Treatment of COVID-19 symptoms with over the counter (OTC) medicines used for treatment of common cold and flu.

Persons suffering from acute upper respiratory tract viral infections (URTI) commonly use over the counter (OTC) medicines to relieve symptoms such as fever, muscle aches, cough, runny nose, sore throat and nasal congestion. At present OTC medicines are only licensed for treatment of common cold and flu symptoms and not for treatment of the same symptoms associated with COVID-19. The innate immune response responsible for the mechanisms of the symptoms of URTI is the same for all respiratory viruses including SARS-CoV-2 and these symptoms can be relieved by treatment with the same OTC medicines as available for treatment of colds and flu. This review provides scientific information that OTC treatments for common cold and flu-like illness caused by respiratory viruses are safe and effective treatments for the same symptoms associated with COVID-19.

SARS-CoV-2 Screening Testing Program for Safe In-person Learning in K-12 Schools.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing is a recommended mitigation strategy for schools, although few descriptions of program implementation are available. METHODS: Kindergarten through 12th grade (K-12) students and staff practicing universal masking during the delta and omicron variant waves from 5 schools in Durham, North Carolina and 8 in Kansas City, Missouri participated; Durham's program was structured as a public health initiative facilitated by school staff, and Kansas City's as a research study facilitated by a research team. Tests included school-based rapid antigen or polymerase chain reaction testing, at-home rapid antigen testing, and off-site nucleic acid amplification testing. RESULTS: We performed nearly 5,700 screening tests on more than 1,600 K-12 school students and staff members. The total cost for the Durham testing program in 5 public charter K-12 schools, each with 500-1000 students, was $246,587 and approximately 752 hours per semester; cost per test was $70 and cost per positive result was $7,076. The total cost for the Kansas City program in 8 public K-12 schools was $292,591 and required approximately 537 hours in personnel time for school-based testing; cost per test was $132 and cost per positive result was $4,818. SARS-CoV-2 positivity rates were generally lower (0-16.16%) than rates in the community (2.7-36.47%) throughout all testing weeks. CONCLUSIONS AND RELEVANCE: Voluntary screening testing programs in K-12 schools are costly and rarely detect asymptomatic positive persons, particularly in universally masked settings.

Circulation of Rhinoviruses and/or Enteroviruses in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US.

Importance: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting. Objective: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals. Design, Setting, and Participants: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought medical care for fever and/or respiratory symptoms at 7 EDs or hospitals within NVSN across the US between December 2016 and February 2021. Persons younger than 18 years were enrolled in NVSN, and respiratory specimens were collected and tested for multiple viruses. Main Outcomes and Measures: Proportion of patients in whom rhinovirus and/or enterovirus, or another virus, was detected by calendar month and by prepandemic (December 1, 2016, to March 11, 2020) or pandemic (March 12, 2020, to February 28, 2021) periods. Month-specific adjusted odds ratios (aORs) for rhinovirus and/or enterovirus-positive test results (among all tested) by setting (ED or inpatient) and age group (<2, 2-4, or 5-17 years) were calculated, comparing each month during the pandemic to equivalent months of previous years. Results: Of the 38 198 children and adolescents who were enrolled and tested, 11 303 (29.6%; mean [SD] age, 2.8 [3.7] years; 6733 boys [59.6%]) had rhinovirus and/or enterovirus-positive test results. In prepandemic and pandemic periods, rhinoviruses and/or enteroviruses were detected in 29.4% (9795 of 33 317) and 30.9% (1508 of 4881) of all patients who were enrolled and tested and in 42.2% (9795 of 23 236) and 73.0% (1508 of 2066) of those with test positivity for any virus, respectively. Rhinoviruses and/or enteroviruses were the most frequently detected viruses in both periods and all age groups in the ED and inpatient setting. From April to September 2020 (pandemic period), rhinoviruses and/or enteroviruses were detectable at similar or lower odds than in prepandemic years, with aORs ranging from 0.08 (95% CI, 0.04-0.19) to 0.76 (95% CI, 0.55-1.05) in the ED and 0.04 (95% CI, 0.01-0.11) to 0.71 (95% CI, 0.47-1.07) in the inpatient setting. However, unlike some other viruses, rhinoviruses and/or enteroviruses soon returned to prepandemic levels and from October 2020 to February 2021 were detected at similar or higher odds than in prepandemic months in both settings, with aORs ranging from 1.47 (95% CI, 1.12-1.93) to 3.01 (95% CI, 2.30-3.94) in the ED and 1.36 (95% CI, 1.03-1.79) to 2.44 (95% CI, 1.78-3.34) in the inpatient setting, and in all age groups. Compared with prepandemic years, during the pandemic, rhinoviruses and/or enteroviruses were detected in patients who were slightly older, although most (74.5% [1124 of 1508]) were younger than 5 years. Conclusions and Relevance: Results of this study show that rhinoviruses and/or enteroviruses persisted and were the most common respiratory virus group detected across all pediatric age groups and in both ED and inpatient settings. Rhinoviruses and/or enteroviruses remain a leading factor in ARI health care burden, and active ARI surveillance in children and adolescents remains critical for defining the health care burden of respiratory viruses.

Disruption of seasonal enterovirus and parechovirus detections in the CSF and plasma of children during the COVID-19 pandemic.

BACKGROUND: Enteroviruses (EV) and parechovirus (PeV) are a common cause of CNS infection in children. Both viruses demonstrate consistent seasonal patterns, with detections mainly in the summer-fall months. While research has shown COVID-19 pandemic-related disruption of traditional seasonality of respiratory pathogens, the pandemic's impact on non-respiratory pathogens is less understood. The aim of this study was to quantify the EV/PeV seasonal variations during pre-COVID years compared to variations observed during the COVID pandemic. METHODS: Patients with EV/PeV testing of CSF/plasma between January 2012 through September 2022 were identified. Restricted cubic spline methods were used to model the detections. Poisson models were utilized to model pre-COVID (2012-2019) EV/PeV detections. The expected seasonal trends from these models were then compared to the observed EV/PeV detections during the COVID pandemic (2020-2022). RESULTS: A total of 5199 patients were included. The annual pre-pandemic proportion of EV detections ranged between 7.5%-20.3%. PeV exhibited a biennial pattern with peak proportions between 8.0%-16.3%. EV/PeV detections during the COVID pandemic period, especially during 2020 and 2021, were considerably lower than would have been expected based on pre-pandemic modeling. However, PeV detections from January through September 2022 nearly reached the pre-pandemic modeled expectation, including instances of exceeded expectations. CONCLUSIONS: A significant disruption in expected seasonal EV/PeV detections was observed during the early phases of the COVID-19 pandemic. However, testing that occurred during summer-fall of 2022, when social mitigation initiatives were relaxed, showed a rapid increase in detections. Additional data are needed to further understand which public health initiatives are effective at decreasing EV/PeV transmission.

Humoral and cellular response to the COVID-19 vaccine in immunocompromised children.

BACKGROUND: A suboptimal response to the 2-dose COVID-19 vaccine series in the immunocompromised population prompted recommendations for a 3rd primary dose. We aimed to determine the humoral and cellular immune response to the 3rd COVID-19 vaccine in immunocompromised children. METHODS: Prospective cohort study of immunocompromised participants, 5-21 years old, who received 2 prior doses of an mRNA COVID-19 vaccine. Humoral and CD4/CD8 T-cell responses were measured to SARS-CoV-2 spike antigens prior to receiving the 3rd vaccine dose and 3-4 weeks after the 3rd dose was given. RESULTS: Of the 37 participants, approximately half were solid organ transplant recipients. The majority (86.5%) had a detectable humoral response after the 2nd and 3rd vaccine doses, with a significant increase in antibody levels after the 3rd dose. Positive T-cell responses increased from being present in 86.5% to 100% of the cohort after the 3rd dose. CONCLUSIONS: Most immunocompromised children mount a humoral and cellular immune response to the 2-dose COVID-19 vaccine series, which is significantly augmented after receiving the 3rd vaccine dose. This supports the utility of the 3rd vaccine dose and the rationale for ongoing emphasis for vaccination against COVID-19 in this population. IMPACT: Most immunocompromised children mount a humoral and cellular immune response to the 2-dose COVID-19 vaccine series, which is significantly augmented after receiving the 3rd vaccine dose. This is the first prospective cohort study to analyze both the humoral and T-cell immune response to the 3rd COVID-19 primary vaccine dose in children who are immunocompromised. The results of this study support the utility of the 3rd vaccine dose and the rationale for ongoing emphasis for vaccination against COVID-19 in the immunosuppressed pediatric population.

Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021.

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years† with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.

Comparative analysis of three multiplex platforms for the detection of respiratory viral pathogens.

BACKGROUND: Acute viral respiratory infections are a major health burden in children worldwide. In recent years, rapid and sensitive multiplex nucleic acid amplification tests (NAATs) have replaced conventional methods for routine virus detection in the clinical laboratory. OBJECTIVE/STUDY DESIGN: We compared BioFire® FilmArray® Respiratory Panel (FilmArray V1.7), Luminex NxTag® Respiratory Pathogen Panel (NxTag RPP) and Applied Biosystems TaqMan Array Card (TAC) for the detection of eight viruses in pediatric respiratory specimens. Results from the three platforms were analyzed with a single-plex real-time RT-PCR (rRT-PCR) assay for each virus. RESULTS: Of the 170/210 single-plex virus-positive samples, FilmArray detected a virus in 166 (97.6%), TAC in 163 (95.8%) and NxTag RPP in 160 (94.1%) samples. The Positive Percent Agreement (PPA) of FilmArray, NxTag RPP and TAC was highest for influenza B (100%, 100% and 95.2% respectively) and lowest for seasonal coronaviruses on both FilmArray (90.2%) and NxTag RPP (81.8%), and for parainfluenza viruses 1- 4 on TAC (84%). The Negative Percent Agreement (NPA) was lowest for rhinovirus/enterovirus (92.9%, 96.7% and 97.3%) on FilmArray, NxTag RPP and TAC respectively. NPA for all three platforms was highest (100%) for both parainfluenza viruses 1- 4 and influenza A and B, and 100% for human metapneumovirus with TAC as well. CONCLUSION: All three multiplex platforms displayed high overall agreement (>90%) and high NPA (>90%), while PPA was pathogen dependent and varied among platforms; high PPA (>90%) was observed for FilmArray for all eight viruses, TAC for six viruses and NxTag RPP for 4 viruses.

Cepheid Xpert Xpress Flu/RSV evaluation performed by minimally trained non-laboratory operators in a CLIA-waived environment.

The COVID-19 pandemic highlighted the significance of readily available and easily performed viral testing for surveillance during future infectious pandemics. The objectives of this study were: to assess the performance of the Xpert Xpress Flu and/or RSV test, a multiplex PCR assay for detecting influenza A and B virus and respiratory syncytial virus nucleic acids in respiratory tract specimens, relative to the Quidel Lyra Influenza A+B assay and the Prodesse ProFlu+ assay, and the system's ease of use by minimally trained operators. Overall, the Xpert Xpress Flu/RSV test demonstrated a high positive and negative percent agreement with the comparator assays, and was easy to use and interpret results, based on the operators' feedback. We concluded that the Xpert Xpress Flu/RSV test is sensitive, specific, and easy to use for the diagnosis of influenza and RSV by minimally trained operators and can be a valuable tool in future infectious clusters or pandemics.

Cross-reactive antibodies elicited to conserved epitopes on SARS-CoV-2 spike protein after infection and vaccination.

SARS-CoV-2 is a novel betacoronavirus that caused coronavirus disease 2019 and has resulted in millions of deaths worldwide. Novel coronavirus infections in humans have steadily become more common. Understanding antibody responses to SARS-CoV-2, and identifying conserved, cross-reactive epitopes among coronavirus strains could inform the design of vaccines and therapeutics with broad application. Here, we determined that individuals with previous SARS-CoV-2 infection or vaccinated with the Pfizer-BioNTech BNT162b2 vaccine produced antibody responses that cross-reacted with related betacoronaviruses. Moreover, we designed a peptide-conjugate vaccine with a conserved SARS-CoV-2 S2 spike epitope, immunized mice and determined cross-reactive antibody binding to SARS-CoV-2 and other related coronaviruses. This conserved spike epitope also shared sequence homology to proteins in commensal gut microbiota and could prime immune responses in humans. Thus, SARS-CoV-2 conserved epitopes elicit cross-reactive immune responses to both related coronaviruses and host bacteria that could serve as future targets for broad coronavirus therapeutics and vaccines.

Differences in pediatric SARS-CoV-2 symptomology and Co-infection rates among COVID-19 Pandemic waves.

An estimated 12.8 million pediatric SARS-CoV-2 infections have occurred within the United States as of March 1 2022, with multiple epidemic waves due to emergence of several SARS-CoV-2 variants. The aim of this study was to compare demographics, clinical presentation, and detected respiratory co-infections during COVID-19 waves to better understand changes in pediatric SARS-CoV-2 epidemiology over time.

Vaccination After SARS-CoV-2 Infection Increased Antibody Avidity Against the Omicron Variant Compared to Vaccination Alone.

The SARS-CoV-2 Omicron variant has caused infections among individuals vaccinated or with prior COVID-19, suggesting immune escape. Here, we showed a decrease in binding and surrogate neutralizing antibody responses to the Omicron variant after 2 doses of the Pfizer COVID-19 mRNA vaccine. Individuals recovered from infection before vaccination had higher antibody levels and avidity to the Omicron variant compared to individuals vaccinated without infection. This suggested that COVID-19 infection before vaccination elicited a higher magnitude and affinity antibody response to the Omicron variant, and repeated exposure through infection or vaccine may be required to improve immunity to emerging SARS-CoV-2 variants.

The Impact of Prior Infection and Age on Antibody Persistence After Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine.

Determining the duration of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is critical for informing the timing of booster immunization. Many genetic and environmental factors could influence both the magnitude and persistence of the antibody response. Here, we showed that SARS-CoV-2 infection before vaccination and age affected the decay of antibody responses to the SARS-CoV-2 messenger RNA vaccine.

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged <18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers† within the New Vaccine Surveillance Network (NVSN) were summarized. This report provides a provisional description of EV-D68 detections during July-November in 2018, 2019 and 2020, and describes the demographic and clinical characteristics of these patients. In 2018, a total of 382 EV-D68 detections in respiratory specimens obtained from patients aged <18 years with ARI were reported by NVSN; the number decreased to six detections in 2019 and 30 in 2020. Among patients aged <18 years with EV-D68 in 2020, 22 (73%) were non-Hispanic Black (Black) persons. EV-D68 detections in 2020 were lower than anticipated based on the biennial circulation pattern observed since 2014. The circulation of EV-D68 in 2020 might have been limited by widespread COVID-19 mitigation measures; how these changes in behavior might influence the timing and levels of circulation in future years is unknown. Ongoing monitoring of EV-D68 detections is warranted for preparedness for EV-D68-associated ARI and AFM.

Humoral immune responses during SARS-CoV-2 mRNA vaccine administration in seropositive and seronegative individuals.

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) is caused by infection with the SARS-CoV-2 virus. Currently, there are three approved vaccines against SARS-CoV-2 in the USA, including two based on messenger RNA (mRNA) technology that has demonstrated high vaccine efficacy. We sought to characterize humoral immune responses, at high resolution, during immunization with the BNT162b2 (Pfizer-BioNTech) vaccine in individuals with or without prior history of natural SARS-CoV-2 infection. METHODS: We determined antibody responses after each dose of the BNT162b2 SARS-CoV-2 vaccine in individuals who had no prior history of SARS-CoV-2 infection (seronegative) and individuals that had previous viral infection 30-60 days prior to first vaccination (seropositive). To do this, we used both an antibody isotype-specific multiplexed bead-based binding assays targeting multiple SARS-CoV-2 viral protein antigens and an assay that identified potential SARS-CoV-2 neutralizing antibody levels. Moreover, we mapped antibody epitope specificity after immunization using SARS-CoV-2 spike protein peptide arrays. RESULTS: Antibody levels were significantly higher after a single dose in seropositive individuals compared to seronegative individuals and were comparable to levels observed in seronegative individuals after two doses. While IgG was boosted by vaccination for both seronegative and seropositive individuals, only seronegative individuals had increased IgA or IgM antibody titers after primary immunization. We identified immunodominant peptides targeted on both SARS-CoV-2 spike S1 and S2 subunits after vaccination. CONCLUSION: These findings demonstrated the antibody responses to SARS-CoV-2 immunization in seropositive and seronegative individuals and provide support for the concept of using prior infection history as a guide for the consideration of future vaccination regimens. Moreover, we identified key epitopes on the SARS-CoV-2 spike protein that are targeted by antibodies after vaccination that could guide future vaccine and immune correlate development.

Diagnostic Yield of Saliva for SARS-CoV-2 Molecular Testing in Children.

Pediatric saliva specimen demonstrated high sensitivity (93%) and specificity (96.2%) compared to paired nasopharyngeal swabs (NPS) by Aptima SARS-CoV-2 Assay (Aptima). Viral loads were comparable in both specimen types. Saliva is a safe, noninvasive, and acceptable alternative specimen for SARS-CoV-2 detection in children.

Acute Respiratory Illnesses in Children During the sars-cov-2 Pandemic: A Prospective Multicenter Surveillance Study

Background: A state of emergency was declared in the United States (US) on March 13, 2020 in response to the SARS-CoV-2 pandemic. Healthcare providers had to alter practice patterns and research priorities. We assessed the frequency of acute respiratory illnesses (ARI) in children, notably those due to respiratory syncytial virus (RSV) and influenza, before and during the pandemic. Methods: We conducted multi-center active prospective ARI surveillance in children as part of the New Vaccine Surveillance Network. Children < 18 years with fever and/or respiratory symptoms were enrolled in emergency department and inpatient settings at seven US medical centers over four respiratory seasons during 2016-2020 (Fig 1). Pandemic-related restrictions to patient access limited enrollment in some sites beginning March 2020. Respiratory specimens were collected and tested at each site for RSV and influenza by qRT-PCR. Data were analyzed by calendar weeks. We compared the cumulative proportions of RSV and influenza detection after week 13 in 2020 to the previous seasons using Fisher's exact test. Results: Of 44,247 eligible children, 25,375 (57%) were enrolled and tested for RSV and/or influenza. A total of 6351/25375 (25%) and 3446/25372 (14%) children were RSV and influenza-positive over the four seasons, respectively. In 2020, we noted a rapid drop in eligible and enrolled ARI subjects after weeks 11-13 (Fig 1). During weeks 13-18 in 2016-2019, the three-year average of eligible and enrolled subjects was 1802 and 978, respectively. However, over the same period in 2020, there were 675 eligible and 278 enrolled subjects, representing declines of 62.5% and 71.6% respectively (Fig 1). In 2020, there were no RSV or influenza cases detected in weeks 15-18, and the cumulative proportions of RSV and influenza detection after week 13 were lower compared to previous seasons (p< 0.001) (Figs 1 and 2). Conclusion: There was a considerable decline in ARI visits and the proportion of RSV and influenza detection across seven distinct geographic sites during the pandemic compared with previous seasons. These findings might be attributable to social distancing measures to lessen the spread of SARS-CoV-2, changes in healthcare-seeking behaviors, and limited access to medical care. (Table Presented).

Comparison of diagnostic performance of five molecular assays for detection of SARS-CoV-2.

We compared the performance of the Abbott Real Time SARS-CoV-2 assay (Abbott assay), Aptima™ SARS-CoV-2 assay (Aptima assay), BGI Real-Time SARS-CoV-2 assay (BGI assay), Lyra® SARS-CoV-2 assay (Lyra assay), and DiaSorin Simplexa™ COVID assay for SARS-CoV-2 detection. Residual nasopharyngeal samples (n = 201) submitted for routine SARS-CoV-2 testing by Simplexa assay during June-July 2020 and January 2021 were salvaged. Aliquots were tested on other assays and compared against the CDC 2019-nCoV Real-Time RT-PCR assay. Viral load in positive samples was determined by droplet digital PCR. Among 201 samples, 99 were positive and 102 were negative by the CDC assay. The Aptima and Abbott assays exhibited the highest positive percent agreement (PPA) at 98.9% while the BGI assay demonstrated the lowest PPA of 89.9% with 10 missed detections. Negative percent agreement for all 5 platforms was comparable, ranging from 96.1% to 100%. The performance of all five assays was comparable.

Immune cell residency in the nasal mucosa may partially explain respiratory disease severity across the age range.

Previous studies focusing on the age disparity in COVID-19 severity have suggested that younger individuals mount a more robust innate immune response in the nasal mucosa after infection with SARS-CoV-2. However, it is unclear if this reflects increased immune activation or increased immune residence in the nasal mucosa. We hypothesized that immune residency in the nasal mucosa of healthy individuals may differ across the age range. We applied single-cell RNA-sequencing and measured the cellular composition and transcriptional profile of the nasal mucosa in 35 SARS-CoV-2 negative children and adults, ranging in age from 4 months to 65 years. We analyzed in total of ~ 30,000 immune and epithelial cells and found that age and immune cell proportion in the nasal mucosa are inversely correlated, with little evidence for structural changes in the transcriptional state of a given cell type across the age range. Orthogonal validation by epigenome sequencing indicate that it is especially cells of the innate immune system that underlie the age-association. Additionally, we characterize the predominate immune cell type in the nasal mucosa: a resident T cell like population with potent antiviral properties. These results demonstrate fundamental changes in the immune cell makeup of the uninfected nasal mucosa over the lifespan. The resource we generate here is an asset for future studies focusing on respiratory infection and immunization strategies.

Acute Respiratory Illnesses in Children in the SARS-CoV-2 Pandemic: Prospective Multicenter Study.

OBJECTIVES: Nonpharmaceutical interventions against coronavirus disease 2019 likely have a role in decreasing viral acute respiratory illnesses (ARIs). We aimed to assess the frequency of respiratory syncytial virus (RSV) and influenza ARIs before and during the coronavirus disease 2019 pandemic. METHODS: This study was a prospective, multicenter, population-based ARI surveillance, including children seen in the emergency departments and inpatient settings in 7 US cities for ARI. Respiratory samples were collected and evaluated by molecular testing. Generalized linear mixed-effects models were used to evaluate the association between community mitigation and number of eligible and proportion of RSV and influenza cases. RESULTS: Overall, 45 759 children were eligible; 25 415 were enrolled and tested; 25% and 14% were RSV-positive and influenza-positive, respectively. In 2020, we noted a decrease in eligible and enrolled ARI subjects after community mitigation measures were introduced, with no RSV or influenza detection from April 5, 2020, to April 30, 2020. Compared with 2016-2019, there was an average of 10.6 fewer eligible ARI cases per week per site and 63.9% and 45.8% lower odds of patients testing positive for RSV and influenza, respectively, during the 2020 community mitigation period. In all sites except Seattle, the proportions of positive tests for RSV and influenza in the 2020 community mitigation period were lower than predicted. CONCLUSIONS: Between March and April 2020, rapid declines in ARI cases and the proportions of RSV and influenza in children were consistently noted across 7 US cities, which could be attributable to community mitigation measures against severe acute respiratory syndrome coronavirus 2.