Incidence of Influenza-associated Neurologic and Psychiatric Complications Requiring Hospitalization in Children Ages 5-17 Years.

BACKGROUND: The spectrum and incidence of influenza-associated neuropsychiatric complications are not well-characterized. The objective of this study was to define the incidence of specific neurologic and psychiatric complications associated with influenza in children and adolescents. METHODS: We assembled a retrospective cohort of children 5-17 years of age with an outpatient or emergency department International Classification of Diseases, 10th revision influenza diagnosis and enrolled in Tennessee Medicaid from 2016 to 2020. Serious neurologic or psychiatric complications requiring hospitalization were identified using a validated algorithm. Incidence rates of complications were expressed per 100,000 person-weeks of influenza and 95% confidence intervals (CIs) were reported. RESULTS: A total of 156,611 influenza encounters (median age of 9.3 years) were included. The overall incidence of neurologic complications was 30.5 (95% CI: 24.0-38.6) per 100,000 person-weeks of influenza and 1880.9 (95% CI: 971.9-3285.5) among children with an underlying neurologic comorbidity. The distribution of antiviral treatment was similar among those with and without neurologic or psychiatric complications. The overall incidence of psychiatric complications was 20.2 (95% CI: 15.1-27.0) per 100,000 person-weeks of influenza and 111.8 (95% CI: 77.9-155.5) among children with an underlying psychiatric comorbidity. Seizures (17.5, 95% CI: 12.8-23.9) were the most common neurologic complications whereas encephalitis (0.5, 95% CI: 0.02-2.5) was rare. Mood disorders (17.5, 95% CI: 12.8-23.9) were the most frequent psychiatric complications and self-harm events (0.9, 95% CI: 0.3-3.3) were the least common. DISCUSSION: Our findings reveal that the incidence of neuropsychiatric complications of influenza is overall low; however, the incidence among children with underlying neurologic or psychiatric condition is significantly higher than among children without these conditions.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

Prognostic clinical decision support for pneumonia in the emergency department: A randomized trial.

BACKGROUND: Hospitalization rates for childhood pneumonia vary widely. Risk-based clinical decision support (CDS) interventions may reduce unwarranted variation. METHODS: We conducted a pragmatic randomized trial in two US pediatric emergency departments (EDs) comparing electronic health record (EHR)-integrated prognostic CDS versus usual care for promoting appropriate ED disposition in children (<18 years) with pneumonia. Encounters were randomized 1:1 to usual care versus custom CDS featuring a validated pneumonia severity score predicting risk for severe in-hospital outcomes. Clinicians retained full decision-making authority. The primary outcome was inappropriate ED disposition, defined as early transition to lower- or higher-level care. Safety and implementation outcomes were also evaluated. RESULTS: The study enrolled 536 encounters (269 usual care and 267 CDS). Baseline characteristics were similar across arms. Inappropriate disposition occurred in 3% of usual care encounters and 2% of CDS encounters (adjusted odds ratio: 0.99, 95% confidence interval: [0.32, 2.95]) Length of stay was also similar and adverse safety outcomes were uncommon in both arms. The tool's custom user interface and content were viewed as strengths by surveyed clinicians (>70% satisfied). Implementation barriers include intrinsic (e.g., reaching the right person at the right time) and extrinsic factors (i.e., global pandemic). CONCLUSIONS: EHR-based prognostic CDS did not improve ED disposition decisions for children with pneumonia. Although the intervention's content was favorably received, low subject accrual and workflow integration problems likely limited effectiveness. Clinical Trials Registration: NCT06033079.

Estimating the Undetected Burden of Respiratory Syncytial Virus Hospitalizations in Adults Through Capture-Recapture Methods.

INTRODUCTION: Traditional surveillance systems may underestimate the burden caused by respiratory syncytial virus (RSV). Capture-recapture methods provide alternatives for estimating the number of RSV-related hospitalizations in a population. METHODS: Capture-recapture methods were used to estimate the number of RSV-related hospitalizations in adults in Middle Tennessee from two independent hospitalization surveillance systems during consecutive respiratory seasons from 2016-2017 to 2019-2020. Data from the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the Emerging Infections Program (EIP) were used. Annual RSV hospitalization rates were calculated using the capture-recapture estimates weighted by hospitals' market share divided by the corresponding census population. RESULTS: Using capture-recapture methods, the estimated overall adult hospitalization rates varied from 8.3 (95% CI: 5.9-15.4) RSV-related hospitalizations per 10,000 persons during the 2016-2017 season to 28.4 (95% CI: 18.2-59.0) hospitalizations per 10,000 persons in the 2019-2020 season. The proportion of hospitalizations that HAIVEN determined ranged from 8.7% to 36.7% of the total capture-recapture estimated hospitalization, whereas EIP detected 23.5% to 52.7% of the total capture-recapture estimated hospitalizations. CONCLUSION: Capture-recapture estimates showed that individual traditional surveillance systems underestimated the hospitalization burden in adults. Using capture-recapture allows for a more comprehensive estimate of RSV hospitalizations.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Accuracy of Influenza ICD-10 Diagnosis Codes in Identifying Influenza Illness in Children.

Importance: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown. Objective: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings. Design, Setting, and Participants: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 US pediatric medical centers affiliated with the Centers for Disease Control and Prevention-sponsored New Vaccine Surveillance Network from December 1, 2016, to March 31, 2020, were included in this cohort study. Nasal and/or throat swabs were collected for research molecular testing for influenza, regardless of clinical testing. Data, including ICD-10 discharge diagnoses and clinical testing for influenza, were obtained through medical record review. Data analysis was performed in August 2023. Main Outcomes and Measures: The accuracy of ICD-10-coded discharge diagnoses was characterized using molecular clinical or research laboratory test results as reference. Measures included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Estimates were stratified by setting (ED vs inpatient) and age (0-1, 2-4, and 5-17 years). Results: A total of 16 867 children in the ED (median [IQR] age, 2.0 [0.0-4.0] years; 9304 boys [55.2%]) and 17 060 inpatients (median [IQR] age, 1.0 [0.0-4.0] years; 9798 boys [57.4%]) were included. In the ED, ICD-10 influenza diagnoses were highly specific (98.0%; 95% CI, 97.8%-98.3%), with high PPV (88.6%; 95% CI, 88.0%-89.2%) and high NPV (85.9%; 95% CI, 85.3%-86.6%), but sensitivity was lower (48.6%; 95% CI, 47.6%-49.5%). Among inpatients, specificity was 98.2% (95% CI, 98.0%-98.5%), PPV was 82.8% (95% CI, 82.1%-83.5%), sensitivity was 70.7% (95% CI, 69.8%-71.5%), and NPV was 96.5% (95% CI, 96.2%-96.9%). Accuracy of ICD-10 diagnoses varied by patient age, influenza season definition, time between disease onset and testing, and clinical setting. Conclusions and Relevance: In this large cohort study, influenza ICD-10 discharge diagnoses were highly specific but moderately sensitive in identifying laboratory-confirmed influenza; the accuracy of influenza diagnoses varied by clinical and epidemiological factors. In the ED and inpatient settings, an ICD-10 diagnosis likely represents a true-positive influenza case.

SARS-CoV-2 Viral Shedding and Rapid Antigen Test Performance - Respiratory Virus Transmission Network, November 2022-May 2023.

As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test).

Impact of respiratory viral infections on nasopharyngeal pneumococcal colonization dynamics in children.

PURPOSE OF REVIEW: Prevention of acute respiratory illnesses (ARI) in children is a global health priority, as these remain a leading cause of pediatric morbidity and mortality throughout the world. As new products and strategies to prevent respiratory infections caused by important pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, respiratory syncytial virus and pneumococcus are advancing, increasing evidence suggests that these and other respiratory viruses and pneumococci may exhibit interactions that are associated with altered colonization and disease dynamics. We aim to review recent data evaluating interactions between respiratory viruses and pneumococci in the upper respiratory tract and their potential impact on pneumococcal colonization patterns and disease outcomes. RECENT FINDINGS: While interactions between influenza infection and subsequent increased susceptibility and transmissibility of colonizing pneumococci have been widely reported in the literature, emerging evidence suggests that human rhinovirus, SARS-CoV-2, and other viruses may also exhibit interactions with pneumococci and alter pneumococcal colonization patterns. Additionally, colonizing pneumococci may play a role in modifying outcomes associated with respiratory viral infections. Recent evidence suggests that vaccination with pneumococcal conjugate vaccines, and prevention of colonization with pneumococcal serotypes included in these vaccines, may be associated with reducing the risk of subsequent viral infection and the severity of the associated illnesses. SUMMARY: Understanding the direction and dynamics of viral-pneumococcal interactions may elucidate the potential effects of existing and emerging viral and bacterial vaccines and other preventive strategies on the health impact of these important respiratory pathogens.

Prescription Opioid Exposure During Pregnancy and Risk of Spontaneous Preterm Delivery.

Importance: Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose. Objective: To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent. Design, Setting, and Participants: This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date). Exposure: Total opioid MME filled during the 60 days prior to the index date. Main Outcomes and Measures: The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications. Results: A total of 25 391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14 748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225 696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89 819 Black [39.8%], 3590 Hispanic [1.6%]; 132 002 non-Hispanic White [58.5%]) (251 087 patients total), with 18 702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08). Conclusions and Relevance: In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021-June 2022.

BACKGROUND: We assessed associations between binding antibody (bAb) concentration <5 days of symptom onset and testing positive for COVID-19 among patients in a test-negative study. METHODS: From October 2021─June 2022, study sites in seven states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent change in odds of COVID-19 by increasing anti-RBD bAb was estimated using logistic regression as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. RESULTS: Out of 2,018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb were lower among COVID-19 cases than SARS-CoV-2 test-negative patients during both the Delta-predominant (112 vs. 498 BAU/mL) and Omicron-predominant (823 vs. 1,189 BAU/mL) periods. Acute phase ancestral spike RBD bAb associated with 50% lower odds of COVID-19 were 1,968 BAU/mL against Delta and 3,375 BAU/mL against Omicron; thresholds may differ in other laboratories. CONCLUSION: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.

SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis.

BACKGROUND: Prolonged SARS-CoV-2 infections in people who are immunocompromised might predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection have not been systematically investigated. We aimed to assess risk factors for prolonged SARS-CoV-2 infection and associated intrahost evolution. METHODS: In this multicentre, prospective analysis, participants were enrolled at five US medical centres. Eligible patients were aged 18 years or older, were SARS-CoV-2-positive in the previous 14 days, and had a moderately or severely immunocompromising condition or treatment. Nasal specimens were tested by real-time RT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. FINDINGS: From April 11, 2022, to Oct 1, 2022, 156 patients began the enrolment process, of whom 150 were enrolled and included in the analyses. Participants had B-cell malignancy or anti-B-cell therapy (n=18), solid organ transplantation or haematopoietic stem-cell transplantation (HSCT; n=59), AIDS (n=5), non-B-cell malignancy (n=23), and autoimmune or autoinflammatory conditions (n=45). 38 (25%) participants were real-time RT-PCR-positive and 12 (8%) were culture-positive 21 days or longer after initial SARS-CoV-2 detection or illness onset. Compared with the group with autoimmune or autoinflammatory conditions, patients with B-cell dysfunction (adjusted hazard ratio 0·32 [95% CI 0·15-0·64]), solid organ transplantation or HSCT (0·60 [0·38-0·94]), and AIDS (0·28 [0·08-1·00]) had longer duration of infection, defined as time to last positive real-time RT-PCR test. There was no significant difference in the non-B-cell malignancy group (0·58 [0·31-1·09]). Consensus de novo spike mutations were identified in five individuals who were real-time RT-PCR-positive longer than 56 days; 14 (61%) of 23 were in the receptor-binding domain. Mutations shared by multiple individuals were rare (<5%) in global circulation. INTERPRETATION: In this cohort, prolonged replication-competent omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting longer than 56 days accumulated spike mutations, which were distinct from those seen globally. Populations at high risk should be targeted for repeated testing and treatment and monitored for the emergence of antiviral resistance. FUNDING: US Centers for Disease Control and Prevention.

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Sex differences in COVID-19 symptom severity and trajectories among ambulatory adults.

Background: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood. Methods: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model. Results: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males (p < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed. Conclusions: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males.

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.

Trends in Outpatient Influenza Antiviral Use Among Children and Adolescents in the United States.

BACKGROUND: Influenza antivirals improve outcomes in children with duration of symptoms <2 days and those at high risk for influenza complications. Real-world prescribing of influenza antivirals in the pediatric population is unknown. METHODS: We performed a cross-sectional study of outpatient and emergency department prescription claims in individuals <18 years of age included in the IBM Marketscan Commercial Claims and Encounters Database between July 1, 2010 and June 30, 2019. Influenza antiviral use was defined as any dispensing of oseltamivir, baloxavir, or zanamivir. The primary outcome was the rate of antiviral dispensing per 1000 enrolled children. Secondary outcomes included antiviral dispensing per 1000 influenza diagnoses and inflation-adjusted costs of antiviral agents. Outcomes were calculated and stratified by age, acute versus prophylactic treatment, influenza season, and geographic region. RESULTS: The analysis included 1 416 764 unique antiviral dispensings between 2010 and 2019. Oseltamivir was the most frequently prescribed antiviral (99.8%). Dispensing rates ranged from 4.4 to 48.6 per 1000 enrolled children. Treatment rates were highest among older children (12-17 years of age), during the 2017 to 2018 influenza season, and in the East South Central region. Guideline-concordant antiviral use among young children (<2 years of age) at a high risk of influenza complications was low (<40%). The inflation-adjusted cost for prescriptions was $208 458 979, and the median cost ranged from $111 to $151. CONCLUSIONS: There is wide variability and underuse associated with influenza antiviral use in children. These findings reveal opportunities for improvement in the prevention and treatment of influenza in children.

Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021-June 2022.

To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.