Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID).

BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Expanding TREC and KREC Utility in Primary Immunodeficiency Diseases Diagnosis.

Primary immunodeficiency diseases (PID) area heterogeneous group of disorders caused by genetic defects of the immune system, which manifest clinically as recurrent infections, autoimmune diseases or malignancies. Early detection of PID remains a challenge, particularly in older children with milder and less specific symptoms. This study aimed to assess TREC and KREC diagnostic ability in PID. Data from children assessed by clinical immunologists at Speransky Children's Hospital, Moscow, Russia with suspected immunodeficiencies were analyzed between May 2013 and August 2016. Peripheral blood samples were sent for TREC/KREC, flow cytometry (CD3, CD4, CD8 and CD19), IgA and IgG analysis. A total of 434 children [189 healthy, 97 with group I and II PID (combined T and B cell immunodeficiencies & well-defined syndromes with immunodeficiency) and 148 group III PID (predominantly antibody deficiencies)] were included. Area under the curve (AUC) for TREC in PID groups I and II diagnosis reached 0.82 (CI = 0.75-0.90), with best model providing sensitivity of 65% and specificity of 92%. Neither TREC, nor KREC had added value in PID group III diagnosis. In this study, the predictive value of TREC and KREC in PID diagnosis was examined. We found that the TREC had some diagnostic utility for groups I and II PID. Possibly, addition of TREC measurements to existing clinical diagnostic algorithms may improve their predictive value. Further investigations on a larger cohort are needed to evaluate TREC/KREC abilities to be used as diagnostic tools on a wider scale.

Statistical Approaches in the Studies Assessing Associations between Human Milk Immune Composition and Allergic Diseases: A Scoping Review.

A growing number of studies are focusing on the associations between human milk (HM) immunological composition and allergic diseases. This scoping review aims to identify statistical methods applied in the field and highlight pitfalls and unmet needs. A comprehensive literature search in MEDLINE and Embase retrieved 13,607 unique records. Following title/abstract screening, 29 studies met the selection criteria and were included in this review. We found that definitions of colostrum and mature milk varied across the studies. A total of 17 out of 29 (59%) studies collected samples longitudinally, but only 12% of these used serial (longitudinal) analyses. Multivariable analysis was used in 45% of the studies, but statistical approaches to modelling varied largely across the studies. Types of variables included as potential confounding factors differed considerably between models. Discrimination analysis was absent from all studies and only a single study reported classification measures. Outcomes of this scoping review highlight lack of standardization, both in data collection and handling, which remains one of the main challenges in the field. Improved standardization could be obtained by a consensus group of researchers and clinicians that could recommend appropriate methods to be applied in future prospective studies, as well as already existing datasets.