SARS-CoV-2 IN CHILDREN & ADOLESCENTS LIVING WITH HIV IN EUROPE & SOUTH AFRICA

Background: Adults living with HIV may have higher risk of SARS-CoV- 2 infection than HIV negative adults. There are no published data on seroprevalence of SARS-CoV-2 in children and adolescents living with HIV (CALWHIV). Method(s): We did a repeat SARS-CoV-2 seroprevalence study in 7 paediatric HIV observational cohorts in 5 countries in the European Pregnancy & Paediatric Infections Cohort Collaboration (EPPICC;Belgium, Greece, Spain, Ukraine, United Kingdom (UK)) and also the Cape Town Adolescent Antiretroviral Cohort (CTAAC), South Africa (SA) (CALWHIV and HIV negative adolescents). Participants gave 2 blood samples for SARS-CoV-2 antibody testing ~6 months apart during routine visits between May 2020 and July 2022, and completed questionnaires on SARS-CoV-2 exposure/infection and vaccine status. Clinical and demographic data were extracted from clinic records. Result(s): Of 906 participants, 53%(477) were female, 89%(803) CALWHIV, median [IQR] age at first visit 17[15-19] years. Most were enrolled in SA (45%, 410/906), UK (23%, 205/906) or Ukraine (18%, 160/906). 85%(767/906) had 2 blood samples and the rest a single sample. For CALWHIV, at time of first sample, 99%(761/765) were on antiretroviral therapy, median CD4 count was 666[478-858] cells/mL, 70%(535/764) had HIV-1 viral load < 50c/mL. Of those with known SARS-CoV-2 vaccine status, 23%(181/773) CALWHIV and 22% (22/100) HIV negative participants received >=1 vaccine dose. 6%(43/762) of CALWHIV had a documented prior SARS-CoV-2 positive PCR (including 2 hospitalised for COVID, neither severe), and 16%(124/762) self-reported previous positive test and/or COVID-19 symptoms, giving a total of 17%(128/762) with any previous infection. Based on serum testing, 63%(562/898) of participants overall were seropositive on at least one sample (55% (269/488) Europe, 67% (205/307) SA CALWHIV, 85% (88/103) SA HIV negative group), and among the unvaccinated subgroup, 53%(408/765) were seropositive (41% (167/412) Europe, 64% (168/263) SA CALWHIV, 81% (73/90) SA HIV negative). Among samples taken prior to or in absence of vaccination, the proportion testing antibody positive increased over time (Figure). Of unvaccinated CALWHIV with >=1 positive result, 17%(52/299) reported any previous SARS-CoV-2 infection. Conclusion(s): Most CALWHIV were SARS-CoV-2 seropositive by mid-2022 despite low vaccine coverage. Fewer had documented or self-reported COVID-19 infection or disease, suggesting most infections were mild or asymptomatic. Seroprevalence of SARS-CoV-2 antibodies in Europe and South Africa, by HIV status and calendar quarter of sampling. Colours indicate dominant variant based on GISAID data for adults and children.

Investigating the clinical characteristics of paediatric COVID-19 in Cape Town, South Africa: Initial results from the University of Cape Town (UCT), Department of Paediatrics and Child Health, COVID-19 paediatric repository

Introduction: Studies show that children account for only 1-5% of diagnosed COVID-19 cases, they have milder disease than adults and deaths are extremely rare. The complete clinical picture of pediatric COVID-19 has not yet been fully reported or defined. Additionally, the South African pediatric population has unique clinical characteristics and risk implications and needs investigating. We aimed to characterize COVID-19 in Cape Town children. Methods: The UCT COVID-19 pediatric repository is a prospective cohort recruited via convenience sampling at 3 Western Cape Hospitals. All patients ≤ 18 years who test COVID-19 positive are eligible for inclusion in the study. Results: To date 227 participants, 56%(125/227) male with median age 2 years (IQR:0-6), have been enrolled. Only 28(12%) participants were in contact with a confirmed COVID-19 positive case, 67% of these, were first degree relatives, 28% second degree relatives and 6% health care workers. Comorbidities were present in 125(56%) participants. Of 32 recorded comorbidities, congenital heart disease (CHD), found in 7% of participants, ranked third. CHD subtypes included PDA (4), Tetralogy of Fallot (3), AVSD (2), Pulmonary atresia with VSD (2), truncus arteriosus (1), Coarctation of the Aorta (1), Congenital aortic valve stenosis (1), and ASD (1). Other cardiac comorbidities were, cardiomyopathy (2), primary pulmonary hypertension (1) and rhabdomyoma (1). On presentation 173 (76%) were symptomatic. Predominant symptoms included cough 40%, history of fever 36%, documented fever 34%, difficulty breathing 28%, and nausea or vomiting 20%. On examination, 65% had abnormal heart rates, 47% abnormal respiratory rates, 35% were in respiratory distress and 24% were hypoxic. Of the 227 patients, 169(74%) were admitted to hospital and 33 (15%) were admitted to ICU. In the ICU 79% of patients required non-invasive and 24% invasive ventilation, median length of ICU admission was 3 days (IQR:2-7.5). During admission 38(17%) patients developed COVID-19 complications: secondary infection 10%, sepsis 4%, MIS-C 2%, and myocarditis or new onset heart failure 1%) and 2(0.9%) died, including one patient with AVSD, who presented with severe pulmonary hypertension and acute heart failure post cardiac surgery. Conclusion: We present the initial findings of the UCT pediatric COVID-19 registry. We anticipate that these data will help to complete the clinical picture of COVID-19 in the South African pediatric population.

The Efficacy and Impact in Heathy Infants of Nirsevimab on Medically Attended RSV Lower Respiratory Tract Infection

Background. Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in infants. Nirsevimab is a single-dose monoclonal antibody with extended half-life that was shown to protect preterm infants 29 to < 35 weeks gestation against RSV LRTI. However, most medically attended (MA) cases occur in otherwise healthy, term infants for whom there is currently no effective RSV prevention strategy. We report the primary analysis of efficacy and safety, along with the impact of nirsevimab in late preterm and term infants (≥ 35 weeks gestation) in the phase 3 MELODY study (NCT03979313). Methods. Infants were randomized 2:1 to receive one intramuscular injection of nirsevimab (50 mg if < 5 kg;100 mg if ≥ 5 kg at dosing) or placebo entering their first RSV season. The primary endpoint was the incidence of MA RSV LRTI over 150 days postdose. Cases met predefined clinical criteria of disease severity and were confirmed by real-time reverse-transcriptase PCR. Safety was evaluated through 360 days postdose. Enrollment started on 23 July 2019 and was suspended following the declaration of the COVID-19 pandemic by the WHO on 11 March 2020. Results. Overall, 1490 infants were randomized and included in the intent-totreat population;1465 (98%) completed the 150-day efficacy follow-up, and 1367 (92%) completed the 360-day safety follow-up. The incidence of MA RSV LRTI was 1.2% (n=12/994) in the nirsevimab group and 5.0% (n=25/496) in the placebo group, giving nirsevimab an efficacy of 74.5% (95% confidence interval [CI]: 49.6, 87.1;p< 0.0001). Nirsevimab averted 93.6 (95% CI 63.0, 124.0) MA LRTIs per 1000 infants dosed. Nirsevimab was well tolerated, with similar rates of adverse events (87.4% nirsevimab;86.8% placebo) and serious adverse events (6.8% nirsevimab;7.3% placebo) between groups. Conclusion. In this phase 3 study, a single dose of nirsevimab protected late preterm and term infants against MA RSV LRTI over an RSV season with a favorable safety profile. Approximately 11 infants need to be immunized to prevent 1 case of LRTI;nirsevimab has the potential to be an important intervention to reduce the burden of RSV LRTI in healthy infants.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Summary of childhood asthma guidelines, 2021: A consensus document

Asthma is the most common chronic illness of childhood. The prevalence is rising and the mortality and morbidity from asthma are unacceptably high in South Africa. It is important to make a correct diagnosis based, most importantly, on the clinical history and supported by investigations. The appropriate drug and device must be chosen to achieve good asthma control. Patients must be followed up regularly and their asthma control must be assessed. The treatment can then be adjusted according to the level of control. The COVID-19 pandemic has placed new challenges on the care of our asthmatics. Asthma education and adherence are important components of management of the condition.

Cross-sectional prevalence of SARS-CoV-2 antibodies in healthcare workers in paediatric facilities in eight countries.

BACKGROUND: Healthcare workers (HCWs) have been disproportionately affected by coronavirus disease 2019 (COVID-19), which may be driven, in part, by nosocomial exposure. If HCW exposure is predominantly nosocomial, HCWs in paediatric facilities, where few patients are admitted with COVID-19, may lack antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and be at increased risk during the current resurgence. AIM: To compare the seroprevalence of SARS-CoV-2 amongst HCWs in paediatric facilities in seven European countries and South Africa (N=8). METHODS: All categories of paediatric HCWs were invited to participate in the study, irrespective of previous symptoms. A single blood sample was taken and data about previous symptoms were documented. Serum was shipped to a central laboratory in London where SARS-CoV-2 immunoglobulin G was measured. FINDINGS: In total, 4114 HCWs were recruited between 1st May and mid-July 2020. The range of seroprevalence was 0-16.93%. The highest seroprevalence was found in London (16.93%), followed by Cape Town, South Africa (10.36%). There were no positive HCWs in the Austrian, Estonian and Latvian cohorts; 2/300 [0.66%, 95% confidence interval (CI) 0.18-2.4] HCWs tested positive in Lithuania; 1/124 (0.81%, 95% CI 0.14-4.3) HCWs tested positive in Romania; and 1/76 (1.3%, 95% CI 0.23-7.0) HCWs tested positive in Greece. CONCLUSION: Overall seroprevalence amongst paediatric HCWs is similar to their national populations and linked to the national COVID-19 burden. Staff working in paediatric facilities in low-burden countries have very low seroprevalence rates and thus are likely to be susceptible to COVID-19. Their susceptibility to infection may affect their ability to provide care in the face of increasing cases of COVID-19, and this highlights the need for appropriate preventative strategies in paediatric healthcare settings.

Diagnosis of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 2)

Background. Accurate diagnosis and attribution of the aetiology of pneumonia are important for measuring the burden of disease, implementing appropriate treatment strategies and developing more effective interventions. Objectives. To produce revised guidelines for the diagnosis of pneumonia in South African (SA) children, encompassing clinical, radiological and aetiological methods. Methods. An expert group was established to review diagnostic evidence and make recommendations for a revised SA guideline. Published evidence was reviewed and graded using the British Thoracic Society grading system. Results. Diagnosis of pneumonia should be considered in a child with acute cough, fast breathing or difficulty breathing. Revised World Health Organization guidelines classify such children into: (i) severe pneumonia;(ii) pneumonia (tachypoea or lower chest indrawing);or (iii) no pneumonia. Malnourished or immunocompromised children with lower chest indrawing should be managed as cases of severe pneumonia. Pulse oximetry should be done, with hospital referral for oxygen saturation <92%. A chest X-ray is indicated in severe pneumonia or when tuberculosis (TB) is suspected. Microbiological investigations are recommended in hospitalised patients or in outbreak settings. Improved aetiological methods show the importance of co-infections. Blood cultures have a low sensitivity (<5%), for diagnosing bacterial pneumonia. Highly sensitive, multiplex tests on upper respiratory samples or sputum detect multiple potential pathogens in most children. However, even in symptomatic children, it may be impossible to distinguish colonising from causative organisms, unless identification of the organism is strongly associated with attribution to causality, e.g. respiratory syncytial virus, Mycobacterium tuberculosis, Bordetella pertussis, influenza, para-influenza or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Investigations for TB should be considered in children with severe pneumonia who have been hospitalised, in a case of a known TB contact, if the tuberculin skin test is positive, if a child is malnourished or has lost weight, and in children living with HIV. Induced sputum may provide a higher yield than upper respiratory sampling for B. pertussis, M. tuberculosis and Pneumocystis jirovecii. Conclusions. Advances in clinical, radiological and aetiological methods have improved the diagnosis of childhood pneumonia.

Prevention of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 4)

BACKGROUND. More comprehensive immunisation regimens, strengthening of HIV prevention and management programmes and improved socioeconomic conditions have impacted on the epidemiology of paediatric community-acquired pneumonia (CAP) in South Africa (SA). OBJECTIVES. To summarise effective preventive strategies to reduce the burden of childhood CAP. METHODS. An expert subgroup reviewed existing SA guidelines and new publications focusing on prevention. Published evidence on pneumonia prevention informed the revisions;in the absence of evidence, expert opinion was used. Evidence was graded using the British Thoracic Society (BTS) grading system. RECOMMENDATIONS. General measures for prevention include minimising exposure to tobacco smoke or air pollution, breastfeeding, optimising nutrition, optimising maternal health from pregnancy onwards, adequate antenatal care and improvement in socioeconomic and living conditions. Prevention of viral transmission, including SARS-CoV-2, can be achieved by hand hygiene, environmental decontamination, use of masks and isolation of infected people. Specific preventive measures include vaccines as contained in the Expanded Programme on Immunisation schedule, isoniazid prophylaxis for tuberculosis, co-trimoxazole prophylaxis for HIV-infected infants and children who are immunosuppressed, and timely diagnosis of HIV, as well as antiretroviral therapy (ART) initiation. HIV-infected children treated with ART from early infancy, and HIV-exposed children, have similar immunogenicity and immune responses to most childhood vaccines as HIV-unexposed infants. VALIDATION. These recommendations are based on available published evidence supplemented by the consensus opinion of SA paediatric experts, and are consistent with those in published international guidelines.