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1.
Commun Med (Lond) ; 1: 47, 2021.
Article in English | MEDLINE | ID: covidwho-1860419

ABSTRACT

Background: Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. Methods: We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. Results: Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. Conclusions: These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334412

ABSTRACT

Background: Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine assessment of household mitigation measures;nasopharyngeal, saliva and stool PCR testing;along with mucosal and systemic SARS-CoV-2 specific antibodies, to comprehensively characterise SARS-CoV-2 infection and transmission in households. Methods: Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following onset of infection with ancestral SARS-CoV-2 variants. Results: The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and non-respiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterised by lower respiratory Ct-values than low transmission families (Median 22.62 vs 32.91;IQR 17.06 to 28.67 vs 30.37 to 34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralising antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. Conclusion: Utilising respiratory and non-respiratory PCR testing, along with measurement of SARS-CoV-2 specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.

3.
JAMA Netw Open ; 5(3): e221313, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1733812

ABSTRACT

Importance: The immune response in children with SARS-CoV-2 infection is not well understood. Objective: To compare seroconversion in nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion. Design, Setting, and Participants: This household cohort study of SARS-CoV-2 infection collected weekly nasopharyngeal and throat swabs and blood samples during the acute (median, 7 days for children and 12 days for adults [IQR, 4-13] days) and convalescent (median, 41 [IQR, 31-49] days) periods after polymerase chain reaction (PCR) diagnosis for analysis. Participants were recruited at The Royal Children's Hospital, Melbourne, Australia, from May 10 to October 28, 2020. Participants included patients who had a SARS-CoV-2-positive nasopharyngeal or oropharyngeal swab specimen using PCR analysis. Main Outcomes and Measures: SARS-CoV-2 immunoglobulin G (IgG) and cellular (T cell and B cell) responses in children and adults. Seroconversion was defined by seropositivity in all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] and 2 commercial assays: a SARS-CoV-2 S1/S2 IgG assay and a SARS-CoV-2 antibody ELISA) serological assays. Results: Among 108 participants with SARS-CoV-2-positive PCR findings, 57 were children (35 boys [61.4%]; median age, 4 [IQR, 2-10] years) and 51 were adults (28 women [54.9%]; median age, 37 [IQR, 34-45] years). Using the 3 established serological assays, a lower proportion of children had seroconversion to IgG compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P < .001). This result was not associated with viral load, which was similar in children and adults (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] vs 24.14 [8.47]; P = .09). In addition, age and sex were not associated with seroconversion within children (median age, 4 [IQR, 2-14] years for both seropositive and seronegative groups; seroconversion by sex, 10 of 21 girls [47.6%] vs 10 of 33 boys [30.3%]) or adults (median ages, 37 years for seropositive and 40 years for seronegative adults [IQR, 34-39 years]; seroconversion by sex, 18 of 24 women [75.0%] vs 14 of 18 men [77.8%]) (P > .05 for all comparisons between seronegative and seropositive groups). Symptomatic adults had 3-fold higher SARS-CoV-2 IgG levels than asymptomatic adults (median, 227.5 [IQR, 133.7-521.6] vs 75.3 [IQR, 36.9-113.6] IU/mL), whereas no differences were observed in children regardless of symptoms. Moreover, differences in cellular immune responses were observed in adults compared with children with seroconversion. Conclusions and Relevance: The findings of this cohort study suggest that among patients with mild COVID-19, children may be less likely to have seroconversion than adults despite similar viral loads. This finding has implications for future protection after SARS-CoV-2 infection in children and for interpretation of serosurveys that involve children. Further research to understand why seroconversion and development of symptoms are potentially less likely in children after SARS-CoV-2 infection and to compare vaccine responses may be of clinical and scientific importance.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Age Factors , COVID-19/epidemiology , COVID-19 Serological Testing , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Middle Aged , Seroconversion , Victoria/epidemiology , Viral Load
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322872

ABSTRACT

Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have mild or asymptomatic infection, but the underlying immunological differences remain unclear. We describe clinical features, virology, longitudinal cellular and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who were repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children were similar to their parents at all timepoints. All family members had salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincided with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child had IgG antibody detected against the S1 protein and virus neutralising activity ranging from just detectable to robust titers. Using a systems serology approach, we show that all family members demonstrated higher levels of SARS-CoV-2-specific antibody features than healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological evidence of infection. This raises the possibility that despite chronic exposure, immunity in children prevents establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may therefore not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306750

ABSTRACT

Background: There are limited data in paediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of COVID-19. We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive (SARS-CoV-2[+]) compared to those testing negative (SARS-CoV-2[-]) at our institution. Method Prospective cohort with nested case-control study of all children tested by PCR for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. Results In total, 179 SARS-CoV-2[+] children (44% female, median age 3.5 yrs, range 0.1 to 19.0 yrs) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 yrs, range 0.1 to 18.3 yrs). The commonest co-morbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs n = 10, 2.3%, p = 0.82). In the SARS-CoV-2 group, the prevalence of symptomatic disease was similar amongst children with and without cardiorespiratory comorbidities (n = 12, 75% vs n = 103, 57%, p = 0.35) who tested positive. A high proportion of children hospitalised with SARS-CoV-2 infection had cardiac comorbidities (23.8%). Conclusions In this single site dataset, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. High rates of comorbid cardiac disease were observed amongst hospitalised children with COVID-19, warranting further research to inform public health measures and vaccine prioritisation.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315422

ABSTRACT

Children have lower hospitalisation and mortality rates for coronavirus disease-2019 (COVID-19) than adults;however, younger children (<4 years of age) 1 may develop more severe disease than older children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterized. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19. Systemic cellular and cytokine profiling showed initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8+ T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4+T (but not CD8+T) cells occurred over time, with predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Significant in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295859

ABSTRACT

Children are at lower risk of developing severe COVID-19, yet the underlying immune mechanisms are understudied. While children’s innate immunity can drive rapid resolution of SARS-CoV-2 infection, the establishment of SARS-CoV-2-specific T-cell and B-cell memory in COVID-19 children remains unexplored. We recruited a household cohort to understand SARS-CoV-2-specific CD4+ and CD8+ T-cell immune responses at one month after mild or asymptomatic SARS-CoV-2 infection in PCR-positive children in comparison to those found in their mothers. We analysed SARS-CoV-2-specific T-cell responses, together with B-cells, directly ex vivo using six HLA class-I tetramers and one class-II tetramer presenting SARS57 CoV-2 T-cell epitopes (A1/ORF1a1637, A2/S269, A3/N361, A24/S1208, B7/N105, B40/N322 and DPB4/S167), and Spike- and Receptor Binding Domain (RBD)-specific B-cell probes. Our in depth profiling of epitope-specific T-cell responses at quantitative, phenotypic and clonal levels found that only children who seroconverted had prominent memory T-cell and B-cell profiles. These children had a high magnitude of SARS-CoV-2-specific T-cells displaying memory phenotypes and prevalent T-cell receptor motifs, which were not observed in PCR+ RBD but IgG-negative children. This suggests that seroconversion but not PCR-positivity defines establishment of adaptive SARS-CoV-2-specific immunological memory in children. Our study suggests that COVID-19 vaccination of children could be a major advantage in terms of establishing T-cell and B-cell immunological memory, especially in children who did not seroconvert after SARS-CoV-2 infection.

8.
BMJ Open ; 11(11): e054510, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1507057

ABSTRACT

OBJECTIVE: To present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation. DESIGN: Prospective, multicentre cohort study. SETTING: Eight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network-Paediatric Active Enhanced Disease (PAEDS). PARTICIPANTS: All children aged <19 years with SARS-CoV-2 infection including COVID-19, Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) and Kawasaki-like disease TS infection (KD-TS) treated at a PAEDS site from 24 March 2020 to 31 December 2020. INTERVENTION: Laboratory-confirmed SARS-CoV-2 infection. MAIN OUTCOME: Incidence of severe disease among children with COVID-19, PIMS-TS and KD-TS. We also compared KD epidemiology before and during the COVID-19 pandemic. RESULTS: Among 386 children with SARS-CoV-2 infection, 381 (98.7%) had COVID-19 (median 6.3 years (IQR 2.1-12.8),53.3% male) and 5 (1.3%) had multisystem inflammatory syndromes (PIMS-TS, n=4; KD-TS, n=1) (median 7.9 years (IQR 7.8-9.8)). Most children with COVID-19 (n=278; 73%) were Australian-born from jurisdictions with highest community transmission. Comorbidities were present in 72 (18.9%); cardiac and respiratory comorbidities were most common (n=32/72;44%). 37 (9.7%) children with COVID-19 were hospitalised, and two (0.5%) required intensive care. Postinfective inflammatory syndromes (PIMS-TS/KD-TS) were uncommon (n=5; 1.3%), all were hospitalised and three (3/5; 60%) required intensive care management. All children recovered and there were no deaths. KD incidence remained stable during the pandemic compared with prepandemic. CONCLUSIONS: Most children with COVID-19 had mild disease. Severe disease was less frequent than reported in high prevalence settings. Preventative strategies, such as vaccination, including children and adolescents, could reduce both the acute and postinfective manifestations of the disease.


Subject(s)
COVID-19 , Adolescent , Australia/epidemiology , COVID-19/complications , Child , Cohort Studies , Female , Hospitals, Pediatric , Humans , Male , Pandemics , Prospective Studies , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
9.
Front Immunol ; 12: 741639, 2021.
Article in English | MEDLINE | ID: covidwho-1497078

ABSTRACT

Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Convalescence , Environmental Exposure , Family Characteristics , Female , Humans , Immunity, Cellular , Immunologic Memory , Infant , Male , Middle Aged , Young Adult
10.
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
11.
J Paediatr Child Health ; 58(4): 618-623, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1480192

ABSTRACT

AIM: Victoria experienced two 'waves' of COVID-19 between March and September 2020 and more cases than any other jurisdiction in Australia. Although world-wide reports of COVID-19 reflect that children are less likely to experience severe disease compared with adults, hospitalisations and deaths have been reported. We report testing and outcomes of children with SARS-CoV-2 infection presenting to a tertiary paediatric hospital in Melbourne. METHODS: We conducted a prospective cohort study at The Royal Children's Hospital (RCH), including all children and adolescents (aged 0-18 years) who presented and were tested for SARS-CoV-2 over a 6-month period, between 21 March 2020, up to the 21 September 2020. Detailed epidemiological and clinical data were recorded. RESULTS: A total of 19 708 tests for SARS-CoV-2 were performed in 14 419 patients. One hundred and eighty patients tested positive for SARS-CoV-2 (1.2%). 110 (61%) were symptomatic, 60 (33%) were asymptomatic and 10 (6%) were pre-symptomatic. Close contacts of a positive case were associated with a higher risk of a testing positive for SARS-CoV-2 (120/2027 (6%) vs. 60/14589 (0.4%), RD 5.5 (95% CI 4.5 to 6.5), P < 0.001). Eighteen (10%) SARS-CoV-2-positive patients were admitted to hospital with one patient requiring intensive care. All patients recovered fully with no deaths. CONCLUSION: In Victorian children presenting to a tertiary hospital, SARS-CoV-2 infection caused predominantly mild or asymptomatic infection, with most children not requiring hospitalisation.


Subject(s)
COVID-19 , Adolescent , Adult , COVID-19/epidemiology , Child , Child, Preschool , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Prospective Studies , SARS-CoV-2 , Tertiary Care Centers , Victoria/epidemiology
12.
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
14.
Pediatr Pulmonol ; 56(12): 3664-3668, 2021 12.
Article in English | MEDLINE | ID: covidwho-1384289

ABSTRACT

BACKGROUND: There are limited data in pediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of coronavirus disease 2019 (COVID-19). We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2[+]) compared with those testing negative (SARS-CoV-2[-]) at our institution. METHOD: Prospective cohort with nested case-control study of all children tested by polymerase chain reaction (PCR) for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. RESULTS: In total, 179 SARS-CoV-2[+] children (44% females, median age 3.5 years, range: 0.1-19.0 years) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 years, range: 0.1-18.3 years). The commonest comorbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs. n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs. n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs. n = 10, 2.3%, p = 0.82). In the SARS-CoV-2[+] group, the prevalence of symptomatic disease was similar among children with and without cardiorespiratory comorbidities (n = 12, 75% vs. n = 103, 57%, p = 0.35). A high proportion of children hospitalized with SARS-CoV-2 infection had cardiac comorbidities (23.8%). CONCLUSIONS: In this single site data set, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. Rates of symptomatic infection were similar between children with and without cardiorespiratory comorbidity. High rates of comorbid cardiac disease were observed among hospitalized children with COVID-19 warranting further research to inform vaccine prioritization.


Subject(s)
COVID-19 , SARS-CoV-2 , Case-Control Studies , Child , Child, Preschool , Comorbidity , Female , Humans , Male , Prospective Studies
15.
Med J Aust ; 215(5): 217-221, 2021 09 06.
Article in English | MEDLINE | ID: covidwho-1355152

ABSTRACT

OBJECTIVES: To examine the epidemiological and clinical characteristics of SARS-CoV-2-positive children in Australia during 2020. DESIGN, SETTING: Multicentre retrospective study in 16 hospitals of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network; eleven in Victoria, five in four other Australian states. PARTICIPANTS: Children aged 0-17 years who presented to hospital-based COVID-19 testing clinics, hospital wards, or emergency departments during 1 February - 30 September 2020 and who were positive for SARS-CoV-2. MAIN OUTCOME MEASURES: Epidemiological and clinical characteristics of children positive for SARS-CoV-2. RESULTS: A total of 393 SARS-CoV-2-positive children (181 girls, 46%) presented to the participating hospitals (426 presentations, including 131 to emergency departments [31%]), the first on 3 February 2020. Thirty-three children presented more than once (8%), including two who were transferred to participating tertiary centres (0.5%). The median age of the children was 5.3 years (IQR, 1.9-12.0 years; range, 10 days to 17.9 years). Hospital admissions followed 51 of 426 presentations (12%; 44 children), including 17 patients who were managed remotely by hospital in the home. Only 16 of the 426 presentations led to hospital medical interventions (4%). Two children (0.5%) were diagnosed with the paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). CONCLUSION: The clinical course for most SARS-CoV-2-positive children who presented to Australian hospitals was mild, and did not require medical intervention.


Subject(s)
COVID-19 Testing/statistics & numerical data , COVID-19/diagnosis , COVID-19/epidemiology , Emergency Service, Hospital/statistics & numerical data , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Adolescent , Ambulatory Care Facilities/statistics & numerical data , Australia , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Symptom Assessment
16.
Med J Aust ; 215(6): 273-278, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1319820

ABSTRACT

OBJECTIVE: To compare the concordance and acceptability of saliva testing with standard-of-care oropharyngeal and bilateral deep nasal swab testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in children and in general practice. DESIGN: Prospective multicentre diagnostic validation study. SETTING: Royal Children's Hospital, and two general practices (cohealth, West Melbourne; Cirqit Health, Altona North) in Melbourne, July-October 2020. PARTICIPANTS: 1050 people who provided paired saliva and oropharyngeal-nasal swabs for SARS-CoV-2 testing. MAIN OUTCOME MEASURES: Numbers of cases in which SARS-CoV-2 was detected in either specimen type by real-time polymerase chain reaction; concordance of results for paired specimens; positive percent agreement (PPA) for virus detection, by specimen type. RESULTS: SARS-CoV-2 was detected in 54 of 1050 people with assessable specimens (5%), including 19 cases (35%) in which both specimens were positive. The overall PPA was 72% (95% CI, 58-84%) for saliva and 63% (95% CI, 49-76%) for oropharyngeal-nasal swabs. For the 35 positive specimens from people aged 10 years or more, PPA was 86% (95% CI, 70-95%) for saliva and 63% (95% CI, 45-79%) for oropharyngeal-nasal swabs. Adding saliva testing to standard-of-care oropharyngeal-nasal swab testing increased overall case detection by 59% (95% CI, 29-95%). Providing saliva was preferred to an oropharyngeal-nasal swab by most participants (75%), including 141 of 153 children under 10 years of age (92%). CONCLUSION: In children over 10 years of age and adults, saliva testing alone may be suitable for SARS-CoV-2 detection, while for children under 10, saliva testing may be suitable as an adjunct to oropharyngeal-nasal swab testing for increasing case detection.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Adolescent , Adult , Age Factors , Aged , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Prospective Studies , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , Saliva/virology , Young Adult
18.
Emerg Infect Dis ; 27(8): 2233-2235, 2021.
Article in English | MEDLINE | ID: covidwho-1238860

ABSTRACT

The duration of the humoral immune response in children infected with severe acute respiratory syndrome coronavirus 2 is unknown. We detected specific IgG 6 months after infection in children who were asymptomatic or had mild symptoms of coronavirus disease. These findings will inform vaccination strategies and other prevention measures.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Australia/epidemiology , Child , Humans , Immunoglobulin G
20.
Nat Commun ; 12(1): 2037, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1164849

ABSTRACT

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.


Subject(s)
Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibody Formation/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19 Vaccines/immunology , Child , Child, Preschool , Cross Reactions/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Middle Aged , Receptors, IgG/immunology , Spike Glycoprotein, Coronavirus/immunology , Young Adult
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