centers performed fewer than five cases annually. Multiple logistic regression, of which the c-index was 0.80, revealed that compared with centers with ≥50 cases, centers with fewer than five cases had an increased risk of mortality (odds ratio, 2.50; 95% confidence interval, 2.08 to 3.01; p0.0001). The predicted probability of operative mortality was similar across the volume strata, but the observed mortality rate varied significantly, with lower volume yielding higher operative mortality.Proximal thoracic aortic surgical procedures for aortic aneurysms in the United States are associated with a low operative mortality rate of 2.2% for elective cases. Risk of operative death decreases significantly at an annual center volume of more than 20 to 25 cases per year.

Background: Dual antiplatelet therapy (DAPT) in patients presenting with acute coronary syndrome (ACS) undergoing CABG is recommended to prevent recurrent ischemic events. The benefit of DAPT post-CABG in patients with stable ischemic heart disease (SIHD) is unknown. The aim of this study was to evaluate the utilization rate of DAPT and associated outcomes in patients with SIHD undergoing CABG via a secondary analysis of Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial data. Methods: In a post-hoc, nonrandomized analysis from the BARI 2D trial, we compared patients receiving DAPT and aspirin monotherapy within 90 days post-randomization. The primary outcome was the risk adjusted 5-year composite of all-cause mortality, nonfatal myocardial infarction (MI), or stroke. We analyzed patients assigned to prompt CABG treatment arm including both the insulin therapy assignments. Results: Of 378 patients, within 90 days post-randomization, 59 (16%) patients received DAPT and 319 (84%) patients received aspirin alone. Cox proportional hazard analysis demonstrated that there was no significant difference in the 5-year composite event of death, MI, and stroke between DAPT and monotherapy cohorts [13 (22.0%) vs. 61 (19.1%); adjusted hazard ratio (HR): 1.06; 95% confidence interval (CI): 0.56 to 2.00; P=0.86]. There also was no significant difference at 1 year in the composite event [6 (10.2%) vs. 30 (9.4%); HR: 1.13; 95% CI: 0.46 to 2.79; P=0.79]. Conclusions: The use of DAPT in patients with diabetes post-CABG in this cohort was low. Compared with aspirin monotherapy, no associated differences were observed in cardiovascular outcomes. Larger prospective studies are needed to further elucidate this observation.

Objectives Cardiac surgery for prosthetic valve endocarditis (PVE) represents one of the highest risk surgeries with in-hospital mortality of 20%. Given the complex nature of the operation, the operative outcome is likely strongly susceptible to the surgeon's experience and centre case volume, as measurements often are not apparent in large observational studies. We sought to evaluate operative outcomes and mid-term survival of patients with PVE compared with those of native valve endocarditis (NVE) at a tertiary care hospital. Methods We conducted a single-institutional retrospective review of 188 consecutive patients (146 NVE and 42 PVE) undergoing cardiac surgery for endocarditis between 2011 and 2016 at a tertiary care hospital in the USA. A logistic regression model was fit to evaluate patient characteristics and perioperative outcomes in PVE and NVE: operative mortality and composite events (death, stroke, prolonged intubation, renal failure and sepsis). The Kaplan-Meier analysis was used to estimate the mid-term survival. The Cox proportional hazard model was fit to assess the adjusted risk associated with mid-term survival. Results Operative mortality was 4.1% for NVE and 0% for PVE (P = 0.34). Composite events occurred in 30.6% and 38.1% of NVE and PVE, respectively (P = 0.45). Multivariable logistic regression for composite events showed that PVE was not associated with increased risk of adverse events [odds ratio 1.4, 95% confidence interval (CI) 0.6-3.4; P = 0.49]. The Kaplan-Meier analysis demonstrated no statistically significant difference in survival (P = 0.99). Finally, the Cox proportional hazard analysis for mid-term mortality demonstrated that PVE was not associated with increased risk for hazard of death: hazard ratio 0.4, 95% CI 0.2-1.1; P = 0.085. Conclusions Surgery for PVE can yield a low mortality rate with mid-term survival comparable with those of NVE. The diagnosis of PVE alone should not deter surgeons from operating on this complex patient population, provided that surgical expertise and experienced multidisciplinary team equipped to handle complex clinical scenarios are available.

Resumption of dual antiplatelet therapy after coronary artery bypass grafting in patients presenting with acute coronary syndrome is recommended, but the current practice pattern in the United States remains unknown. We aimed to investigate the current pattern of dual antiplatelet therapy use after coronary artery bypass grafting at the Yale-New Haven Hospital.We conducted a single-center retrospective review of patients who presented with acute coronary syndrome and underwent coronary artery bypass grafting between 2014 and 2016. The primary outcome was hospital discharge with dual antiplatelet therapy. Mixed-effect multivariate logistic regression was used to evaluate predictors of dual antiplatelet therapy use or nonuse, accounting for surgeon-specific preference. The discriminatory ability of the model was evaluated with receiver operating characteristics analysis.Of 572 patients included, only 29% were discharged with dual antiplatelet therapy. In the mixed-effect multivariate model isolating surgeon preferences, increase in age (odds ratio, 0.95; 95% confidence interval, 0.92-0.98; P .001) and discharge with anticoagulants (odds ratio, 0.20; 95% confidence interval, 0.07-0.55; P = .002) were associated with lower odds of dual antiplatelet therapy use. Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting was associated with increased odds of dual antiplatelet therapy use (odds ratio, 31.5; 95% confidence interval, 12.8-77.2; P .001). C-index of the prediction model was 0.74.The overall rate of dual antiplatelet therapy use in patients with acute coronary syndrome who underwent coronary artery bypass grafting was low and variable among surgeons. The use or nonuse was guided by previously established risk factors of recurrent ischemia and bleeding, along with surgeon preference.

Objectives Favourable results have been reported for monitored anaesthesia care that includes local anaesthesia and conscious sedation [minimalist approach (MA)] for transfemoral transcatheter aortic valve replacement (TAVR). However, the efficacy of MA is still controversial in Japan. We describe our experience from a Japanese multicentre registry. Methods Between October 2013 and April 2016, 1215 consecutive Japanese patients with symptomatic, severe aortic stenosis undergoing TAVR with self-expandable or balloon-expandable valves were prospectively included in the Optimized transCathEter vAlvular intervention-Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. Of these patients, we retrospectively reviewed 921 consecutive patients who underwent elective transfemoral-TAVR. We evaluated the perioperative results of MA-TAVR and non-minimalist approach (NMA) TAVR using propensity score matching analysis. Results A total of 118 patients underwent MA-TAVR, and 802 patients underwent NMA-TAVR [median age 84 vs 85 years, P = 0.25; Society of Thoracic Surgeons (STS) score 7.6 vs 6.4, P = 0.01]. One hundred eighteen matched pairs were compared after propensity score matching. In-hospital mortality and stroke/transient ischaemic attack were not significantly different between the MA-TAVR and the NMA-TAVR groups (2.5% vs 0.8%, P = 0.3; 1.7% vs 0.8%, P = 0.6, respectively). Major or life-threatening bleeding and the transfusion rate were significantly lower in the MA-TAVR group (3.4% vs 17%, P = 0.003; 6.8% vs 29%, P = 0.0002, respectively). The total intensive care unit days and length of hospital stay were significantly lower in the MA-TAVR group (P ≤ 0.0002). Conclusions MA-TAVR has similar results to NMA-TAVR in terms of mortality and stroke in this Japanese multicentre registry. Shorter procedure time and hospital stays were seen in the MA-TAVR group. MA-TAVR is as safe and effective as NMA-TAVR.

Norovirus is the leading cause of endemic and epidemic acute gastroenteritis in the United States (1). New variant strains of norovirus GII.4 emerge every 2-4 years (2-4) and are often associated with increased disease and health care visits (5-7). Since 2009, CDC has obtained epidemiologic data on norovirus outbreaks from state health departments through the National Outbreak Reporting System (NORS) (8) and laboratory data through CaliciNet (9). NORS is a web-based platform for reporting waterborne, foodborne, and enteric disease outbreaks of all etiologies, including norovirus, to CDC. CaliciNet, a nationwide electronic surveillance system of local and state public health and regulatory agency laboratories, collects genetic sequences of norovirus strains associated with gastroenteritis outbreaks. Because these two independent reporting systems contain complementary data, integration of NORS and CaliciNet records could provide valuable public health information about norovirus outbreaks. However, reporting lags and inconsistent identification codes in NORS and CaliciNet records have been an obstacle to developing an integrated surveillance system.

Background Passive surveillance data are often the only available source of data that can be used to evaluate the population-level impact of vaccination, but such data often suffer from important limitations such as changes in surveillance efforts. This study provides an example of how to identify important signatures of rotavirus vaccine impact, including evaluating the overall effectiveness and changes in rotavirus seasonal dynamics. Methods We used data from a standardized sentinel rotavirus surveillance network in six Latin American countries (Bolivia, El Salvador, Guatemala, Honduras, Paraguay, and Venezuela) from 2004 to 2017. A random-effects model was used to evaluate changes in the proportion of rotavirus-associated hospitalizations following vaccine introduction. Harmonic regression models were used to estimate vaccine impact on the number of rotavirus hospitalizations, controlling for trends in rotavirus-negative cases. Changes to rotavirus seasonality were evaluated using center of gravity analysis, wavelet analysis, and harmonic regression. Results All countries observed declines in the proportion of rotavirus-positive acute diarrhea samples with a mean reduction of 16% (95% confidence interval: 10–22%). We estimate that each 10% increase in vaccine coverage was associated with declines in the number of rotavirus-positive cases, ranging from 4.3% (1.3–7.2%) in Honduras to 21.4% (16.8–25.9%) in Venezuela. The strength of the seasonal peak in rotavirus incidence became smaller after vaccine introduction in Guatemala, Honduras, and Venezuela. Seasonal peaks also shifted later in the surveillance year, especially in higher-mortality countries. Conclusions The combination of methods we applied have different strengths that allow us to identify common signatures of rotavirus vaccine impact.

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children, Despite health gains achieved through rotavirus vaccination, rotavirus remains the most common cause of severe, hospitalized diarrhea among children in Malawi. There is a pressing need to identify strategies to improve rotavirus vaccine performance in low-income countries with a high disease burden.

Background In heart failure, a high systemic vascular resistance index (SVRI), high central venous pressure (CVP), and low cardiac index (CI) predict poor outcomes. Conversely, late hemodynamic manifestations of failing Fontan circulation and associations with end-organ dysfunction are not well understood. Methods A retrospective review of right-heart catheterization data of adult Fontan patients between 2002 and 2014 was conducted. Relationships between hemodynamic variables and serious adverse events (death or heart transplant) were examined using the Cox proportional hazard analysis. Correlations between the hemodynamic measurements and signs of end-organ dysfunction (MELD-XI, Child-Pugh, VAST score, estimated glomerular filtration rate [eGFR]) were analyzed. Results Sixty post-Fontan patients (85% systemic left ventricle, 40% atriopulmonary Fontan, mean age of 28 years, and mean time since Fontan operation of 21.9 years) were included. At baseline, those with an event were statistically younger, had lower transcutaneous oxygen saturations, were more likely to have an atriopulmonary Fontan, and were more likely to have a pacemaker. Eighteen experienced a cardiovascularly significant event. Using univariate analysis to compare the event and nonevent groups, mean CI was 2.8 ± 0.9 vs. 2.4 ± 0.5 L/min/m2 (P = .004), and CVP was 18.6 ± 6.5 vs. 16.1 ± 4.3 mmHg (P = .03). However, the statistical significances did not persist in the multivariate model. Higher CVP and pulmonary capillary wedge pressure (PCWP) were associated with higher MELD-XI and Child-Pugh scores, and the VAST score was only associated with PCWP. Conclusions Symptomatic adult Fontan patients who experienced an event manifested with a higher CI and CVP, although the multivariate Cox proportional hazard analysis did not yield any significant associations. The presences of hepatic dysfunction and portal venous outflow obstruction were associated with a higher CVP and PCWP. Renal dysfunction was prevalent but no statistically significant association between the hemodynamic measurements was identified, although trends toward a higher CVP and transpulmonary gradient were identified.

Background: Pneumococcal conjugate vaccines (PCVs) have prevented deaths due to pneumonia among children. The effect may differ between higher- and lower-income populations due to various factors, such as differences in the distribution of pneumococcal serotypes, healthcare access, and PCV uptake. This study aims to evaluate an association between increasing PCV coverage and population-level declines in death due to pneumonia and its variation by socioeconomic status of subnational regions. Methods: We analyzed municipality-level mortality data from 2005 and 2015 for children aged 2-23 months in Brazil, Colombia, and Peru. We fit Poisson regression models to estimate the relationship between changes in PCV uptake and deaths due to all-cause pneumonia among subnational regions with different income levels. We controlled for changes unrelated to PCV by using data on non-respiratory deaths over time. Results: Uptake of the third dose of PCV varied across subnational regions and was higher in high-income regions. Higher uptake of PCV was associated with larger declines in pneumonia mortality. This association did not differ by income level of the region in Brazil and Colombia. In Peru, low-income regions observed larger declines in pneumonia deaths, but there was large uncertainty in the difference between the low- and high-income regions. We estimated that, with 90% coverage, there would be 4-38% declines in all-cause pneumonia mortality across income levels and countries. Conclusions: Regions with higher PCV coverage experienced larger declines in pneumonia deaths, regardless of the income level. Having more reliable data on mortality records and vaccine uptake would improve the reliability of vaccine impact estimates.

The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.

Supplemental Digital Content is available in the text., Background: The synthetic control model is a powerful tool to quantify the population-level impact of vaccines because it can adjust for trends unrelated to vaccination using a composite of control diseases. Because vaccine impact studies are often conducted using smaller, subnational datasets, we evaluated the performance of synthetic control models with sparse time series data. To obtain more robust estimates of vaccine impacts from noisy time series, we proposed a possible alternative approach, STL+PCA method (seasonal-trend decomposition plus principal component analysis), which first extracts smoothed trends from the control time series and uses them to adjust the outcome. Methods: Using both the synthetic control and STL+PCA models, we estimated the impact of 10-valent pneumococcal conjugate vaccine on pneumonia hospitalizations among cases

Norovirus is increasingly recognized as a major cause of acute gastroenteritis among children

Background Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the state-of-the-art diagnostic for norovirus. Cycle threshold (Ct), an indicator of viral load, may be associated with symptomatic disease as well as demographic and outbreak characteristics. Methods Data on (1) outbreak and sporadic cases and (2) asymptomatic controls in the United States and Latin America were analyzed. With multivariate regression models, we assessed relationships between various factors and Ct values, and we calculated odds ratios (ORs) for the presence of symptoms and attributable fractions of norovirus. Receiver-operating characteristic analysis was performed to define an optimal Ct cutoff to identify disease-causing infections. Results Cycle threshold values were lower (ie, higher viral loads) among symptomatic cases (model-adjusted mean ± standard error: 25.3 ± 1.2) compared with asymptomatic controls (28.5 ± 1.4). Cycle threshold values were significantly different across age groups, norovirus genogroups, timing of specimen collection, outbreak settings, and transmission modes. Genogroup II (GII) Ct values were associated with presence of symptoms (OR = 1.1), allowing us to estimate that 16% of diarrheal disease was attributable to norovirus. The optimized Ct cutoff led to poor sensitivity and specificity for genogroup I and GII. Conclusions Cycle threshold values were associated with host, pathogen, and outbreak factors. Cycle threshold values may not effectively distinguish disease-causing infection for individual patients, but they are useful for epidemiological studies aiming to attribute disease.

Background During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. Methods Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. Results From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/µL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/µL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. Conclusions Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM.

Factors contributing to the failure of Fontan circulation in adults are poorly understood. Reduced superior mesenteric arterial (SMA) flow has been identified in pediatric Fontan patients with protein-losing enteropathy. SMA flow has not been profiled in an adult Fontan population and its association with adverse events is unknown. We aimed to examine associations between SMA flow patterns and adverse events in adult Fontan patients. We performed a retrospective review of adult Fontan patients who underwent echocardiograms between 2008 and 2014. SMA Doppler data included peak systolic and end-diastolic velocity and velocity time integral (VTI). Systolic/diastolic (S/D) ratio and resistive index were calculated. The relationship between SMA flow parameters and major adverse events (death or transplantation) was examined using proportional hazard Cox regression analyses. Kaplan–Meyer analysis was conducted to construct survival curve of patients with and without adverse events. 91 post-Fontan adult patients (76 % systemic left ventricle, 20 % atriopulmonary Fontan, mean age 27.9 years) were analyzed. Adverse events occurred in nine patients (death = 4, transplant = 5). When compared with the non-event group, the event group had increased end-diastolic velocity [hazard ratio (HR) 1.5, 95 % confidence interval (CI) 1.1–1.8; p = 0.002], increased systolic VTI (HR 1.5, 95 % CI 1.1–2.2, p = 0.02), increased diastolic VTI (HR 1.7, 95 % CI 1.2–2.4, p = 0.004), decreased S/D velocity ratio (HR 0.32, 95 % CI 0.14–0.71, p = 0.006), decreased S/D VTI ratio (HR 0.76, 95 % CI 0.61–0.97, p = 0.02), and decreased resistive index (HR 0.29, 95 % CI 0.14–0.60, p = 0.0007). Increased end-diastolic velocity and VTI in mesenteric arterial flow, with lower systolic/diastolic ratio and resistive index, were associated with death and need for heart transplant in adult Fontan patients. The mesenteric hyperemic flow was also associated with clinical signs of portal venous outflow obstruction, suggesting the presence of vasodilatory state in end-stage adult Fontan circulation.