Coronavirus spike protein-specific antibodies indicate frequent infections and reinfections in infancy and among BNT162b2-vaccinated healthcare workers.

The prevalence of seasonal human coronavirus (HCoV) infections in early childhood and adults has not been well analyzed in longitudinal serological studies. Here we analyzed the changes in HCoV (229E, HKU1, NL63, OC43, MERS, and SARS-CoV-2) spike-specific antibody levels in follow-up serum specimens of 140 children at the age of 1, 2, and 3 years, and of 113 healthcare workers vaccinated for Covid-19 with BNT162b2-vaccine. IgG antibody levels against six recombinant HCoV spike subunit 1 (S1) proteins were measured by enzyme immunoassay. We show that by the age of three years the cumulative seropositivity for seasonal HCoVs increased to 38-81% depending on virus type. BNT162b2 vaccinations increased anti-SARS-CoV-2 S1 antibodies, but no increase in seasonal coronavirus antibodies associated with vaccinations. In healthcare workers (HCWs), during a 1-year follow-up, diagnostic antibody rises were seen in 5, 4 and 14% of the cases against 229E, NL63 and OC43 viruses, respectively, correlating well with the circulating HCoVs. In 6% of the HCWs, a diagnostic antibody rise was seen against S1 of HKU1, however, these rises coincided with anti-OC43 S1 antibody rises. Rabbit and guinea pig immune sera against HCoV S1 proteins indicated immunological cross-reactivity within alpha-CoV (229E and NL63) and beta-CoV (HKU1 and OC43) genera.

Biomarkers of viral and bacterial infection in rhinovirus pneumonia.

Background: Rhinovirus (RV) is often detected in children hospitalized with pneumonia, but the role of RV in causing pneumonia is still unclear. Methods: White blood cell count, C-reactive protein, procalcitonin, and myxovirus resistance protein A (MxA) levels were determined from blood samples in children (n = 24) hospitalized with radiologically verified pneumonia. Respiratory viruses were identified from nasal swabs by using reverse transcription polymerase chain reaction assays. Among RV-positive children, the cycle threshold value, RV subtyping by sequence analysis, and the clearance of RV by weekly nasal swabs were determined. RV-positive children with pneumonia were compared to other virus-positive children with pneumonia, and to children (n = 13) with RV-positive upper respiratory tract infection from a separate earlier study. Results: RV was detected in 6 children and other viruses in 10 children with pneumonia (viral co-detections excluded). All RV-positive children with pneumonia had high white blood cell counts, plasma C-reactive protein or procalcitonin levels, or alveolar changes in chest radiograph strongly indicating bacterial infection. The median cycle threshold value for RV was low (23.2) indicating a high RV load, and a rapid clearance of RV was observed in all. Blood level of viral biomarker MxA was lower among RV-positive children with pneumonia (median 100 µg/L) than among other virus-positive children with pneumonia (median 495 µg/L, p = 0.034) or children with RV-positive upper respiratory tract infection (median 620 µg/L, p = 0.011). Conclusions: Our observations suggest a true viral-bacterial coinfection in RV-positive pneumonia. Low MxA levels in RV-associated pneumonia need further studies.

Parental socioeconomic and psychological determinants of the 2009 pandemic influenza A(H1N1) vaccine uptake in children.

BACKGROUND: Before COVID-19, the previous pandemic was caused by influenza A(H1N1)pdm09 virus in 2009. Identification of factors behind parental decisions to have their child vaccinated against pandemic influenza could be helpful in planning of other pandemic vaccination programmes. We investigated the association of parental socioeconomic and psychosocial factors with uptake of the pandemic influenza vaccine in children in 2009-2010. METHODS: This study was conducted within a prospective birth-cohort study (STEPS Study), where children born in 2008-2010 are followed from pregnancy to adulthood. Demographic and socioeconomic factors of parents were collected through questionnaires and vaccination data from electronic registers. Before and after the birth of the child, the mother's and father's individual and relational psychosocial well-being, i.e. depressive symptoms, dissatisfaction with the relationship, experienced social and emotional loneliness, and maternal anxiety during pregnancy, were measured by validated questionnaires (BDI-II, RDAS, PRAQ, and UCLA). RESULTS: Of 1020 children aged 6-20 months at the beginning of pandemic influenza vaccinations, 820 (80%) received and 200 (20%) did not receive the vaccine against influenza A(H1N1)pdm09. All measures of parents' psychosocial well-being were similar between vaccinated and non-vaccinated children. Children of younger mothers had a higher risk of not receiving the influenza A(H1N1)pdm09 vaccine than children of older mothers (OR 2.59, 95% CI 1.52-4.43, for mothers < 27.7 years compared to ≥ 33.6 years of age). Children of mothers with lower educational level had an increased risk of not receiving the vaccine (OR 1.46, 95% CI 1.00-2.14). CONCLUSIONS: Mother's younger age and lower education level were associated with an increased risk for the child not to receive the 2009 pandemic influenza vaccine, but individual or relational psychosocial well-being of parents was not associated with children's vaccination. Our findings suggest that young and poorly educated mothers should receive targeted support in order to promote children's vaccinations during a pandemic.

Serological Follow-Up Study Indicates High Seasonal Coronavirus Infection and Reinfection Rates in Early Childhood.

Seasonal human coronaviruses (HCoVs) cause respiratory infections, especially in children. Currently, the knowledge on early childhood seasonal coronavirus infections and the duration of antibody levels following the first infections is limited. Here we analyzed serological follow-up samples to estimate the rate of primary infection and reinfection(s) caused by seasonal coronaviruses in early childhood. Serum specimens were collected from 140 children at ages of 13, 24, and 36 months (1, 2, and 3 years), and IgG antibody levels against recombinant HCoV nucleoproteins (N) were measured by enzyme immunoassay (EIA). Altogether, 84% (118/140) of the children were seropositive for at least one seasonal coronavirus N by the age of 3 years. Cumulative seroprevalences for HCoVs 229E, HKU1, NL63, and OC43 increased by age, and they were 45%, 27%, 70%, and 44%, respectively, at the age of 3 years. Increased antibody levels between yearly samples indicated reinfections by 229E, NL63, and OC43 viruses in 20-48% of previously seropositive children by the age of 3 years. Antibody levels declined 54-73% or 31-77% during the year after seropositivity in children initially seropositive at 1 or 2 years of age, respectively, in case there was no reinfection. The correlation of 229E and NL63, and OC43 and HKU1 EIA results, suggested potential cross-reactivity between the N specific antibodies inside the coronavirus genera. The data shows that seasonal coronavirus infections and reinfections are common in early childhood and the antibody levels decline relatively rapidly. IMPORTANCE The rapid spread of COVID-19 requires better knowledge on the rate of coronavirus infections and coronavirus specific antibody responses in different population groups. In this work we analyzed changes in seasonal human coronavirus specific antibodies in young children participating in a prospective 3-year serological follow-up study. We show that based on seropositivity and changes in serum coronavirus antibody levels, coronavirus infections and reinfections are common in early childhood and the antibodies elicited by the infection decline relatively rapidly. These observations provide further information on the characteristics of humoral immune responses of coronavirus infections in children.

Longitudinal Changes in Early Nasal Microbiota and the Risk of Childhood Asthma.

OBJECTIVES: Although the airway microbiota is a highly dynamic ecology, the role of longitudinal changes in airway microbiota during early childhood in asthma development is unclear. We aimed to investigate the association of longitudinal changes in early nasal microbiota with the risk of developing asthma. METHODS: In this prospective, population-based birth cohort study, we followed children from birth to age 7 years. The nasal microbiota was tested by using 16S ribosomal RNA gene sequencing at ages 2, 13, and 24 months. We applied an unsupervised machine learning approach to identify longitudinal nasal microbiota profiles during age 2 to 13 months (the primary exposure) and during age 2 to 24 months (the secondary exposure) and examined the association of these profiles with the risk of physician-diagnosed asthma at age 7 years. RESULTS: Of the analytic cohort of 704 children, 57 (8%) later developed asthma. We identified 4 distinct longitudinal nasal microbiota profiles during age 2 to 13 months. In the multivariable analysis, compared with the persistent Moraxella dominance profile during age 2 to 13 months, the persistent Moraxella sparsity profile was associated with a significantly higher risk of asthma (adjusted odds ratio, 2.74; 95% confidence interval, 1.20-6.27). Similar associations were observed between the longitudinal changes in nasal microbiota during age 2 to 24 months and risk of asthma. CONCLUSIONS: Children with an altered longitudinal pattern in the nasal microbiota during early childhood had a high risk of developing asthma. Our data guide the development of primary prevention strategies (eg, early identification of children at high risk and modification of microbiota) for childhood asthma. These observations present a new avenue for risk modification for asthma (eg, microbiota modification).