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1.
Pathogens ; 11(3)2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1760795

ABSTRACT

In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children's difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using "omic-"techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use.

2.
Virus Evol ; 8(1): veac002, 2022.
Article in English | MEDLINE | ID: covidwho-1746220

ABSTRACT

Transmission chains within small urban areas (accommodating ∼30 per cent of the European population) greatly contribute to case burden and economic impact during the ongoing coronavirus pandemic and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in a European urban area, Basel-City (Switzerland). We combined detailed epidemiological, intra-city mobility and socio-economic data sets with whole-genome sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44 per cent of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60 per cent of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare system burden (intensive care unit (ICU) occupancy). Transmissions were driven by socio-economically weaker and highly mobile population groups with mostly cryptic transmissions which lacked genetic and identifiable epidemiological links. Amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90 per cent transmission reduction and 70-90 per cent reduction of severe cases showed that prioritising mobile, socio-economically weaker populations for vaccination would effectively reduce case numbers. However, long-term ICU occupation would also be effectively reduced if senior population groups were prioritised, provided there were no changes in testing and prevention strategies. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323069

ABSTRACT

Background: 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 laboratory-confirmed 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.Methods: Data were collected through the Swiss Paediatric Surveillance Unit from children < 18 years with laboratory-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.Findings: In total, 678 children were included. The median age was 12.2 (IQR 5.0 – 14.6) years, 316 (47%) were female and 106 (16%) 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). 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 the hospitalised children, oxygen treatment was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%). Complications were reported in 28 (4.1%) children with cardiovascular complications being most frequent (11 [1.6%]). Three deaths were recorded.Interpretation: 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.Funding: The study is supported by the Swiss Federal Office of Public Health and has received grants from the Swiss Society of Paediatrics and the Paediatric Infectious Disease Group of Switzerland.Declaration of Interest: None to declare.Ethical Approval: The study has received ethical approval by the Ethikkommission Nordwest- undZentralschweiz (EKNZ 2020-01130).

5.
Eur J Pediatr ; 181(3): 1245-1255, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1540222

ABSTRACT

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.


Subject(s)
COVID-19 , Adolescent , Adult , COVID-19/epidemiology , COVID-19/therapy , Child , Child, Preschool , Critical Care , Female , Hospitalization , Hospitals, Pediatric , Humans , Intensive Care Units , Prospective Studies , SARS-CoV-2
6.
Swiss Med Wkly ; 151: w30057, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1403974

ABSTRACT

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance.


Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Humans , Infant , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/prevention & control , SARS-CoV-2 , Switzerland/epidemiology
7.
Front Pediatr ; 9: 691024, 2021.
Article in English | MEDLINE | ID: covidwho-1367755

ABSTRACT

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.

8.
Front Pediatr ; 9: 667507, 2021.
Article in English | MEDLINE | ID: covidwho-1268270

ABSTRACT

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce. Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing. Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance. Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation. Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged.

9.
Eur J Pediatr ; 180(6): 1965-1967, 2021 06.
Article in English | MEDLINE | ID: covidwho-1111273
10.
JAMA Pediatr ; 174(12): 1216, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-979853
11.
Paediatr Respir Rev ; 36: 57-64, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-935867

ABSTRACT

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.


Subject(s)
Adjuvants, Immunologic/therapeutic use , BCG Vaccine/therapeutic use , Cross Protection/immunology , Immunity, Heterologous/immunology , Mycobacterium Infections, Nontuberculous/prevention & control , Tuberculosis Vaccines/therapeutic use , Tuberculosis/prevention & control , BCG Vaccine/immunology , Buruli Ulcer/microbiology , Buruli Ulcer/prevention & control , COVID-19/prevention & control , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/immunology , Humans , Hypersensitivity/epidemiology , Hypersensitivity/immunology , Infant , Infant Mortality , Leprosy/microbiology , Leprosy/prevention & control , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/immunology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/immunology , Tuberculosis Vaccines/immunology
12.
Lancet Child Adolesc Health ; 4(9): 653-661, 2020 09.
Article in English | MEDLINE | ID: covidwho-613887

ABSTRACT

BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Intensive Care Units/organization & administration , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/therapy , Europe/epidemiology , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Patient Admission/trends , Pneumonia, Viral/therapy , Risk Factors , SARS-CoV-2
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