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Abstract Introduction Nearly all existing respiratory syncytial virus (RSV) incidence estimates are based on real-time polymerase chain reaction (RT–PCR) testing of nasal or nasopharyngeal (NP) swabs. Adding testing of additional specimen types to NP swab RT–PCR increases RSV detection. However, prior studies only made pairwise comparisons and the synergistic effect of adding multiple specimen types has not been quantified. We compared RSV diagnosis by NP swab RT–PCR alone versus NP swab plus saliva, sputum, and serology. Methods This was a prospective cohort study over two study periods (27 December 2021 to 1 April 2022 and 22 August 2022 to 11 November 2022) of patients aged ≥ 40 years hospitalized for acute respiratory illness (ARI) in Louisville, KY. NP swab, saliva, and sputum specimens were collected at enrollment and PCR tested (Luminex ARIES platform). Serology specimens were obtained at acute and convalescent timepoints (enrollment and 30–60-day visit). RSV detection rate was calculated for NP swab alone and for NP swab plus all other specimen type/test. Results Among 1766 patients enrolled, 100% had NP swab, 99% saliva, 34% sputum, and 21% paired serology specimens. RSV was diagnosed in 56 (3.2%) patients by NP swab alone, and in 109 (6.2%) patients by NP swab plus additional specimens, corresponding to a 1.95 times higher rate [95% confidence interval (CI) 1.62, 2.34]. Limiting the comparison to the 150 subjects with all four specimen types available (i.e., NP swab, saliva, sputum, and serology), there was a 2.60-fold increase (95% CI 1.31, 5.17) compared to NP swab alone (3.3% versus 8.7%). Sensitivities by specimen type were: NP swab 51%, saliva 70%, sputum 72%, and serology 79%. Conclusions Diagnosis of RSV in adults was several-fold greater when additional specimen types were added to NP swab, even with a relatively low percentage of subjects with sputum and serology results available. Hospitalized RSV ARI burden estimates in adults based solely on NP swab RT–PCR should be adjusted for underestimation.

SARS-CoV-2 and influenza are primary causes of viral community-acquired pneumonia (CAP). Both pathogens have exhibited high transmissibility and are recognized causes of pandemics. Controversy still exists regarding the clinical outcomes between patients hospitalized with CAP due to these viruses. This secondary analysis identified patients with either influenza or SARS-CoV-2 infections from three cohorts of patients hospitalized for CAP. Clinical outcomes between patients with CAP due to influenza or due to SARS-CoV-2 were evaluated. Primary outcomes included length of stay and in-hospital mortality. To account for population differences between cohorts, each case of influenza CAP was matched to two controls with SARS-CoV-2 CAP. Matching criteria included sex, age, and nursing home residency. Stratified cox-proportional hazards regression or conditional logistic regression were used where appropriate. A total of 259 patients with influenza CAP were matched to two controls with SARS-CoV-2 CAP, totaling to 518 controls. Patients with SARS-CoV-2 CAP were 2.23 times more likely to remain hospitalized at any point in time (95% confidence interval: 1.77–2.80), and had 3.84 times higher odds of dying in-hospital (95% confidence interval: 1.91–7.76) when compared to patients with influenza CAP. After matching and adjusting for confounding variables, patients admitted with SARS-CoV-2 CAP had consistently worse outcomes in comparison to their influenza CAP counterparts. This information can help clinicians decide on the level of care needed for patients with confirmed infections due to these pathogens. Additionally, estimates of disease burden can inform individuals at-risk for poor clinical outcomes, and further highlight the importance of effective preventative strategies.

Controversy exists regarding the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the prevention of serotype-specific community-acquired pneumonia (CAP). The objective of this study was to define the effectiveness of PPSV23 for the prevention of CAP hospitalizations due to vaccine-contained serotypes. This secondary analysis was a nested case–control, test-negative study design of adult patients hospitalized for CAP between 1 June 2014 and 31 March 2017. Cases included patients with CAP due to a S. pneumoniae serotype contained in the PPSV23. Urinary antigen detection of the 23 serotypes was performed. In the study, PPSV23 vaccination alone and no other pneumococcal vaccination was the primary exposure of interest. Vaccine effectiveness was calculated as (1-OR) × 100. Adjusted estimates were obtained from a logistic regression model that controlled for confounding variables. A total of 3686 patients were included in the analysis. The PPSV23 vaccination was documented in 608 (16%) patients, and the PPSV23-serotype CAP was detected in 48 (8%) PPSV23-vaccinated patients and in 288 (9%) non-vaccinated patients. Unadjusted vaccine effectiveness for preventing PPSV23-serotype CAP was 17% (95% CI: −13% to 40%). Adjusted estimates for preventing PPSV23-serotype CAP was 14% (95% CI: −17% to 38%). In this study, PPSV23 vaccination offered no protection against PPSV23-serotype CAP hospitalization in adults. This is the first PPSV23 vaccine effectiveness study from United States that utilized a urinary antigen detection assay as the main method for S. pneumoniae serotyping. This study highlights the need for more effective vaccines in the prevention of hospitalization due to S. pneumoniae CAP.

S. pneumoniae is a primary etiologic agent of CAP in immunocompromised adults (ICA). Data on clinical outcomes of ICA hospitalized with pneumococcal pneumonia (PP) is limited. The objectives of this study were (1) to define clinical presentation and outcomes of ICA hospitalized with PP and (2) to compare the data to non-immunocompromised adults (non-ICA) hospitalized with PP. This was a case–control study of ICA hospitalized with PP (cases) and non-ICA hospitalized with PP (controls). Data were collected on clinical presentation, treatment, and outcomes. Evaluated clinical outcomes included time to clinical stability (TCS), length of hospitalization (LOH), clinical failure (CF), cardiovascular events (CE), and in-hospital mortality (IHM). One ICA was matched to two non-ICA through propensity score matching. A total of 93 ICA hospitalized with PP and 186 non-ICA hospitalized with PP were evaluated. Antibiotic therapy was appropriate in all patients. Clinical outcomes for ICA versus non-ICA were as follows: TCS 2 days vs. 2 days (p = 0.392); LOH 5 days vs. 5 days (p = 0.067); CF 4% vs. 6% (p = 0.618); CE 10% vs. 6% (p = 0.375); and IHM 5% vs. 3% (p = 0.296). In hospitalized patients with PP who are treated with appropriate antibiotic therapy, the presence of an abnormal immune system does influence clinical outcomes.

The biotrophic fungal pathogen Blumeria graminis causes the powdery mildew disease of cereals and grasses. We present the first crystal structure of a B. graminis effector of pathogenicity (CSEP0064/BEC1054), demonstrating it has a ribonuclease (RNase)-like fold. This effector is part of a group of RNase-like proteins (termed RALPHs) which comprise the largest set of secreted effector candidates within the B. graminis genomes. Their exceptional abundance suggests they play crucial functions during pathogenesis. We show that transgenic expression of RALPH CSEP0064/BEC1054 increases susceptibility to infection in both monocotyledonous and dicotyledonous plants. CSEP0064/BEC1054 interacts in planta with the pathogenesis-related protein PR10. The effector protein associates with total RNA and weakly with DNA. Methyl jasmonate (MeJA) levels modulate susceptibility to aniline-induced host RNA fragmentation. In planta expression of CSEP0064/BEC1054 reduces the formation of this RNA fragment. We propose CSEP0064/BEC1054 is a pseudoenzyme that binds to host ribosomes, thereby inhibiting the action of plant ribosome-inactivating proteins (RIPs) that would otherwise lead to host cell death, an unviable interaction and demise of the fungus.