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A lack of fine, spatially-resolute case data for the U.S. has prevented the examination of how COVID-19 burden has been distributed across neighborhoods, a known geographic unit of both risk and resilience, and is hampering efforts to identify and mitigate the long-term fallout from COVID-19 in vulnerable communities. Using spatially-referenced data from 21 states at the ZIP code or census tract level, we documented how the distribution of COVID-19 at the neighborhood-level varies significantly within and between states. The median case count per neighborhood (IQR) in Oregon was 3,608 (2,487) per 100,000 population, indicating a more homogenous distribution of COVID-19 burden, whereas in Vermont the median case count per neighborhood (IQR) was 8,142 (11,031) per 100,000. We also found that the association between features of the neighborhood social environment and burden varied in magnitude and direction by state. Our findings underscore the importance of local contexts when addressing the long-term social and economic fallout communities will face from COVID-19.

Background Respiratory syncytial virus (RSV) is a substantial source of severe illnesses including acute lower respiratory infections (ALRIs) like pneumonia. However, its burden in older children remains less well understood. Methods Using a community-based prospective cohort, we assessed the burden of symptomatic reverse-transcription polymerase chain reaction–confirmed RSV among Nicaraguan children aged 0–14 years from 2011 to 2016. ALRI was defined as physician diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity. Results Between 2011 and 2016, 2575 children participated in the cohort. Of these, 630 (24.5%) had at least 1 episode of symptomatic RSV and 194 (7.5%) had multiple episodes. Subtype was identified in 571 (69.3%) episodes with 408 (71.5%) RSV-A, 157 (27.5%) RSV-B, and 6 (1%) positive for both. Children aged Conclusions There is a substantial burden of symptomatic and severe RSV in children. While older children did present with RSV, the rates of symptomatic and severe RSV decreased by as much as 95% beyond age 5.

The impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding of the burden of COVID-19 among children and their risk of reinfection is crucial, as they will be among the last groups vaccinated.To characterize the burden of COVID-19 and assess how risk of symptomatic reinfection may vary by age among children.In this prospective, community-based pediatric cohort study conducted from March 1, 2020, to October 15, 2021, 1964 nonimmunocompromised children aged 0 to 14 years were enrolled by random selection from the Nicaraguan Pediatric Influenza Cohort, a community-based cohort in District 2 of Managua, Nicaragua. Additional newborn infants aged 4 weeks or younger were randomly selected and enrolled monthly via home visits.Prior COVID-19 infection as confirmed by positive anti-SARS-CoV-2 antibodies (receptor binding domain and spike protein) or real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 infection at least 60 days before current COVID-19 infection.Symptomatic COVID-19 cases confirmed by real-time RT-PCR and hospitalization within 28 days of symptom onset of a confirmed COVID-19 case.This cohort study assessed 1964 children (mean [SD] age, 6.9 [4.4] years; 985 [50.2%] male). Of 1824 children who were tested, 908 (49.8%; 95% CI, 47.5%-52.1%) were seropositive during the study. There were also 207 PCR-confirmed COVID-19 cases, 12 (5.8%) of which were severe enough to require hospitalization. Incidence of COVID-19 was highest among children younger than 2 years (16.1 cases per 100 person-years; 95% CI, 12.5-20.5 cases per 100 person-years), which was approximately 3 times the incidence rate in any other child age group assessed. In addition, 41 symptomatic SARS-CoV-2 episodes (19.8%; 95% CI, 14.4%-25.2%) were reinfections.In this prospective, community-based pediatric cohort study, rates of symptomatic and severe COVID-19 were highest among the youngest participants, with rates stabilizing at approximately 5 years of age. In addition, symptomatic reinfections represented a large proportion of symptomatic COVID-19 cases.

Background Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. Methods In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). Findings In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800–28 100), and 45 700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). Interpretation RSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. Funding EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, it is unclear if SARS-CoV-2 infections are distinct in symptom presentation, duration, and severity from endemic coronavirus infections in children. We compared symptom risk and duration of endemic human coronavirus (HCoV) infections from 2011-2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Blood samples were collected from study participants annually in February-April. Respiratory samples were collected from participants that met testing criteria. Blood samples collected in were tested for SARS-CoV-2 antibodies and a subset of 2011-2016 blood samples from four-year-old children were tested for endemic HCoV antibodies. Respiratory samples were tested for each of the endemic HCoVs from 2011-2016 and for SARS-CoV-2 from 2020-2021 via rt-PCR. By April 2021, 854 (49%) cohort participants were ELISA positive for SARS-CoV-2 antibodies. Most participants had antibodies against one alpha and one beta coronavirus by age four. We observed 595 symptomatic endemic HCoV infections from 2011-2016 and 121 symptomatic with SARS-CoV-2 infections from March 2020-September 2021. Symptom presentation of SARS-CoV-2 infection and endemic coronavirus infections were very similar, and SARS-CoV-2 symptomatic infections were as or less severe on average than endemic HCoV infections. This suggests that, for children, SARS-CoV-2 may be just another endemic coronavirus. However, questions about the impact of variants and the long-term effects of SARS-CoV-2 remain.

BackgroundAn immune correlate of protection from SARS-CoV-2 infection is urgently needed.MethodsWe used an ongoing household cohort with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity. Sequencing was performed to determine circulating strains of SARS-CoV-2. We investigated the protection associated with seropositivity resulting from prior infection, the anti-spike antibody titers needed for protection, and we compared the severity of first and second infections.ResultsIn March 2021, 62.3% of the cohort was seropositive. After March 2021, gamma and delta variants predominated. Seropositivity was associated with 69.2% protection from any infection (95% CI: 60.7%-75.9%), with higher protection against moderate or severe infection (79.4%, 95% CI: 64.9%-87.9%). Anti-spike titers of 327 and 2,551 were associated with 50% and 80% protection from any infection; titers of 284 and 656 were sufficient for protection against moderate or severe disease. Second infections were less severe than first infections (Relative Risk (RR) of moderated or severe disease: 0.6, 95% CI: 0.38-0.98; RR of subclinical disease:1.9, 95% CI: 1.33-2.73).ConclusionsPrior infection-induced immunity is protective against infection when predominantly gamma and delta SARS-CoV-2 circulated. The protective antibody titers presented may be useful for vaccine policy and control measures. While second infections were somewhat less severe, they were not as mild as ideal. A strategy involving vaccination will be needed to ease the burden of the SARS-CoV-2 pandemic.

The period of protection from repeat infection following symptomatic influenza is not well established due to limited availability of longitudinal data. Using data from a pediatric cohort in Managua, Nicaragua, we examine the effects of natural influenza virus infection on subsequent infection with the same influenza virus subtype/lineage across multiple seasons, totaling 2,170 RT-PCR-confirmed symptomatic influenza infections. Logistic regression models assessed whether infection in the prior influenza season protected against homologous reinfection. We sequenced viruses from 2011–2019 identifying dominant clades and measuring antigenic distances between hemagglutinin clades. We observe homotypic protection from repeat infection in children infected with influenza A/H1N1pdm (OR 0.12, CI 0.02–0.88), A/H3N2 (OR 0.41, CI 0.24–0.73), and B/Victoria (OR 0.00, CI 0.00–0.14), but not with B/Yamagata viruses (OR 0.60, CI 0.09–2.10). Overall, protection wanes as time or antigenic distance increases. Individuals infected with one subtype or lineage of influenza virus have significantly lower odds of homologous reinfection for the following one to two years; after two years this protection wanes. This protection is demonstrated across multiple seasons, subtypes, and lineages among children.

Background There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings. Methods We followed 2338 people in Managua, Nicaragua, aged, A community-based cohort in Managua, Nicaragua, had very high severe acute respiratory syndrome coronavirus 2 seropositivity but lower-than-expected severity. Overall, 69% of infections were asymptomatic or subclinical and 1.1% of infections were severe. Seropositivity was associated with 93.6% protection from symptomatic reinfection through March 2021.

Influenza is associated with primary viral and secondary bacterial pneumonias; however, the dynamics of this relationship in populations with varied levels of pneumococcal vaccination remain unclear. We conducted nested matched case-control studies in 2 prospective cohorts of Nicaraguan children aged 2–14 years: 1 before pneumococcal conjugate vaccine introduction (2008–2010) and 1 following introduction and near universal adoption (2011–2018). The association between influenza and pneumonia was similar in both cohorts. Participants with influenza (across types/subtypes) had higher odds of developing pneumonia in the month following influenza infection. These findings underscore the importance of considering influenza in interventions to reduce global pneumonia burden.

Background Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined. Methods We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0–14 years from 2011 through 2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian nonlinear survival model to estimate pneumonia hazard following influenza. Results Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR], 2.7 [95% confidence interval {CI}, 1.9–3.9]). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR, 3.7 [95% CI, 2.0–6.9]), followed by influenza B and A(H3N2). Participants’ odds of pneumonia following influenza were not constant, showing distinct peaks 0–6 days (mOR, 8.3 [95% CI, 4.8–14.5] days) and 14–20 (mOR, 2.5 [95% CI, 1.1–5.5] days) after influenza infection. Conclusions Influenza is a significant driver of both primary and secondary pneumonia among children. The presence of distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.

Seasonal and pandemic respiratory viruses such as influenza and the novel coronavirus (SARS-COV-2) currently sweeping the globe have often been described as ‘equal opportunity infectors’, implying little socioeconomic disparity in susceptibility. However, early data from the COVID-19 pandemic has underscored that the burden of respiratory viruses actually reflect and magnify existing socioeconomic inequalities. We review the literature on socioeconomic and racial disparities in acute respiratory infection (ARI), as well as ARI-associated hospitalization and mortality. Our goal is to identify key principles of the relationship between socioeconomic inequality and ARI outcomes, as well as highlighting poorly understood areas that need to be addressed by research and policy in the wake of the COVID-19 pandemic. We find that there has been descriptive work in this area, but that there is a distinct lack of cohesive methodology in the literature exploring social determinants and ARI. We propose the fundamental cause theory is a useful framework for guiding future research of disparities in ARI and for the design of interventions to alleviate these disparities.

Background Respiratory syncytial virus (RSV) causes substantial morbidity and mortality among children worldwide, commonly through acute lower respiratory tract infections (ALRI). To assess the incidence rate of symptomatic RSV illness among young children, we conducted a prospective birth cohort study following children from 0–2 years of age in Managua, Nicaragua. Methods Children meeting the testing criteria (fever, history of fever, or severe respiratory symptoms [apnea, stridor, nasal flaring, wheezing, chest indrawing, and/or central cyanosis]) were tested for RSV infections using real-time reverse transcriptase-polymerase chain reaction. An acute lower respiratory infection was defined as a diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity. The incidence rate was calculated, and 95% confidence intervals were estimated using a Poisson distribution. Results A total of 833 children participated in the cohort: 289 (34.7%) had at least 1 episode of laboratory-confirmed RSV, and 156 (18.7%) of had an episode of RSV-associated ALRI (RSV-ALRI). The incidence rate of symptomatic RSV was 248.1 cases per 1000 person-years (95% confidence interval [CI] 223.2–275.7). While infants aged 6–11 months had the highest incidence of symptomatic RSV (361.3/1000 person-years, 95% CI 304.4–428.8), infants, Around one-third of medical deaths among Nicaraguan children under 2 years were respiratory syncytial virus–associated, suggesting it’s an important driver of infant mortality in highly vaccinated populations with little human immunodeficiency virus or malaria.

Background Infectious disease epidemiologists have long recognised the importance of social variables as drivers of epidemics and disease risk, yet few apply analytic approaches from social epidemiology. We quantified and evaluated the extent to which recent infectious disease research is employing the perspectives and methods of social epidemiology by replicating the methodology used by Cohen et al in a 2007 study. Methods 2 search strategies were used to identify and review articles published from 1 January 2005 to 31 December 2013. First, we performed a keyword search of ‘social epidemiology’ in the title/abstract/text of published studies identified in PubMed, PsychInfo and ISI Web of Science, and classified each study as pertaining to infectious, non-infectious or other outcomes. A second PubMed search identified articles that were cross-referenced under non-infectious or infectious, and search terms relating to social variables. The abstracts of all articles were read, classified and examined to identify patterns over time. Results Findings suggest that infectious disease research publications that explicitly or implicitly incorporate social epidemiological approaches have stagnated in recent years. While the number of publications that were explicitly self-classified as ‘social epidemiology’ has risen, the proportion that investigated infectious disease outcomes has declined. Furthermore, infectious diseases accounted for the smallest proportion of articles that were cross-referenced with Medical Subject Headings (MeSH) terms related to social factors, and most of these involved sexually transmitted diseases. Conclusions The current landscape of infectious disease epidemiology could benefit from new approaches to understanding how the social and biophysical environment sustains transmission and exacerbates disparities. The framework of social epidemiology provides infectious disease researchers with such a perspective and research opportunity.