SARS-CoV-2 incidence, seroprevalence, and antibody dynamics in a rural, population-based cohort: March 2020 - July 2022.

Studies of SARS-CoV-2 incidence are important for response to continued transmission and future pandemics. We followed a rural community cohort with broad age representation with active surveillance for SARS-CoV-2 identification from November 2020 through July 2022. Participants provided serum specimens at regular intervals and following SARS-CoV-2 infection or vaccination. We estimated the incidence of SARS-CoV-2 infection identified by study RT-PCR, electronic health record documentation or self-report of a positive test, or serology. We also estimated the seroprevalence of SARS-CoV-2 spike and nucleocapsid antibodies measured by ELISA. Overall, 65% of the cohort had ≥1 SARS-CoV-2 infection by July 2022, and 19% of those with primary infection were reinfected. Infection and vaccination contributed to high seroprevalence, 98% (95% CI: 95%, 99%) of participants were spike or nucleocapsid seropositive at the end of follow-up. Among those seropositive, 82% were vaccinated. Participants were more likely to be seropositive to spike than nucleocapsid following infection. Infection among seropositive individuals could be identified by increases in nucleocapsid, but not spike, ELISA optical density values. Nucleocapsid antibodies waned more quickly after infection than spike antibodies. High levels of SARS-CoV-2 population immunity, as found in this study, are leading to changing epidemiology necessitating ongoing surveillance and policy evaluation.

Epidemiology of RSV in Adults and Children with Medically-Attended Acute Respiratory Illness over Three Seasons.

BACKGROUND: Data on the true prevalence of RSV among medically-attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over three seasons, which is informative in light of the recommendations for shared decision-making for vaccination in older adults. METHODS: Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated Multimorbidity-Weighted Index (MWI) were collected by in-person survey and electronic medical record review. RESULTS: Over three surveillance seasons (fall 2017 to spring 2020), 9.9% (n=441) of 4,442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months-4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). CONCLUSIONS: RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision-making for vaccination.

Ipsilateral and contralateral coadministration of influenza and COVID-19 vaccines produce similar antibody responses.

BACKGROUND: World Health Organisation (WHO) and USA Centers for Disease Control and Prevention (U.S. CDC) recommendations now allow simultaneous administration of COVID-19 and other vaccines. We compared antibody responses after coadministration of influenza and bivalent COVID-19 vaccines in the same (ipsilateral) arm vs. different (contralateral) arms. METHODS: Pre- and post-vaccination serum samples from individuals in the Prospective Assessment of COVID-19 in a Community (PACC) cohort were used to conduct haemaglutination inhibition (HI) assays with the viruses in the 2022-2023 seasonal influenza vaccine and focus reduction neutralisation tests (FRNT) using a BA.5 SARS-CoV-2 virus. The effect of ipsilateral vs. contralateral vaccination on immune responses was inferred in a model that accounted for higher variance in vaccine responses at lower pre-vaccination titers. FINDINGS: Ipsilateral vaccination did not cause higher influenza vaccine responses compared to contralateral vaccination. The response to SARS-CoV-2 was slightly increased in the ipsilateral group, but equivalence was not excluded. INTERPRETATION: Coadministration of influenza and bivalent COVID-19 vaccines in the same arm or different arms did not strongly influence the antibody response to either vaccine. FUNDING: This work was supported by the U.S. CDC (grant number: 75D30120C09259).

A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended ß-lactam-resistant Pseudomonas aeruginosa.

OBJECTIVES: To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-ß-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. METHODS: This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. RESULTS: A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. CONCLUSIONS: Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.

Incidence and outcomes of hospital-associated respiratory virus infections by viral species.

BACKGROUND: Although the incidence of hospital-associated respiratory virus infection (HARVI) is well recognized, the risk factors for infection and impact on patient outcomes are not well characterized. METHODS: We identified a cohort of all inpatient admissions ≥24 hours duration at a single academic medical center from 2017 to 2020. HARVI were defined as respiratory virus detected in a test ordered after the 95th percentile of the virus-specific incubation period. Risk factors for HARVI were assessed using Cox proportional hazards models of the competing outcomes of HARVI and discharge. The associations between time-varying HARVI status and the rates of ICU admission, discharge, and in-hospital death were estimated using Cox-proportional hazards models in a competing risk framework. RESULTS: HARVI incidences were 8.8 and 3.0 per 10,000 admission days for pediatric and adult patients, respectively. For adults, congestive heart failure, renal disease, and cancer increased HARVI risk independent of their associations with length of stay. HARVI risk was also elevated for patients admitted in September-June relative to July admissions. For pediatric patients, cardiovascular and respiratory conditions, cancer, medical device dependence, and admission in December increased HARVI risk. Lengths of stay were longer for adults with HARVI compared to those without, and hospital-associated influenza A was associated with increased risk of death. Rates of ICU admission were increased in the 5 days after HARVI identification for adult and pediatric patients. HARVI was not associated with length of stay or death among pediatric patients. CONCLUSIONS: HARVI is associated chronic health conditions and increases morbidity and mortality.

Neutralizing Immunity Against Antigenically Advanced Omicron BA.5 in Children After SARS-CoV-2 Infection.

We assessed serum neutralization of Omicron BA.5 in children following SARS-CoV-2 infection during the Delta or Omicron BA.1/BA.2 variant period. Convalescent BA.5 titers were higher following infections during the Omicron BA.1/BA.2 vs Delta variant period, and in vaccinated vs unvaccinated children. Titers against BA.5 did not differ by age group.

Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Immune response to COVID-19 vaccination in a population with a history of elevated exposure to per- and polyfluoroalkyl substances (PFAS) through drinking water.

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to lower vaccine-induced antibody concentrations in children, while data from adults remains limited and equivocal. Characteristics of PFAS exposure and age at vaccination may modify such effects. OBJECTIVE: We used the mass administration of novel COVID-19 vaccines to test the hypothesis that prior exposure to environmentally-relevant concentrations of PFAS affect antibody response to vaccines in adolescents and adults. METHODS: Between April and June 2021, 226 participants aged 12-90 years with a history of exposure to PFAS in drinking water and who received an mRNA COVID-19 vaccine participated in our prospective cohort study. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies (IgG) were quantified before the first and second vaccine doses and again at two follow-ups in the following months (up to 103 days post dose 1). Serum PFAS concentrations (n = 39 individual PFAS) were measured once for each participant during baseline, before their first vaccination. The association between PFAS exposure and immune response to vaccination was investigated using linear regression and generalized estimating equation (GEE) models with adjustment for covariates that affect antibody response. PFAS mixture effects were assessed using weighted quantile sum and Bayesian kernel machine regression methods. RESULTS: The geometric mean (standard deviation) of perfluorooctane sulfonate and perfluorooctanoic acid serum concentrations in this population was 10.49 (3.22) and 3.90 (4.90) µg/L, respectively. PFAS concentrations were not associated with peak anti-spike antibody response, the initial increase in anti-spike antibody response following vaccination, or the waning over time of the anti-spike antibody response. Neither individual PFAS concentrations nor their evaluation as a mixture was associated with antibody response to mRNA vaccination against COVID-19. IMPACT STATEMENT: Given the importance of understanding vaccine response among populations exposed to environmental contaminants and the current gaps in understanding this relationship outside of early life/childhood vaccinations, our manuscript contributes meaningful data from an adolescent and adult population receiving a novel vaccination.

K-medoids clustering of hospital admission characteristics to classify severity of influenza virus infection.

Background: Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist and to examine the association between cluster membership and in-hospital outcomes. Methods: Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n = 242) and 2018/2019 (n = 115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 h of the hospital stay. K-medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth's logistic regression were used to examine the association between cluster membership and clinical outcomes. Results: Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C171 had 5.6 times the odds of mechanical ventilator use than those in C172 (95% CI: 1.49, 21.1) and a significantly longer mean hospital length of stay than those in both C172 (mean 1.5 days longer, 95% CI: 0.2, 2.7) and C173 (mean 1.4 days longer, 95% CI: 0.3, 2.5). Similar results were seen between the two clusters selected for 2018/2019. Conclusion: In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation.

Respiratory virus circulation during the first year of the COVID-19 pandemic in the Household Influenza Vaccine Evaluation (HIVE) cohort.

Background: The annual reappearance of respiratory viruses has been recognized for decades. COVID-19 mitigation measures taken during the pandemic were targeted at respiratory transmission and broadly impacted the burden of acute respiratory illnesses (ARIs). Methods: We used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort in southeast Michigan to characterize the circulation of respiratory viruses from March 1, 2020, to June 30, 2021, using RT-PCR of respiratory specimens collected at illness onset. Participants were surveyed twice during the study period, and SARS-CoV-2 antibodies were measured in serum by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were compared between the study period and a preceding pre-pandemic period of similar duration. Results: Overall, 437 participants reported a total of 772 ARIs; 42.6% had respiratory viruses detected. Rhinoviruses were the most frequent virus, but seasonal coronaviruses, excluding SARS-CoV-2, were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Seropositivity for SARS-CoV-2 was 5.3% in summer 2020 and increased to 11.3% in spring 2021. The incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p < 0.001) than the incidence rate from a pre-pandemic comparison period (March 1, 2016, to June 30, 2017). Conclusions: The burden of ARI in the HIVE cohort during the COVID-19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. Rhinovirus and seasonal coronaviruses continued to circulate even when influenza and SARS-CoV-2 circulation was low.

Effectiveness of first and second COVID-19 mRNA vaccine monovalent booster doses during a period of circulation of Omicron variant sublineages: December 2021-July 2022.

Background: US recommendations for COVID-19 vaccine boosters have expanded in terms of age groups covered and numbers of doses recommended, whereas evolution of Omicron sublineages raises questions about ongoing vaccine effectiveness. Methods: We estimated effectiveness of monovalent COVID-19 mRNA booster vaccination versus two-dose primary series during a period of Omicron variant virus circulation in a community cohort with active illness surveillance. Hazard ratios comparing SARS-CoV-2 infection between booster versus primary series vaccinated individuals were estimated using Cox proportional hazards models with time-varying booster status. Models were adjusted for age and prior SARS-CoV-2 infection. The effectiveness of a second booster among adults ≥50 years of age was similarly estimated. Results: The analysis included 883 participants ranging in age, from 5 to >90 years. Relative effectiveness was 51% (95% CI: 34%, 64%) favoring the booster compared with primary series vaccination and did not vary by prior infection status. Relative effectiveness was 74% (95% CI: 57%, 84%) at 15 to 90 days after booster receipt, but declined to 42% (95% CI: 16%, 61%) after 91 to 180 days, and to 36% (95% CI: 3%, 58%) after 180 days. The relative effectiveness of a second booster compared to a single booster was 24% (95% CI: -40% to 61%). Conclusions: An mRNA vaccine booster dose added significant protection against SARS-CoV-2 infection, but protection decreased over time. A second booster did not add significant protection for adults ≥50 years of age. Uptake of recommended bivalent boosters should be encouraged to increase protection against Omicron BA.4/BA.5 sublineages.

Investigating Epidemiologic and Molecular Links Between Patients With Community- and Hospital-Acquired Influenza A: 2017-2018 and 2019-2020, Michigan.

Background: Hospital-acquired influenza virus infection (HAII) can cause severe morbidity and mortality. Identifying potential transmission routes can inform prevention strategies. Methods: We identified all hospitalized patients testing positive for influenza A virus at a large, tertiary care hospital during the 2017-2018 and 2019-2020 influenza seasons. Hospital admission dates, locations of inpatient service, and clinical influenza testing information were retrieved from the electronic medical record. Time-location groups of epidemiologically linked influenza patients were defined and contained ≥1 presumed HAII case (first positive ≥48 hours after admission). Genetic relatedness within time-location groups was assessed by whole genome sequencing. Results: During the 2017-2018 season, 230 patients tested positive for influenza A(H3N2) or unsubtyped influenza A including 26 HAIIs. There were 159 influenza A(H1N1)pdm09 or unsubtyped influenza A-positive patients identified during the 2019-2020 season including 33 HAIIs. Consensus sequences were obtained for 177 (77%) and 57 (36%) of influenza A cases in 2017-2018 and 2019-2020, respectively. Among all influenza A cases, there were 10 time-location groups identified in 2017-2018 and 13 in 2019-2020; 19 of 23 groups included ≤4 patients. In 2017-2018, 6 of 10 groups had ≥2 patients with sequence data, including ≥1 HAII case. Two of 13 groups met this criteria in 2019-2020. Two time-location groups from 2017-2018 each contained 3 genetically linked cases. Conclusions: Our results suggest that HAIIs arise from outbreak transmission from nosocomial sources as well as single infections from unique community introductions.

Comparing the Etiology of Viral Acute Respiratory Illnesses Between Children Who Do and Do Not Attend Childcare.

BACKGROUND AND OBJECTIVE: Childcare attendance is a common risk factor for acute respiratory illness (ARI) in young children. Our goal was to better understand the specific respiratory viruses that predominate in childcare, which may support the development of tailored illness prevention and intervention strategies in childcare settings. METHODS: Using data from a prospective household cohort of ARI surveillance, we assessed specimen from 1418 ARIs reported by 359 childcare-aged children over 6 study seasons (2012/2013 through 2017/2018). Respiratory swabs were tested by polymerase chain reaction for 9 respiratory viruses. A mixed-effect logistic regression model was used to compare odds of various viral detection outcomes. The Shannon's Diversity index was used to compare the richness (ie, number of species) and diversity (ie, relative species abundance) associated with respiratory viruses detected in both groups. RESULTS: At least 1 virus was detected in 75.5% of childcare-associated ARIs and in 80.1% of homecare ARIs. Compared with illnesses among homecare children, childcare illnesses were associated with significantly higher odds of detected adenovirus (odds ratio = 1.86, 95% confidence interval = 1.05-3.28) and human metapneumovirus (odds ratio = 1.76, 95% confidence interval = 1.03-3.0). The pool of viruses associated with childcare ARI was found to be significantly richer and more diverse than that of viruses associated with homecare ARI ( P < 0.0001). CONCLUSIONS: Children attending childcare experience a higher risk of adenovirus and human metapneumovirus infection and are regularly exposed to a rich and diverse pool of respiratory viruses in childcare environments. Our results underscore the necessity of thorough and multifaceted viral prevention strategies in childcare settings.

Interim Estimates of 2022-23 Seasonal Influenza Vaccine Effectiveness - Wisconsin, October 2022-February 2023.

In the United States, 2022-23 influenza activity began earlier than usual, increasing in October 2022, and has been associated with high rates of hospitalizations among children* (1). Influenza A(H3N2) represented most influenza viruses detected and subtyped during this period, but A(H1N1)pdm09 viruses cocirculated as well. Most viruses characterized were in the same genetic subclade as and antigenically similar to the viruses included in the 2022-23 Northern Hemisphere influenza vaccine (1,2). Effectiveness of influenza vaccine varies by season, influenza virus subtype, and antigenic match with circulating viruses. This interim report used data from two concurrent studies conducted at Marshfield Clinic Health System (MCHS) in Wisconsin during October 23, 2022-February 10, 2023, to estimate influenza vaccine effectiveness (VE). Overall, VE was 54% against medically attended outpatient acute respiratory illness (ARI) associated with laboratory-confirmed influenza A among patients aged 6 months-64 years. In a community cohort of children and adolescents aged <18 years, VE was 71% against symptomatic laboratory-confirmed influenza A virus infection. These interim analyses indicate that influenza vaccination substantially reduced the risk for medically attended influenza among persons aged <65 years and for symptomatic influenza in children and adolescents. Annual influenza vaccination is the best strategy for preventing influenza and its complications. CDC recommends that health care providers continue to administer annual influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating (2).

Respiratory Virus Circulation during the First Year of the COVID-19 Pandemic in the Household Influenza Vaccine Evaluation (HIVE) Cohort.

Background: The annual reappearance of respiratory viruses has been recognized for decades. The onset of the COVID-19 pandemic altered typical respiratory virus transmission patterns. COVID-19 mitigation measures taken during the pandemic were targeted at SARS-CoV-2 respiratory transmission and thus broadly impacted the burden of acute respiratory illnesses (ARIs), in general. Methods: We used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort of households in southeast Michigan to characterize mitigation strategy adherence, respiratory illness burden, and the circulation of 15 respiratory viruses during the COVID-19 pandemic determined by RT-PCR of respiratory specimens collected at illness onset. Study participants were surveyed twice during the study period (March 1, 2020, to June 30, 2021), and serologic specimens were collected for antibody measurement by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were calculated and compared using incidence rate ratios for the study period and a pre-pandemic period of similar length. Results: Overall, 437 participants reported a total of 772 ARIs and 329 specimens (42.6%) had respiratory viruses detected. Rhinoviruses were the most frequently detected organism, but seasonal coronaviruses-excluding SARS-CoV-2-were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Study participants were more adherent to mitigation measures in the first survey compared with the second survey. Supplemental serology surveillance identified 5.3% seropositivity for SARS-CoV-2 in summer 2020; 3.0% between fall 2020 and winter 2021; and 11.3% in spring 2021. Compared to a pre-pandemic period of similar length, the incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p<0.001) than the incidence rate from March 1, 2016, to June 30, 2017. Conclusions: The burden of ARI in the HIVE cohort during the COVID-19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. It is notable, however, that rhinovirus and seasonal coronaviruses continued to circulate even as influenza and SARS-CoV-2 circulation was low.

The variant-specific burden of SARS-CoV-2 in Michigan: March 2020 through November 2021.

Accurate estimates of the total burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to inform policy, planning, and response. We sought to quantify SARS-CoV-2 cases, hospitalizations, and deaths by age in Michigan. Coronavirus disease 2019 cases reported to the Michigan Disease Surveillance System were multiplied by age and time-specific adjustment factors to correct for under-detection. Adjustment factors were estimated in a model fit to incidence data and seroprevalence estimates. Age-specific incidence of SARS-CoV-2 hospitalization, death, vaccination, and variant proportions were estimated from publicly available data. We estimated substantial under-detection of infection that varied by age and time. Accounting for under-detection, we estimate the cumulative incidence of infection in Michigan reached 75% by mid-November 2021, and over 87% of Michigan residents were estimated to have had ≥1 vaccination dose and/or previous infection. Comparing pandemic waves, the relative burden among children increased over time. In general, the proportion of cases who were hospitalized or who died decreased over time. Our results highlight the ongoing risk of periods of high SARS-CoV-2 incidence despite widespread prior infection and vaccination. This underscores the need for long-term planning for surveillance, vaccination, and other mitigation measures amidst continued response to the acute pandemic.

The 2009 Pandemic H1N1 Hemagglutinin Stalk Remained Antigenically Stable after Circulating in Humans for a Decade.

An H1N1 influenza virus caused a pandemic in 2009, and descendants of this virus continue to circulate seasonally in humans. Upon infection with the 2009 H1N1 pandemic strain (pH1N1), many humans produced antibodies against epitopes in the hemagglutinin (HA) stalk. HA stalk-focused antibody responses were common among pH1N1-infected individuals because HA stalk epitopes were conserved between the pH1N1 strain and previously circulating H1N1 strains. Here, we completed a series of experiments to determine if the pH1N1 HA stalk has acquired substitutions since 2009 that prevent the binding of human antibodies. We identified several amino acid substitutions that accrued in the pH1N1 HA stalk from 2009 to 2019. We completed enzyme-linked immunosorbent assays, absorption-based binding assays, and surface plasmon resonance experiments to determine if these substitutions affect antibody binding. Using sera collected from 230 humans (aged 21 to 80 years), we found that pH1N1 HA stalk substitutions that have emerged since 2009 do not affect antibody binding. Our data suggest that the HA stalk domain of pH1N1 viruses remained antigenically stable after circulating in humans for a decade. IMPORTANCE In 2009, a new pandemic H1N1 (pH1N1) virus began circulating in humans. Many individuals mounted hemagglutinin (HA) stalk-focused antibody responses upon infection with the 2009 pH1N1 strain, since the HA stalk of this virus was relatively conserved with other seasonal H1N1 strains. Here, we completed a series of studies to determine if the 2009 pH1N1 strain has undergone antigenic drift in the HA stalk domain over the past decade. We found that serum antibodies from 230 humans could not antigenically distinguish the 2009 and 2019 HA stalk. These data suggest that the HA stalk of pH1N1 has remained antigenically stable, despite the presence of high levels of HA stalk antibodies within the human population.

Improving antibiotic use for sinusitis and upper respiratory tract infections: A virtual-visit antibiotic stewardship initiative.

BACKGROUND: Asynchronous virtual patient care is increasingly used; however, the effectiveness of virtually delivering guideline-concordant care in conjunction with antibiotic stewardship initiatives remains uncertain. We developed a bundled stewardship intervention to improve antibiotic use in E-visits for upper respiratory tract infections (URTIs). METHODS: In this before-and-after study, adult patients who completed E-visits for "cough," "flu," or "sinus symptoms" at Michigan Medicine between January 1, 2018, and September 30, 2020, were included. Patient demographics, diagnoses, and antibiotic details were collected. The multifaceted intervention occurred over 6 months. Segmented linear regression was performed to estimate the effect of the intervention on appropriate antibiotic use for URTI diagnoses (defined as no antibiotic prescribed) and sinusitis (defined as guideline-concordant antibiotic selection and duration). Regression lines were fit to data before the bundled intervention (January 2019) and after the bundled intervention (May 2019). RESULTS: In total, 5,151 E-visits were included. The intervention decreased the number of visits for flu, cough, or sinus symptoms prescribed antibiotics from 43.2% to 28.9% (P < .001). Guideline concordance of antibiotic prescriptions improved following the intervention: first-line amoxicillin-clavulanate rose from 37.9% of prescriptions to 66.1% of prescriptions (P < .001), second-line doxycycline rose from 13.8% to 22.7% (P < .001); and median duration of antibiotics decreased from 10 days to 5 days (P < .001). CONCLUSIONS: A multifaceted stewardship bundle for E-visits involving both changes in the EMR and audit and feedback improved guideline-concordant antibiotic use for URTIs. This approach can aid stewardship efforts in the ambulatory care setting with regard to telemedicine.

Distinct influenza surveillance networks and their agreement in recording regional influenza circulation: Experience from Southeast Michigan.

INTRODUCTION: In Southeast Michigan, active surveillance studies monitor influenza activity in hospitals, ambulatory clinics, and community households. Across five respiratory seasons, we assessed the contribution of data from each of the three networks towards improving our overall understanding of regional influenza circulation. METHODS: All three networks used case definitions for acute respiratory illness (ARI) and molecularly tested for influenza from research-collected respiratory specimens. Age- and network-stratified epidemic curves were created for influenza A and B. We compared stratified epidemic curves visually and by centering at seasonal midpoints. RESULTS: Across all seasons (from 2014/2015 through 2018/2019), epidemic curves from each of the three networks were comparable in terms of both timing and magnitude. Small discrepancies in epidemics recorded by each network support previous conclusions about broader characteristics of particular influenza seasons. CONCLUSION: Influenza surveillance systems based in hospital, ambulatory clinic, and community household settings appear to provide largely similar information regarding regional epidemic activity. Together, multiple levels of influenza surveillance provide a detailed view of regional influenza epidemics, but a single surveillance system-regardless of population subgroup monitored-appears to be sufficient in providing vital information regarding community influenza epidemics.

Health Care-Acquired Viral Respiratory Diseases.

Health care-acquired viral respiratory infections are common and cause increased patient morbidity and mortality. Although the threat of viral respiratory infection has been underscored by the coronavirus disease 2019 (COVID-19) pandemic, respiratory viruses have a significant impact in health care settings even under normal circumstances. Studies report decreased nosocomial transmission when aggressive infection control measures are implemented, with more success noted when using a multicomponent approach. Influenza vaccination of health care personnel furthers decrease rates of transmission; thus, mandatory vaccination is becoming more common. This article discusses the epidemiology, transmission, and control of health care-associated respiratory viral infections.