Innovation, conservation, and repurposing of gene function in root cell type development.

Plant species have evolved myriads of solutions, including complex cell type development and regulation, to adapt to dynamic environments. To understand this cellular diversity, we profiled tomato root cell type translatomes. Using xylem differentiation in tomato, examples of functional innovation, repurposing, and conservation of transcription factors are described, relative to the model plant Arabidopsis. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Comparative translatome analyses of rice, tomato, and Arabidopsis cell populations suggest increased expression conservation of root meristems compared with other homologous populations. In addition, the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher order properties of cell type and pan-cell type regulation are evolutionarily conserved between plants and animals.

Misdiagnosis of Clostridioides difficile Infections by Standard-of-Care Specimen Collection and Testing among Hospitalized Adults, Louisville, Kentucky, USA, 2019-20201.

Although Clostridioides difficile infection (CDI) incidence is high in the United States, standard-of-care (SOC) stool collection and testing practices might result in incidence overestimation or underestimation. We conducted diarrhea surveillance among inpatients >50 years of age in Louisville, Kentucky, USA, during October 14, 2019-October 13, 2020; concurrent SOC stool collection and CDI testing occurred independently. A study CDI case was nucleic acid amplification test‒/cytotoxicity neutralization assay‒positive or nucleic acid amplification test‒positive stool in a patient with pseudomembranous colitis. Study incidence was adjusted for hospitalization share and specimen collection rate and, in a sensitivity analysis, for diarrhea cases without study testing. SOC hospitalized CDI incidence was 121/100,000 population/year; study incidence was 154/100,000 population/year and, in sensitivity analysis, 202/100,000 population/year. Of 75 SOC CDI cases, 12 (16.0%) were not study diagnosed; of 109 study CDI cases, 44 (40.4%) were not SOC diagnosed. CDI incidence estimates based on SOC CDI testing are probably underestimated.

Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study.

BACKGROUND: Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. We aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer-BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system. METHODS: In this retrospective cohort study, we analysed electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA), to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. This study was registered with ClinicalTrials.gov, NCT04848584. FINDINGS: Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29-61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72-74) and against COVID-19-related hospital admissions was 90% (89-92). Effectiveness against infections declined from 88% (95% CI 86-89) during the first month after full vaccination to 47% (43-51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85-97]) but declined to 53% [39-65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95-99), but waned to 67% (45-80) at 4-5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84-96]) up to 6 months. INTERPRETATION: Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection. FUNDING: Pfizer.

Population-based incidence of hospitalized Clostridioides difficile infection among older adults in Ota-ku, Japan: A prospective surveillance study.

OBJECTIVES: Clostridioides difficile infection (CDI) burden is not well-characterized in Japan. Therefore, we conducted a population-based, hospitalized CDI incidence study, compared the results with standard-of-care (SOC) CDI testing, and generalized the results for nationwide incidence estimates. METHODS: Surveillance identified inpatients ≥50 years-of-age with diarrhea in nine Tokyo hospitals from December 17, 2018-March 30, 2020. A CDI case was defined as a patient with a PCR-positive/cell cytotoxicity neutralization assay (CCNA)-positive stool or a PCR-positive stool and pseudomembranous colitis (PMC). Incidence estimates were adjusted for the hospitalization share of participating hospitals and, in the sensitivity analysis, for missing CDI test results. SOC specimen collection and CDI testing occurred independently. RESULTS: Surveillance during 318 840 patient-days identified 4633 inpatients with diarrhea. Sixty-three CDI cases were identified; 11 (17·5%) had PMC, eight (12·7%) recurrent CDI, and nine (14·3%) died. The hospitalized CDI incidence was 97/100 000 population per year (PPY) in persons ≥50 years-of-age and, in the sensitivity analysis, 324/100 000 PPY. The incidence was 170 and 481/100 000 PPY in persons ≥65 and ≥85 years-of-age, respectively; these estimates increased to 569 and 1609/100 000 PPY in the sensitivity analysis, respectively. There were 12 primary SOC CDI cases in persons ≥50 years-of-age (18/100 000 PPY). CONCLUSIONS: The CDI incidence was high in older adults, with severe clinical consequences. SOC specimen collection and testing under-estimated CDI burden. There are >57 000 hospitalized CDI cases per year in Japan in persons ≥50 years-of-age. Public health interventions are needed to reduce the CDI burden in Japan.

Translational regulation contributes to the elevated CO2 response in two Solanum species.

Understanding the impact of elevated CO2 (eCO2 ) in global agriculture is important given climate change projections. Breeding climate-resilient crops depends on genetic variation within naturally varying populations. The effect of genetic variation in response to eCO2 is poorly understood, especially in crop species. We describe the different ways in which Solanum lycopersicum and its wild relative S. pennellii respond to eCO2 , from cell anatomy, to the transcriptome, and metabolome. We further validate the importance of translational regulation as a potential mechanism for plants to adaptively respond to rising levels of atmospheric CO2 .

Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-acquired Pneumonia in Hospitalized US Adults.

BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.

Plant developmental responses to climate change.

Climate change is multi-faceted, and includes changing concentrations of greenhouse gases in the atmosphere, rising temperatures, changes in precipitation patterns, and increasing frequency of extreme weather events. Here, we focus on the effects of rising atmospheric CO2 concentrations, rising temperature, and drought stress and their interaction on plant developmental processes in leaves, roots, and in reproductive structures. While in some cases these responses are conserved across species, such as decreased root elongation, perturbation of root growth angle and reduced seed yield in response to drought, or an increase in root biomass in shallow soil in response to elevated CO2, most responses are variable within and between species and are dependent on developmental stage. These variable responses include species-specific thresholds that arrest development of reproductive structures, reduce root growth rate and the rate of leaf initiation and expansion in response to elevated temperature. Leaf developmental responses to elevated CO2 vary by cell type and by species. Variability also exists between C3 and C4 species in response to elevated CO2, especially in terms of growth and seed yield stimulation. At the molecular level, significantly less is understood regarding conservation and variability in molecular mechanisms underlying these traits. Abscisic acid-mediated changes in cell wall expansion likely underlie reductions in growth rate in response to drought, and changes in known regulators of flowering time likely underlie altered reproductive transitions in response to elevated temperature and CO2. Genes that underlie most other organ or tissue-level responses have largely only been identified in a single species in response to a single stress and their level of conservation is unknown. We conclude that there is a need for further research regarding the molecular mechanisms of plant developmental responses to climate change factors in general, and that this lack of data is particularly prevalent in the case of interactive effects of multiple climate change factors. As future growing conditions will likely expose plants to multiple climate change factors simultaneously, with a sum negative influence on global agriculture, further research in this area is critical.

Prospective, population-based surveillance of the burden of Streptococcus pneumoniae in community-acquired pneumonia in older adults, Chrzanów County, Poland, 2010 to 2012.

INTRODUCTION: Community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae is a substantial cause of morbidity and mortality among older adults. This study estimated incidences of CAP, chest x-ray-confirmed CAP (CXR+CAP), S pneumonia- positive CAP, S pneumonia-positive CXR+CAP, and S. pneumoniae serotype distribution among 46,000 at-risk adults aged ≥ 50 years residing in Chrzanów County, Poland. MATERIAL AND METHODS: From January 2010 to January 2012, all facilities providing ambulatory and inpatient care enrolled all consenting resident patients with suspicion of CAP. Chest x-rays, urine, blood, and sputum samples were analyzed. Annualized incidence rates were determined. Presence of S pneumonia-positive CAP and/or S. pneumoniae serotype distribution was determined using the urine antigen detection assay (capable of detecting the serotypes in the 13-valent pneumococcal conjugate vaccine [PCV13]), BinaxNOW®, and/or microbiology cultures. RESULTS: Among 5055 enrolled patients, 1195 (23.7%) were diagnosed with CAP and 1166 (23.4%) had CXR+CAP. S. pneumoniae was detected in 144 (12.1%) and 131 (11.2%) patients from the CAP and CXR+CAP cohorts, respectively. Annualized incidence rates of CAP, CXR+CAP, S pneumonia-positive CAP, and S. pneumonia-positive CXR+CAP were 12.8, 12.5, 1.6, and 1.4 per 1000 residents, respectively. Among CXR+CAP patients, 39.7% were aged 50 to 64 years and 60.3% were aged ≥ 65 years. Incidence rates generally increased with age. The most common serotypes in S. pneumoniae-positive CXR+CAP patients were 3 (n = 15), 23F (n = 10), 18C (n = 9), and 9V (n = 6). CONCLUSIONS: CAP due to PCV13 serotypes is a source of morbidity among adults >50 years and may be reduced by greater access to pneumococcal vaccines.

Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction.

AIMS: This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. METHODS: Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. RESULTS: In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. CONCLUSIONS: From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years.

Global warming can negate the expected CO2 stimulation in photosynthesis and productivity for soybean grown in the Midwestern United States.

Extensive evidence shows that increasing carbon dioxide concentration ([CO2]) stimulates, and increasing temperature decreases, both net photosynthetic carbon assimilation (A) and biomass production for C3 plants. However the [CO2]-induced stimulation in A is projected to increase further with warmer temperature. While the influence of increasing temperature and [CO2], independent of each other, on A and biomass production have been widely investigated, the interaction between these two major global changes has not been tested on field-grown crops. Here, the interactive effect of both elevated [CO2] (approximately 585 µmol mol(-1)) and temperature (+3.5°C) on soybean (Glycine max) A, biomass, and yield were tested over two growing seasons in the Temperature by Free-Air CO2 Enrichment experiment at the Soybean Free Air CO2 Enrichment facility. Measurements of A, stomatal conductance, and intercellular [CO2] were collected along with meteorological, water potential, and growth data. Elevated temperatures caused lower A, which was largely attributed to declines in stomatal conductance and intercellular [CO2] and led in turn to lower yields. Increasing both [CO2] and temperature stimulated A relative to elevated [CO2] alone on only two sampling days during 2009 and on no days in 2011. In 2011, the warmer of the two years, there were no observed increases in yield in the elevated temperature plots regardless of whether [CO2] was elevated. All treatments lowered the harvest index for soybean, although the effect of elevated [CO2] in 2011 was not statistically significant. These results provide a better understanding of the physiological responses of soybean to future climate change conditions and suggest that the potential is limited for elevated [CO2] to mitigate the influence of rising temperatures on photosynthesis, growth, and yields of C3 crops.

Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae serotypes in US adults aged ≥50 years with community-acquired pneumonia.

BACKGROUND: Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP. METHODS: Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion. S. pneumoniae was identified using microbiological cultures, BinaxNOW® S. pneumoniae assay, or urine antigen detection (UAD) assay capable of detecting 13-valent pneumococcal conjugate vaccine (PCV13)-associated serotypes. RESULTS: Among 710 subjects enrolled, the median age was 65.4 years; 54.2% of subjects were male, 22.4% of radiographically confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were hospitalized. S. pneumoniae was detected in 98 subjects (13.8%) by any test, and PCV13-associated serotype(s) were identified by UAD in 78 (11.0%). Serotype 19A was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7-valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive isolates. CONCLUSIONS: Pneumococcal serotypes causing noninvasive pneumonia in adults may differ significantly from those causing invasive disease, with PCV7-associated serotypes overrepresented. Serotype 5, rarely seen in contemporary surveillance of invasive disease in the United States, substantially contributed to the observed cases of S. pneumoniae-positive CAP or HCAP.

[Clinical burden of multi-cause and pneumococcal pneumonia, meningitis, and septicemia in Hungary. Results of a retrospective study (2006-2011)]. / Pneumococcus, illetve bármely kórokú pneumonia, meningitis és septikaemia miatti hospitalizáció és halálozás Magyarországon. Egy retrospektív értékelés eredménye (2006-2011).

INTRODUCTION: Assessment of the impact of pneumococcal conjugate vaccines on the burden of pneumonia, meningitis, and septicemia in Hungary is limited. AIM: The aim of this retrospective study was to quantify rates of hospitalized multi-cause and pneumococcal pneumonia, meningitis, and septicemia in all age groups in Hungary between 2006 and 2011. METHOD: Aggregate data were obtained from the Hungarian National Healthcare Fund using pre-specified ICD-10 codes. Comparisons included average rates pre-vaccine (2006-2007) versus post-vaccine (2010-2011) using a χ2 test. RESULTS: Hospitalization rates among children aged 0-4 years significantly declined for multi-cause pneumonia and meningitis, but increased for septicemia. There were significant increases in multi-cause pneumonia and septicemia in other age groups. In-hospital mortality rates increased with age. Limited use of pneumococcal-specific codes led to inconclusive findings for pneumococcal diseases. CONCLUSIONS: Declines in multi-cause pneumonia and meningitis in children aged 0-4 years suggest direct effects of pneumococcal conjugate vaccination on hospitalization rates.

A suberized exodermis is required for tomato drought tolerance.

Plant roots integrate environmental signals with development using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates flow of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation but is absent in the tomato endodermis. Instead, suberin is present in the exodermis, a cell type that is absent in the model organism Arabidopsis thaliana. Here we demonstrate that the suberin regulatory network has the same parts driving suberin production in the tomato exodermis and the Arabidopsis endodermis. Despite this co-option of network components, the network has undergone rewiring to drive distinct spatial expression and with distinct contributions of specific genes. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response and that the exodermal barrier serves an equivalent function to that of the endodermis and can act in its place.

A retrospective study of hospitalized pneumonia in two Polish counties (2006-2008).

INTRODUCTION: In Poland, multi-cause pneumonia is not well characterized, and there is limited pneumococcal vaccination in the youngest and oldest age groups. The goal of this study was to assess hospitalized pneumonia across all age groups in two Polish counties. MATERIAL AND METHODS: Using electronic administrative databases, cases were identified as county residents hospitalized at Chrzanów and Inowroclaw County Hospitals from 2006-2008, assigned a diagnosis of pneumonia. Calculations by admission year, sex, and age category were: hospitalization rates per 1000 persons; in-hospital mortality rates per 100 persons; and median length of stay (LOS). RESULTS: There were 1444 and 2956 hospitalizations for new episodes of pneumonia with rates of 3.76 (95% confidence interval [CI] 3.57-3.96) and 5.99 (95% CI 5.77-6.21) per 1000 persons in Chrzanów and Inowroclaw counties, respectively. In combined data, the highest hospitalization rate was among patients aged 0-4 years (30.77; 95% CI 29.06-32.55) followed by those aged ≥ 75 years (25.39; 95% CI 24.01-26.83). In-hospital mortality rates increased with age at both sites. The median LOS was 8 days. CONCLUSIONS: Pneumonia hospitalizations were substantial, especially for the youngest and oldest age groups. Future public health interventions aimed at these age groups might improve disease outlook.

Severity of Omicron (B.1.1.529) and Delta (B.1.617.2) SARS-CoV-2 infection among hospitalised adults: A prospective cohort study in Bristol, United Kingdom.

Background: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity. Methods: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection. Findings: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 [Relative Risk (RR) = 0.42 (95%CI: 0.34-0.52), P < 0.001], WHO outcome score >5 [RR = 0.33 (95%CI: 0.21-0.50), P < 0.001], and to have had a LOS > 3 days [RR = 0.84 (95%CI: 0.76-0.92), P < 0.001]. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Interpretation: We provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

Incidence of acute lower respiratory tract disease hospitalisations, including pneumonia, among adults in Bristol, UK, 2019, estimated using both a prospective and retrospective methodology.

OBJECTIVES: To determine the disease burden of acute lower respiratory tract disease (aLRTD) and its subsets (pneumonia, lower respiratory tract infection (LRTI) and heart failure) in hospitalised adults in Bristol, UK. SETTING: Single-centre, secondary care hospital, Bristol, UK. DESIGN: We estimated aLRTD hospitalisations incidence in adults (≥18 years) in Bristol, UK, using two approaches. First, retrospective International Classification of Diseases 10th revision (ICD-10) code analysis (first five positions/hospitalisation) identified aLRTD events over a 12-month period (March 2018 to February 2019). Second, during a 21-day prospective review (19 August 2019 to 9 September 2019), aLRTD admissions were identified, categorised by diagnosis and subsequently annualised. Hospital catchment denominators were calculated using linked general practice and hospitalisation data, with each practice's denominator contribution calculated based on practice population and per cent of the practices' hospitalisations admitted to the study hospital. PARTICIPANTS: Prospective review: 1322 adults screened; 410 identified with aLRTD. Retrospective review: 7727 adult admissions. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence of aLRTD and its subsets in the adult population of Southmead Hospital, Bristol UK. RESULTS: Based on ICD-10 code analysis, annual incidences per 100 000 population were: aLRTD, 1901; pneumonia, 591; LRTI, 739; heart failure, 402. aLRTD incidence was highest among those ≥65 years: 65-74 (3684 per 100 000 adults), 75-84 (6962 per 100 000 adults) and ≥85 (11 430 per 100 000 adults). During the prospective review, 410/1322 (31%) hospitalised adults had aLRTD signs/symptoms and annualised incidences closely replicated retrospective analysis results. CONCLUSIONS: The aLRTD disease burden was high, increasing sharply with age. The aLRTD incidence is probably higher than estimated previously due to criteria specifying respiratory-specific symptoms or radiological change, usage of only the first diagnosis code and mismatch between case count sources and population denominators. This may have significant consequences for healthcare planning, including usage of current and future vaccinations against respiratory infection.

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.

Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: A retrospective cohort study.

Background: Globally, recommendations are expanding for third (booster) doses of BNT162b2 (Pfizer-BioNTech). In the United States, as of November 19, 2021, boosters were recommended for all adults aged 18 years and older. We evaluated the effectiveness of a third dose of BNT162b2 among adults in a large US integrated health system. Methods: In this retrospective cohort study, we analyzed electronic health records from Kaiser Permanente Southern California between Dec 14, 2020 and Dec 5, 2021 to assess vaccine effectiveness (VE) of two and three doses of BNT162b2 against SARS-CoV-2 infections (without hospital admission) andCOVID-19-related hospital admission. VE was calculated using hazards ratios from adjusted Cox models. Findings: After only two doses, VE against infection declined from 85% (95% CI 83-86) during the first month to 49% (46-51) ≥ 7 months following vaccination. Overall VE against hospitalization was 90% (95% CI 86-92) within one month and did not wane, however, effectiveness against hospitalization appeared to wane among immunocompromised individuals but was not statistically significant (93% [72-98] at 1 month to 74% [45-88] after ≥ 7 months; p=0·490). Three-dose VE (median follow-up 1·3 months [SD 0·6]) was 88% (95% CI 86-89) against infection and 97% (95-98) against hospitalization. Effectiveness after three doses was higher than that seen one month after receiving only two doses for both outcomes. Relative VE of three doses compared to two (with at least six months after the second dose) was 75% (95% CI 71-78) against infections and 70% (48-83) against hospital admissions. Interpretation: These data support the benefit of broad BNT162b2 booster recommendations, as three doses confers comparable, if not better, protection against SARS-CoV-2 infections and hospital admission as was seen soon after receiving two doses. Funding: Pfizer Inc.

Incidence of community acquired lower respiratory tract disease in Bristol, UK during the COVID-19 pandemic: A prospective cohort study.

Background: The emergence of COVID-19 and public health measures implemented to reduce SARS-CoV-2 infections have both affected acute lower respiratory tract disease (aLRTD) epidemiology and incidence trends. The severity of COVID-19 and non-SARS-CoV-2 aLRTD during this period have not been compared in detail. Methods: We conducted a prospective cohort study of adults age ≥18 years admitted to either of two acute care hospitals in Bristol, UK, from August 2020 to November 2021. Patients were included if they presented with signs or symptoms of aLRTD (e.g., cough, pleurisy), or a clinical or radiological aLRTD diagnosis. Findings: 12,557 adult aLRTD hospitalisations occurred: 10,087 were associated with infection (pneumonia or non-pneumonic lower respiratory tract infection [NP-LRTI]), 2161 with no infective cause, with 306 providing a minimal surveillance dataset. Confirmed SARS-CoV-2 infection accounted for 32% (3178/10,087) of respiratory infections. Annual incidences of overall, COVID-19, and non- SARS-CoV-2 pneumonia were 714.1, 264.2, and 449.9, and NP-LRTI were 346.2, 43.8, and 302.4 per 100,000 adults, respectively. Weekly incidence trends in COVID-19 aLRTD showed large surges (median 6.5 [IQR 0.7-10.2] admissions per 100,000 adults per week), while other infective aLRTD events were more stable (median 14.3 [IQR 12.8-16.4] admissions per 100,000 adults per week) as were non-infective aLRTD events (median 4.4 [IQR 3.5-5.5] admissions per 100,000 adults per week). Interpretation: While COVID-19 disease was a large component of total aLRTD during this pandemic period, non- SARS-CoV-2 infection still caused the majority of respiratory infection hospitalisations. COVID-19 disease showed significant temporal fluctuations in frequency, which were less apparent in non-SARS-CoV-2 infection. Despite public health interventions to reduce respiratory infection, disease incidence remains high. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.