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1.
PLoS Biol ; 20(8): e3001728, 2022 08.
Article in English | MEDLINE | ID: covidwho-1974223

ABSTRACT

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Child , Epithelial Cells , Humans , SARS-CoV-2/genetics
3.
BMC Infect Dis ; 21(1): 1170, 2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1526605

ABSTRACT

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
4.
Med J Aust ; 216(5): 255-263, 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1481137

ABSTRACT

INTRODUCTION: The epidemiology and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are different in children and adolescents compared with adults. Although coronavirus disease 2019 (COVID-19) appears to be less common in children, with milder disease overall, severe complications may occur, including paediatric inflammatory multisystem syndrome (PIMS-TS). Recognising the distinct needs of this population, the National COVID-19 Clinical Evidence Taskforce formed a Paediatric and Adolescent Care Panel to provide living guidelines for Australian clinicians to manage children and adolescents with COVID-19 and COVID-19 complications. Living guidelines mean that these evidence-based recommendations are updated in near real time to give reliable, contemporaneous advice to Australian clinicians providing paediatric care. MAIN RECOMMENDATIONS: To date, the Taskforce has made 20 specific recommendations for children and adolescents, including definitions of disease severity, recommendations for therapy, respiratory support, and venous thromboembolism prophylaxis for COVID-19 and for the management of PIMS-TS. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: The Taskforce currently recommends corticosteroids as first line treatment for acute COVID-19 in children and adolescents who require oxygen. Tocilizumab could be considered, and remdesivir should not be administered routinely in this population. Non-invasive ventilation or high flow nasal cannulae should be considered in children and adolescents with hypoxaemia or respiratory distress unresponsive to low flow oxygen if appropriate infection control measures can be used. Children and adolescents with PIMS-TS should be managed by a multidisciplinary team. Intravenous immunoglobulin and corticosteroids, with concomitant aspirin and thromboprophylaxis, should be considered for the treatment of PIMS-TS. The latest updates and full recommendations are available at www.covid19evidence.net.au.


Subject(s)
COVID-19/complications , COVID-19/therapy , Adolescent , Age Factors , Australia , COVID-19/diagnosis , Child , Child, Preschool , Humans , Infant , Infant, Newborn
5.
J Paediatr Child Health ; 58(1): 46-53, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1480193

ABSTRACT

The global disruption of the COVID-19 pandemic has impacted the life of every child either directly or indirectly. This review explores the pathophysiology, immune response, clinical presentation and treatment of COVID-19 in children, summarising the most up-to-date data including recent developments regarding variants of concern. The acute infection with SARS-CoV-2 is generally mild in children, whilst the post-infectious manifestations, including paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and 'long COVID' in children, are more complex. Given that most research on COVID-19 has focused on adult cohorts and that clinical manifestations, treatment availability and impacts differ markedly in children, research that specifically examines COVID-19 in children needs to be prioritised.


Subject(s)
COVID-19 , COVID-19/complications , Child , Humans , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
6.
J Paediatr Child Health ; 58(1): 39-45, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1467589

ABSTRACT

Children globally have been profoundly impacted by the coronavirus disease 2019 (COVID-19) pandemic. This review explores the direct and indirect public health impacts of COVID-19 on children. We discuss in detail the transmission dynamics, vaccination strategies and, importantly, the 'shadow pandemic', encompassing underappreciated indirect impacts of the pandemic on children. The indirect effects of COVID-19 will have a long-term impact beyond the immediate pandemic period. These include the mental health and wellbeing risks, disruption to family income and attendant stressors including increased family violence, delayed medical attention and the critical issue of prolonged loss of face-to-face learning in a normal school environment. Amplification of existing inequities and creation of new disadvantage are likely additional sequelae, with children from vulnerable families disproportionately affected. We emphasise the responsibility of paediatricians to advocate on behalf of this vulnerable group to ensure the longer-term effects of COVID-19 public health responses on the health and wellbeing of children are fully considered.


Subject(s)
COVID-19 , Domestic Violence , Child , Humans , Mental Health , Pandemics , SARS-CoV-2
7.
Lancet Glob Health ; 9(10): e1423-e1430, 2021 10.
Article in English | MEDLINE | ID: covidwho-1363482

ABSTRACT

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.


Subject(s)
Rheumatic Fever , Rheumatic Heart Disease , Humans , Incidence , Prospective Studies , Rheumatic Fever/diagnosis , Rheumatic Fever/epidemiology , Rheumatic Heart Disease/diagnosis , Rheumatic Heart Disease/epidemiology , Uganda/epidemiology
8.
Arch Dis Child ; 107(3): e7, 2022 03.
Article in English | MEDLINE | ID: covidwho-1373947

ABSTRACT

BACKGROUND: Following a relative absence in winter 2020, a large resurgence of respiratory syncytial virus (RSV) detections occurred during the 2020/2021 summer in Western Australia. This seasonal shift was linked to SARS-CoV-2 public health measures. We examine the epidemiology and RSV testing of respiratory-coded admissions, and compare clinical phenotype of RSV-positive admissions between 2019 and 2020. METHOD: At a single tertiary paediatric centre, International Classification of Diseases, 10th edition Australian Modification-coded respiratory admissions longer than 12 hours were combined with laboratory data from 1 January 2019 to 31 December 2020. Data were grouped into bronchiolitis, other acute lower respiratory infection (OALRI) and wheeze, to assess RSV testing practices. For RSV-positive admissions, demographics and clinical features were compared between 2019 and 2020. RESULTS: RSV-positive admissions peaked in early summer 2020, following an absent winter season. Testing was higher in 2020: bronchiolitis, 94.8% vs 89.2% (p=0.01); OALRI, 88.6% vs 82.6% (p=0.02); and wheeze, 62.8% vs 25.5% (p<0.001). The 2020 peak month, December, contributed almost 75% of RSV-positive admissions, 2.5 times the 2019 peak. The median age in 2020 was twice that observed in 2019 (16.4 vs 8.1 months, p<0.001). The proportion of RSV-positive OALRI admissions was greater in 2020 (32.6% vs 24.9%, p=0.01). There were no clinically meaningful differences in length of stay or disease severity. INTERPRETATION: The 2020 RSV season was in summer, with a larger than expected peak. There was an increase in RSV-positive non-bronchiolitis admissions, consistent with infection in older RSV-naïve children. This resurgence raises concern for regions experiencing longer and more stringent SARS-CoV-2 public health measures.


Subject(s)
Respiratory Syncytial Virus Infections/epidemiology , Seasons , Bronchiolitis/epidemiology , Bronchiolitis/virology , COVID-19/epidemiology , Female , Hospitalization , Humans , Infant , Male , Pandemics , Respiratory Sounds/etiology , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus, Human , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , SARS-CoV-2 , Western Australia/epidemiology
10.
Clin Infect Dis ; 72(12): e1146-e1153, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1269565

ABSTRACT

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Child , Family Characteristics , Humans , Incidence , Pandemics
11.
J Paediatr Child Health ; 57(9): 1362-1369, 2021 09.
Article in English | MEDLINE | ID: covidwho-1261157

ABSTRACT

In 2020, school and early childhood educational centre (ECEC) closures affected over 1.5 billion school-aged children globally as part of the COVID-19 pandemic response. Attendance at school and access to ECEC is critical to a child's learning, well-being and health. School closures increase inequities by disproportionately affecting vulnerable children. Here, we summarise the role of children and adolescents in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and that of schools and ECECs in community transmission and describe the Australian experience. In Australia, most SARS-CoV-2 cases in schools were solitary (77% in NSW and 67% in Victoria); of those that did progress to an outbreak, >90% involved fewer than 10 cases. Australian and global experience has demonstrated that SARS-CoV-2 is predominantly introduced into schools and ECECs during periods of heightened community transmission. Implementation of public health mitigation strategies, including effective testing, tracing and isolation of contacts, means schools and ECECs can be safe, not drivers of transmission. Schools and ECEC are essential services and so they should be prioritised to stay open for face-to-face learning. This is particularly critical as we continue to manage the next phase of the COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , Adolescent , Child , Child, Preschool , Humans , Pandemics/prevention & control , SARS-CoV-2 , Schools , Victoria
12.
Front Public Health ; 9: 636921, 2021.
Article in English | MEDLINE | ID: covidwho-1128014

ABSTRACT

Introduction: Amidst the evolving COVID-19 pandemic, understanding the transmission dynamics of the SARS-CoV-2 virus is key to providing peace of mind for the community and informing policy-making decisions. While available data suggest that school-aged children are not significant spreaders of SARS-CoV-2, the possibility of transmission in schools remains an ongoing concern, especially among an aging teaching workforce. Even in low-prevalence settings, communities must balance the potential risk of transmission with the need for students' ongoing education. Through the roll out of high-throughput school-based SARS-CoV-2 testing, enhanced follow-up for individuals exposed to COVID-19 and wellbeing surveys, this study investigates the dynamics of SARS-CoV-2 transmission and the current psychosocial wellbeing impacts of the pandemic in school communities. Methods: The DETECT Schools Study is a prospective observational cohort surveillance study in 79 schools across Western Australia (WA), Australia. To investigate the incidence, transmission and impact of SARS-CoV-2 in schools, the study comprises three "modules": Module 1) Spot-testing in schools to screen for asymptomatic SARS-CoV-2; Module 2) Enhanced surveillance of close contacts following the identification of any COVID-19 case to determine the secondary attack rate of SARS-CoV-2 in a school setting; and Module 3) Survey monitoring of school staff, students and their parents to assess psycho-social wellbeing following the first wave of the COVID-19 pandemic in WA. Clinical Trial Registration: Trial registration number: ACTRN12620000922976.


Subject(s)
COVID-19 Testing/statistics & numerical data , COVID-19/diagnosis , COVID-19/psychology , Parents/psychology , Schools/statistics & numerical data , Students/psychology , Students/statistics & numerical data , Adolescent , Adult , Australia , COVID-19/epidemiology , Child , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pandemics/statistics & numerical data , Prevalence , Prospective Studies , SARS-CoV-2 , Western Australia/epidemiology
13.
Med J Aust ; 214(4): 188-188.e1, 2021 03.
Article in English | MEDLINE | ID: covidwho-1110637
14.
Intern Med J ; 50(10): 1267-1271, 2020 10.
Article in English | MEDLINE | ID: covidwho-780902

ABSTRACT

During a pandemic when hospitals are stretched and patients need isolation, the role of hospital-in-the-home (HITH) providing acute medical care at home has never been more relevant. We aimed to define and address the challenges to acute home care services posed by the COVID-19 pandemic. Planning for service operation involves staffing, equipment availability and cleaning, upskilling in telehealth and communication. Planning for clinical care involves maximising cohorts of patients without COVID-19 and new clinical pathways for patients with COVID-19. The risk of SARS-CoV-2 transmission, specific COVID-19 clinical pathways and the well-being of patients and staff should be addressed in advance.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Home Care Services/organization & administration , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Australasia/epidemiology , Betacoronavirus , COVID-19 , Communication , Equipment and Supplies, Hospital/supply & distribution , Health Workforce/organization & administration , Humans , Infection Control/organization & administration , Occupational Exposure/prevention & control , Pandemics , Patient-Centered Care/organization & administration , SARS-CoV-2 , Workload
15.
J Paediatr Child Health ; 56(8): 1219-1224, 2020 08.
Article in English | MEDLINE | ID: covidwho-175866

ABSTRACT

AIMS: COVID-19 is now a global pandemic. At the time of survey, fewer than 150 children in Australia and New Zealand had documented infection. The aim of this study was to assess attitudes, readiness and confidence in the early stages of the COVID-19 pandemic through an online survey of paediatric physicians and sub-specialists across Australia and New Zealand. METHODS: Multiple email list groups were used to contact paediatric physicians to undertake an online Likert scale survey between 17 and 24 March. Respondents' specialty, experience and work setting were recorded. Ordinal logistic regression was used to determine respondent factors. RESULTS: There were 542 respondents from across Australia and New Zealand: an estimated 11% of the paediatric physician workforce. A minority (36.6%) agreed that their national response had been well coordinated; the majority (92.7%) agreed that senior-level hospital administrators were taking the situation seriously. Most reported a good understanding of the natural history of COVID-19 in children, and knowledge of where to find local information. A large proportion of physicians (86.1%) were worried about becoming infected through their work; few (5.8%) reported that they would not come to work to avoid infection. Closure of school and childcares would reduce the ability to continue work at current capacity for 23.6% of respondents. CONCLUSION: Despite limited experience in pandemics, most paediatric physicians felt informed. Concern about exposure at work is common; most were willing to work regardless. The closure of schools and daycares may have an impact on staffing. Coordination and leadership will be critical.


Subject(s)
Attitude of Health Personnel , Betacoronavirus , Coronavirus Infections/epidemiology , Health Services Administration , Pandemics/prevention & control , Pediatricians , Pneumonia, Viral/epidemiology , Australia/epidemiology , COVID-19 , Delivery of Health Care/organization & administration , Female , Health Care Surveys , Humans , Male , New Zealand/epidemiology , Pediatrics , SARS-CoV-2
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