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Background Studies show that past SARS-CoV-2 infection provides a protective immune response against subsequent COVID-19, but the degree of protection from prior infection has not been determined. History of previous SARS-COV-2 Infection and Current SARS-COV-2 Infection Status at Admission. *Adjusted for chronic respiratory disease and prior COVID-19 vaccination Methods From May 2021 through Feb 2022, adults (≥ 18 years of age) hospitalized at Emory University Hospital and Emory University Hospital Midtown with acute respiratory infection (ARI) symptoms, who were PCR tested for SARS-CoV-2 were enrolled. A prior history of SARS-CoV-2 infection was obtained from patient interview and medical record review. Previous infection was defined as a self-reported prior SARS-CoV-2 infection or previous evidence of a positive SARS-CoV-2 PCR test ≥ 90 days before ARI hospital admission. We performed a test negative design to evaluate the protection provided by prior SARS-CoV-2 infection against subsequent COVID-19-related hospitalization. Effectiveness was determined using logistic regression analysis adjusted for patient sociodemographic and clinical characteristics and COVID-19 vaccination status. Results Of 1152 adults hospitalized for ARI, 704/1152 (61%) were SARS-CoV-2 positive. 96/1152 (8%) had a prior SARS-CoV-2 infection before hospital admission. Patients with a previous history of SARS-CoV-2 infection were less likely to test positive for SARS-CoV-2 upon admission for ARI compared to those who did not have evidence of prior infection (31/96 [32%] vs 673/1056 [64%]; adjusted OR: 0.25 [0.15, 0.41] (Table). Conclusion Reinfections represented a small proportion (< 10%) of COVID-19-related hospitalizations. Prior SARS-CoV-2 infection provided meaningful protection against subsequent COVID-19-related hospitalization. The durability of this infection-induced immunity, variant-specific estimates, and the additive impact of vaccination are needed to further elucidate these findings. Disclosures Laura A. Puzniak, PhD. MPH, Merck & Co., Inc.: Stocks/Bonds|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Srinivas Valluri, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant Satoshi Kamidani, MD, NIH: His institution (Emory University) receives funds from Pfizer for his work as a co-investigator on clinical trials of Pfizer COVID-19 vaccine.|Pfizer: His institution (Emory University) receives funds from Pfizer for his work as a co-investigator on clinical trials of Pfizer COVID-19 vaccine. Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur.: Grant/Research Support|Meissa Vaccines, Inc.: Co-inventor of RSV vaccine technology licensed to Meissa Vaccines, Inc.|NIH (Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines): Grant/Research Support John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc: Data Safety Monitoring Board|MedImmune: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Grant/Research Support|Micron: Grant/Research Support|NIH: Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines|PaxVax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data Adjudication and Data Safety Monitoring Boards|WCG and ACI Clinical: Data Adjudication Board.

Background During the COVID-19 pandemic, social interventions such as social distancing and mask wearing have been encouraged. Social risk factors for SARS-CoV-2 infection and subsequent hospitalization remain uncertain. Methods Adult patients were eligible if admitted to Emory University Hospital or Emory University Hospital Midtown with acute respiratory infection (ARI) symptoms (≤ 14 days) or an admitting ARI diagnosis from May 2021 – Feb 2022. After enrollment, an in-depth interview identified demographic and social factors (e.g., employment status, smoking history, alcohol use), household characteristics, and pandemic social behaviors. All patients were tested for SARS-CoV-2 using PCR. We evaluated whether these demographic and social factors were related to a positive SARS-CoV-2 test upon admission to hospital with ARI using a logistic regression model. Results 1141 subjects were enrolled and had SARS-CoV-2 PCR results available (700 positive and 441 negative). The median age was greater in the SARS-CoV-2 negative cohort than in the positive cohort (60 and 53 years, respectively; P< .0001). Those who tested positive were more likely to have had at least some college education compared to those who tested negative (64.3% vs 52.3%, P< .0001; adjusted odds ratio [aOR]: 1.4 [95%CI: 1.1, 2.0]). Compared to those who tested negative, those who were SARS-CoV-2 positive were also more likely to be employed (48.9% vs 26.5%, P< .0001; aOR: 1.7 [95%CI: 1.1, 2.3]), have children 5-17 yo at home (27.6% vs 17.9%, P=.0002; aOR: 1.5 [95%CI: 1.1, 2.1]). Those with COVID-19 were less likely to receive home healthcare (6.2% vs 13.3%, P< .0001; aOR: 0.5 [95%CI: 0.4, 0.9]) and to be a current or previous smoker (7.6% vs 17.7%, P< .0001; aOR: 0.3 [95%CI: 0.2, 0.5]). Conclusion Among adults admitted to the hospital for ARI, those who tested positive for SARS-CoV-2 were typically younger, more likely to care for school-aged children, more likely to work outside the home, but were less likely to receive home healthcare or smoke. Personal and public health strategies to mitigate COVID-19 should take into consideration modifiable social risk factors. Disclosures Laura A. Puzniak, PhD. MPH, Merck & Co., Inc.: Stocks/Bonds|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Srinivas Valluri, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant Satoshi Kamidani, MD, NIH: His institution (Emory University) receives funds from Pfizer for his work as a co-investigator on clinical trials of Pfizer COVID-19 vaccine.|Pfizer: His institution (Emory University) receives funds from Pfizer for his work as a co-investigator on clinical trials of Pfizer COVID-19 vaccine. Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur.: Grant/Research Support|Meissa Vaccines, Inc.: Co-inventor of RSV vaccine technology licensed to Meissa Vaccines, Inc.|NIH (Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines): Grant/Research Support John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc: Data Safety Monitoring Board|MedImmune: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Grant/Research Support|Micron: Grant/Research Support|NIH: Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines|PaxVax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data Adjudication and Data Safety Monitoring Boards|WCG and ACI Clinical: Data Adjudication Board.

Background Whether receipt of COVID-19 vaccine associates with receipt of other routinely-recommended adult vaccines such as, influenza and pneumococcal vaccines is not well described. We evaluated this relationship in a population of adults who were hospitalized for acute respiratory infection (ARI). *Odds ratio describing odds of receiving at least one COVID-19 vaccine (vs not) by influenza vaccination status adjusted for race, employment status, chronic cardiac diseases, cancer, solid organ transplant, and chronic kidney disease.**Odds ratio describing odds of receiving at least one COVID-19 vaccine (vs not) by pneumococcal vaccination status adjusted for race and chronic kidney disease. Methods We enrolled adults (≥ 18 years of age) who were hospitalized at Emory University Hospital and Emory University Hospital Midtown with symptoms consistent with ARI. Participants were interviewed and medical records abstracted to gather demographic information, including social behaviors during the pandemic, medical history, and prior vaccination history (i.e., COVID-19, influenza, and pneumococcal). Using two separate logistic regression analyses, we determined the association between i) receipt of influenza vaccine in the prior year among adults ≥ 18 years and ii) receipt of any pneumococcal vaccine in the prior 5 years among adults ≥ 65 years on the receipt of at least one COVID-19 vaccine≥ 14 days prior to admission. Adjusted models included demographic information (e.g., age, sex, race/ethnicity, employment status), social behaviors, and history of chronic medical conditions. Results Overall, 1056 participants were enrolled and had vaccination records available. Of whom, 509/1056 (48.2%) had received at least one dose of COVID-19 vaccine. Adults ≥ 18 years who received influenza vaccine were more likely to have received ≥1 dose of COVID-19 vaccine compared to those who did not (267/373 [71.6%] vs 242/683 [35.4%] P=< .0001; adjusted odds ratio [OR]: 3.3 [95%CI: 2.4, 4.4]). Similarly, adults ≥65 years who received pneumococcal vaccine were more likely to have received ≥ 1 dose of COVID-19 vaccine compared to those who did not (195/257 [75.9%] vs 41/84 [48.8%] P=< .0001; adjusted odds ratio [OR]: 3.0 [95%CI: 1.8, 5.1]). Conclusion In this study of adults hospitalized for ARI, receipt of influenza and pneumococcal vaccination strongly correlated with receipt of COVID-19 vaccination. Continued efforts are needed to reach adults who remain hesitant to not only receive COVID-19 vaccines, but also other vaccines that lessen the burden of respiratory illness. Disclosures Laura A. Puzniak, PhD. MPH, Merck & Co., Inc.: Stocks/Bonds|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Srinivas Valluri, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant Satoshi Kamidani, MD, NIH: His institution (Emory University) receives funds from Pfizer for his work as a co-investigator on clinical trials of Pfizer COVID-19 vaccine.|Pfizer: His institution (Emory University) receives funds from Pfizer for his work as a co-investigator on clinical trials of Pfizer COVID-19 vaccine. Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur.: Grant/Research Support|Meissa Vaccines, Inc.: Co-inventor of RSV vaccine technology licensed to Meissa Vaccines, Inc.|NIH (Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines): Grant/Research Support John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc: Data Safety Monitoring Board|MedImmune: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Grant/Research Support|Micron: Grant/Research Support|NIH: Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines|PaxVax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data Adjudication and Data Safety Monitoring Boards|WCG and ACI Clinical: Data Adjudication Board.

Background In hospitalized patients, nasopharyngeal (NP) swabs are the most common samples obtained for Respiratory Syncytial Virus (RSV) PCR testing. However, adding sputum is known to increase diagnostic yield, and saliva has been successfully used for viral respiratory infection diagnosis. We sought to compare RSV prevalence detected by PCR testing of NP swab alone versus NP swab plus saliva and sputum in adult patients hospitalized with acute respiratory illness (ARI). Methods This ongoing, prospective cohort study enrolled patients aged ≥40 years hospitalized for ARI in 4 hospitals in Louisville, Kentucky (Season 1: 27 Dec 21 – 1 Apr 22). NP swab, saliva, and sputum samples were obtained at enrollment or scavenged from standard-of-care specimens (all collected ≤3 days of admission), and PCR tested with Luminex ARIES FluA/B/RSV platform. We produced Venn diagrams of RSV positive samples by sample type for all patients and restricted to those with all 3 sample types. RSV prevalence for NP swab alone was calculated as number of patients with RSV-positive NP swabs divided by total number of patients tested. RSV prevalence by NP swab plus saliva and sputum was calculated as number of patients with RSV-positive NP swab, saliva, or sputum samples divided by total number of patients tested. Results We enrolled 653 patients and collected NP swabs (100% of patients), saliva (96%), and sputum (43% overall and 93% of the 303 sputum-producing patients). Among all patients, 28 patients tested RSV positive (Figure 1A), and when restricted to those with all 3 samples (Figure 1B), 14 tested positive. The overall cohort’s RSV prevalence by NP swab alone was 1.8% (12/653) and by NP swab plus saliva and/or sputum was 4.3% (28/653): 2.33 times higher with addition of saliva and sputum samples. Among patients with all 3 specimen types, the RSV prevalence increase was the same, and none were positive by NP swab only. Figure 1.Venn diagrams of positive RSV PCR tests (Left) A. Positive RSV PCR tests for 653 patients in overall cohort (Right) B. Positive RSV PCR tests for 275 patients with all 3 samples obtained. Conclusion RSV was most commonly detected in saliva samples. Current standard-of-care utilizing NP swab for RSV PCR testing appears to underestimate true RSV prevalence in hospitalized adult patients with ARI by more than 2-fold. Disclosures Alan Junkins, PhD, D(ABMM), Biomerieux: Advisor/Consultant Paul S. Schulz, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria Robin Hubler, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds|Pfizer, Inc: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds|Pfizer, Inc: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: I am a full time employee of Pfizer and hold Pfizer stocks Bradford J. Gessner, M.D., M.P.H., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds.

Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

Background The burden of Respiratory Syncytial Virus (RSV)-associated hospitalization in adults is incompletely understood. The COVID-19 pandemic has resulted in multiple public health measures (e.g., social distancing, handwashing, masking) to decrease SARS-CoV-2 transmission, which could impact RSV-associated hospitalizations. We sought to compare RSV-associated hospitalizations from 2 pre- and one mid-COVID-19 winter viral respiratory seasons. Methods We conducted an IRB-approved prospective surveillance at two Atlanta-area hospitals during the winter respiratory viral seasons from Oct 2018–Apr 2021 for adults ≥ 50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region surrounding Atlanta, Georgia. Those with symptoms > 14 days were excluded. Standard of care test results were included. Asymptomatic adults ≥ 50 years of age were enrolled as controls in Seasons 1 and 2. Nasopharyngeal swabs from cases and controls were tested for RSV using BioFire® FilmArray® Respiratory Viral Panel (RVP). We compared the demographic features and outcomes of RSV+ cases and controls. Results RSV was detected in 71/2,728 (2.6%) hospitalized adults with ARI, CHF, or COPD and 4/466 (0.9%) controls. In Season 1, RSV occurred in 5.9% (35/596 patients), in Season 2 3.6% (35/970 patients), but in only 0.09% (1/1,162 patients) in Season 3 (P < 0.001 for both seasons). RSV detection in Season 3 was similar to RSV detection among controls during Seasons 1 and 2 (P=0.6). Median age of cases and controls was 67 years (Table 1). Of cases with RSV 11% were admitted to the ICU and two required mechanical ventilation. The majority of hospitalized patients were discharged home (95.8%) with a median length of hospitalization of three days (IQR 2-7). Table 1. Demographic Features and Outcomes Among RSV-Positive Hospitalized Adults. Conclusion Over 3 seasons, RSV was detected in 2.6% of adults admitted to the hospital with ARI, CHF or COPD. The rate of RSV dramatically declined during the 2020-21 winter respiratory viral season, likely due to public health measures implemented in response to COVID-19. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

Background A prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag. Methods In this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18–64 years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo. Functional immune responses were measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding inhibition (FBI) assays; antigen-specific immunogenicity was assessed using a four-plex competitive Luminex® immunoassay (cLIA). Results A high proportion of SA4Ag recipients met the pre-defined antibody thresholds for each antigen at Day 29. A substantial and dose-level dependent immune response was observed for rP305A, with up to 18-fold rises in cLIA titres at Day 29. Robust functional responses were demonstrated, with >80-fold and >20-fold rises in OPA assay titres at Day 29 using S. aureus strains expressing capsular polysaccharide serotypes 5 and 8, respectively. Durable antibody responses were observed through month 12, gradually waning from peak levels achieved by days 11–15. SA4Ag was well tolerated, and no vaccine-related serious adverse events were reported. Conclusions Single-dose vaccination of SA4Ag in healthy adults aged 18–64 years safely induced rapid and robust functional immune responses that were durable through month 12, supporting further development of this vaccine. Trial registration number: NCT01364571

Introduction Native Americans in the southwestern United States have a higher risk for many infectious diseases and may be at higher risk for Staphylococcus aureus due to the high prevalence of risk factors for S. aureus. Recent data on invasive S. aureus infections among Native Americans are limited. Methods Active population- and laboratory-based surveillance was conducted in 2016–2017 on the Navajo Nation to document the rate of invasive S. aureus. A case of invasive S.aureus infection was defined as a Native American individual with S. aureus isolated from a normally sterile body site whose reported community of residence was on or around the Navajo Nation. Results One hundred and fifty-nine cases of invasive S. aureus from 152 individuals were identified. The median age of cases was 56.3 years and 35% were female. Thirty-five percent of cases had community-acquired infections. Ninety-three percent of cases had underlying medical conditions, including diabetes (60%) and obesity (42%), 28% of cases had a documented prior S. aureus infection, and 33% were infected with methicillin-resistant S. aureus. The annual incidence of invasive S. aureus and of invasive methicillin-resistant S. aureus was 64.9/100,000 persons and 21.2/100,000 persons, respectively. Conclusions This community has a high burden of invasive S. aureus infections. Further research is needed to identify prevention strategies and opportunities for intervention.

Invasive pneumococcal disease (IPD) is vaccine-preventable but few data on the incidence of PD exist for Indian children.To assess the feasibility of implementing prospective, population-based surveillance for PD among children less than five years of age. Settings and Design :Hospitals and health agencies, Bangalore, India. Retrospective review and analysis of hospitalization records as well as public health and demographic data.Records for 2006 hospitalizations for pneumococcal disease-associated syndromes (meningitis, pneumonia and sepsis) were identified at three pediatric referral hospitals (Indira Gandhi Institute of Child Health, Kempegowda Institute of Child Health and Vani Vilas Hospital) in Bangalore using International Classification of Diseases, 9th revision codes. Hospital microbiology laboratory records were assessed to ensure capacity for identifying S. pneumoniae. Population data were identified from national census and polio surveillance data.The Bangalore city southern zone includes 33 wards occupying 51 Km 2 with 150,945 children between 0-5 years of age served by three referral pediatric hospitals. From January--December 2006, records of these three hospitals showed 2,219 hospitalizations of children less than five years of age (967 pneumonia, 768 sepsis, and 484 meningitis) with PD-associated diagnoses (southern zone area incidence: 0.15/100,000 PD-associated hospitalizations, less than five years of age). There were 178 deaths in children less than five years of age, of which 87 were attributable to sepsis, 56 to pneumonia and 35 to meningitis.Our analysis suggests that the PD-associated disease burden in Bangalore is high and local institutions have capacity for population-based surveillance. In a prospective study, systematic attention to potential barriers in identifying children with pneumococcal infections will improve estimation of IPD incidence in India.

Objective.To assess consumption of resources in the infection control management of healthcare workers (HCWs) exposed to pertussis and to assess avoidability of exposure.Setting.Tertiary care children's medical center.Methods.Analysis of the extent of and reasons for HCW exposure to pertussis during contact with children with the disease, whether exposures were avoidable (because of the failure to recognize a case or to order or adhere to isolation precautions) or unavoidable (because the case was not recognizable or because another diagnosis was confirmed), and the cost of implementing exposure management.Interventions.Interventions consisted of an investigation of every HCW encounter with any patient who was confirmed later to have pertussis from the time of hospital admission of the patient, use of azithromycin as postexposure prophylaxis (PEP) for exposed HCWs, performance of 21-day surveillance for cough illness, testing of symptomatic exposed HCWs for Bordetella pertussis, and enhanced preexposure education of HCWs.Results.From September 2003 through April 2005, pertussis was confirmed in 28 patients (median age, 62 days); 24 patients were admitted. For 11 patients, pertussis was suspected, appropriate precautions were taken, and no HCW was exposed. Inadequate precautions for 17 patients led to 355 HCW exposures. The median number of HCWs exposed per exposing patient was 9 (range, 1-86 HCWs; first quartile mean, 2; fourth quartile mean, 61). Exposure was definitely avoidable for only 61 (17%) of 355 HCWs and was probably unavoidable for 294 HCWs (83%). The cost of 20-month infection control management of HCWs exposed to pertussis was $69,770. The entire cohort of HCWs involved in direct patient care at the facility could be immunized for approximately $60,000.Conclusions.Exposure of HCWs to pertussis during contact with children who have the disease is largely unavoidable, and management of this exposure is resource intensive. Universal preexposure vaccination of HCWs is a better utilization of resources than is case-based postexposure management.

Coagulase-negative staphylococci (CoNS) are important pathogens in premature neonates; decreasing glycopeptide susceptibility has been observed among these isolates. The epidemiology of colonization with CoNS, the organisms' vancomycin susceptibilities, and genetic relatedness were studied over 6 months in a tertiary-care neonatal unit. A total of 321 isolates of CoNS were isolated. Seventy-five percent of the infants were colonized at admission, and virtually all were colonized thereafter. Common species were Staphylococcus epidermidis (69%), S. warneri (12%), S. haemolyticus (9.7%), and S. hominis (5.6%). A total of 3.9% of CoNS isolates had decreased vancomycin susceptibility (DVS) (MICs > 2.0 μg/ml); isolate recovery was associated with a stay in a neonatal intensive care unit for >28 days ( P = 0.039), vancomycin exposure ( P = 0.021), and S. warneri colonization ( P < 0.0001). Nine of 12 (75%) CoNS with DVS were S. warneri , had enhanceable high-level resistance in vitro, were indistinguishable or closely related by pulsed-field gel electrophoresis, and were different from 29 vancomycin-susceptible S. warneri isolates. Epidemiological analysis suggested unsuspected nosocomial spread. Species determination in certain settings may aid in the understanding of emerging nosocomial problems.

Background :Invasive pneumococcal disease (IPD) is vaccine-preventable but few data on the incidence of PD exist for Indian children. Aims: To assess the feasibility of implementing prospective, population-based surveillance for PD among children less than five years of age. Settings and Design :Hospitals and health agencies, Bangalore, India. Retrospective review and analysis of hospitalization records as well as public health and demographic data. Material and Methods : Records for 2006 hospitalizations for pneumococcal disease-associated syndromes (meningitis, pneumonia and sepsis) were identified at three pediatric referral hospitals (Indira Gandhi Institute of Child Health, Kempegowda Institute of Child Health and Vani Vilas Hospital) in Bangalore using International Classification of Diseases, 9th revision codes. Hospital microbiology laboratory records were assessed to ensure capacity for identifying S. pneumoniae. Population data were identified from national census and polio surveillance data. Results : The Bangalore city southern zone includes 33 wards occupying 51 Km 2 with 150,945 children between 0-5 years of age served by three referral pediatric hospitals. From January--December 2006, records of these three hospitals showed 2,219 hospitalizations of children less than five years of age (967 pneumonia, 768 sepsis, and 484 meningitis) with PD-associated diagnoses (southern zone area incidence: 0.15/100,000 PD-associated hospitalizations, less than five years of age). There were 178 deaths in children less than five years of age, of which 87 were attributable to sepsis, 56 to pneumonia and 35 to meningitis. Conclusion : Our analysis suggests that the PD-associated disease burden in Bangalore is high and local institutions have capacity for population-based surveillance. In a prospective study, systematic attention to potential barriers in identifying children with pneumococcal infections will improve estimation of IPD incidence in India.