Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Responses After Community Infections in Children and Adults.

Background: We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated. Methods: During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models. Results: Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178). Conclusions: The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination.

Epidemiology of Human Parainfluenza Virus Type 3 and Respiratory Syncytial Virus Infections in the Time of Coronavirus Disease 2019: Findings From a Household Cohort in Maryland.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, human parainfluenza type 3 (HPIV-3) and respiratory syncytial virus (RSV) circulation increased as nonpharmaceutical interventions were relaxed. Using data from 175 households (n = 690 members) followed between November 2020 and October 2021, we characterized HPIV-3 and RSV epidemiology in children aged 0-4 years and their households. METHODS: Households with ≥1 child aged 0-4 years were enrolled; members collected weekly nasal swabs (NS) and additional NS with respiratory illnesses (RI). We tested NS from RI episodes in children aged 0-4 years for HPIV-3, RSV, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse-transcriptase polymerase chain reaction (RT-PCR). Among children with HPIV-3 or RSV infection, we tested contemporaneous NS from household members. We compared incidence rates (IRs) of RI with each virus during epidemic periods and identified household primary cases (the earliest detected household infection), and associated community exposures. RESULTS: 41 of 175 (23.4%) households had individuals with HPIV-3 (n = 45) or RSV (n = 46) infections. Among children aged 0-4 years, RI IRs /1000 person-weeks were 8.7 [6.0, 12.2] for HPIV-3, 7.6 [4.8, 11.4] for RSV, and 1.9 [1.0, 3.5] for SARS-CoV-2. Children aged 0-4 years accounted for 35 of 36 primary HPIV-3 or RSV cases. Children attending childcare or preschool had higher odds of primary infection (odds ratio, 10.81; 95% confidence interval, 3.14-37.23). CONCLUSIONS: Among children aged 0-4 years, RI IRs for HPIV-3 and RSV infection were 4-fold higher than for SARS-CoV-2 during epidemic periods. HPIV-3 and RSV were almost exclusively introduced into households by young children.

Factors Associated with Intention to Vaccinate Children 0-11 Years of Age Against COVID-19.

BACKGROUND: Millions of children have tested positive for SARS-CoV-2, and over 1000 children have died in the US. However, vaccination rates for children 5 to 11 years old are low. METHODS: Starting in August 2020, we conducted a prospective SARS-CoV-2 household surveillance study in Spanish and English-speaking households in New York City and Utah. From October 21 to 25, 2021, we asked caregivers about their likelihood of getting COVID-19 vaccine for their child, and reasons that they might or might not vaccinate that child. We compared intent to vaccinate by site, demographic characteristics, SARS-CoV-2 infection detected by study surveillance, and parents' COVID-19 vaccination status using Chi-square tests and a multivariable logistic regression model, accounting for within-household clustering. RESULTS: Among parents or caregivers of 309 children (0 to 11 years) in 172 households, 87% were very or somewhat likely to intend to vaccinate their child. The most prevalent reasons for intending to vaccinate were to protect family and friends and the community; individual prevention was mentioned less often. The most prevalent reasons for not intending to vaccinate were side effect concerns and wanting to wait and see.In multivariable analysis, parents had much lower odds of intending to vaccinate if someone in the household had tested SARS-CoV-2-positive during the study (adjusted odds ratio = 0.09; 95% confidence interval, 0.03-0.3). CONCLUSION: This study highlighted several themes for clinicians and public health officials to consider including the importance and safety of vaccination for this age-group even if infected previously, and the benefits of vaccination to protect family, friends, and community.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference.

The reliability of sequence-based inference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with a reverse transcription-PCR cycle threshold of ≤30 underwent whole-genome sequencing. Intrahost single-nucleotide variants (iSNV) were identified at a ≥5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole-genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had ≥1 consensus sequence that differed by 1 to 2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and in 6 of 11 with distinct ones. In multiple-infection households, whole-genome consensus sequences differed by 0 to 1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. IMPORTANCE We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.

Predictors of Severe Acute Respiratory Syndrome Coronavirus 2 Seropositivity Before Coronavirus Disease 2019 Vaccination Among Children 0-4 Years and Their Household Members in the SEARCh Study.

Background: Estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and risk factors for seropositivity are scarce. Using data from a prospective cohort study of households during the pre-coronavirus disease 2019 (COVID-19) vaccine period, we estimated SARS-CoV-2 seroprevalence by age and evaluated risk factors for SARS-CoV-2 seropositivity. Methods: The SARS-CoV-2 Epidemiology and Response in Children (SEARCh) study enrolled 175 Maryland households (690 participants) with ≥1 child aged 0-4 years during November 2020-March 2021; individuals vaccinated against COVID-19 were ineligible. At enrollment, participants completed questionnaires about sociodemographic and health status and work, school, and daycare attendance. Participants were tested for SARS-CoV-2 antibodies in sera. Logistic regression models with generalized estimating equations (GEE) to account for correlation within households assessed predictors of individual- and household-level SARS-CoV-2 seropositivity. Results: Of 681 (98.7%) participants with enrollment serology results, 55 (8.1%; 95% confidence interval [CI], 6.3%-10.4%) participants from 21 (12.0%) households were seropositive for SARS-CoV-2. Among seropositive participants, fewer children than adults reported being tested for SARS-CoV-2 infection before enrollment (odds ratio [OR] = 0.23; 95% CI, .06-.73). Seropositivity was similar by age (GEE OR vs 0-4 years: 1.19 for 5-17 years, 1.36 for adults; P = .16) and was significantly higher among adults working outside the home (GEE adjusted OR = 2.2; 95% CI, 1.1-4.4) but not among children attending daycare or school. Conclusions: Before study enrollment, children and adults in this cohort had similar rates of SARS-CoV-2 infection as measured by serology. An adult household member working outside the home increased a household's odds of SARS-CoV-2 infection, whereas a child attending daycare or school in person did not.

Assessment of Clinical and Virological Characteristics of SARS-CoV-2 Infection Among Children Aged 0 to 4 Years and Their Household Members.

Importance: Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies. Objective: To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults. Design, Setting, and Participants: This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment and at approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies. Main Outcomes and Measures: Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage. Results: Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R = 0.69; P < .001) but not children (ages 0-4 years: R = 0.02; P = .91; ages 5-17 years: R = 0.18; P = .58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P = .009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P = .006). Conclusions and Relevance: In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children.

Self-medication and ILI etiologies among individuals presenting at pharmacies with influenza-like illness: Guatemala City, 2018 influenza season.

OBJECTIVES: We aimed to characterize the proportion of clients presenting to community pharmacies with influenza-like illness (ILI) and the severity of their illness; the proportion with detectable influenza A, influenza B, and other pathogens (i.e., parainfluenza I, II, and III, adenovirus, respiratory syncytial virus, human metapneumovirus); and to describe their self-medication practices. METHODS: A cross-sectional study was conducted in six pharmacies in Guatemala City. Study personnel collected nasopharyngeal and oropharyngeal swabs from participants who met the ILI case definition and who were self-medicating for the current episode. Participants were tested for influenza A and B and other pathogens using real-time RT-PCR. Participants' ILI-associated self-medication practices were documented using a questionnaire. RESULTS: Of all patients entering the pharmacy during peak hours who responded to a screening survey (n = 18,016) 6% (n = 1029) self-reported ILI symptoms, of which 45% (n = 470/1029) met the study case definition of ILI. Thirty-one percent (148/470) met inclusion criteria, of which 87% (130/148) accepted participation and were enrolled in the study. Among 130 participants, nearly half tested positive for viral infection (n = 55, 42.3%) and belonged to groups at low risk for complications from influenza. The prevalence of influenza A was 29% (n = 35). Thirteen percent of the study population (n = 17) tested positive for a respiratory virus other than influenza. Sixty-four percent of participants (n = 83) reported interest in receiving influenza vaccination if it were to become available in the pharmacy. Medications purchased included symptom-relieving multi-ingredient cold medications (n = 43/100, 43%), nonsteroidal anti-inflammatory drugs (n = 23, 23%), and antibiotics (n = 16, 16%). Antibiotic use was essentially equal among antibiotic users regardless of viral status. The broad-spectrum antibiotics ceftriaxone and azithromycin were the most common antibiotics purchased. CONCLUSIONS: During a typical influenza season, a relatively low proportion of all pharmacy visitors were experiencing influenza symptoms. A high proportion of clients presenting to pharmacies with ILI tested positive for a respiratory virus. Programs that guide appropriate use of antibiotics in this population are needed and become increasingly important during pandemics caused by respiratory viral pathogens.

Impact of Age and Symptom Development on SARS-CoV-2 Transmission in Households With Children-Maryland, New York, and Utah, August 2020-October 2021.

Background: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. Methods: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. Results: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). Conclusions: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

Detection and Stability of SARS-CoV-2 in Three Self-Collected Specimen Types: Flocked Midturbinate Swab (MTS) in Viral Transport Media, Foam MTS, and Saliva.

Respiratory specimen collection materials shortages hampers severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We compared specimen alternatives and evaluated SARS-CoV-2 RNA stability under simulated shipping conditions. We compared concordance of RT-PCR detection of SARS-CoV-2 from flocked midturbinate swabs (MTS) in viral transport media (VTM), foam MTS without VTM, and saliva. Specimens were collected between August 2020 and April 2021 from three prospective cohorts. We compared RT-PCR cycle quantification (Cq) for Spike (S), Nucleocapsid (N), and the Open Reading Frame 1ab (ORF) genes for flocked MTS and saliva specimens tested before and after exposure to a range of storage temperatures (4-30°C) and times (2, 3, and 7 days). Of 1,900 illnesses with ≥2 specimen types tested, 335 (18%) had SARS-CoV-2 detected in ≥1 specimen; 304 (91%) were concordant across specimen types. Among illnesses with SARS-CoV-2 detection, 97% (95% confidence interval [CI]: 94-98%) were positive on flocked MTS, 99% (95% CI: 97-100%) on saliva, and 89% (95% CI: 84-93%) on foam MTS. SARS-CoV-2 RNA was detected in flocked MTS and saliva stored up to 30°C for 7 days. All specimen types provided highly concordant SARS-CoV-2 results. These findings support a range of viable options for specimen types, collection, and transport methods that may facilitate SARS-CoV-2 testing during supply and personnel shortages. IMPORTANCE Findings from this analysis indicate that (1) self-collection of flocked and foam MTS and saliva samples is feasible in both adults and children, (2) foam MTS with VTM and saliva are both viable and reasonable alternatives to traditional flocked MTS in VTM for SARS-CoV-2 detection, and (3) these sample types may be stored and transported at ambient temperatures for up to 7 days without compromising sample quality. These findings support methods of sample collection for SARS-CoV-2 detection that may facilitate widespread community testing in the setting of supply and personnel shortages during the current pandemic.

Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults.

BackgroundSARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children.MethodsWe compared receptor binding domain-binding antibody (RBDAb) titers and SARS-CoV-2-neutralizing antibody titers, measured by pseudovirus-neutralizing antibody assay in serum specimens obtained from children aged 0-4 years and 5-17 years and in adults aged 18-62 years at the time of enrollment in a prospective longitudinal household study of SARS-CoV-2 infection.ResultsAmong 56 seropositive participants at enrollment, children aged 0-4 years had more than 10-fold higher RBDAb titers than adults (416 vs. 31, P < 0.0001) and the highest RBDAb titers in 11 of 12 households with seropositive children and adults. Children aged 0-4 years had only 2-fold higher neutralizing antibody than adults, resulting in higher binding-to-neutralizing antibody ratios compared with adults (2.36 vs. 0.35 for ID50, P = 0.0004).ConclusionThese findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutralizing antibody to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years.FundingCDC (award 75D30120C08737).

Incidence Rates, Household Infection Risk, and Clinical Characteristics of SARS-CoV-2 Infection Among Children and Adults in Utah and New York City, New York.

Importance: Data about the risk of SARS-CoV-2 infection among children compared with adults are needed to inform COVID-19 risk communication and prevention strategies, including COVID-19 vaccination policies for children. Objective: To compare incidence rates and clinical characteristics of SARS-CoV-2 infection among adults and children and estimated household infection risks within a prospective household cohort. Design, Setting, and Participants: Households with at least 1 child aged 0 to 17 years in selected counties in Utah and New York City, New York, were eligible for enrollment. From September 2020 through April 2021, participants self-collected midturbinate nasal swabs for reverse transcription-polymerase chain reaction testing for SARS-CoV-2 and responded to symptom questionnaires each week. Participants also self-collected additional respiratory specimens with onset of COVID-19-like illness. For children unable to self-collect respiratory specimens, an adult caregiver collected the specimens. Main Outcomes and Measures: The primary outcome was incident cases of any SARS-CoV-2 infection, including asymptomatic and symptomatic infections. Additional measures were the asymptomatic fraction of infection calculated by dividing incidence rates of asymptomatic infection by rates of any infection, clinical characteristics of infection, and household infection risks. Primary outcomes were compared by participant age group. Results: A total of 1236 participants in 310 households participated in surveillance, including 176 participants (14%) who were aged 0 to 4 years, 313 (25%) aged 5 to 11 years, 163 (13%) aged 12 to 17 years, and 584 (47%) 18 years or older. Overall incidence rates of SARS-CoV-2 infection were 3.8 (95% CI, 2.4-5.9) and 7.7 (95% CI, 4.1-14.5) per 1000 person-weeks among the Utah and New York City cohorts, respectively. Site-adjusted incidence rates per 1000 person-weeks were similar by age group: 6.3 (95% CI, 3.6-11.0) for children 0 to 4 years, 4.4 (95% CI, 2.5-7.5) for children 5 to 11 years, 6.0 (95% CI, 3.0-11.7) for children 12 to 17 years, and 5.1 (95% CI, 3.3-7.8) for adults (≥18 years). The asymptomatic fractions of infection by age group were 52%, 50%, 45%, and 12% among individuals aged 0 to 4 years, 5 to 11 years, 12 to 17 years, and 18 years or older, respectively. Among 40 households with 1 or more SARS-CoV-2 infections, the mean risk of SARS-CoV-2 infection among all enrolled household members was 52% (range, 11%-100%), with higher risks in New York City compared with Utah (80% [95% CI, 64%-91%] vs 44% [95% CI, 36%-53%]; P < .001). Conclusions and Relevance: In this study, children had similar incidence rates of SARS-CoV-2 infection compared with adults, but a larger proportion of infections among children were asymptomatic.