Reliability of Self-Sampling for Accurate Assessment of Respiratory Virus Viral and Immunologic Kinetics.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with mid-nasal foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate that nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

Assessment of indirect protection from maternal influenza immunization among non-vaccinated household family members in a randomized controlled trial in Sarlahi, Nepal.

Influenza is a significant cause of morbidity and mortality worldwide, and the World Health Organization highly recommends maternal vaccination during pregnancy. The indirect effect of maternal vaccination on other close contacts other than newborns is unknown. To evaluate this, we conducted a nested substudy between 2011 and 2012 of influenza and acute respiratory illness (ARI) among household members of pregnant women enrolled in a randomized placebo-controlled trial of antenatal influenza vaccination in the rural district of Sarlahi, Nepal. Women were assigned to receive influenza vaccination or placebo during pregnancy and then they and their household members were followed up to 6 months postpartum with weekly symptom surveillance and nasal swab collection. Swabs were tested by RT-PCR for influenza. Rates of laboratory-confirmed influenza and of ARI were compared between vaccine and placebo groups using generalized estimating equations with a Poisson link function. Overall, 1752 individuals in 520 households were eligible for inclusion. There were 82 laboratory-confirmed influenza illness episodes, for a rate of 7.0 per 100 person-years overall. Of the influenza strains able to be typed, 29 were influenza A, 40 were influenza B, and 6 were coinfections with influenza A and B. The rate did not differ significantly whether the household was in the vaccine or placebo group (rate ratio (RR) 1.37, 95% confidence interval (CI) 0.83-2.26). The rate of ARI was 28.5 per 100 person-years overall and did not differ by household group (RR 0.99, 95% CI 0.72-1.36). Influenza vaccination of pregnant women did not provide indirect protection of unvaccinated household members.

Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics.

The SARS-CoV-2 pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with foam swabs at home is well-tolerated and provides quantitative viral output concordant with flocked swabs. Nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction using mathematical models. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

Burden and Risk Factors for Coronavirus Infections in Infants in Rural Nepal.

Background: Knowledge of risk factors for symptomatic human coronavirus (HCoV) infections in children in community settings is limited. We estimated the disease burden and impact of birth-related, maternal, household, and seasonal factors on HCoV infections among children from birth to 6 months old in rural Nepal. Methods: Prospective, active, weekly surveillance for acute respiratory infections (ARIs) was conducted in infants over a period of 3 years during 2 consecutive, population-based randomized trials of maternal influenza immunization. Midnasal swabs were collected for acute respiratory symptoms and tested for HCoV and other viruses by reverse-transcription polymerase chain reaction. Association between HCoV incidence and potential risk factors was modeled using Poisson regression. Results: Overall, 282 of 3505 (8%) infants experienced an HCoV ARI within the first 6 months of life. HCoV incidence overall was 255.6 (95% confidence interval [CI], 227.3-286.5) per 1000 person-years, and was more than twice as high among nonneonates than among neonates (incidence rate ratio [IRR], 2.53; 95% CI, 1.52-4.21). HCoV ARI incidence was also positively associated with the number of children <5 years of age per room in a household (IRR, 1.13; 95% CI, 1.01-1.28). Of the 296 HCoV infections detected, 46% were coinfections with other respiratory viruses. While HCoVs were detected throughout the study period, seasonal variation was also observed, with incidence peaking in 2 winters (December-February) and 1 autumn (September-November). Conclusions: HCoV is associated with a substantial proportion of illnesses among young infants in rural Nepal. There is an increased risk of HCoV infection beyond the first month of life.

Respiratory syncytial virus infection in infants in rural Nepal.

OBJECTIVES: Respiratory syncytial virus (RSV) pneumonia is a leading cause of infant mortality worldwide. The risk of RSV infection associated with preterm birth is not well-characterized in resource-limited settings. We aimed to obtain precise estimates of risk factors and disease burden of RSV in infants in rural southern Nepal. METHODS: Pregnant women were enrolled, and along with their infants, followed to six months after birth with active weekly home-based surveillance for acute respiratory illness (ARI). Mid-nasal swabs were obtained and tested for RSV by PCR for all illness episodes. Birth outcomes were assessed at a postpartum home visit. RESULTS: 311 (9%) of 3509 infants had an RSV ARI. RSV ARI incidence decreased from 551/1000 person-years in infants born between 28 and 31 weeks to 195/1000 person-years in infants born full-term (p = 0.017). Of 220 infants (71%) evaluated in the health system, 41 (19%) visited a hospital or physician. Of 287 infants with an assessment performed, 203 (71%) had a lower respiratory tract infection. CONCLUSIONS: In a rural south Asian setting with intensive home-based surveillance, RSV caused a significant burden of respiratory illness. Preterm infants had the highest incidence of RSV ARI, and should be considered a priority group for RSV preventive interventions in resource-limited settings.