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.

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.

Comparison of influenza and COVID-19-associated hospitalizations among children < 18 years old in the United States-FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021).

BACKGROUND: Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. METHODS: Influenza and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, two population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (October 1, 2020-September 30, 2021) was compared to influenza-associated hospitalization rates during the 2017-18 through 2019-20 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. RESULTS: Among children <18 years old, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-18 (33.5), 2018-19 (33.8), and 2019-20 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years old, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; p < 0.01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; p = 0.28). CONCLUSIONS: In the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years old compared with influenza during the three seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses.

Association of Culturable-Virus Detection and Household Transmission of SARS-CoV-2, California and Tennessee, 2020-2022.

From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable virus detected after onset. Regardless of duration of culturable virus, most secondary infections (70%, 28/40) had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection, and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.

Developing a sampling methodology for timely reporting of population-based COVID-19-associated hospitalization surveillance in the United States, COVID-NET 2020-2021.

BACKGROUND: The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) required a sampling methodology that allowed for production of timely population-based clinical estimates to inform the ongoing US COVID-19 pandemic response. METHODS: We developed a flexible sampling approach that considered reporting delays, differential hospitalized case burden across surveillance sites, and changing geographic and demographic trends over time. We incorporated weighting methods to adjust for the probability of selection and non-response, and to calibrate the sampled case distribution to the population distribution on demographics. We additionally developed procedures for variance estimation. RESULTS: Between March 2020 and June 2021, 19,293 (10.4%) of all adult hospitalized cases were sampled for chart abstraction. Variance estimates for select variables of interest were within desired ranges. CONCLUSIONS: COVID-NET's sampling methodology allowed for reporting of robust and timely, population-based data on the clinical epidemiology of COVID-19-associated hospitalizations and evolving trends over time, while attempting to reduce data collection burden on surveillance sites. Such methods may provide a general framework for other surveillance systems needing to quickly and efficiently collect and disseminate data for public health action.

Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza - United States, 2021-22 Influenza Season.

The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),§ and notifiable pediatric deaths associated¶ with influenza virus and SARS-CoV-2 coinfection (October 3, 2021-October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.†† To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months.

Relative Risks of COVID-19-Associated Hospitalizations and Clinical Outcomes by Age and Race/Ethnicity-March 2020-March 2021.

Background: Limited data exist on population-based risks and risk ratios (RRs) of coronavirus disease 2019 (COVID-19)-associated hospitalizations and clinical outcomes stratified by age and race/ethnicity. Methods: Using data from electronic health records and claims from 4 US health systems for the period March 2020-March 2021, we calculated risk and RR by age and race/ethnicity for COVID-19-associated hospitalizations and clinical outcomes among adults (≥18 years). COVID-19-associated hospitalizations were defined based on COVID-19 discharge codes or a positive severe acute respiratory syndrome coronavirus 2 result. Proportions of acute exacerbations of underlying conditions were estimated among hospitalized patients with select underlying conditions, stratified by age and race/ethnicity. Results: Among 2.6 million adults included in the patient cohort, 6879 had COVID-19-associated hospitalizations during March 2020-March 2021 (risk: 264 per 100 000 population). Compared with younger, non-Hispanic White adults, non-Hispanic Black and Hispanic adults aged ≥65 years had the highest hospitalization risk ratios (RR, 8.6; 95% CI, 7.6-9.9; and RR, 9.3; 95% CI, 8.5-10.3, respectively). Among hospitalized adults with COVID-19 and renal disease or cardiovascular disease, the highest proportion of acute renal failure (55.5%) or congestive heart failure (43.9%) occurred in older, non-Hispanic Black patients. Among hospitalized adults with chronic lung disease or asthma, the highest proportion of respiratory failure (62.9%) or asthma exacerbation (66.7%) occurred in older, Hispanic patients. Conclusions: During the first year of the US COVID-19 pandemic in this cohort, older non-Hispanic Black and Hispanic adults had the highest relative risks of COVID-19-associated hospitalization and adverse outcomes and, among those with select underlying conditions, the highest occurrences of acute exacerbations of underlying conditions.

Estimated Number of COVID-19 Infections, Hospitalizations, and Deaths Prevented Among Vaccinated Persons in the US, December 2020 to September 2021.

Importance: The number of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented among vaccinated persons, independent of the effect of reduced transmission, is a key measure of vaccine impact. Objective: To estimate the number of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented among vaccinated adults in the US. Design, Setting, and Participants: In this modeling study, a multiplier model was used to extrapolate the number of SARS-CoV-2 infections and COVID-19-associated deaths from data on the number of COVID-19-associated hospitalizations stratified by state, month, and age group (18-49, 50-64, and ≥65 years) in the US from December 1, 2020, to September 30, 2021. These estimates were combined with data on vaccine coverage and effectiveness to estimate the risks of infections, hospitalizations, and deaths. Risks were applied to the US population 18 years or older to estimate the expected burden in that population without vaccination. The estimated burden in the US population 18 years or older given observed levels of vaccination was subtracted from the expected burden in the US population 18 years or older without vaccination (ie, counterfactual) to estimate the impact of vaccination among vaccinated persons. Exposures: Completion of the COVID-19 vaccination course, defined as 2 doses of messenger RNA (BNT162b2 or mRNA-1273) vaccines or 1 dose of JNJ-78436735 vaccine. Main Outcomes and Measures: Monthly numbers and percentages of SARS-CoV-2 infections and COVID-19-associated hospitalizations and deaths prevented were estimated among those who have been vaccinated in the US. Results: COVID-19 vaccination was estimated to prevent approximately 27 million (95% uncertainty interval [UI], 22 million to 34 million) infections, 1.6 million (95% UI, 1.4 million to 1.8 million) hospitalizations, and 235 000 (95% UI, 175 000-305 000) deaths in the US from December 1, 2020, to September 30, 2021, among vaccinated adults 18 years or older. From September 1 to September 30, 2021, vaccination was estimated to prevent 52% (95% UI, 45%-62%) of expected infections, 56% (95% UI, 52%-62%) of expected hospitalizations, and 58% (95% UI, 53%-63%) of expected deaths in adults 18 years or older. Conclusions and Relevance: These findings indicate that the US COVID-19 vaccination program prevented a substantial burden of morbidity and mortality through direct protection of vaccinated individuals.

SARS-CoV-2 Virus Dynamics in Recently Infected People-Data From a Household Transmission Study.

We used daily real-time reverse-transcription polymerase chain reaction (RT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020-May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset.

Estimating COVID-19 Hospitalizations in the United States With Surveillance Data Using a Bayesian Hierarchical Model: Modeling Study.

BACKGROUND: In the United States, COVID-19 is a nationally notifiable disease, meaning cases and hospitalizations are reported by states to the Centers for Disease Control and Prevention (CDC). Identifying and reporting every case from every facility in the United States may not be feasible in the long term. Creating sustainable methods for estimating the burden of COVID-19 from established sentinel surveillance systems is becoming more important. OBJECTIVE: We aimed to provide a method leveraging surveillance data to create a long-term solution to estimate monthly rates of hospitalizations for COVID-19. METHODS: We estimated monthly hospitalization rates for COVID-19 from May 2020 through April 2021 for the 50 states using surveillance data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) and a Bayesian hierarchical model for extrapolation. Hospitalization rates were calculated from patients hospitalized with a lab-confirmed SARS-CoV-2 test during or within 14 days before admission. We created a model for 6 age groups (0-17, 18-49, 50-64, 65-74, 75-84, and ≥85 years) separately. We identified covariates from multiple data sources that varied by age, state, and month and performed covariate selection for each age group based on 2 methods, Least Absolute Shrinkage and Selection Operator (LASSO) and spike and slab selection methods. We validated our method by checking the sensitivity of model estimates to covariate selection and model extrapolation as well as comparing our results to external data. RESULTS: We estimated 3,583,100 (90% credible interval [CrI] 3,250,500-3,945,400) hospitalizations for a cumulative incidence of 1093.9 (992.4-1204.6) hospitalizations per 100,000 population with COVID-19 in the United States from May 2020 through April 2021. Cumulative incidence varied from 359 to 1856 per 100,000 between states. The age group with the highest cumulative incidence was those aged ≥85 years (5575.6; 90% CrI 5066.4-6133.7). The monthly hospitalization rate was highest in December (183.7; 90% CrI 154.3-217.4). Our monthly estimates by state showed variations in magnitudes of peak rates, number of peaks, and timing of peaks between states. CONCLUSIONS: Our novel approach to estimate hospitalizations for COVID-19 has potential to provide sustainable estimates for monitoring COVID-19 burden as well as a flexible framework leveraging surveillance data.

Use of At-Home COVID-19 Tests - United States, August 23, 2021-March 12, 2022.

COVID-19 testing provides information regarding exposure and transmission risks, guides preventative measures (e.g., if and when to start and end isolation and quarantine), identifies opportunities for appropriate treatments, and helps assess disease prevalence (1). At-home rapid COVID-19 antigen tests (at-home tests) are a convenient and accessible alternative to laboratory-based diagnostic nucleic acid amplification tests (NAATs) for SARS-CoV-2, the virus that causes COVID-19 (2-4). With the emergence of the SARS-CoV-2 B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants in 2021, demand for at-home tests increased† (5). At-home tests are commonly used for school- or employer-mandated testing and for confirmation of SARS-CoV-2 infection in a COVID-19-like illness or following exposure (6). Mandated COVID-19 reporting requirements omit at-home tests, and there are no standard processes for test takers or manufacturers to share results with appropriate health officials (2). Therefore, with increased COVID-19 at-home test use, laboratory-based reporting systems might increasingly underreport the actual incidence of infection. Data from a cross-sectional, nonprobability-based online survey (August 23, 2021-March 12, 2022) of U.S. adults aged ≥18 years were used to estimate self-reported at-home test use over time, and by demographic characteristics, geography, symptoms/syndromes, and reasons for testing. From the Delta-predominant period (August 23-December 11, 2021) to the Omicron-predominant period (December 19, 2021-March 12, 2022)§ (7), at-home test use among respondents with self-reported COVID-19-like illness¶ more than tripled from 5.7% to 20.1%. The two most commonly reported reasons for testing among persons who used an at-home test were COVID-19 exposure (39.4%) and COVID-19-like symptoms (28.9%). At-home test use differed by race (e.g., self-identified as White [5.9%] versus self-identified as Black [2.8%]), age (adults aged 30-39 years [6.4%] versus adults aged ≥75 years [3.6%]), household income (>$150,000 [9.5%] versus $50,000-$74,999 [4.7%]), education (postgraduate degree [8.4%] versus high school or less [3.5%]), and geography (New England division [9.6%] versus West South Central division [3.7%]). COVID-19 testing, including at-home tests, along with prevention measures, such as quarantine and isolation when warranted, wearing a well-fitted mask when recommended after a positive test or known exposure, and staying up to date with vaccination,** can help reduce the spread of COVID-19. Further, providing reliable and low-cost or free at-home test kits to underserved populations with otherwise limited access to COVID-19 testing could assist with continued prevention efforts.

Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence and Reported Coronavirus Disease 2019 Cases in US Children, August 2020-May 2021.

BACKGROUND: Case-based surveillance of pediatric coronavirus disease 2019 (COVID-19) cases underestimates the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children and adolescents. Our objectives were to estimate monthly SARS-CoV-2 antibody seroprevalence and calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 8 US states. METHODS: Using data from the Nationwide Commercial Laboratory Seroprevalence Survey, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. We calculated and compared cumulative incidence of SARS-CoV-2 infection extrapolated from population-standardized seroprevalence of antibodies to SARS-CoV-2, cumulative COVID-19 case reports since March 2020, and infection-to-case ratios among persons of all ages and children aged 0-17 years for each state. RESULTS: Of 41 583 residual serum specimens tested, children aged 0-4, 5-11, and 12-17 years accounted for 1619 (3.9%), 10 507 (25.3%), and 29 457 (70.8%), respectively. Median SARS-CoV-2 antibody seroprevalence among children increased from 8% (range, 6%-20%) in August 2020 to 37% (range, 26%-44%) in May 2021. Estimated ratios of SARS-CoV-2 infections to reported COVID-19 cases in May 2021 ranged by state from 4.7-8.9 among children and adolescents to 2.2-3.9 for all ages combined. CONCLUSIONS: Through May 2021 in selected states, the majority of children with serum specimens included in serosurveys did not have evidence of prior SARS-CoV-2 infection. Case-based surveillance underestimated the number of children infected with SARS-CoV-2 more than among all ages. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.

Household Transmission and Clinical Features of SARS-CoV-2 Infections.

OBJECTIVES: Examine age differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risk from primary cases and infection risk among household contacts and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower in primary cases age 12 to 17 years than from primary cases 18 to 49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contact pairs age ≥65 years (76%) and 5 to 11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.

Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence and Reported Coronavirus Disease 2019 Cases in US Children, August 2020–May 2021

Background Case-based surveillance of pediatric coronavirus disease 2019 (COVID-19) cases underestimates the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children and adolescents. Our objectives were to estimate monthly SARS-CoV-2 antibody seroprevalence and calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 8 US states. Methods Using data from the Nationwide Commercial Laboratory Seroprevalence Survey, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0–17 years from August 2020 through May 2021. We calculated and compared cumulative incidence of SARS-CoV-2 infection extrapolated from population-standardized seroprevalence of antibodies to SARS-CoV-2, cumulative COVID-19 case reports since March 2020, and infection-to-case ratios among persons of all ages and children aged 0–17 years for each state. Results Of 41 583 residual serum specimens tested, children aged 0–4, 5–11, and 12–17 years accounted for 1619 (3.9%), 10 507 (25.3%), and 29 457 (70.8%), respectively. Median SARS-CoV-2 antibody seroprevalence among children increased from 8% (range, 6%–20%) in August 2020 to 37% (range, 26%–44%) in May 2021. Estimated ratios of SARS-CoV-2 infections to reported COVID-19 cases in May 2021 ranged by state from 4.7–8.9 among children and adolescents to 2.2–3.9 for all ages combined. Conclusions Through May 2021 in selected states, the majority of children with serum specimens included in serosurveys did not have evidence of prior SARS-CoV-2 infection. Case-based surveillance underestimated the number of children infected with SARS-CoV-2 more than among all ages. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies. We estimated monthly pediatric SARS-CoV-2 infections from antibody seroprevalence compared to reported COVID-19 cases among children in 8 US states. As of May 2021, estimated numbers of children infected were 5 times higher than reported pediatric COVID-19 cases in included states.

Severity of the COVID-19 pandemic assessed with all-cause mortality in the United States during 2020.

BACKGROUND: In the United States, infection with SARS-CoV-2 caused 380,000 reported deaths from March to December 2020. METHODS: We adapted the Moving Epidemic Method to all-cause mortality data from the United States to assess the severity of the COVID-19 pandemic across age groups and all 50 states. By comparing all-cause mortality during the pandemic with intensity thresholds derived from recent, historical all-cause mortality, we categorized each week from March to December 2020 as either low severity, moderate severity, high severity, or very high severity. RESULTS: Nationally for all ages combined, all-cause mortality was in the very high severity category for 9 weeks. Among people 18 to 49 years of age, there were 29 weeks of consecutive very high severity mortality. Forty-seven states, the District of Columbia, and New York City each experienced at least 1 week of very high severity mortality for all ages combined. CONCLUSIONS: These periods of very high severity of mortality during March through December 2020 are likely directly or indirectly attributable to the COVID-19 pandemic. This method for standardized comparison of severity over time across different geographies and demographic groups provides valuable information to understand the impact of the COVID-19 pandemic and to identify specific locations or subgroups for deeper investigations into differences in severity.

Application of Bayesian spatial-temporal models for estimating unrecognized COVID-19 deaths in the United States.

In the United States, COVID-19 has become a leading cause of death since 2020. However, the number of COVID-19 deaths reported from death certificates is likely to represent an underestimate of the total deaths related to SARS-CoV-2 infections. Estimating those deaths not captured through death certificates is important to understanding the full burden of COVID-19 on mortality. In this work, we explored enhancements to an existing approach by employing Bayesian hierarchical models to estimate unrecognized deaths attributed to COVID-19 using weekly state-level COVID-19 viral surveillance and mortality data in the United States from March 2020 to April 2021. We demonstrated our model using those aged ≥ 85 years who died. First, we used a spatial-temporal binomial regression model to estimate the percent of positive SARS-CoV-2 test results. A spatial-temporal negative-binomial model was then used to estimate unrecognized COVID-19 deaths by exploiting the spatial-temporal association between SARS-CoV-2 percent positive and all-cause mortality counts using an excess mortality approach. Computationally efficient Bayesian inference was accomplished via the Polya-Gamma representation of the binomial and negative-binomial models. Among those aged ≥ 85 years, we estimated 58,200 (95% CI: 51,300, 64,900) unrecognized COVID-19 deaths, which accounts for 26% (95% CI: 24%, 29%) of total COVID-19 deaths in this age group. Our modeling results suggest that COVID-19 mortality and the proportion of unrecognized deaths among deaths attributed to COVID-19 vary by time and across states.

Performance of Self-Collected Anterior Nasal Swabs and Saliva Specimens for Detection of SARS-CoV-2 During Symptomatic and Asymptomatic Periods.

BACKGROUND: Anterior nasal swabs (ANS) are established specimen collection methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detection. While saliva (SA) specimens provide an alternative, few studies have comprehensively characterized the performance of SA specimens in longitudinal studies. METHODS: We compared SARS-CoV-2 detections between paired self-collected ANS and SA specimens from a household transmission study. Participants recorded symptoms and paired ANS and SA specimens daily for 14 days. Specimens were tested using RT-PCR. We calculated the proportion of detections identified by each specimen type among the detections from both types combined. We computed percent agreement and Kappa statistics to assess concordance in detections. We also computed estimates stratified by presence of symptoms and examined the influence of traditional and inactivating transport media on the performance of ANS. RESULTS: We examined 2535 self-collected paired specimens from 216 participants. Among 1238 (49%) paired specimens with detections by either specimen type, ANS identified 77.1% (954; 95% CI, 74.6% to 79.3%) and SA 81.9% (1014; 95% CI, 79.7% to 84.0%), with a difference of 4.9% (95% CI, 1.4% to 8.5%). Overall agreement was 80.0%, and Kappa was 0.6 (95% CI, 0.5 to 0.6). Nevertheless, the difference in the proportion of detections identified by ANS and SA using traditional and inactivating transport media was 32.5% (95% CI, 26.8% to 38.0%) and -9.5% (95% CI, -13.7% to -5.2%), respectively. Among participants who remained asymptomatic, the difference in detections between SA and ANS was 51.2% (95% CI, 31.8% to 66.0%) and 26.1% (95% CI, 0% to 48.5%) using traditional and inactivating media, respectively. CONCLUSIONS: Self-collected saliva specimens provide a noninvasive alternative to nasal swabs, especially to those collected in traditional transport media, for longitudinal field studies that aim to detect both symptomatic and asymptomatic SARS-CoV-2 infections.

Changes in Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence Over Time in 10 Sites in the United States, March-August, 2020.

BACKGROUND: Monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence can complement case reporting to inform more accurate estimates of SARS-CoV-2 infection burden, but few studies have undertaken repeated sampling over time on a broad geographic scale. METHODS: We performed serologic testing on a convenience sample of residual serum obtained from persons of all ages, at 10 sites in the United States from 23 March through 14 August 2020, from routine clinical testing at commercial laboratories. We standardized our seroprevalence rates by age and sex, using census population projections and adjusted for laboratory assay performance. Confidence intervals were generated with a 2-stage bootstrap. We used bayesian modeling to test whether seroprevalence changes over time were statistically significant. RESULTS: Seroprevalence remained below 10% at all sites except New York and Florida, where it reached 23.2% and 13.3%, respectively. Statistically significant increases in seroprevalence followed peaks in reported cases in New York, South Florida, Utah, Missouri, and Louisiana. In the absence of such peaks, some significant decreases were observed over time in New York, Missouri, Utah, and Western Washington. The estimated cumulative number of infections with detectable antibody response continued to exceed reported cases in all sites. CONCLUSIONS: Estimated seroprevalence was low in most sites, indicating that most people in the United States had not been infected with SARS-CoV-2 as of July 2020. The majority of infections are likely not reported. Decreases in seroprevalence may be related to changes in healthcare-seeking behavior, or evidence of waning of detectable anti-SARS-CoV-2 antibody levels at the population level. Thus, seroprevalence estimates may underestimate the cumulative incidence of infection.

Hospitalizations Associated with COVID-19 Among Children and Adolescents - COVID-NET, 14 States, March 1, 2020-August 14, 2021.

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,† COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.§ Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)¶ data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,†† and quarantining as recommended after exposure to persons with COVID-19.§§.

SARS-CoV-2 Transmission: Preliminary Findings from a Household-based Study

Background: Social distancing measures, such as shelter-in-place or stay-at-home orders, are recommended for control of community transmission of SARS-CoV-2. Few studies, however, have characterized the transmission of SARS-CoV-2 infections in households. Method(s): We conducted a case-ascertained study of household transmission in Nashville, TN starting in April 2020, after recommendations to stay at home were enacted. Index cases were ambulatory patients identified through clinical RT-PCR testing at Vanderbilt walk-in-clinics dispersed across the Nashville metropolitan area. For this study, the index case was the first person presenting with respiratory or compatible symptoms in a household and who lived with at least one other household member. After informed consent was obtained, household members were remotely trained in the self-collection of nasal swabs and use of REDCap electronic questionnaires. Household members completed daily symptom diaries and collected daily nasal swabs for 14 days. Contact patterns within households before and after disease onset were ascertained. Nasal swab samples were tested using RT-PCR at an academic research laboratory. Result(s): At the time of writing, 18 families were enrolled (including 18 index cases and 34 household members) with at least 1 follow-up nasal swab tested. The median age of index cases and household members was 37 years (IQR: 26-46) and 27 years (15-39), respectively. The median number of days from index patient onset of symptoms to first sample collected in the household was 4 (2-5). Before onset of symptoms, 83% of index cases spent >4 hours in the same room with at least one other household member, whereas after disease onset and diagnosis, 44% did. Among 34 non-index household members, 18 (53%) had a positive test during follow-up;the median number of days from index case's symptoms onset to first positive detection in a household member was 4.5 (3-5) days. Interestingly, 13 (72%) of 18 secondary infections were detected within the first 3 days of follow-up, whereas 5 (28%) were detected during subsequent days. Conclusion(s): These observations suggest that transmission of SARS-CoV-2 within households is high, with many infections detected during the initial days of study follow-up.