Short-term outcomes of South African children with multisystem inflammatory syndrome in children: a prospective cohort study.

BACKGROUND: Despite the life-threatening presentation of multisystem inflammatory syndrome in children (MIS-C), the overall prognosis is favourable in centres with access to appropriate supportive care. In this study, we investigate the short-term outcomes in children with MIS-C in Cape Town, South Africa. METHODS: This prospective observational cohort study included children <13 years who fulfilled the WHO case definition of MIS-C and were admitted to Tygerberg Hospital in Cape Town, South Africa between 1 June 2020 and 31 October 2021. Clinical features were recorded at baseline and at follow-up at the 6-week cardiology and 3-month rheumatology-immunology clinics, respectively. FINDINGS: Fifty-three children with a median age of 7.4 years (IQR 4.2-9.9) were included. There was a slight male predominance (30/53; 56.6%) and the majority was of mixed ancestry (28/53; 52.83%) or black African ancestry (24/53; 45.3%). Fourteen children (14/53; 26.4%) had comorbid disease. The median length of hospital stay was 8 days (IQR 6-10). All children had an echocardiogram performed at baseline of which 39 were abnormal (39/53; 73.6%). All children were discharged alive. The median days from discharge to cardiology follow-up was 39 days (IQR 33.5-41.5) and for rheumatology-immunology clinic was 70.5 days (IQR 59.5-85.0). Eleven children (11/41; 26.8%) had a persistently abnormal echocardiogram at cardiology follow-up. Systemic inflammation and organ dysfunction resolved in most. INTERPRETATION: Although the short-term outcomes of MIS-C in our cohort were generally good, the cardiac morbidity needs further characterisation and follow-up.

Clinical Presentation and Outcome of Acute Respiratory Illnesses in South African Children During the COVID-19 Pandemic.

BACKGROUND: Data from low- and middle-income countries (LMICs) show higher morbidity and mortality in children with acute respiratory illness (ARI) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, whether SARS-CoV-2 infection is distinct from other causes of ARI in this regard is unclear. We describe clinical characteristics and outcomes of South African children with SARS-CoV-2 and non-SARS-CoV-2 ARIs. METHODS: We performed a cross-sectional study including 0-13 years old children admitted to Tygerberg Hospital between May and December 2020 with an ARI. Routine clinical data were collected by the attending clinicians. All children underwent SARS-CoV-2 polymerase chain reaction testing. For severity of disease, the need for respiratory support and duration of support was considered. Multivariable logistic regression models were built to determine the factors associated with SARS-CoV-2 infection and severity. RESULTS: Data for 176 children were available, 38 (22%) children were SARS-CoV-2 polymerase chain reaction positive and 138 (78%) were negative. SARS-CoV-2 positive children were more likely to be female (OR: 2.68, 95% CI: 1.18-6.07), had lower weight-for-age Z score (OR: 0.76, 95% CI: 0.63-0.93), presented more frequently with fever (OR: 3.56, 95% CI: 1.54-8.24) and less often with cough (OR: 0.27, 95% CI: 0.11-0.66). SARS-CoV-2 infection was associated with significantly longer duration of oxygen treatment (median 8 vs. 3 days; OR: 1.1, 95% CI: 1.01-1.20). Overall, 66% of children had viral coinfection, with no significant difference between the groups. In total, 18% of SARS-CoV-2 positive children were readmitted within 3 months for a respiratory reason, compared with 15% SARS-CoV-2 negative children (P = 0.64). CONCLUSIONS: Our data show that ARIs from SARS-CoV-2 cannot be easily differentiated, but were associated with a higher morbidity compared with ARIs from other causes. Overall outcomes were good. The long-term implications of severe SARS-CoV-2 pneumonia in young children in low- and middle-income countries require further study.

Chronic lung disease in children due to SARS-CoV-2 pneumonia: Case series.

The reported prevalence of chronic lung disease (CLD) due to coronavirus 2 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2)]) pneumonia with the severe acute respiratory syndrome in children is unknown and rarely reported in English literature. In contrast to most other respiratory viruses, children generally have less severe symptoms when infected with SARS-CoV-2. Although only a minority of children with SARS-CoV-2 infection require hospitalization, severe cases have been reported. More severe SARS-CoV-2 respiratory disease in infants has been reported in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe our experience of five cases of CLD in children due to SARS-CoV-2 collected between April 2020 and August 2022. We included children who had a history of a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen test or a positive antibody test in the serum. Three patterns of CLD related to SARS-CoV-2 were identified: (1) CLD in infants postventilation for severe pneumonia (n = 3); (2) small airway disease with bronchiolitis obliterans picture (n = 1) and (3) adolescent with adult-like post-SARS-CoV-2 disease (n = 1). Chest computerized tomography scans showed airspace disease and ground-glass opacities involving both lungs with the development of coarse interstitial markings seen in four patients, reflecting the long-term fibrotic consequences of diffuse alveolar damage that occur in children post-SARS-CoV-2 infection. Children with SARS-CoV-2 infection mostly have mild symptoms with little to no long-term sequelae, but the severe long-term respiratory disease can develop.

UMOYA: a prospective longitudinal cohort study to evaluate novel diagnostic tools and to assess long-term impact on lung health in South African children with presumptive pulmonary TB-a study protocol.

BACKGROUND: Despite a high paediatric tuberculosis (TB) burden globally, sensitive and specific diagnostic tools are lacking. In addition, no data exist on the impact of pulmonary TB on long-term child lung health in low- and middle-income countries. The prospective observational UMOYA study aims (1) to build a state-of-the-art clinical, radiological, and biological repository of well-characterised children with presumptive pulmonary TB as a platform for future studies to explore new emerging diagnostic tools and biomarkers for early diagnosis and treatment response; and (2) to investigate the short and long-term impact of pulmonary TB on lung health and quality of life in children. METHODS: We will recruit up to 600 children (0-13 years) with presumptive pulmonary TB and 100 healthy controls. Recruitment started in November 2017 and is expected to continue until May 2023. Sputum and non-sputum-based samples are collected at enrolment and during follow-up in TB cases and symptomatic controls. TB treatment is started by routine care services. Intensive follow-up for 6 months will allow for TB cases to retrospectively be classified according to international consensus clinical case definitions for TB. Long-term follow-up, including imaging, comprehensive assessment of lung function and quality of life questionnaires, are done yearly up to 4 years after recruitment. DISCUSSION: The UMOYA study will provide a unique platform to evaluate new emerging diagnostic tools and biomarkers for early diagnosis and treatment response and to investigate long-term outcomes of pulmonary TB and other respiratory events on lung health in children.

Pediatric coronavirus disease 2019 in Africa.

PURPOSE OF REVIEW: Three years into the coronavirus disease 2019 (COVID-19) pandemic, data on pediatric COVID-19 from African settings is limited. Understanding the impact of the pandemic in this setting with a high burden of communicable and noncommunicable diseases is critical to implementing effective interventions in public health programs. RECENT FINDINGS: More severe COVID-19 has been reported in African settings, with especially infants and children with underlying comorbidities at highest risk for more severe disease. Data on the role of tuberculosis and HIV remain sparse. Compared to better resourced settings more children with multisystem inflammatory disease (MISC) are younger than 5 years and there is higher morbidity in all settings and increased mortality in some settings. Several reports suggest decreasing prevalence and severity of MIS-C disease with subsequent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant waves. Whether this decrease continues remains to be determined. Thus far, data on long-COVID in African settings is lacking and urgently needed considering the severity of the disease seen in the African population. SUMMARY: Considering the differences seen in the severity of disease and short-term outcomes, there is an urgent need to establish long-term outcomes in children with COVID-19 and MIS-C in African children, including lung health assessment.

The Impact of SARS-CoV-2 Variants on the Clinical Phenotype and Severity of Multisystem Inflammatory Syndrome in Children in South Africa.

The effects of SARS-CoV-2 variants on disease phenotype and severity of multisystem inflammatory syndrome in children (MIS-C) are unknown. We compared the clinical phenotype of MIS-C in 129 South African children across four distinct (Ancestral type, Beta, Delta, and Omicron) variant-driven waves and found that MIS-C remains a severe disease with a stable clinical presentation, regardless of variant.

SARS-CoV-2 in children and their accompanying caregivers: Implications for testing strategies in resource limited hospitals.

Background: Identification of SARS-CoV-2 infected individuals is imperative to prevent hospital transmission, but symptom-based screening may fail to identify asymptomatic/mildly symptomatic infectious children and their caregivers. Methods: A COVID-19 period prevalence study was conducted between 13 and 26 August 2020 at Tygerberg Hospital, testing all children and their accompanying asymptomatic caregivers after initial symptom screening. One nasopharyngeal swab was submitted for SARS-CoV-2 using real-time reverse-transcription polymerase chain reaction (rRT-PCR). An additional Respiratory Viral 16-multiplex rRT-PCR test was simultaneously done in children presenting with symptoms compatible with possible SARS-CoV-2 infection. Results: SARS-Co-V 2 RT-PCR tests from 196 children and 116 caregivers were included in the analysis. The SARS-CoV-2 period prevalence in children was 5.6% (11/196) versus 15.5% (18/116) in asymptomatic caregivers (p<0.01). Presenting symptoms did not correlate with SARS-CoV-2 test positivity; children without typical symptoms of SARS-CoV-2 were more likely to be positive than those with typical symptoms (10.2% [10/99] vs 1% [1/97]; p<0.01). Children with typical symptoms (97/196; 49.5%) mainly presented with acute respiratory (68/97; 70.1%), fever (17/97; 17.5%), or gastro-intestinal complaints (12/97; 12.4%); Human Rhinovirus (23/81; 28.4%) and Respiratory Syncytial Virus (18/81; 22.2%) were frequently identified in this group. Children-caregiver pairs' SARS-CoV-2 tests were discordant in 83.3%; 15/18 infected caregivers' children tested negative. Symptom-based COVID-19 screening alone would have missed 90% of the positive children and 100% of asymptomatic but positive caregivers. Conclusion: Given the poor correlation between SARS-CoV-2 symptoms and RT-PCR test positivity, universal testing of children and their accompanying caregivers should be considered for emergency and inpatient paediatric admissions during high COVID-19 community transmission periods. Universal PPE and optimising ventilation is likely the most effective way to control transmission of respiratory viral infections, including SARS-CoV-2, where universal testing is not feasible. In these settings, repeated point prevalence studies may be useful to inform local testing and cohorting strategies.

Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries.

IMPORTANCE: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. OBJECTIVE: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. EXPOSURES: Age, sex, preexisting comorbidities, and region of residence. MAIN OUTCOMES AND MEASURES: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. RESULTS: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. CONCLUSIONS AND RELEVANCE: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

Clinical Experience With Severe Acute Respiratory Syndrome Coronavirus 2-Related Illness in Children: Hospital Experience in Cape Town, South Africa.

BACKGROUND: Children seem relatively protected from serious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease, but little is known about children living in settings with high tuberculosis and human immunodeficiency virus (HIV) burden. This study reflects clinical data on South African children with SARS-CoV-2. METHODS: We collected clinical data of children aged <13 years with laboratory-confirmed SARS-CoV-2 presenting to Tygerberg Hospital, Cape Town, between 17 April and 24 July 2020. RESULTS: One hundred fifty-nine children (median age, 48.0 months [interquartile range {IQR}, 12.0-106.0 months]) were included. Hospitalized children (n = 62), with a median age of 13.5 months (IQR, 1.8-43.5 months) were younger than children not admitted (n = 97; median age, 81.0 months [IQR, 34.5-120.5 months]; P < .01.). Thirty-three of 159 (20.8%) children had preexisting medical conditions. Fifty-one of 62 (82.3%) hospitalized children were symptomatic; lower respiratory tract infection was diagnosed in 21 of 51 (41.2%) children, and in 11 of 16 (68.8%) children <3 months of age. Respiratory support was required in 25 of 51 (49.0%) children; 13 of these (52.0%) were <3 months of age. One child was HIV infected and 11 of 51 (21.2%) were HIV exposed but uninfected, and 7 of 51 (13.7%) children had a recent or new diagnosis of tuberculosis. CONCLUSIONS: Children <1 year of age hospitalized with SARS-CoV-2 in Cape Town frequently required respiratory support. Access to oxygen may be limited in some low- and middle-income countries, which could potentially drive morbidity and mortality. HIV infection was uncommon but a relationship between HIV exposure, tuberculosis, and SARS-CoV-2 should be explored.