Association of Symptoms and Viral Culture Positivity for SARS-CoV-2-Tennessee, April-July 2020.

BACKGROUND: Understanding how symptoms are associated with SARS-CoV-2 culture positivity is important for isolation and transmission control guidelines. METHODS: Individuals acutely infected with SARS-CoV-2 in Tennessee and their household contacts were recruited into a prospective study. All participants self-collected nasal swabs daily for 14 days and completed symptom diaries from the day of illness onset through day 14 postenrollment. Nasal specimens were tested for SARS-CoV-2 using RT-qPCR. Positive specimens with cycle threshold values < 40 were sent to the Centers for Disease Control and Prevention (CDC) for viral culture. First, we modeled the association between symptoms and the risk of culture positivity using an age-adjusted generalized additive model (GAM) accounting for repeated measurements within participants and a symptom-day spline. Next, we investigated how timing of symptom resolution was associated with the timing of culture resolution. RESULTS: In a GAM restricted to follow-up days after symptoms began, the odds of a specimen being culture positive was significantly increased on days when wheezing, loss of taste or smell, runny nose, nasal congestion, sore throat, fever, or any symptom were reported. For all symptoms except sore throat, it was more common for participants to have culture resolution before symptom resolution than for culture to resolve after or on the same day as symptom resolution. CONCLUSIONS: Overall, symptomatic individuals were more likely to be SARS-CoV-2 viral culture positive. For most symptoms, culture positivity was more likely to end before symptoms resolved. However, a proportion of individuals remained culture positive after symptom resolved, across all symptoms.

Diagnostic Accuracy of the Abbott BinaxNOW COVID-19 Antigen Card Test, Puerto Rico.

BACKGROUND: The COVID-19 pandemic underscored the need for rapid and accurate diagnostic tools. In August 2020, the Abbott BinaxNOW COVID-19 Antigen Card test became available as a timely and affordable alternative for SARS-CoV-2 molecular testing, but its performance may vary due to factors including timing and symptomatology. This study evaluates BinaxNOW diagnostic performance in diverse epidemiological contexts. METHODS: Using RT-PCR as reference, we assessed performance of the BinaxNOW COVID-19 test for SARS-CoV-2 detection in anterior nasal swabs from participants of two studies in Puerto Rico from December 2020 to May 2023. Test performance was assessed by days post symptom onset, collection strategy, vaccination status, symptomatology, repeated testing, and RT-PCR cycle threshold (Ct) values. RESULTS: BinaxNOW demonstrated an overall sensitivity of 84.1% and specificity of 98.8%. Sensitivity peaked within 1-6 days after symptom onset (93.2%) and was higher for symptomatic (86.3%) than asymptomatic (67.3%) participants. Sensitivity declined over the course of infection, dropping from 96.3% in the initial test to 48.4% in testing performed 7-14 days later. BinaxNOW showed 99.5% sensitivity in participants with low Ct values (≤ 25) but lower sensitivity (18.2%) for participants with higher Cts (36-40). CONCLUSIONS: BinaxNOW demonstrated high sensitivity and specificity, particularly in early-stage infections and symptomatic participants. In situations where test sensitivity is crucial for clinical decision-making, nucleic acid amplification tests are preferred. These findings highlight the importance of considering clinical and epidemiological context when interpreting test results and emphasize the need for ongoing research to adapt testing strategies to emerging SARS-CoV-2 variants.

Asymptomatic and mildly symptomatic influenza virus infections by season -- Case-ascertained household transmission studies, United States, 2017-2023.

Asymptomatic influenza virus infection occurs but may vary by factors such as age, influenza vaccination status, or influenza season. We examined the frequency of influenza virus infection and associated symptoms using data from two case-ascertained household transmission studies (conducted from 2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had non-respiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing the effectiveness of symptom-based surveillance systems.

Absenteeism and Health Behavior Trends Associated With Acute Respiratory Illness Before and During the COVID-19 Pandemic in a Community Household Cohort, King County, Washington.

Introduction: Longitudinal data on how acute respiratory illness (ARI) affects behavior, namely school or work participation, and nonpharmaceutical intervention (NPI) usage before and during the COVID-19 pandemic is limited. The authors assessed how ARIs and specific symptoms affected school, work, and health-related behaviors over time. Methods: From November 2019 to June 2021, participating households with children in King County, Washington, were remotely monitored for ARI symptoms weekly. Following ARIs, participants reported illness-related effects on school, work, and NPI use. Using logistic regression with generalized estimating equations, the authors examined associations between symptoms and behaviors. Results: Of 1,861 participants, 581 (31%) from 293 households reported 884 ARIs and completed one-week follow-up surveys. Compared with the prepandemic period, during the period of the pandemic pre-COVID-19 vaccine, ARI-related school (56% vs 10%, p<0.001) absenteeism decreased and masking increased (3% vs 28%, p<0.001). After vaccine authorization in December 2020, more ARIs resulted in masking (3% vs 48%, p<0.001), avoiding contact with non-household members (26% vs 58%, p<0.001), and staying home (37% vs 69%, p<0.001) compared with the prepandemic period. Constitutional symptoms such as fever were associated with work disruptions (OR=1.91; 95% CI=1.06, 3.43), staying home (OR=1.55; 95% CI=1.06, 2.27), and decreased contact with non-household members (OR=1.58; 95% CI=1.05, 2.36). Conclusions: This remote household study permitted uninterrupted tracking of behavioral changes in families with children before and during the COVID-19 pandemic, identifying increased use of some NPIs when ill but no additional illness-associated work or school disruptions.

SARS-CoV-2 incidence, seroprevalence, and antibody dynamics in a rural, population-based cohort: March 2020 - July 2022.

Studies of SARS-CoV-2 incidence are important for response to continued transmission and future pandemics. We followed a rural community cohort with broad age representation with active surveillance for SARS-CoV-2 identification from November 2020 through July 2022. Participants provided serum specimens at regular intervals and following SARS-CoV-2 infection or vaccination. We estimated the incidence of SARS-CoV-2 infection identified by study RT-PCR, electronic health record documentation or self-report of a positive test, or serology. We also estimated the seroprevalence of SARS-CoV-2 spike and nucleocapsid antibodies measured by ELISA. Overall, 65% of the cohort had ≥1 SARS-CoV-2 infection by July 2022, and 19% of those with primary infection were reinfected. Infection and vaccination contributed to high seroprevalence, 98% (95% CI: 95%, 99%) of participants were spike or nucleocapsid seropositive at the end of follow-up. Among those seropositive, 82% were vaccinated. Participants were more likely to be seropositive to spike than nucleocapsid following infection. Infection among seropositive individuals could be identified by increases in nucleocapsid, but not spike, ELISA optical density values. Nucleocapsid antibodies waned more quickly after infection than spike antibodies. High levels of SARS-CoV-2 population immunity, as found in this study, are leading to changing epidemiology necessitating ongoing surveillance and policy evaluation.

Estimating averted illnesses from influenza vaccination for children and pregnant women - El Salvador, Panama, and Peru, 2011-2018.

BACKGROUND: Estimating the burden of disease averted by vaccination can assist policymakers to implement, adjust, and communicate the value of vaccination programs. Demonstrating the use of a newly available modeling tool, we estimated the burden of influenza illnesses averted by seasonal influenza vaccination in El Salvador, Panama, and Peru during 2011-2017 among two influenza vaccine target populations: children aged 6-23 months and pregnant women. METHODS: We derived model inputs, including incidence, vaccine coverage, vaccine effectiveness, and multipliers from publicly available country-level influenza surveillance data and cohort studies. We also estimated changes in illnesses averted when countries' vaccine coverage was achieved using four different vaccine deployment strategies. RESULTS: Among children aged 6-23 months, influenza vaccination averted an estimated cumulative 2,161 hospitalizations, 81,907 medically-attended illnesses, and 126,987 overall illnesses during the study period, with a prevented fraction ranging from 0.3 % to 12.5 %. Among pregnant women, influenza vaccination averted an estimated cumulative 173 hospitalizations, 6,122 medically attended illnesses, and 16,412 overall illnesses, with a prevented fraction ranging from 0.2 % to 10.9 %. Compared to an influenza vaccine campaign with equal vaccine distribution during March-June, scenarios in which total cumulative coverage was achieved in March and April consistently resulted in the greatest increase in averted illness (23 %-3,129 % increase among young children and 22 %-3,260 % increase among pregnant women). DISCUSSION: Influenza vaccination campaigns in El Salvador, Panama, and Peru conducted between 2011 and 2018 prevented hundreds to thousands of influenza-associated hospitalizations and illnesses in young children and pregnant women. Existing vaccination programs could prevent additional illnesses, using the same number of vaccines, by achieving the highest possible coverage within the first two months of an influenza vaccine campaign.

Remote surveillance and detection of SARS-CoV-2 transmission among household members in King County, Washington.

BACKGROUND: Early during the COVID-19 pandemic, it was important to better understand transmission dynamics of SARS-CoV-2, the virus that causes COVID-19. Household contacts of infected individuals are particularly at risk for infection, but delays in contact tracing, delays in testing contacts, and isolation and quarantine posed challenges to accurately capturing secondary household cases. METHODS: In this study, 346 households in the Seattle region were provided with respiratory specimen collection kits and remotely monitored using web-based surveys for respiratory illness symptoms weekly between October 1, 2020, and June 20, 2021. Symptomatic participants collected respiratory specimens at symptom onset and mailed specimens to the central laboratory in Seattle. Specimens were tested for SARS-CoV-2 using RT-PCR with whole genome sequencing attempted when positive. SARS-CoV-2-infected individuals were notified, and their household contacts submitted specimens every 2 days for 14 days. RESULTS: In total, 1371 participants collected 2029 specimens that were tested; 16 individuals (1.2%) within 6 households tested positive for SARS-CoV-2 during the study period. Full genome sequences were generated from 11 individuals within 4 households. Very little genetic variation was found among SARS-CoV-2 viruses sequenced from different individuals in the same household, supporting transmission within the household. CONCLUSIONS: This study indicates web-based surveillance of respiratory symptoms, combined with rapid and longitudinal specimen collection and remote contact tracing, provides a viable strategy to monitor households and detect household transmission of SARS-CoV-2. TRIAL REGISTRATION IDENTIFIER: NCT04141930, Date of registration 28/10/2019.

Neutralizing Immunity Against Antigenically Advanced Omicron BA.5 in Children After SARS-CoV-2 Infection.

We assessed serum neutralization of Omicron BA.5 in children following SARS-CoV-2 infection during the Delta or Omicron BA.1/BA.2 variant period. Convalescent BA.5 titers were higher following infections during the Omicron BA.1/BA.2 vs Delta variant period, and in vaccinated vs unvaccinated children. Titers against BA.5 did not differ by age group.

The role of asymptomatic infections in influenza transmission: what do we really know.

Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps.

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

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