Factors associated with hospital and intensive care admission in paediatric SARS-CoV-2 infection: a prospective nationwide observational cohort study.

Coronavirus disease 2019 (COVID-19) is usually less severe in children compared to adults. This study describes detailed clinical characteristics, treatment and outcomes of children with COVID-19 in a non-hospitalised and hospitalised setting and quantifies factors associated with admission to hospital and intensive care unit in children with SARS-CoV-2 infection on a nationwide level. Data were collected through the Swiss Paediatric Surveillance Unit from children < 18 years with confirmed SARS-CoV-2 infection. All 33 paediatric hospitals in Switzerland reported non-hospitalised and hospitalised cases from March 1 to October 31, 2020 during both pandemic peaks. In total, 678 children were included. The median age was 12.2 years (IQR 5.0-14.6), 316 (46.6%) were female and 106 (15.6%) had comorbidities. Overall, 126 (18.6%) children were hospitalised of whom 16 (12.7%) required ICU admission. Comorbidities were the only factor associated with hospital admission in a multivariable regression analysis (odds ratio 3.23, 95%CI 1.89 to 5.50; p-value < 0.01). Children with preexisting comorbidities did not require ICU admission more often. Hospitalised children more often presented with fever (96 [76.2%] vs 209 [38.1%], p-value < 0.01) and rash (16 [12.8%] vs 6 [1.1%], p-value < 0.01). Anosmia/dysgeusia was more prevalent in non-hospitalised children (73 [13.3%] vs 3 [2.4%], p-value < 0.01). In hospitalised children, oxygen treatment was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%) cases. Complications were reported in 28 (4.1%) children with cardiovascular complications being most frequent (12 [1.8%]). Three deaths were recorded.Conclusion: This study confirms that COVID-19 is mostly a mild disease in children. Fever, rash and comorbidities are associated with higher admission rates. Continuous observation is necessary to further understand paediatric COVID-19, guide therapy and evaluate the necessity for vaccination in children. What is Known: • Clinical manifestations of SARS-CoV-2 infection in children vary from asymptomatic to critical disease requiring intensive care unit admission. • Most studies are based on hospitalised children only; currently, there is limited data on non-hospitalised children. What is New: • The clinical spectrum and severity of COVID-19 is influenced by age: in children less than 2 years, fever, cough and rhinorrhoea are the most common symptoms and in adolescents, fever, cough and headache are more common. • Hospitalised children more often presented with fever and rash, while anosmia/dysgeusia is more prevalent in non-hospitalised children. • Children with pre-existing comorbidities are more frequently hospitalised but do not require ICU admission more often.

[Treatment of SARS-CoV-2 in paediatrics : what is the evidence to date?] / Traitement du SARS-CoV-2 en pédiatrie : quelles évidences et quelle utilité ?

Although SARS-CoV-2 infects individuals of all ages, children show less severe symptoms. Nevertheless, the very rare COVID-19 severe cases in paediatrics require our full attention. Much research has been conducted and is still ongoing on effective treatments. On the antiviral front, no molecule has been proven effective yet and the results of several studies on the benefit of monoclonal antibodies and convalescent plasma are pending. On the side of immunomodulators, the benefit of steroids has been demonstrated for patients severely ill. Other molecules are being investigated. However, all these studies focused on adults and paediatric data are warranted.

Bien que le SARS-CoV-2 infecte des individus de tout âge, les enfants montrent des symptômes moins sévères. Les cas de Covid-19 graves sont exceptionnels en pédiatrie mais nécessitent néanmoins toute notre attention. De nombreuses études ont été menées et sont encore en cours à la recherche de traitements efficaces. Sur le plan antiviral, aucune molécule n'a fait ses preuves à l'heure actuelle. Les résultats de plusieurs travaux sur le bénéfice des anticorps monoclonaux et du plasma convalescent sont attendus avec impatience. Du côté des immunomodulateurs, le bénéfice des stéroïdes a pu être démontré chez les patients présentant une infection pulmonaire sévère. D'autres molécules sont à l'étude. Cependant, toutes ces études s'intéressent aux adultes et les données pédiatriques sont quasiment inexistantes.

Gen Z and HIV-Strategies for Optimizing the Care of the Next Generation of Adolescents Living with HIV.

The management of adolescents living with HIV represents a particular challenge in the global response to HIV. The challenges specific to this age group include difficulties engaging and maintaining them in care, challenges with transition to adult care, and limited therapeutic options for treatment-experienced patients, all of which have been jeopardized by the COVID-19 pandemic. This paper summarizes some of the challenges in managing adolescents living with HIV, as well as some of the most recent and innovative therapeutic approaches in this population.

Neonates with SARS-CoV-2 infection: spectrum of disease from a prospective nationwide observational cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can be more severe in infants than in older children. To date, only a few case series have reported data on neonates with COVID-19, including mostly asymptomatic neonates who were tested because of exposure to maternal SARS-CoV-2 infection. This study summarises nationwide epidemiological data, clinical characteristics, treatment and outcomes of neonates presenting with symptomatic SARS-CoV-2 infection. METHODS: Data were prospectively collected through the Swiss Paediatric Surveillance Unit from hospitalised neonates with laboratory-confirmed SARS-CoV-2 infection (positive polymerase chain reaction on a respiratory sample) from 1 March 2020 to 31 September 2021. All 29 paediatric hospitals in Switzerland reported cases. RESULTS: In total, 73 neonates were included; 7 (10%) were preterm. The median age at presentation was 17 days (interquartile range [IQR] 11-23); 40 (55%) were female. The majority of neonates (64, 88%) were admitted from home. Nine (12%) had a pre-existing medical condition. Overall, the most common symptom recorded was fever in 52 (71%), followed by rhinorrhoea or nasal congestion in 32 (44%) and respiratory distress in 19 (26%). Twenty (27%) neonates presented with fever without a source. Seven (10%) neonates were admitted to an intensive care unit (5 for respiratory failure and 2 for monitoring). One (1%) neonate required inotropic support. The median length of hospital stay in term neonates was 4 days (IQR 3-5). Two (3%) were treated with corticosteroids and 1 (1%) with remdesivir. In total, 60 (82%) neonates had contact with a known or suspected SARS-CoV-2 index case. All of the 71 neonates for whom data were available were discharged to their homes without symptoms. CONCLUSION: In neonates, COVID-19 mainly presents with fever, and symptoms of upper and lower respiratory tract infection. The clinical course is mostly mild, requiring a short period of hospitalisation. COVID-19 needs to be added as a differential diagnosis in neonates who present with fever without a source. However, the presence of SARS-CoV-2 should not deter from the search for a serious bacterial infection. Further data from surveillance studies are needed to better understand COVID-19 in neonates, guide therapy and to evaluate whether the clinical spectrum is changing with new SARS-CoV-2 variants.

Unexpected associations between respiratory viruses and bacteria with Pulmonary Function Testing in children suffering from Cystic Fibrosis (MUCOVIB study).

BACKGROUND: Various bacterial and viral assemblages composing Cystic Fibrosis (CF) lung microbiota contribute to long-term lung function decline over time. Yet, the impact of individual microorganisms on pulmonary functions remains uncertain in children with CF. METHODS: As part of the 'Mucoviscidosis, respiratory VIruses, intracellular Bacteria and fastidious organisms'' project, children with CF were longitudinally followed in a Swiss multicentric study. Respiratory samples included mainly throat swabs and sputa samples for bacterial culture and 16S rRNA metagenomics and nasopharyngeal swabs for respiratory virus detection by molecular assays. Percentage of predicted Forced Expiratory Volume in one second (FEV1%) and Lung Clearance Index (LCI) were recorded. RESULTS: Sixty-one children, of whom 20 (32.8%) presented with at least one pulmonary exacerbation, were included. Almost half of the 363 nasopharyngeal swabs tested by RT-PCR were positive for a respiratory virus, mainly rhinovirus (26.5%). From linear mixed-effects regression models, P. aeruginosa (-11.35, 95%CI [-17.90; -4.80], p = 0.001) was significantly associated with a decreased FEV1%, whereas rhinovirus was associated with a significantly higher FEV1% (+4.24 95%CI [1.67; 6.81], p = 0.001). Compared to conventional culture, 16S rRNA metagenomics showed a sensitivity and specificity of 80.0% and 85.4%, respectively for detection of typical CF pathogens. However, metagenomics detected a bacteria almost twice more often than culture. CONCLUSIONS: As expected, P. aeruginosa impacted negatively on FEV1% while rhinovirus was surprisingly associated with better FEV1%. Culture-free assays identifie significantly more pathogens than standard culture, with disputable clinical correlation.

Performance of RT-PCR on Saliva Specimens Compared With Nasopharyngeal Swabs for the Detection of SARS-CoV-2 in Children: A Prospective Comparative Clinical Trial.

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.

Prevalence of tuberculosis in migrant children in Switzerland and relevance of current screening guidelines.

AIMS: Since 2016, Swiss guidelines recommend screening of all migrant children <5 years of age for tuberculosis (TB) and to screen older children only if they have risk factors for TB. Our goals were to describe the epidemiology of latent tuberculosis (LTBI) in migrant children at the Lausanne University Hospital, to identify determinants of LTBI and tuberculosis disease (TBD), and to evaluate the risk of a false-positive tuberculin skin test (TST) when using a positivity limit of 5 mm. METHODS: Newly arrived migrant children 0–18 years of age were prospectively enrolled from 31 August 2015 to 31 August 2017. Every migrant child was assessed for the risk of TB exposure and TBD and was administered a TST. A TB-spot test was performed in children ≥5 years of age when the TST was positive. Children with clinical and/or radiological signs of TBD were further investigated. Children ≥5 years of age with a positive TB-spot test and children <5 years of age with a positive TST, without clinico-radiological signs of TBD received a diagnosis of LTBI. A false-positive TST result was diagnosed in children ≥5 years of age when the TB-spot test was negative. Potential determinants of TB (LTBI and TBD) and of false-positive TSTs were identified. Student’s t-test or the Kruskal-Wallis test were used for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. All variables with a p-value <0.05 were included in a multivariate logistic regression model. RESULTS: Two hundred and fifty-three patients were eligible for the study. The median age of the patients was 8.1 years (interquartile range [IQR] 4.5–12.8) and 104 (41%) were female. Twenty-four percent of the patients (62/253) came from a country with a moderate–high incidence of TBD (≥80 cases per 100,000 individuals). Twenty-eight patients (11%) had positive TSTs, and TB was confirmed in 17 (6.7%) of these patients (16 with LTBI and 1 with TBD). On multivariate analysis, moderate–high incidence of TBD in the country of origin (adjusted odds ratio [aOR] 18.8, 95% confidence interval [CI] 5.1–68.6; p <0.001), older age (aOR 1.1, 95% CI 1.0–1.3; p = 0.025), and contact with a TBD patient (aOR 8, 95% CI 1.8–36.2; p = 0.007) were associated with a diagnosis of TB. Among the 23 children over 5 years of age who had a positive TST with measurement available, a measure between 5–9 mm was more frequent in case of a false-positive TST (5/9, 56% vs 0/14, 0%, p = 0.002). BCG vaccination was the only predictor of a false-positive TST (p = 0.03). CONCLUSION: Screening migrant children ≥5 years of age for TB could confer a public health benefit even in the absence of other risk factors. The limit of TST positivity could be raised from ≥5 mm to ≥10 mm to decrease the rate of false-positive results. A national assessment of migrant children between the ages of 5 and 15 should be carried out to confirm our findings.

Case Report: Case Series of Children With Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Switzerland.

Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal presentation. Intravenous immunoglobulin (IVIG) is recommended as first line therapy in KD. Recent evidence suggests intravenous immunoglobulins (IVIG) resistance in some cases of SARS-CoV-2 related MIS-C, thereby questioning the benefit of immunomodulators such as IL-1 or IL-6 blocking agents. We report on a cohort of 6 Swiss children with SARS-CoV2 related MIS-C presenting with clinical features compatible with Incomplete KD and Toxic Shock Syndrome associated to a cytokine storm. Serum cytokine profile investigations showed increased IL1RA levels (8 to 22-fold) in 5 of the 6 patients (one patient had not been tested), whereas, IL-6 serum levels were increased only in the 3 patients of the 6 who were tested. With exception of one patient who had only benefited by Anakinra, all patients received at least one dose of IVIG. One patient has only received Anakinra with favorable evolution, and three patients had also a steroid treatment. In addition to all this anti-inflammatory medication two patients have also received one dose of anti-IL6. In conclusion, our case series reports on clinical and laboratory findings of most of Swiss cases with MIS-C and suggests the use of Anakinra as an alternative to steroids in these children, most of whom presented with high IL-1RA levels.

Single doses of diphtheria-tetanus-pertussis and poliomyelitis vaccines are sufficient to generate a booster-type response to tetanus in most migrant children.

BACKGROUND: Immunization coverage for three doses of the diphtheria-tetanus-pertussis and poliomyelitis vaccines in infants is high worldwide, therefore despite the lack of documentation of past vaccinations, most migrant children do not require complete revaccination. Our strategy was to administer a single dose of a tetanus toxoid containing vaccine (TTCV) to migrant children followed by anti-tetanus toxoid (TT) serology to determine whether additional vaccine doses were required. Our goal was to estimate the basic TTCV coverage and to identify potential determinants of the vaccination response. METHODS: Newly arrived migrant children were prospectively enrolled between October 2014 and August 2017. We included patients aged 1-18 years with no proof of past vaccinations who accepted a single dose of TTCV. Anti-TT serology was performed after 4-6 weeks, and an anti-TT level ≥ 1 IU/mL was considered a booster-type antibody response with no need for additional doses of TTCV. Potential determinants of the vaccination response were identified using univariate and multivariate linear regression analyses. RESULTS: Two hundred and eight children were eligible for analysis. The mean age of the children was 9 (±4.5) years and 100 (48%) were female. The majority (n = 129, 62%) of the children came from the WHO Eastern Mediterranean region. Only three patients (1.4%) required additional vaccine doses. A Syrian origin (p < 0.001) and direct arrival primarily by airplane into Switzerland without transiting through other European countries (p = 0.029) associated with higher anti-TT levels in a multivariate regression model (multiple r2 = 0.210, p < 0.001). CONCLUSION: A single dose of TTCV is enough to generate long-term protection in most migrant children. In the context of high basic vaccination coverage, the strategy, which consists of administration of a single dose of TTCV followed by anti-TT serology, can be considered where serotesting is available and economical.

High coverage of hepatitis B vaccination and low prevalence of chronic hepatitis B in migrant children dictate a new catch-up vaccination strategy.

BACKGROUND: Worldwide coverage of hepatitis B (HB) vaccination is increasing. This should be considered when determining the best strategy for catch-up HB vaccination in migrant children, who rarely have written proof of past immunizations. This study aimed to estimate HB vaccine protection, chronic HB prevalence and to identify determinants of vaccine protection. METHODS: Newly arrived migrant children at Lausanne University Hospital from October 2014 to July 2017 were prospectively enrolled. Children and adolescents aged 1-18 years were approached for inclusion if they had no proof of past vaccinations and accepted a single dose of injected HB vaccine. HB surface antibody (anti-HBs) serology was performed after 4-6 weeks. Anti-HBs ≥100 IU/L were considered consistent with a booster-type antibody response. Patients with anti-HBs <100 IU/L received additional dose(s) of HB vaccine, after exclusion of chronic HB in children with anti-HBs <10 IU/L. Potential determinants of vaccine response were compared between children with and without booster-type response. RESULTS: Two hundred children were available for analysis. Median age was 8.9 years (IQR 4.8-12.9), and 97 (49%) were female. The majority (n = 124, 62%) came from the region classified by the WHO as eastern Mediterranean. One hundred and sixty-one children (81%) had a booster-type antibody response. Only 1 patient (<1%) had chronic HB. In the multivariate analysis, younger age (OR per decreasing-year, 1.28; 95%CI, 1.05-1.57; p = 0.017) and migration from an urban area (OR 1.16; 95%CI, 1.01-1.33; p = 0.043) were the only significant determinants of booster-type response. CONCLUSION: Post-vaccine serology may be used to identify a high proportion of individuals in our pediatric migrant population with previous immunization for HB. Our study also showed extremely low prevalence of chronic HB. No variable could definitively determine the results of serology. Post-vaccine serology represents the most effective strategy in this context of high vaccine coverage.