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.

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Background: Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. Methods: In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Results: Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Conclusions: Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

Healthcare-Associated Respiratory Syncytial Virus in Children's Hospitals.

BACKGROUND: Outbreaks of healthcare-associated respiratory syncytial virus (HA-RSV) infections in children are well described, but less is known about sporadic HA-RSV infections. We assessed the epidemiology and clinical outcomes associated with sporadic HA-RSV infections. METHODS: We retrospectively identified hospitalized children ≤18 years old with HA-RSV infections in six children's hospitals in the United States during the respiratory viral seasons October-April in 2016-2017, 2017-2018, and 2018-2019 and prospectively from October 2020 through November 2021. We evaluated outcomes temporally associated with HA-RSV infections including escalation of respiratory support, transfer to the pediatric intensive care unit (PICU), and in-hospital mortality. We assessed demographic characteristics and comorbid conditions associated with escalation of respiratory support. RESULTS: We identified 122 children (median age 16.0 months [IQR 6, 60 months]) with HA-RSV. The median onset of HA-RSV infections was hospital day 14 (IQR 7, 34 days). Overall, 78 (63.9%) children had two or more comorbid conditions; cardiovascular, gastrointestinal, neurologic/neuromuscular, respiratory, and premature/ neonatal comorbidities were most common. Fifty-five (45.1%) children required escalation of respiratory support and 18 (14.8%) were transferred to the PICU. Five (4.1%) died during hospitalization. In the multivariable analysis, respiratory comorbidities (aOR: 3.36 [CI95 1.41, 8.01]) were associated with increased odds of escalation of respiratory support. CONCLUSIONS: HA-RSV infections cause preventable morbidity and increase healthcare resource utilization. Further study of effective mitigation strategies for HA-respiratory viral infections should be prioritized; this priority is further supported by the impact of the COVID-19 pandemic on seasonal viral infections.

Acceptability, Feasibility, and Validity of Detecting Respiratory Pathogens During Acute Respiratory Illness in Participant-Collected Swabs in a Low-Income, Community Sample.

Background: Community surveillance for acute respiratory illness (ARI) can include unsupervised participant-collected nasal swabs. Little is known about use of self-swabs in low-income populations or among households including extended family members and the validity of self-collected swabs. We assessed the acceptability, feasibility, and validity of unsupervised participant-collected nasal swabs in a low-income, community sample. Methods: This was a substudy of a larger prospective community-based ARI surveillance study in 405 households in New York City. Participating household members self-collected swabs on the day of a research home visit for an index case, and for 3-6 subsequent days. Demographics associated with agreement to participate and swab collection were assessed, and index case self-collected versus research staff-collected swab results were compared. Results: Most households (n = 292 [89.6%]) agreed to participate, including 1310 members. Being <18 years old, female, and the household reporter or member of the nuclear family (parents and children) were associated with both agreement to participate and self-swab collection. Being born in the United States or immigrating ≥10 years ago was associated with participation, and being Spanish-speaking and having less than a high school education were associated with swab collection. In all, 84.4% collected at least 1 self-swabbed specimen; self-swabbing rates were highest during the first 4 collection days. Concordance between research staff-collected swabs and self-swabs was 88.4% for negative swabs, 75.0% for influenza, and 69.4% for noninfluenza pathogens. Conclusions: Self-swabbing was acceptable, feasible, and valid in this low-income, minoritized population. Some differences in participation and swab collection were identified that could be noted by future researchers and modelers.

Household Transmission of Influenza A Viruses in 2021-2022.

Importance: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. Objective: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. Design, Setting, and Participants: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. Exposures: Household contacts living with a primary case. Main Outcomes and Measures: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. Results: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. Conclusions and Relevance: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.

Agreement Between Pregnant Individuals' Self-Report of Coronavirus Disease 2019 (COVID-19) Vaccination and Medical Record Documentation.

For public health research such as vaccine uptake or effectiveness assessments, self-reported coronavirus disease 2019 (COVID-19) vaccination status may be a more efficient measure than verifying vaccination status from medical records if agreement between sources is high. We assessed agreement between self-reported and medical record-documented COVID-19 vaccination status among pregnant individuals followed in a cohort during August 2020-October 2021. At end of pregnancy, participants completed questionnaires about COVID-19 vaccine receipt during pregnancy; staff verified vaccination status using medical records. Agreement was assessed between self-reported and medical record vaccination status using Cohen's kappa. There was high agreement between self-reported and medical record vaccination status (Kappa coefficient=0.94, 95% CI 0.91-0.98), suggesting that self-report may be acceptable for ascertaining COVID-19 vaccination status during pregnancy.

Clinical and socioeconomic burden of rhinoviruses/enteroviruses in the community.

BACKGROUND: The epidemiology, clinical features, and socioeconomic burden associated with detection of rhinoviruses (RV)/enteroviruses (EV) from individuals in the community with acute respiratory infections (ARIs) are not fully understood. METHODS: To assess the clinical and socioeconomic burden associated with RV/EV, a secondary analysis of data collected during a prospective, community-based ARI surveillance study was performed. From December 2012 to September 2017, adult and pediatric participants with ARIs had nasopharyngeal specimens obtained and tested by multiplex polymerase chain reaction assay. Characteristics and socioeconomic burden including missed school or work and/or antibiotic use among participants who did and did not seek medical care and among participants with and without co-detection of another respiratory pathogen with RV/EV were compared. RESULTS: Throughout the study period, RV/EV was detected in 54.7% (885/1617) of ARIs with a respiratory pathogen detected. Most ARI episodes associated with RV/EV occurred in females (59.1%) and children ≤17 years old (64.2%). Those ≤17 years were more likely to seek medical care. Compared to those not seeking medical care (n = 686), those seeking medical care (n = 199) had a longer duration of illness (5 vs. 7 days) and were more likely to miss work/school (16.4% vs. 47.7%) and/or use antibiotics (3.6% vs. 34.2%). Co-detection occurred in 8% of ARIs of which 81% occurred in children. Co-detection was not associated with longer illness, more missed work/or school, or antibiotic use. CONCLUSION: Non-medically attended and medically attended ARIs associated with RV/EV resulted in clinical and socioeconomic burden, regardless of co-detection of other respiratory pathogens.

Five-Year Community Surveillance Study for Acute Respiratory Infections Using Text Messaging: Findings From the MoSAIC Study.

BACKGROUND: Acute respiratory infections (ARI) are the most common infectious diseases globally. Community surveillance may provide a more comprehensive picture of disease burden than medically attended illness alone. METHODS: In this longitudinal study conducted from 2012 to 2017 in the Washington Heights/Inwood area of New York City, we enrolled 405 households with 1915 individuals. Households were sent research text messages twice weekly inquiring about ARI symptoms. Research staff confirmed symptoms by follow-up call. If ≥2 criteria for ARI were met (fever/feverish, cough, congestion, pharyngitis, myalgias), staff obtained a mid-turbinate nasal swab in participants' homes. Swabs were tested using the FilmArray reverse transcription polymerase chain reaction (RT-PCR) respiratory panel. RESULTS: Among participants, 43.9% were children, and 12.8% had a chronic respiratory condition. During the 5 years, 114 724 text messages were sent; the average response rate was 78.8% ± 6.8%. Swabs were collected for 91.4% (2756/3016) of confirmed ARI; 58.7% had a pathogen detected. Rhino/enteroviruses (51.9%), human coronaviruses (13.9%), and influenza (13.2%) were most commonly detected. The overall incidence was 0.62 ARI/person-year, highest (1.73) in <2 year-olds and lowest (0.46) in 18-49 year-olds. Approximately one-fourth of those with ARI sought healthcare; percents differed by pathogen, demographic factors, and presence of a chronic respiratory condition. CONCLUSIONS: Text messaging is a novel method for community-based surveillance that could be used both seasonally as well as during outbreaks, epidemics and pandemics. The importance of community surveillance to accurately estimate disease burden is underscored by the findings of low rates of care-seeking that varied by demographic factors and pathogens.

Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019-2020 Influenza Season.

BACKGROUND: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. METHODS: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. RESULTS: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. CONCLUSIONS: Peripartum respiratory infections may be underrecognized.

Incidence and Clinical Characteristics of and Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Pregnant Individuals in the United States.

BACKGROUND: Data about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant individuals are needed to inform infection-prevention guidance and counseling for this population. METHODS: We prospectively followed a cohort of pregnant individuals during August 2020-March 2021 at 3 US sites. The 3 primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly midturbinate nasal swabs for SARS-CoV-2 reverse transcription-polymerase chain reaction testing, completed weekly illness symptom questionnaires, and submitted additional swabs with coronavirus disease 2019 (COVID-19)-like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. RESULTS: Among 1098 pregnant individuals followed for a mean of 10 weeks, 9% (99/1098) had SARS-CoV-2 infections during the study. Population-weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1000 (95% confidence interval, 5.7-14.3) person-weeks for any infection, 5.7 per 1000 (1.7-9.7) for symptomatic infections, and 3.5 per 1000 (0-7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infections and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. Median symptom duration was 10 (interquartile range, 6-16) days. CONCLUSIONS: Pregnant individuals in this study had a 1% risk of SARS-CoV-2 infection per week, underscoring the importance of COVID-19 vaccination and other prevention measures during pregnancy while SARS-CoV-2 is circulating in the community.

Attitudes Toward COVID-19 Illness and COVID-19 Vaccination among Pregnant Women: A Cross-Sectional Multicenter Study during August-December 2020.

OBJECTIVE: The aim of the study was to evaluate pregnant women's attitudes toward COVID-19 illness and vaccination and identify factors associated with vaccine acceptability. STUDY DESIGN: This was a cross-sectional survey among pregnant women enrolled in a prospective COVID-19 cohort study in Salt Lake City, UT, Birmingham, AL, and New York, NY, from August 9 to December 10, 2020. Women were eligible if they were 18 to 50 years old and <28 weeks of gestation. Upon enrollment, women completed surveys regarding concerns about COVID-19 illness and likelihood of getting COVID-19 vaccine if one were available during pregnancy. Vaccine acceptability was defined as a response of "very likely" or "somewhat likely" on a 4-point Likert scale. Factors associated with vaccine acceptability were assessed with multivariable logistic regression. RESULTS: Of 939 pregnant women eligible for the main cohort study, 915 (97%) consented to participate. Among these 915 women, 39% self-identified as White, 23% Black, 33% Hispanic, and 4% Other. Sixty-two percent received an influenza vaccine last season. Seventy-two percent worried about getting sick with COVID-19. If they were to get sick, 92% worried about harm to their pregnancy and 80% about harm to themselves. Only 41% reported they would get a vaccine. Of women who were unlikely to get vaccinated, the most frequently cited concern was vaccine safety for their pregnancy (82%). Non-Hispanic Black and Hispanic women had lower odds of accepting a vaccine compared with non-Hispanic White women (adjusted odds ratios [aOR] 0.4, 95% CI 0.2-0.6 for both). Receipt of influenza vaccine during the previous season was associated with higher odds of vaccine acceptability (aOR 2.1, 95% CI 1.5-3.0). CONCLUSION: Although most pregnant women worried about COVID-19 illness, <50% were willing to get vaccinated during pregnancy. Racial and ethnic disparities in plans to accept COVID-19 vaccine highlight the need to prioritize strategies to address perceived barriers among groups at high risk for COVID-19. KEY POINTS: · Less than half of pregnant patients stated they would get a COVID-19 vaccine.. · Protecting their baby was the most common reason for acceptance and refusal of the COVID-19 vaccine.. · Patients of minority race/ethnicity and those without prior influenza vaccination were less likely to accept the COVID-19 vaccine..

The Retail Outlet Health Kiosk Hypertension Trial (ROKHYT): Pilot Results.

BACKGROUND: Blood pressure (BP) control was only 43.7% in the National Health and Nutrition Survey (NHANES) survey in 2017-2018. Scalable, nonclinic-based strategies to control BP are needed. We therefore conducted a pilot trial of a text-messaging intervention in a national network of retail outlet health kiosks with BP devices. All study procedures were conducted remotely. METHODS: Eligible individuals (N = 140), based on average BP greater than or equal to 140/90 mm Hg at kiosks during the prior year, were randomized to intervention vs. usual care. Intervention consisted of tailored text messages providing educational information with embedded links to educational videos on topics related to BP control. BP measurements were obtained at kiosks at 3, 6, and 12 months following randomization; control was defined as BP < 140/90 mm Hg. Follow-up at 12 months was curtailed due to SARS-CoV-2. We therefore combined 12-month (N = 62) or carried forward 6-month (N = 61) data as the primary end point. RESULTS: Participants were 51.4% male, 70.7% white/Caucasian, had mean age of 52.1 years, and mean baseline BP 145.5/91.8 mm Hg. At the end point, 37.7% intervention vs. 27.4% usual care subjects achieved BP control (difference, 10.3%, 95% confidence interval -6.2%, 26.8%). In an intention-to-treat analysis with multiple imputation of missing data, 12-month BP control was 29.0% vs. 19.8% favoring intervention (difference, 9.2%. 95% confidence interval -7.3%, 25.7%); intervention vs. control differences in adjusted mean BP levels were systolic BP: -5.4 mm Hg (95% confidence interval: -13.5, 2.7) and diastolic BP: +0.6 mm Hg (95% confidence interval: -4.2, 5.4). CONCLUSIONS: These pilot results support the potential for a highly scalable text-messaging intervention to improve BP. CLINICAL TRIALS REGISTRATION: Trial Number NCT03515681.

Severe Clinical Outcomes Among Adults Hospitalized With Respiratory Syncytial Virus Infections, New York City, 2017-2019.

OBJECTIVES: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. We assessed severe clinical outcomes among hospitalized adults that were associated with RSV infections. METHODS: We performed a nested retrospective study in 3 New York City hospitals during 2 respiratory viral seasons, October 2017-April 2018 and October 2018-April 2019, to determine the proportion of patients with laboratory-confirmed RSV infection who experienced severe outcomes defined as intensive care unit (ICU) admission, mechanical ventilation, and/or death. We assessed factors associated with these severe outcomes and explored the effect of RSV-associated hospitalizations on changes in the living situations of surviving patients. RESULTS: Of the 403 patients studied (median age, 69 years), 119 (29.5%) were aged ≥80. Severe outcomes occurred in 19.1% of patients, including ICU admissions (16.4%), mechanical ventilation (12.4%), and/or death (6.7%). Patients admitted from residential living facilities had a 4.43 times higher likelihood of severe RSV infection compared with patients who were living in the community with or without assistance from family or home health aides. At discharge, 56 (15.1%) patients required a higher level of care than at admission. CONCLUSIONS: RSV infection was associated with severe outcomes in adults. Living in a residential facility at admission was a risk factor for severe outcomes and could be a proxy for frailty rather than an independent risk factor. Our data support the development of prevention strategies for RSV infection in older populations, especially older adults living in residential living facilities.

Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017-2020.

BACKGROUND: Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. METHODS: Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017-2018, 2018-2019, and 2019-2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. RESULTS: Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group-specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18-49, 50-64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3-13, 4-7, and 4-33 times, respectively, the incidence in patients without these conditions. CONCLUSIONS: We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults.

Household transmission of influenza A and B within a prospective cohort during the 2013-2014 and 2014-2015 seasons.

People living within the same household as someone ill with influenza are at increased risk of infection. Here, we use Markov chain Monte Carlo methods to partition the hazard of influenza illness within a cohort into the hazard from the community and the hazard from the household. During the 2013-2014 influenza season, 49 (4.7%) of the 1044 people enrolled in a community surveillance cohort had an acute respiratory illness (ARI) attributable to influenza. During the 2014-2015 influenza season, 50 (4.7%) of the 1063 people in the cohort had an ARI attributable to influenza. The secondary attack rate from a household member was 2.3% for influenza A (H1) during 2013-2014, 5.3% for influenza B during 2013-2014, and 7.6% for influenza A (H3) during 2014-2015. Living in a household with a person ill with influenza increased the risk of an ARI attributable to influenza up to 350%, depending on the season and the influenza virus circulating within the household.

Epidemiology, clinical features, and resource utilization associated with respiratory syncytial virus in the community and hospital.

BACKGROUND: The epidemiology, clinical features, and resource utilization of respiratory syncytial virus (RSV) cases in the community and the hospital are not fully characterized. METHODS: We identified individuals of all ages with laboratory-confirmed RSV from two sources, a community cohort undergoing surveillance for acute respiratory infections (ARIs) and hospitalized patients from the same geographic area of New York City between 2013 and 15. The epidemiology, clinical features, and resource utilization (antibiotic/steroid/ribavirin usage, chest X-rays, respiratory-support (continuous positive airway pressure [CPAP], mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and indicators of disease severity (respiratory-support, and/or ICU admission or death)) were compared among age groups using univariate and bivariate analyses. RESULTS: In the community cohort (1777 people with 1805 ARIs), 66(3.7%) tested RSV-positive (3.8% of <1-year-olds; 3.8% of adults ≥65); 40.9% were medically attended, and 23.1% reported antibiotic usage. Among 40,461 tests performed on hospital patients, 2.7% were RSV-positive within ± 2 days of admission (37.3% <1 year old; 17.4% ≥65 years old). Among RSV-positive hospitalized adults ≥65%, 92.7%, 89.6% and 78.1% received a chest X-ray, antibiotics and/or steroids respectively, compared with 48.9%, 45.7%, and 48.7% of children <1. Severe illness occurred in 27.0% RSV-positive hospitalized <1-year-olds and 19.8% ≥65-year-olds. CONCLUSIONS: Respiratory syncytial virus had a demonstrated impact in the community and hospital. Only 40% of RSV community cases were medically attended. In the hospitalized-cohort, <1- and ≥ 65-year-olds accounted for the majority of patients and had similar rates of severe illness. In addition, resource utilization was high in older adults, making both young children and older adults important potential RSV vaccine targets.

Seasonality and clinical impact of human parainfluenza viruses.

BACKGROUND: Widespread availability of rapid diagnostic testing for respiratory viruses allows more in-depth studies of human parainfluenza viruses (HPIV). OBJECTIVES: This study aimed to assess seasonality of HPIV types 1-4, clinical outcomes by HPIV type, and risk factors for illness severity. PATIENTS/METHODS: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. Seasonality trends by HPIV type were compared between the community and hospital groups. The associations between HPIV type, demographics, clinical characteristics, and illness severity were assessed. RESULTS: HPIV was detected in 69 (4%) of 1753 community surveillance participants (median age 9.2 years) and 680 hospitalized patients (median age 6.8 years). Seasonality for HPIV types 1-3 agreed with previously described patterns; HPIV-4 occurred annually in late summer and fall. In the community cohort, 22 (32%) participants sought medical care, 9 (13%) reported antibiotic use, and 20 (29%) reported ≥1 day of missed work or school. Among hospitalized patients, 24% had ≥4 chronic conditions. Multivariable ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV-4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults. CONCLUSIONS: HPIV-4 presented late summer and early fall annually and was associated with increased severity of illness in hospitalized children.

Assessment of temporally-related acute respiratory illness following influenza vaccination.

BACKGROUND: A barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods. METHODS: We conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons. RESULTS: Of the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]). CONCLUSION: Among children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by influenza.

Comparison of outpatient medically attended and community-level influenza-like illness-New York City, 2013-2015.

BACKGROUND: Surveillance of influenza-like illness (ILI) in the United States is primarily conducted through medical settings despite a significant burden of non-medically attended ILI. OBJECTIVES: To assess consistency between surveillance for respiratory viruses in outpatient and community settings using ILI surveillance from the Centers for Disease Control and Prevention Influenza Incidence Surveillance Project (IISP) and the Mobile Surveillance for Acute Respiratory Infections (ARI) and Influenza-Like Illness in the Community (MoSAIC) Study. METHODS: The Influenza Incidence Surveillance Project conducts ILI surveillance in 3 primary care clinics in New York City, and MoSAIC conducts community-based ILI/ARI surveillance through text messaging among a cohort of New York City residents. Both systems obtain respiratory specimens from participants with ILI/ARI and test for multiple pathogens. We conducted a retrospective review of ILI cases in IISP and MoSAIC from January 2013 to May 2015 with descriptive analyses of clinical and laboratory data. RESULTS: Five-hundred twelve MoSAIC and 669 IISP participants met an ILI criteria (fever with cough or sore throat) and were included. Forty percent of MoSAIC participants sought care; the majority primary care. Pathogens were detected in 63% of MoSAIC and 70% of IISP cases. The relative distribution of influenza and other respiratory viruses detected was similar; however, there were statistically significant differences in the frequency that were not explained by care seeking. CONCLUSIONS: Outpatient and community-based surveillance in the one found similar timing and relative distribution of respiratory viruses, but community surveillance in a single neighborhood may not fully capture the variations in ILI etiology that occur more broadly.

Epidemiology and Clinical Features of Human Coronaviruses in the Pediatric Population.

BACKGROUND: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. METHODS: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children's hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. RESULTS: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9-13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6-9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1-7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7-12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1-7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types. CONCLUSIONS: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.