Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).

Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

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.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Association of breastfeeding with mental disorders in mother and child: a systematic review and meta-analysis.

BACKGROUND: Breastfeeding has long been associated with numerous benefits for both mothers and infants. While some observational studies have explored the relationship between breastfeeding and mental health outcomes in mothers and children, a systematic review of the available evidence is lacking. The purpose of this study is to systematically evaluate the association between breastfeeding and mental health disorders in mothers and children. METHODS: We systematically searched MEDLINE and EMBASE from inception to June 2, 2023. The inclusion criteria consisted of all studies evaluating links between breastfeeding and development of mental health disorders in children and mothers. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) while grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. A random-effects meta-analysis was used if possible, to estimate the odds ratio for the association between breastfeeding and mental health outcomes. The Mantel-Haenszel method was utilised for pooling ORs across studies. Study heterogeneity was assessed using the I2 statistic. RESULTS: Our review identified twenty-one original study. Of these, 18 focused on the association between breastfeeding and child health, assessing depressive disorders, schizophrenia, anxiety disorders, eating disorders and borderline personality disorder. Three studies evaluated the associations between breastfeeding and maternal mental health disorders. Three studies looking at outcomes in children showed no significant association between breastfeeding and occurrence of schizophrenia later in life (OR 0.98; 95% CI 0.57-1.71; I2 = 29%). For depressive disorders (5 studies) and anxiety disorders (3 studies), we found conflicting evidence with some studies showing a small protective effect while others found no effect. The GRADE certainty for all these findings was very low due to multiple limitations. Three studies looking at association between breastfeeding and maternal mental health, were too heterogeneous to draw any firm conclusions. CONCLUSIONS: We found limited evidence to support a protective association between breastfeeding and the development of mental health disorders in children later in life. The data regarding the association between breastfeeding and maternal mental health beyond the postnatal period is also limited. The methodological limitations of the published literature prevent definitive conclusions, and further research is needed to better understand the relationship between breastfeeding and mental health in mothers and children.

Formula milk companies and allergy healthcare professionals in India.

India is a low-middle income country with a population of 1.4 billion and home to one quarter of the world's children. Exclusive breastfeeding until 6 months and continued breastfeeding until at least 2 years as per global recommendations are common practice. The Indian government and associated organisations have strived to protect breastfeeding, which is important in a country with high under-5 mortality, malnutrition and stunting. Allergic disease is under-recognised in India, but despite the absence of a dedicated allergy medical specialty, awareness of allergy is increasing among healthcare practitioners and in the general population. In high-income countries, overdiagnosis of allergy has become recognised as an issue in recent years. Allergy healthcare professionals have also attracted criticism for close relationships with the formula industry, which appear to have contributed to excessive use of specialised formula products and undermining of breastfeeding. Specialised formula has been used unnecessarily for preventing allergy, based on fraudulent and selectively reported science; and for managing normal infant symptoms which are mislabelled as milk allergy. This forms part of a broader formula industry corporate strategy to widen the boundaries of illness in order to expand sales and markets. In India, allergic disease management is hindered by limited understanding of the disease entity among practitioners, low access to diagnostics, limited healthcare resources, high exposure to air pollution and a large, diverse population. Data specific to India on allergic disease prevalence and interpreting allergy diagnostics are incomplete. The knowledge gaps mean allergy management in India is often extrapolated from guidance developed in high-income countries with low breastfeeding rates. As the allergy specialty develops in India, local guidance and practice will need to recognise the threat that current allergy practice poses to India's normative infant feeding culture, and ensure that breastfeeding continues to be supported at all levels.

Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies.

OBJECTIVE: The role of allergy as a risk factor for Long-COVID (LC) is unclear and has not been thoroughly examined yet. We aimed to systematically review and appraise the epidemiological evidence on allergic diseases as risk factors for LC. DESIGN: This is an initial systematic review. Two reviewers independently performed the study selection and data extraction using Covidence. Risk of bias (RoB) and certainty of evidence (GRADE) were assessed. Random effects meta-analyses were used to pool unadjusted ORs within homogeneous data subsets. DATA SOURCES: We retrieved articles published between January 1st, 2020 and January 19th, 2023 from MEDLINE via PubMed, Scopus, the WHO-COVID-19 database and the LOVE platform (Epistemonikos Foundation). In addition, citations and reference lists were searched. ELIGIBILITY CRITERIA: We included prospective cohort studies recruiting individuals of all ages with confirmed SARS-CoV-2 infection that were followed up for at least 12 months for LC symptoms where information on pre-existing allergic diseases was available. We excluded all study designs that were not prospective cohort studies and all publication types that were not original articles. RESULTS: We identified 13 studies (9967 participants, range 39-1950 per study), all assessed as high RoB, due to population selection and methods used to ascertain the exposures and the outcome. Four studies did not provide sufficient data to calculate Odds Ratios. The evidence supported a possible relationship between LC and allergy, but was very uncertain. For example, pre-existing asthma measured in hospital-based populations (6 studies, 4019 participants) may be associated with increased risk of LC (Odds Ratio 1.94, 95% CI 1.08, 3.50) and findings were similar for pre-existing rhinitis (3 studies, 1141 participants; Odds Ratio 1.96, 95% CI 1.61, 2.39), both very low certainty evidence. CONCLUSIONS: Pre-existing asthma or rhinitis may increase the risk of LC.

Outcomes reported in randomized controlled trials for mixed and non-IgE-mediated food allergy: Systematic review.

BACKGROUND: Mixed and non-IgE-mediated food allergy is a subset of immune-mediated adverse food reactions that can impose a major burden on the quality of life of affected patients and their families. Clinical trials to study these diseases are reliant upon consistent and valid outcome measures that are relevant to both patients and clinicians, but the degree to which such stringent outcome reporting takes place is poorly studied. OBJECTIVE: As part of the Core Outcome Measures for Food Allergy (COMFA) project, we identified outcomes reported in randomized clinical trials (RCT) of treatments for mixed or non-IgE-mediated food allergy. DESIGN: In this systematic review, we searched the Ovid, MEDLINE and Embase databases for RCTs in children or adults investigating treatments for food protein-induced enterocolitis syndrome, food protein-induced allergic proctocolitis, food protein-induced enteropathy and eosinophilic gastrointestinal disorders including eosinophilic esophagitis [EoE], eosinophilic gastritis and eosinophilic colitis published until 14 October 2022. RESULTS: Twenty-six eligible studies were identified, with 23 focused on EoE (88%). Most interventions were corticosteroids or monoclonal antibodies. All EoE studies assessed patient-reported dysphagia, usually using a non-validated questionnaire. Twenty-two of 23 EoE studies used peak tissue eosinophil count as the primary outcome, usually using a non-validated assessment method, and other immunological markers were only exploratory. Thirteen (57%) EoE studies reported endoscopic outcomes of which six used a validated scoring tool recently recommended as a core outcome for EoE trials. Funding source was not obviously associated with likelihood of an RCT reporting mechanistic versus patient-reported outcomes. Only 3 (12%) RCTs concerned forms of food allergy other than EoE, and they reported on fecal immunological markers and patient-reported outcomes. CONCLUSIONS: Outcomes measured in clinical trials of EoE and non-IgE-mediated food allergy are heterogeneous and largely non-validated. Core outcomes for EoE have been developed and need to be used in future trials. For other forms of mixed or non-IgE-mediated food allergies, core outcome development is needed to support the development of effective treatments. SYSTEMATIC REVIEW REGISTRATION: OSF public registry DOI:10.17605/OSF.IO/AZX8S.

Intranasal analgesia for acute moderate to severe pain in children - a systematic review and meta-analysis.

BACKGROUND: Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may be an alternative to other parenteral routes of administration. Our review compares the efficacy, safety, and acceptability of intranasal analgesia to intravenous (IV) and intramuscular (IM) administration; and to compare different intranasal agents. METHODS: We searched Cochrane Library, MEDLINE/PubMed, Embase, Web of Knowledge, Clinicaltrials.gov, Controlled-trials.com/mrcr, Clinicaltrialsregister.eu, Apps.who.int/trialsearch. We also screened reference lists of included trials and relevant systematic reviews. Studies in English from any year were included. Two authors independently assessed all studies. We included randomised trials (RCTs) of children 0-16, with moderate to severe pain; comparing intranasal analgesia to intravenous or intramuscular analgesia, or to other intranasal agents. We excluded studies of procedural sedation or analgesia. We extracted study characteristics and outcome data and assessed risk of bias with the ROB 2.0-tool. We conducted meta-analysis and narrative review, evaluating the certainty of evidence using GRADE. Outcomes included pain reduction, adverse events, acceptability, rescue medication, ease of and time to administration. RESULTS: We included 12 RCTs with a total of 1163 children aged 3 to 20, most below 10 years old, with a variety of conditions. Our review shows that: - There may be little or no difference in pain relief (single dose IN vs IV fentanyl MD 4 mm, 95% CI -8 to 16 at 30 min by 100 mm VAS; multiple doses IN vs IV fentanyl MD 0, 95%CI -0.35 to 0.35 at 15 min by Hannallah score; single dose IN vs IV ketorolac MD 0.8, 95% CI -0.4 to 1.9 by Faces Pain Scale-Revised), adverse events (single dose IN vs IV fentanyl RR 3.09, 95% CI 0.34 to 28.28; multiple doses IN vs IV fentanyl RR 1.50, 95%CI 0.29 to 7.81); single dose IN vs IV ketorolac RR 0.716, 95% CI 0.23 to 2.26), or acceptability (single dose IN vs IV ketorolac RR 0.83, 95% CI 0.66 to 1.04) between intranasal and intravenous analgesia (low certainty evidence). - Intranasal diamorphine or fentanyl probably give similar pain relief to intramuscular morphine (narrative review), and are probably more acceptable (RR 1.60, 95% CI 1.42 to 1.81) and tolerated better (RR 0.061, 95% CI 0.03 to 0.13 for uncooperative/negative reaction) (moderate certainty); adverse events may be similar (narrative review) (low certainty). - Intranasal ketamine gives similar pain relief to intranasal fentanyl (SMD 0.05, 95% CI -0.20 to 0.29 at 30 min), while having a higher risk of light sedation (RR 1.74, 95% CI 1.30 to 2.35) and mild side effects (RR 2.16, 95% CI 1.72 to 2.71) (high certainty). Need for rescue analgesia is probably similar (RR 0.85, 95% CI 0.62 to 1.17) (moderate certainty), and acceptability may be similar (RR 1.15, 95% CI 0.89 to 1.48) (low certainty). CONCLUSIONS: Our review suggests that intranasal analgesics are probably a good alternative to intramuscular analgesics in children with acute moderate to severe pain; and may be an alternative to intravenous administration. Intranasal ketamine gives similar pain relief to fentanyl, but causes more sedation, which should inform the choice of intranasal agent.

Studying the post-COVID-19 condition: research challenges, strategies, and importance of Core Outcome Set development.

BACKGROUND: A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden. MAIN TEXT: While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data. CONCLUSIONS: A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.

Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study.

BACKGROUND: The long-term sequelae of coronavirus disease 2019 (COVID-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with COVID-19 and associated risk factors. METHODS: This is a prospective cohort study of children (≤18 years old) admitted to hospital with confirmed COVID-19. Children admitted between 2 April 2020 and 26 August 2020 were included. Telephone interviews used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Health and Wellbeing Follow-up Survey for Children. Persistent symptoms (>5 months) were further categorised by system(s) involved. RESULTS: 518 out of 853 (61%) eligible children were available for the follow-up assessment and included in the study. Median (interquartile range (IQR)) age was 10.4 (3-15.2) years and 270 (52.1%) were girls. Median (IQR) follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms, among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age "6-11 years" (OR 2.74, 95% CI 1.37-5.75) and "12-18 years" (OR 2.68, 95% CI 1.41-5.4), and a history of allergic diseases (OR 1.67, 95% CI 1.04-2.67). CONCLUSIONS: A quarter of children experienced persistent symptoms months after hospitalisation with acute COVID-19 infection, with almost one in 10 experiencing multisystem involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.

Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (StopCOVID).

BACKGROUND: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors. METHODS: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge. RESULTS: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47-53) in adults and 20% (95% CI 16-24) in children at 6 months, with decline to 34% (95% CI 31-37) and 11% (95% CI 8-14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47). CONCLUSIONS: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.

Detection and management of milk allergy: Delphi consensus study.

BACKGROUND: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. METHODS: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. FINDINGS: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. INTERPRETATION: These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.

Protocol for a systematic review of the diagnostic test accuracy of tests for IgE-mediated food allergy.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30 September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE-mediated food allergy. METHODS: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1 October 2012 to 30 June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS-2 tool. All evaluations will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta-analysis will be performed if there are three or more studies of the same index test and food. RESULTS: A protocol for the systematic review and meta-analyses is presented and was registered using Prospero prior to commencing the literature search. DISCUSSION: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.

Allergic diseases and immunodeficiencies in children, lessons learnt from COVID-19 pandemic by 2022: A statement from the EAACI-section on pediatrics.

By the April 12, 2022, the COVID-19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short- and long-term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health-care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID-19 or dying from infection. Allergic diseases are not associated with a higher COVID-19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high-standard care. Although children faced a multitude of pandemic-related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Stop COVID Cohort: An Observational Study of 3480 Patients Admitted to the Sechenov University Hospital Network in Moscow City for Suspected Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: The epidemiology, clinical course, and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Russian population are unknown. Information on the differences between laboratory-confirmed and clinically diagnosed COVID-19 in real-life settings is lacking. METHODS: We extracted data from the medical records of adult patients who were consecutively admitted for suspected COVID-19 infection in Moscow between 8 April and 28 May 2020. RESULTS: Of the 4261 patients hospitalized for suspected COVID-19, outcomes were available for 3480 patients (median age, 56 years; interquartile range, 45-66). The most common comorbidities were hypertension, obesity, chronic cardiovascular disease, and diabetes. Half of the patients (n = 1728) had a positive reverse transcriptase-polymerase chain reaction (RT-PCR), while 1748 had a negative RT-PCR but had clinical symptoms and characteristic computed tomography signs suggestive of COVID-19. No significant differences in frequency of symptoms, laboratory test results, and risk factors for in-hospital mortality were found between those exclusively clinically diagnosed or with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR. In a multivariable logistic regression model the following were associated with in-hospital mortality: older age (per 1-year increase; odds ratio, 1.05; 95% confidence interval, 1.03-1.06), male sex (1.71; 1.24-2.37), chronic kidney disease (2.99; 1.89-4.64), diabetes (2.1; 1.46-2.99), chronic cardiovascular disease (1.78; 1.24-2.57), and dementia (2.73; 1.34-5.47). CONCLUSIONS: Age, male sex, and chronic comorbidities were risk factors for in-hospital mortality. The combination of clinical features was sufficient to diagnose COVID-19 infection, indicating that laboratory testing is not critical in real-life clinical practice.

Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19.

BACKGROUND: The long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors. METHODS: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire. RESULTS: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). CONCLUSIONS: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms.

Media Influence on Anxiety, Health Utility, and Health Beliefs Early in the SARS-CoV-2 Pandemic-a Survey Study.

BACKGROUND: The psychological effects from the COVID-19 pandemic and response are poorly understood. OBJECTIVE: To understand the effects of the pandemic and response on anxiety and health utility in a nationally representative sample of US adults. DESIGN: A de-identified, cross-sectional survey was administered at the end of April 2020. Probability weights were assigned using estimates from the 2018 American Community Survey and Integrated Public Use Microdata Series Estimates. PARTICIPANTS: US adults 18-85 years of age with landline, texting-enabled cellphone, or internet access. INTERVENTION: Seven split-half survey blocks of 30 questions, assessing demographics, COVID-19-related health attitudes, and standardized measures of generalized self-efficacy, anxiety, depression, personality, and generic health utility. MAIN MEASURES: State/Trait anxiety scores, EQ-5D-3L Visual Analog Scale (VAS) score, and demographic predictors of these scores. KEY RESULTS: Among 4855 respondents, 56.7% checked COVID-19-related news several times daily, and 84.4% at least once daily. Only 65.7% desired SARS-CoV-2 vaccination for themselves, and 70.1% for their child. Mean state anxiety (S-anxiety) score was significantly higher than mean trait anxiety (T-anxiety) score (44.9, 95%CI 43.5-46.3 vs. 41.6, 95%CI 38.7-44.5; p = 0.03), with both scores significantly higher than previously published norms. In an adjusted regression model, less frequent news viewing was associated with significantly lower S-anxiety score. Mean EQ-5D-3L VAS score for the population was significantly lower vs. established US normative data (71.4 CI 67.4-75.5, std. error 2 vs. societal mean 80, std. error 0.1; p < 0.001). EQ-5D-3L VAS score was bimodal (highest with hourly and no viewing) and significantly reduced with less media viewership in an adjusted model. CONCLUSIONS: Among a nationally representative sample, there were higher S-anxiety and lower EQ-5D-3L VAS scores compared to non-pandemic normative data, indicative of a potential detrimental acute effect of the pandemic. More frequent daily media viewership was significantly associated with higher S-anxiety but also predictive of higher health utility, as measured by EQ-5D-3L VAS scores.