Influenza Vaccine Effectiveness Pre-pandemic Among Adults Hospitalized With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease and Older Adults.

BACKGROUND: Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. METHODS: We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). RESULTS: Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8-75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9-72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3-93.9%). CONCLUSIONS: Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018-2020 seasons.

Estimating the Burden of Clinically Significant Staphylococcus aureus Infections and Predictors for Hospitalization for Skin and Soft Tissue Infections, Fulton County, Georgia, 2017.

Background: Incidence estimates of Staphylococcus aureus infections rarely include the full spectrum of clinically relevant disease from both community and healthcare settings. Methods: We conducted a prospective study capturing all S aureus infections in Fulton County, Georgia, during 2017. Medical records of patients with any incident infection (clinical cultures growing S aureus from any site, without prior positive culture in previous 14 days) were reviewed. Estimates of disease incidence were calculated using age-, race-, and sex-specific population denominators accounting for weighted sampling methods. Multivariable logistic regression models were used to identify risk factors for hospitalization among patients with skin and soft tissue infections (SSTIs). Results: The overall incidence of clinically relevant S aureus infection was 405.7 cases per 100 000 people (standard error [SE], 5.62 [range, 400.1-411.3]). Overall incidence for those of Black race was 500.84 cases per 100 000 people (SE, 14.55), whereas White patients had overall incidence of 363.67 cases per 100 000 people (SE, 13.8). SSTIs were the most common infection (2351; 225.8 cases per 100 000 people [SE, 7.1]), and 30% required hospitalization. Among SSTIs, after adjusting for invasive disease, cellulitis, diabetes, and demographics, independent predictors of hospitalization included methicillin-resistant S aureus (adjusted odds ratio [aOR], 1.6 [95% confidence interval {CI}, 1.0-2.7]) and homelessness (aOR, 4.9 [95% CI, 1.1-22]). Conclusions: The burden of clinically relevant S aureus infections is high, particularly among the Black population, and risks for hospitalization among SSTIs include isolate factors and factors related to patients' vulnerability.

Long-Term effects of COVID-19: a review of current perspectives and mechanistic insights.

Although SARS-CoV-2, responsible for COVID-19, is primarily a respiratory infection, a broad spectrum of cardiac, pulmonary, neurologic, and metabolic complications can occur. More than 50 long-term symptoms of COVID-19 have been described, and as many as 80% of patients may develop ≥1 long-term symptom. To summarize current perspectives of long-term sequelae of COVID-19, we conducted a PubMed search describing the long-term cardiovascular, pulmonary, gastrointestinal, and neurologic effects post-SARS-CoV-2 infection and mechanistic insights and risk factors for the above-mentioned sequelae. Emerging risk factors of long-term sequelae include older age (≥65 years), female sex, Black or Asian race, Hispanic ethnicity, and presence of comorbidities. There is an urgent need to better understand ongoing effects of COVID-19. Prospective studies evaluating long-term effects of COVID-19 in all body systems and patient groups will facilitate appropriate management and assess burden of care. Clinicians should ensure patients are followed up and managed appropriately, especially those in at-risk groups. Healthcare systems worldwide need to develop approaches to follow-up and support patients recovering from COVID-19. Surveillance programs can enhance prevention and treatment efforts for those most vulnerable.

The impact of COVID-19 vaccination in the US: Averted burden of SARS-COV-2-related cases, hospitalizations and deaths.

By August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.

Estimated preventable COVID-19-associated deaths due to non-vaccination in the United States.

While some studies have previously estimated lives saved by COVID-19 vaccination, we estimate how many deaths could have been averted by vaccination in the US but were not because of a failure to vaccinate. We used a simple method based on a nationally representative dataset to estimate the preventable deaths among unvaccinated individuals in the US from May 30, 2021 to September 3, 2022 adjusted for the effects of age and time. We estimated that at least 232,000 deaths could have been prevented among unvaccinated adults during the 15 months had they been vaccinated with at least a primary series. While uncertainties exist regarding the exact number of preventable deaths and more granular data are needed on other factors causing differences in death rates between the vaccinated and unvaccinated groups to inform these estimates, this method is a rapid assessment on vaccine-preventable deaths due to SARS-CoV-2 that has crucial public health implications. The same rapid method can be used for future public health emergencies.

Leveraging Serosurveillance and Postmortem Surveillance to Quantify the Impact of Coronavirus Disease 2019 in Africa.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact on global health, the magnitude of which appears to differ intercontinentally: For example, reports suggest that 271 900 per million people have been infected in Europe versus 8800 per million people in Africa. While Africa is the second-largest continent by population, its reported COVID-19 cases comprise <3% of global cases. Although social and environmental explanations have been proposed to clarify this discrepancy, systematic underascertainment of infections may be equally responsible. METHODS: We sought to quantify magnitudes of underascertainment in COVID-19's cumulative incidence in Africa. Using serosurveillance and postmortem surveillance, we constructed multiplicative factors estimating ratios of true infections to reported cases in Africa since March 2020. RESULTS: Multiplicative factors derived from serology data (subset of 12 nations) suggested a range of COVID-19 reporting rates, from 1 in 2 infections reported in Cape Verde (July 2020) to 1 in 3795 infections reported in Malawi (June 2020). A similar set of multiplicative factors for all nations derived from postmortem data points toward the same conclusion: Reported COVID-19 cases are unrepresentative of true infections, suggesting that a key reason for low case burden in many African nations is significant underdetection and underreporting. CONCLUSIONS: While estimating the exact burden of COVID-19 is challenging, the multiplicative factors we present furnish incidence estimates reflecting likely-to-worst-case ranges of infection. Our results stress the need for expansive surveillance to allocate resources in areas experiencing discrepancies between reported cases, projected infections, and deaths.

Methods for early characterisation of the severity and dynamics of SARS-CoV-2 variants: a population-based time series analysis in South Africa.

BACKGROUND: Assessment of disease severity associated with a novel pathogen or variant provides crucial information needed by public health agencies and governments to develop appropriate responses. The SARS-CoV-2 omicron variant of concern (VOC) spread rapidly through populations worldwide before robust epidemiological and laboratory data were available to investigate its relative severity. Here we develop a set of methods that make use of non-linked, aggregate data to promptly estimate the severity of a novel variant, compare its characteristics with those of previous VOCs, and inform data-driven public health responses. METHODS: Using daily population-level surveillance data from the National Institute for Communicable Diseases in South Africa (March 2, 2020, to Jan 28, 2022), we determined lag intervals most consistent with time from case ascertainment to hospital admission and within-hospital death through optimisation of the distance correlation coefficient in a time series analysis. We then used these intervals to estimate and compare age-stratified case-hospitalisation and case-fatality ratios across the four epidemic waves that South Africa has faced, each dominated by a different variant. FINDINGS: A total of 3 569 621 cases, 494 186 hospitalisations, and 99 954 deaths attributable to COVID-19 were included in the analyses. We found that lag intervals and disease severity were dependent on age and variant. At an aggregate level, fluctuations in cases were generally followed by a similar trend in hospitalisations within 7 days and deaths within 15 days. We noted a marked reduction in disease severity throughout the omicron period relative to previous waves (age-standardised case-fatality ratios were consistently reduced by >50%), most substantial for age strata with individuals 50 years or older. INTERPRETATION: This population-level time series analysis method, which calculates an optimal lag interval that is then used to inform the numerator of severity metrics including the case-hospitalisation and case-fatality ratio, provides useful and timely estimates of the relative effects of novel SARS-CoV-2 VOCs, especially for application in settings where resources are limited. FUNDING: National Institute for Communicable Diseases of South Africa, South African National Government.

Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta-analysis.

Background: Adult respiratory syncytial virus (RSV) vaccines are in the late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making. Methods: We performed a systematic review and meta-analysis of studies describing the incidence of medically attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab reverse transcription polymerase chain reaction (RT-PCR) results with paired serology (4-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum). Results: We identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100 000 adults ≥65 years of age was 178 (95% CI, 152‒204; n = 8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95% CI, 0‒319; n = 2) emergency department (ED) admissions, and 1519 (95% CI, 1109‒1929; n = 3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100 000 adults age ≥65 years were 267 hospitalizations (uncertainty interval [UI], 228‒306; prospective: 282; model-based: 236), 200 ED admissions (UI, 0‒478), and 2278 outpatient visits (UI, 1663‒2893). Persons <65 years with chronic medical conditions were 1.2-28 times more likely to be hospitalized for RSV depending on risk condition. Conclusions: The true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public health impact.

Population Attributable Fractions of Underlying Medical Conditions for Coronavirus Disease 2019 (COVID-19) Diagnosis and COVID-19 Hospitalizations, Ventilations, and Deaths Among Adults in the United States.

Background: Several underlying medical conditions have been reported to be associated with an increased risk of coronavirus disease 2019 (COVID-19) and related hospitalization and death. Population attributable fractions (PAFs) describing the proportion of disease burden attributable to underlying medical conditions for COVID-19 diagnosis and outcomes have not been reported. Methods: A retrospective population-based cohort study was conducted using Optum's de-identified Clinformatics Data Mart database. Individuals were followed up from 20 January 2020 to 31 December 2020 for diagnosis and clinical progression, including hospitalization, intensive care unit admission, intubation and mechanical ventilation or extracorporeal membrane oxygenation, and death. Adjusted rate ratios and PAFs of underlying medical conditions for COVID-19 diagnosis and disease progression outcomes were estimated by age (18-49, 50-64, 65-74, or ≥75 years), sex, and race/ethnicity. Results: Of 10 679 566 cohort members, 391 964 (3.7%) were diagnosed with COVID-19, of whom 87 526 (22.3%) were hospitalized. Of those hospitalized, 26 640 (30.4%) died. Overall, cardiovascular disease and diabetes had the highest PAFs for COVID-19 diagnosis and outcomes of increasing severity across age groups (up to 0.49 and 0.35, respectively). Among adults ≥75 years of age, neurologic disease had the second-highest PAFs (0.05‒0.27) after cardiovascular disease (0.26‒0.44). PAFs were generally higher in Black persons than in other race/ethnicity groups for the same conditions, particularly in the 2 younger age groups. Conclusions: A substantial fraction of the COVID-19 disease burden in the United States is attributable to cardiovascular disease and diabetes, highlighting the continued importance of COVID-19 prevention ( eg, vaccination, mask wearing, social distancing) and disease management of patients with certain underlying medical conditions.

Immune Response to COVID-19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review.

Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.

COVID-19 disease and vaccination in pregnant and lactating women.

BACKGROUND: More than 325,000 cases of coronavirus disease 2019 (COVID-19) have been reported among pregnant women in the Americas. AIMS: This review examines the impact of COVID-19 in pregnant women and describes available evidence on the safety, effectiveness, and immune response(s) to vaccination among pregnant and lactating women. CONTENT: Multiple studies indicate that pregnant women are more susceptible to adverse COVID-19 outcomes, including hospitalization, intensive care unit admission, and invasive ventilation than non-pregnant women with COVID-19. Furthermore, COVID-19 in pregnancy is associated with adverse maternal and neonatal outcomes. Adverse COVID-19 outcomes appear to disproportionately affect pregnant women from low- and middle-income countries, likely reflecting inequities in access to quality healthcare. Despite the absence of safety and efficacy data from randomized clinical trials in this subpopulation, observational studies and data from pregnancy registries thus far have demonstrated that vaccination of pregnant or lactating women against COVID-19 is safe, effective, and results in robust immune responses including transfer of antibodies to the newborn via the placenta and breast milk, respectively. IMPLICATIONS: These data support vaccination recommendations intending to help protect these vulnerable individuals against COVID-19 and its sequelae. Randomized clinical studies will further evaluate the safety and immunogenicity of COVID-19 vaccines in these populations. This review examines the impact of COVID-19 in pregnant women and describes available evidence on the safety, effectiveness, and immune response(s) to vaccination among pregnant and lactating women.

Frequency of stool specimen collection and testing for Clostridioides difficile of hospitalized adults and long-term care facility residents with new-onset diarrhea in Louisville, Kentucky.

OBJECTIVES: This study aimed to determine the stool specimen collection and Clostridioides difficile (C. difficile) testing frequency from inpatients and long-term care facility (LTCF) residents with new-onset diarrhea. METHODS: A cross-sectional study was conducted in all wards of 9 adult hospitals (3532 beds) and 14 LTCFs (1205 beds) in Louisville, Kentucky to identify new-onset diarrhea (≥3 loose stools in the past 24 h and not present in the preceding 24 h) among Louisville adults via electronic medical record review, nurse interviews, and patient interviews during a 1-2 week observation period in 2018-2019. RESULTS: Among Louisville-resident inpatients, 167 patients with 9731 inpatient-days had new-onset diarrhea (1.7/100 inpatient-days). Stool specimens were collected from 32% (53/167); 12 (23%) specimens were laboratory-confirmed for C. difficile infection (CDI) (12.3 cases/10,000 inpatient-days). Among LTCF residents, 63 with 10,402 LTCF resident-days had new-onset diarrhea (0.6/100 LTCF resident-days). Stool specimens were collected from 32% (20/63); 9 (45%) specimens were laboratory-confirmed for CDI (8.6 cases/10,000 LTCF resident-days). CONCLUSIONS: New-onset diarrhea was common among inpatients and LTCF residents. Only one-third of patients with new-onset diarrhea had a stool specimen collected and tested for C. difficile-indicative of a potential CDI underdiagnosis-although, further studies are needed to confirm the extent of CDI underdiagnosis.

COVID-19 Vaccine Effectiveness: A Review of the First 6 Months of COVID-19 Vaccine Availability (1 January-30 June 2021).

Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines.

County-level vaccination coverage and rates of COVID-19 cases and deaths in the United States: An ecological analysis.

BACKGROUND: On Dec 14, 2020, the United States initiated a nationwide COVID-19 vaccination campaign. Demonstrating clear population-level impact following vaccine introduction helps to further elucidate and quantify the public-health benefits of vaccination. METHODS: Using a negative binomial regression model we evaluated the ecological association between county-level COVID-19 vaccine uptake and rates of COVID-19 cases and deaths in the United States from April 1, 2021 through October 31, 2021 controlling for a broad set of county-level environmental, sociodemographic, economic, and health-status-related characteristics. County-level data were obtained from several publicly available databases that were merged for analysis. FINDINGS: After adjustment for county-level characteristics, US counties with ≥ 80% of their residents ≥ 12 years of age fully vaccinated against COVID-19 had 30% (95% CI: 25-35; P < .001) and 46% (38-52; P < .001) lower rates of COVID-19 cases and deaths, respectively, versus those with <50% coverage (reference group). A dose response was observed: counties with 70-79% uptake had 20% (95% CI: 16-24; P < .001) and 35% (29-40; P < .001) lower rates of cases and deaths, respectively; counties with 60-69% uptake had 8% (5-11; P < .001) and 20% (15-24; P < .001) lower rates; and counties with 50-59% uptake had 2% (0-4; P =.09) and 8% (4-12; P < .001) lower rates. Restricting the analysis to the period when the Delta variant was predominant (June 1, 2021 ‒ October 31, 2021) showed similar findings. INTERPRETATION: Our results showed that US counties with higher proportions of persons ≥ 12 years of age fully vaccinated against COVID-19 had substantially lower rates of COVID-19 cases and deaths-a finding that showed dose response and persisted even in the period when Delta was predominant. FUNDING: Pfizer.

Evolution of invasive meningococcal disease epidemiology in Europe, 2008 to 2017.

BackgroundInvasive meningococcal disease (IMD) epidemiology has fluctuated over the past 25 years and varies among serogroups, age groups and geographical locations.AimThis study analysed the evolution of European IMD epidemiology from 2008 to 2017 to identify trends.MethodsReported number of IMD cases and associated incidence were extracted from the European Centre for Disease Prevention and Control Surveillance Atlas for Infectious Diseases for individual European countries. Epidemiology and its evolution were analysed by serogroup and age group.ResultsOverall IMD incidence decreased by 34.4% between 2008 and 2017. Serogroup B remained predominant in 2017; despite a 56.1% decrease over the 10-year period, the rate of decrease has slowed in recent years and varies by age group. Serogroup C was the second most prevalent serogroup until 2016. Its incidence decreased among individuals aged 1-24 years, the main population targeted by MenC vaccination campaigns, but increases have occurred in other age groups. Incidences of serogroups W and Y were low but increased by > 500% and > 130% (to 0.10 and 0.07/100,000) respectively, from 2008 to 2017. Considering all serogroups, a marked modification of the evolution trends by age group has occurred, with increases in incidence mainly affecting older age groups.ConclusionAlthough the overall IMD incidence decreased in Europe between 2008 and 2017, increases were observed for serogroups W and Y, and in the older population when considering all serogroups. It may be necessary to adapt current vaccination strategies to reflect epidemiological changes and their likely future evolution.

Pandemic-related declines in hospitalization for non-COVID-19-related illness in the United States from January through July 2020.

BACKGROUND: The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has substantially impacted healthcare utilization worldwide. The objective of this retrospective analysis of a large hospital discharge database was to compare all-cause and cause-specific hospitalizations during the first six months of the pandemic in the United States with the same months in the previous four years. METHODS: Data were collected from all hospitals in the Premier Healthcare Database (PHD) and PHD Special Release reporting hospitalizations from January through July for each year from 2016 through 2020. Hospitalization trends were analyzed stratified by age group, major diagnostic categories (MDCs), and geographic region. RESULTS: The analysis included 286 hospitals from all 9 US Census divisions. The number of all-cause hospitalizations per month was relatively stable from 2016 through 2019 and then fell by 21% (57,281 fewer hospitalizations) between March and April 2020, particularly in hospitalizations for non-respiratory illnesses. From April onward there was a rise in the number of monthly hospitalizations per month. Hospitalizations per month, nationally and in each Census division, decreased for 20 of 25 MDCs between March and April 2020. There was also a decrease in hospitalizations per month for all age groups between March and April 2020 with the greatest decreases in hospitalizations observed for patients 50-64 and ≥65 years of age. CONCLUSIONS: Rates of hospitalization declined substantially during the first months of the COVID-19 pandemic, suggesting delayed routine, elective, and emergency care in the United States. These lapses in care for illnesses not related to COVID-19 may lead to increases in morbidity and mortality for other conditions. Thus, in the current stage of the pandemic, clinicians and public-health officials should work, not only to prevent SARS-CoV-2 transmission, but also to ensure that care for non-COVID-19 conditions is not delayed.

Estimates of Presumed Population Immunity to SARS-CoV-2 by State in the United States, August 2021.

BACKGROUND: Information is needed to monitor progress toward a level of population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sufficient to disrupt viral transmission. We estimated the percentage of the US population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021. METHODS: Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates with a range of population immunity thresholds. RESULTS: In our main analysis, which was the most optimistic scenario, presumed population immunity varied among states (43.1% to 70.6%), with 19 states with ≤60% of their population having been infected or vaccinated. Four states had presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (≥78%). CONCLUSIONS: The United States remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.

Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study.

BACKGROUND: On Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths averted by the nationwide vaccination campaign. METHODS: In this retrospective surveillance study, we used national surveillance data routinely collected by the Israeli Ministry of Health from the first 112 days (Dec 20, 2020, up to our data cutoff of April 10, 2021) of Israel's vaccination campaign to estimate the averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalisations, severe or critical hospitalisations, and deaths. As part of the campaign, all individuals aged 16 years and older were eligible for inoculation with the BNT162b2 vaccine in a two-dose schedule 21 days apart. We estimated the direct effects of the immunisation programme for all susceptible individuals (ie, with no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partly vaccinated (at least one dose and at least 14 days of follow-up after the first dose). We estimated the number of SARS-CoV-2 infection-related outcomes averted on the basis of cumulative daily, age-specific rate differences, comparing rates among unvaccinated individuals with those of at least partly vaccinated individuals for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partly vaccinated. FINDINGS: We estimated that Israel's vaccination campaign averted 158 665 (95% CI 144 640-172 690) SARS-CoV-2 infections, 24 597 (18 942-30 252) hospitalisations, 17 432 (12 770-22 094) severe or critical hospitalisations, and 5532 (3085-7982) deaths. 16 213 (65·9%) of 24 597 hospitalisations and 5035 (91·0%) of 5532 of deaths averted were estimated to be among those aged 65 years and older. We estimated 116 000 (73·1%) SARS-CoV-2 infections, 19 467 (79·1%) COVID-19-related hospitalisations, and 4351 (79%) deaths averted were accounted for by the fully vaccinated population. INTERPRETATION: Without the national vaccination campaign, Israel probably would have had triple the number of hospitalisations and deaths compared with what actually occurred during its largest wave of the pandemic to date, and the health-care system might have become overwhelmed. Indirect effects and long-term benefits of the programme, which could be substantial, were not included in these estimates and warrant future research. FUNDING: Israel Ministry of Health and Pfizer.

Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis.

BACKGROUND: Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design. METHODS: We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates. RESULTS: We reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8-12.2) that were half that of studies based on administrative claims (21.4; 19.5-23.3) or modeling approaches (23.2; 20.2-26.2). CONCLUSIONS: Applying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680-86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.

Effectiveness of BNT162b2 mRNA COVID-19 vaccine against SARS-CoV-2 variant Beta (B.1.351) among persons identified through contact tracing in Israel: A prospective cohort study.

BACKGROUND: SARS-CoV-2 variant Beta (B.1.351) was designated as a Variant of Concern (VoC) after becoming the dominant strain in South Africa and spreading internationally. BNT162b2 showed lower levels of neutralizing antibodies against Beta than against other strains raising concerns about effectiveness of vaccines against infections caused by Beta. We estimated BNT162b2 vaccine effectiveness (VE) against Beta infections in Israel, a country with high vaccine uptake. METHODS: The Ministry of Health (MoH) identified Beta cases through mandatory reporting of SARS-CoV-2 cases and whole genome sequencing (WGS) of specimens from vaccination-breakthrough infections, reinfections, arriving international travelers, and a selection of other infected persons. A cohort analysis was conducted of exposure events of contacts of primary Beta cases. WGS was conducted on available PCR-positive specimens collected from contacts. VE estimates with 95% confidence intervals (CIs) against confirmed and probable Beta infections were determined by comparing infection risk between unvaccinated and fully-vaccinated (≥7 days after the second dose) contacts, and between unvaccinated and partially-vaccinated (<7 days after the second dose) contacts. FINDINGS: MoH identified 310 Beta cases through Jun 27, 2021. During the study period (Dec 11, 2020 - Mar 25, 2021), 164 non-institutionalized primary Beta cases, with 552 contacts aged ≥16 years, were identified. 343/552 (62%) contacts were interviewed and tested. 71/343 (21%) contacts were PCR-positive. WGS was performed on 7/71 (10%) PCR-positive specimens; all were Beta. Among SARS-CoV-2-infected contacts, 48/71 (68%) were symptomatic, 10/71 (14%) hospitalized, and 2/71 (3%) died. Fully-vaccinated VE against confirmed or probable Beta infections was 72% (95% CI -5 - 97%; p=0·04) and against symptomatic confirmed or probable Beta infections was 100% (95% CI 19 - 100%; p=0·01). There was no evidence of protection in partially-vaccinated contacts. INTERPRETATION: In a prospective observational study, two doses of BNT162b2 were effective against confirmed and probable Beta infections. Through the end of June 2021, introductions of Beta did not interrupt control of the pandemic in Israel. FUNDING: Israel Ministry of Health and Pfizer.