BURDEN AND SEVERITY OF COVID-19 IN CHILDREN HOSPITALISED OVER FIVE COVID-19 WAVES IN SOWETO, SOUTH AFRICA

Intro There is sparse data on SARS-CoV-2 infection among paediatric patients from low-middle income countries (LMICs), including from sub-Saharan Africa. We describe the burden and severity of disease in children treated with SARS- CoV-2 infection at an academic hospital in Soweto, South Africa from 30 March 2020 through 30 June 2022. Methods SARS-CoV-2 was detected using reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal swab specimens. Clinical diagnoses, HIV status, admission C-reactive protein (CRP), blood culture results and clinical outcomes were captured. Epidemic waves were designated as follows: Wave 1 (01 March to 14 October 2020);Wave 2 (15 October 2020 to 17 May 2021);Wave 3 (18 May to 14 November 2021);Wave 4 (15 November 2021 to 14 March 2022);Wave 5 (15 March to 30 June 2022). Findings There were 797 SARS-CoV-2 positive paediatric hospitalisations in the study period. SARS-CoV-2 detection prevalence was 4.6% (77/1,673) in Wave 1, 3.9% (134/3,426) in Wave 2, 7.1% (187/2,618) in Wave 3, 12.5% (261/2,088) in Wave 4 and 5.9% (138/2,320) in Wave 5. Among SARS-CoV-2 positive cases, the prevalence of respiratory admission diagnoses increased over time (16.9% in Wave 1 to 42.8% in Wave 5). Conversely, the prevalence of multisystem inflammatory syndrom of childhood (MIS-C) and case fatailty ratios (CFRs) declined from Wave 1 to Wave 5 (MIS-C: 20.8% to 2.2%;CFR: 9.1% to 3.6%). Death was significantly associated with younger age (median age 3.4 versus 16.9 months), positive admission blood cultures (24.0% versus 8.4%), MIS-C (20.7% versus 6.5%), and HIV infection (21.1% versus 4.5%). Conclusion The omicron dominated fourth and fifth waves of SARS-CoV-2 infection were associated with a higher prevalence of respiratory admission diagnoses, but lower case fatality compared to the ancestral first wave in South African children. Optimisation of antenatal maternal SARS-CoV-2 vaccination and early HIV diagnosis may impact on paediatric SARS-CoV-2 CFR.

Children caught in the long shadow of COVID-19

Despite the more transmissible delta variant being associated with higher rates of COVID-19 in unvaccinated adolescents, children have remained relatively spared from severe disease. Nevertheless, children are indirectly affected by the COVID-19 pandemic, which threatens to have far-reaching consequences. The effect of disruptions of seasonal patterns of circulation of respiratory pathogens on future immunity against such pathogens, childhood immunisation programmes, and HIV and tuberculosis treatment programmes poses a threat to the future wellbeing of children. Furthermore, the economic devastation caused by the pandemic, including an increase in unemployment, gives rise to numerous challenges, such as food insecurity, which is likely to worsen childhood nutritional status. Also, COVID-19 has ongoing effects on the mental wellbeing of children, driven in part by the interruption of schooling and other opportunities to socialise. An increase in psychological illnesses has manifested in children consequent to the stresses of the pandemic, lockdowns, caregiver deaths. In this article, we highlight the indirect effects of COVID-19 on children, and suggest solutions to mitigate against the long-term sequelae. A focused health, nutrition, education and child protection response is required from government and healthcare practitioners to safeguard the health and wellbeing of South African children. © 2021, Health and Medical Publishing Group. All rights reserved.

COVID-19 herd immunity v. learning to live with the virus.

Mutations of SARS-CoV-2 have been associated with increased transmissibility and occasionally reduced sensitivity to neutralising antibody activity induced by past ancestry virus infection or current COVID-19 vaccines. Nevertheless, COVID-19 vaccines have consistently demonstrated high efficacy and effectiveness against COVID-19 severe disease, hospitalisation and death, including disease caused by designated variants of concern. In contrast, COVID-19 vaccines are more heterogeneous in reducing the risk of infection and mild COVID19, and are modestly effective in interrupting virus transmission. Ongoing mutations of SARS-CoV-2 resulting in increased transmissibility and relative evasion of neutralising antibody activity induced by past virus infection or COVID-19 vaccines are likely. The duration of protection induced by COVID-19 vaccines is modelled to be relatively short in protecting against infection and mild COVID-19, but is likely to be 2 - 3 years against severe disease. Current experience from the UK and Israel demonstrates that even with high levels of COVID19 vaccine coverage (>85% of the adult population), resurgences with new variants of concern remain a strong probability. Nevertheless, such resurgences are not mirrored by high rates of hospitalisation and death compared with what was experienced in relatively COVID-19 vaccine-naive populations. Even though COVID-19 vaccines are unlikely to result in a herd immunity state, their ability to protect against severe COVID-19 and death could allow for a return to normalcy once a large enough proportion of the adult population in a country has been vaccinated.

A call to action: Temporal trends of COVID-19 deaths in the South African Muslim community.

Letter by Omar on letter by Jassat et al. (Jassat W, Brey Z, Parker S, et al. A call to action: Temporal trends of COVID-19 deaths in the South African Muslim community. S Afr Med J 2021;111(8):692-694. https://doi.org/10.7196/SAMJ.2021.v111i8.15878); and response by Jassat et al.

COVID-19 vaccines - less obfuscation, more transparency and action

Letter by Venter et al. on editorial by Schoub (Dial down the rhetoric over COVID-19 vaccines. S Afr Med J 2021;111(6):522-523. https://doi.org/10.7196/SAMJ.2021.v111i6.15740).

Asymptomatic COVID-19 in South Africa - implications for the control of transmission.

Asymptomatic COVID-19 may contribute significantly to the pandemic trajectory based on global biological, epidemiological and modelling evidence. A retrospective analysis was done to determine the proportion of asymptomatic COVID-19 in the workplace during the lockdown period from 27 March to 31 May 2020. We found that nearly 45% of cases were asymptomatic at the time of the first test. This high proportion of asymptomatic COVID-19 cases has implications for interventions, such as enforcing quarantine of all close contacts of COVID-19 cases regardless of symptoms.

Le COVID-19 a symptomatique pourrait contribuer significativement à la trajectoire de la pandémie en se basant sur des preuves mondiales, biologique et épidémiologiques, et en modélisant les preuves. Une analyse rétrospective a été réalisée afin de décrire la proportion d'infections asymptomatiques de SARS-CoV-2 parmi les clusters essentiels sur les lieux de travail en Afrique du Sud où des investigations de flambée ont été réalisées durant la période de confinement très restrictive du 27 mars au 31 mai 2020. Près de 45% des cas étaient asymptomatique lors du premier test. Cette proportion élevée des cas de COVID-19 asymptomatiques a des implications en ce qui concerne les interventions nonpharmaceutique comme le renforcement de la quarantaine de tous les contacts étroits des cas de SARS-CoV-2 sans tenir compte des symptômes.

Efficacy of the ChAdOxl nCoV-19 Covid-19 Vaccine against the B.1.351 Variant

BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiradetory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOxl nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5x1O10 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D6146 virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS: Between June 24 and November 9,2020, we enrolled 2026 HIV-negative adults (median age, 30 years);1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid49 developed in 23 of 717 placebo recipients (3.296) and in 19 of750 vaccine recipients (2.596), for an efficacy of 21.9% (95% confidence interval ICI], -49.9 to 59.8). Among the 42 participants with Covid49, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant;vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, 76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOxl nCoV-19 vaccine did not show protection against mild-to-moderate Covid49 due to the B.1.351 variant. [ABSTRACT FROM AUTHOR] Copyright of New England Journal of Medicine is the property of New England Journal of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Long-COVID: An evolving problem with an extensive impact

Persistence of symptoms or development of new symptoms relating to SARS-CoV-2 infection late in the course of COVID-19 is an increasingly recognised problem facing the globally infected population and its health systems. 'Long-COVID' or 'COVID long-haulers' generally describes those persons with COVID-19 who experience symptoms for >28 days after diagnosis, whether laboratory confirmed or clinical. Symptoms are as markedly heterogeneous as seen in acute COVID-19 and may be constant, fluctuate, or appear and be replaced by symptoms relating to other systems with varying frequency. Such multisystem involvement requires a holistic approach to management of long-COVID, and descriptions of cohorts from low- and middle-income countries are eagerly awaited. Although many persons with long-COVID will be managed in primary care, others will require greater input from rehabilitation medicine experts. For both eventualities, planning is urgently required to ensure that the South African public health service is ready and able to respond.

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.

COVID-19 antibody testing: From hype to immunological reality.

The potential role for serological tests in the current COVID-19 pandemic has generated very considerable recent interest across many sectors worldwide, inter alia pathologists seeking additional weapons for their armoury of diagnostic tests; epidemiologists seeking tools to gain seroprevalence data that will inform improved models of the spread of disease; research scientists seeking tools to study the natural history of COVID-19 disease; vaccine developers seeking tools to assess vaccine efficacy in clinical trials; and companies and governments seeking tools to aid return-to-work decision-making. However, much of the local debate to date has centred on questions surrounding whether regulatory approval processes are limiting access to serological tests, and has not paused to consider the intrinsically limiting impact of underlying fundamental biology and immunology on where and how different COVID-19 serological tests can usefully be deployed in the response to the current pandemic. We review, from an immunological perspective, recent experimental evidence on the time-dependency of adaptive immune responses following SARS-CoV-2 infection and the impact of this on the sensitivity and specificity of COVID-19 antibody tests made at different time points post infection. We interpret this scientific evidence in terms of mooted clinical applications for current COVID-19 antibody tests in identifying acute infections, in confirming recent or past infections at the individual and population level, and in detecting re-infection and protective immunity. We conclude with guidance on where current COVID-19 antibody tests can make a genuine impact in the pandemic.