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Introduction: Despite the extra mortality associated with Covid-19 death globally, little is known on COVID-19- related pediatric mortality in Africa. We assessed predictors of critical care needs and in-hospital mortality in South African children with laboratory-confirmed SARS-CoV-2 infection. Method(s): A secondary analysis of AFREhealth cohort children (large cohort of paediatric Covid-19 clinical outcomes across six African countries) admitted to Inkosi-Albert-Luthuli hospital, KwaZulu-Natal, South Africa. We used multivariable logistic regression and cox-proportional hazards models to explore predictors for intensive care and inhospital death. Result(s): Of the 82 children with PCR-confirmed SARS-CoV-2 infection, 35(42.7%) were younger than one year and 59(71%) had a comorbidity. 37(45.2%) children required critical care and 14(17%) died. Significant predictors of critical care need were age<=1year (vs.10-12years)(aOR:5.38,95%CI:1.28- 22.54,p=0.02), >=1comorbidity (aOR:6.62,95%CI:1.49-29.53,p=0.01) and increase in blood urea nitrogen/BUN (aOR:1.53,95%CI:1.13-2.07,p=0.001). HIV-infection (aHR:8.46,95%CI:1.45-49.26,p=0.02), invasive ventilation (aHR:3.59,95%CI:1.01-12.16,p=0.0.048), and BUN (aHR:1.06,95%CI:1.01-1.11,p=0.017) predicted death. Children admitted primarily (vs referred)to a quaternary hospital were less likely to die. Conclusion(s): Children with Covid-19 have a significant hospital death rate. A timely referral system and triage of children at risk for critical care and death, like those under 1 year and with comorbidities, should minimize excess mortality, especially in high HIV-infection burden regions.
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Background: SARS-CoV-2 antibody responses after COVID-19 vaccination are attenuated in people living with MS on high efficacy DMTs such as Fingolimod and Ocrelizumab. Uncertainties on how to manage vaccination schedule and DMT administration persist. Furthermore, data on effects of newer related DMTs like Siponimod and Ofatumumab are limited. Objective(s): We aimed to determine the seroprevalance of Spike antibody and the longevity of antibody mediatedimmune protection after COVID-19 vaccination in MS patients. Method(s): Spike IgG antibodies against Wuhan SARS CoV-2 were assessed in sera (n=520) of MS patients collected pre-vaccination (baseline n= 304), 1 month post second dose (n=172), 6 months post second dose (n=23) and 1 month post third dose (n=21). Demographic and clinical information including age, gender, DMT treatment and timing of COVID-19 vaccination were collected from 160 of these MS patients. Result(s): 151/172 sera at 1 month post second dose, 20/23 sera at 6 months post second dose, and 15/21 sera at 1 month post third dose were positive for Spike antibodies. Seropositive patients were treated on Alemtuzumab;n=3, Cladribine;n=32, Dimethyl fumarate;n=8, Fingolimod;n=16, IFN;n =4, Ocrelizumab;n=14, Ofatumumab;n=4, Natalizumab;n=11, Siponimod;n=1 and Teriflunomide;n=1. Out of the 21 patients who did not seroconvert at a month post second dose, treatment information was available in 12 patients. n=9 were treated by Ocrelizumab and n=2 were treated by Cladribine and n=1 was treated by Fingolimod, confirming certain DMTs prevent seroconversion. Out of the 151 patients that did seroconvert, 120 had titers that were comparable to controls (healthy general population) and 31 had reduced titres. Treatment information was available in 21/31 of these patients. Interestingly, 9/21 were on Ocrelizumab, 8/21 were on Fingolimod, 2/21 were on Ofatumumab, 1/21 was on Natalizumab and 1/21 was on Siponimod. This finding confirmed that certain DMTs such as Fingolimod, Ocrelizumab, Ofatumumab and Siponimod cause a reduction in post-vaccination Spike antibody titers in MS patients in comparison to general population. Expectedly, 304/304 sera were negative at baseline. Conclusion(s): Some High efficacy DMTs reduce Spike Ab titers or even prevent seroconversion. To maximize vaccine-mediated immune protection against COVID-19, timing of DMT administration and vaccine schedule may need intricate co-ordination in people living with MS.
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Background: Current SARS-CoV-2 vaccines rely on protective immunity against early clade SARS-CoV-2 and have resulted in seroconversion in a subset of MS patients receiving immunosuppressive DMTs. However, it is unknown if SARS-CoV-2 spike antibodies afford immunity against emerging variants of concern, such as Delta and Omicron. Objective(s): To determine the binding of spike antibodies to early clade, Delta, and Omicron SARS-CoV-2 in patients with MS receiving different DMTs. Method(s): Spike antibody binding to early clade SARS-CoV-2, Delta and Omicron was assessed by flow cytometry using sera collected from 58 patients one month post second dose and one patient 1 month post third dose. All patients were previously determined to be seropositive against Wuhan (early clade spike). Clinical and demographic information including DMT treatment and vaccination timing was collected. Result(s): 53 patients were seropositive for Wuhan, Delta and Omicron spike antibodies. Wuhan Spike antibody titres were high at one month post second vaccination, whereas Delta and Omicron Spike antibody titres were significantly decreased. We observed a 70% and 93% decrease of in immunoreactivity to Delta and Omicron, respectively. Although ocrelizumab and fingolimod decrease Spike antibody titres after vaccination, they did not affect immunoreactivity to variants, in comparison to other DMTS. Conclusion(s): All 53 patients were able to generate a positive antibody response following vaccination. However, there was an observable decrease in the antibody titres and immunoreactivity to the Delta and Omicron variants, in comparison to Wuhan.
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Background: COVID-19 vaccination induces protective Spike antibodies. Some responses are attenuated in people with multiple sclerosis (MS) on high efficacy disease-modifying therapies (DMT).Whether antibodies afford immunity against emerging SARS-CoV-2 Variants of Concern (VoC) such as Delta and Omicron is unknown. Aim(s): To assess the longevity and breadth of Spike antibody in MS patients after COVID-19 vaccination. Objective(s): To determine seroconversion and antibody binding toVoC Spike. Method(s): Spike antibodies to Clade A SARS-CoV-2 were assessed in 535 MS sera at baseline (n=292), 1 (n=141) and 6 month (n=67) post-second dose, and 1 month post-third dose (n=35), and 489 health worker controls. When known, COVID- 19 vaccines were BNT162b2 (n= 489 controls, n=108 MS patients) and ChAdOx1-S (n=37).Spike antibody binding to VoC Delta and Omicron BA1 was assessed in 68 sera 1 month post-second dose. Demographic and DMT information was available in 269 patients. Result(s): 123/141 sera at 1 month post-second dose, 66/67 at 6 months post-second dose, and 26/35 at 1 month post-third dose were positive for Spike antibodies.Patients who did not seroconvert at 1 and 6 month post-second and 1 month post-third dose (n=28) were treated with ocrelizumab (n=22), cladribine (n=1), fingolimod (n=4), and siponimod (n=1). At 1 month post-second dose, the median and IQR Spike antibody levels were 67,224+/- 101,251 in the seroconverted MS group compared to 145,510+/- 99,669 in controls (n=489). When patient sera were assessed for binding to Clade A Spike, and VoC Delta and Omicron BA1 Spikes, most sera were able to bind the three different Spike antigens (n=61). However, Spike antibody immunoreactivity was decreased by 70% against Delta Spike and 90% for Omicron BA1 Spike compared to the original clade A Spike.As observed for Clade A Spike antibody, DMTs, such as ocrelizumab, fingolimod, and ofatumumab, decreased the antibody binding to Delta and Omicron Spike. Still, the pattern of antibody recognition was similar between the three Spikes and all DMTs analysed, i.e. alemtuzumab, natalizumab, teriflunomide, and interferons. Our data suggest that, irrespectively of DMTs, antibodies generated after vaccination did not bind Spike from recent VoCs to the same extent as the original Spike used in COVID-19 vaccines. Conclusion(s): Some DMTs reduce Spike antibody titres or prevent seroconversion. The sequence of Spike used in the first generation of vaccines may need to be updated for emerging VoC.
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Background: Patients (pts) with indolent lymphomas are at increased risk of severe COVID-19 infection. We have shown limited seroconversion and live viral neutralisation (VN), but preserved COVID-specific T cell responses after 2 doses of mRNA COVID-19 vaccination in such pts. (Beaton, B ASH 2021, 149348). A 3rd vaccine dose to complete primary vaccination has since been recommended. Aims: To assess humoral & cellular immune responses to a 3rd COVID-19 (mRNA) vaccination in pts with follicular lymphoma (FL) & Waldenström Macroglobulinemia (WM), including assessment of response after pausing BTKi therapy in WM pts. Methods: Patients with WM, FL & healthy controls (HC) were enrolled in a prospective observational study to measure immune responses 21-28 days after a 3rd mRNA COVID-19 vaccine. Immune response was measured by mean fluorescence intensity (MFI) of anti-SARS-CoV-2 spike antibodies (ASAb) obtained using a high-sensitivity live cell assay, live VN to a panel of SARS-CoV-2 variants of concern, and CD4+ & CD8+ antigen-specific T cell responses. The associated TRIBECA (TReatment Interruption of BTKi to Enhance COVID-19 Antibody response) study sought to determine if a superior immune response could be gained by pause of BTKi therapy prior to and up to 4 weeks after 3rd vaccine dose. Patients were closely monitored during the BTKi pause with weekly clinical, full blood count and IgM assessments. WM pts receiving a 3rd dose while continuing on BTKi served as a control. Statistical analysis of medians between cohorts were compared by the non-parametric Mann-Whitney (Graphpad Prism). Comparison of medians between paired grouped data was assessed by 2-way ANOVA. Results: To date, 56 of 125 pts had their ASAb measured following 3rd vaccine dose administered between October 2021 and January 2022: 28 WM pts (including 6/9 WM pts on the BTKi pause sub-study), 24 FL pts and 4 HC. Median age was 68 years with 21 females and 35 males. Median follow up from 2nd dose was 140 days (range: 79- 170 days). In antibody responders, median MFI fell from 163042 (IQR 82663-249934) 28 days post 2nd dose to 52117 (IQR 19942-60973) (p<0.0001) immediately before the 3rd dose. Median MFI in all FL & WM pts pre- 3rd dose vaccine was 17111 (IQR 0-52650), rising significantly post 3rd dose to a median of 86730 (IQR 0-221937). Only 4/20 pts without measurable ASAb prior to the 3rd dose (2 WM, 2 FL) developed measurable ASAb following the 3rd dose: 16/20 patients (8 WM, 8FL, all treated) had no ASAb response. The median MFI in pts who underwent a BTKi treatment pause rose from 9151 (IQR 1671-21232) pre-3rd dose to 87720 (IQR 2785-152195) post 3rd dose, significantly higher than the median MFI in WM pts who did not pause their BTKi , which rose from 16769 (IQR 218-22447) pre- to 20252 (IQR 168-114262) post 3rd dose, (p = 0.016). Of the 5/125 with COVID infection in the study to date, only one patient (without measurable ASAb) in this 3-dose cohort had COVID, requiring intensive care support. Summary/Conclusion: Most WM & FL pts who responded to a 2nd dose COVID vaccine showed a decline in ASAb titre over time which increased following a 3rd mRNA vaccine. Only 20% of pts without detectable ASAb pre- 3rd dose showed improvement post 3rd dose, highlighting the importance of other COVID protection strategies in these pts. Although initial numbers are small, there may be a higher increment in ASAb when BTKi therapy is paused around the time of vaccination. Comprehensive immune analysis, including VN and T-cell response on the entire FL & WM cohort will be presented at the EHA congress.
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During a public health emergency, coordination and management are essential for ensuring timeous, decisive, and harmonised leadership. In this paper, the governance structures utilised in South Africa (SA) during the COVID-19 pandemic are recorded and the key strengths and weaknesses of response in the country are discussed. A qualitative methodology is used for the case study and comprises insights from stakeholders who were at the forefront of SA???s response as well as from documentation that was used to guide the response. Structured, transparent, science-based and agile coordination and management systems are necessary to gain the public???s trust during a public health emergency. This case study contributes to the literature on governing a pandemic and shares lessons learned from the COVID-19 response. The lessons learned by the stakeholders within the SA governance structures can be leveraged in future public health emergencies within SA and other low-and middle-income countries.
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BACKGROUND: In recent years, the number of people pursuing a surgical career in the UK has decreased. The COVID-19 pandemic has led to the cancellation of surgical placements for medical students and has affected surgical education. This study evaluates the perceptions and impact of a 1-day virtual surgical conference for medical students considering pursuing a surgical career. METHODS: All delegates of the 2021 Barts and The London International Surgical Conference were invited to participate in two online surveys pre- and post-conference. Data were collected and analysed to evaluate delegates' reasons for attending the conference, and attitudes towards virtual conferences and a surgical career before and after the conference. RESULTS: Out of 132 participants, 106 (80.3%) completed both the pre- and post-conference surveys. Clinical students showed a statistically significant difference in interest in pursuing a surgical career after the conference than before (P=0.03), unlike pre-clinical students (P=0.12). Post-conference, 43 (40.6%) preferred a virtual to a face-to-face conference, which was a slight increase from 40 (37.7%) pre-conference, while 73 (68.9%) and 80 (75.5%) participants favoured virtual talks and presentations respectively. In contrast, only 12 (11.3%) and 21 (19.8%) students preferred workshops and networking virtually. Furthermore, delegates liked the global accessibility and environmentally-friendly nature of virtual conferences but found they can be less engaging and be disrupted by a poor internet connection. CONCLUSIONS: Virtual surgical conferences have many benefits and can help encourage medical students towards a surgical career. They could help bridge the surgical educational gap in medical school during these unprecedented times. Virtual conferences, which have a broader and more inclusive reach, could be an important complement to conventional conferences after the pandemic.
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COVID-19 , Students, Medical , Humans , Pandemics , SARS-CoV-2 , Schools, MedicalABSTRACT
The purpose of the study on which this paper is based was to explore how self-identified female African university students understand the influence of their home environments on their experiences of online education. The study took place during the COVID-19 pandemic when universities in South Africa and elsewhere introduced online teaching and learning. Using a qualitative approach to a single case study design within a critical feminist paradigm, we carried out an inductive thematic analysis of the data from seven in-depth, open-ended questionnaires and metaphors. We found that home environments play an important role in the education of female African students, particularly in a context characterised by gender inequalities exacerbated by inequities in material resources. However, a sense of agency, displayed by some participants, indicated their determination to rise above the many forms of marginalisation and discrimination they experienced.
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The shift to Emergency Remote Teaching and Learning (ERTL) in response to the COVID-19 pandemic has necessitated online learning at home for South African (and other) students. Using a critical paradigm, qualitative approach and case study design, this study, underpinned by critical theory, used interviews, voice notes and text messages to generate data to explore how South African university students’ home contexts shape their experiences of ERTL. Using thematic analysis, the findings indicated that student learning at home was negatively impacted by poor internet connectivity, home responsibilities, cramped living conditions, lack of safety, and financial and psycho-social stresses. The findings exposed the lived realities of students’ home contexts, made more difficult through the pandemic. This study adds to the literature on student adaptation to learning in the pandemic within home contexts characterised by resource poverty and challenging psycho-social conditions. © The Author/s 2021.
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To limit the spread of the COVID-19 virus conditions of lockdown were enforced by countries globally. Universities and schools revised the mode of delivery from contact teaching to online teaching and learning. This qualitative research was conducted at one university in South Africa and explored STEM discipline lecturers’ reflections on the use of online technologies and the factors which enable or constrain online teaching and learn-ing. Three lecturers from STEM disciplines involved in online teaching were purpo-sively selected to participate in this study. Data were generated via semi-structured interviews and reflective journals. The findings reveal that lecturers supplement the use of Moodle and Zoom with WhatsApp, the factor that enabled online teaching was the availability of data to lecturers and students. In contrast, the factors that constrained online teaching and learning were the technical training received for online teaching, the mismatch between pedagogy and students’ learning styles, the pressure of balancing work-home life and assumptions made about the availability of conducive home environments for learning, connectivity, and availability of devices for online learning. These findings have implications for professional development for online teaching and recommend that universities adopt WhatsApp to be a formal platform for online teaching and learning. © 2020, Scientia Socialis Ltd. All rights reserved.
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Information Retrieval is the task of satisfying an information need by retrieving relevant information from large collections. Recently, deep neural networks have achieved several performance breakthroughs in the field, owing to the availability of large-scale training sets. When training data is limited, however, neural retrieval systems vastly underperform. To compensate for the lack of training data, researchers have turned to transfer learning by relying on labelled data from other search domains. Despite having access to several publicly available datasets, researchers are currently unguided in selecting the best training set for their particular applications. To address this knowledge gap, we propose a rigorous method to select an optimal training set for a specific search domain. We validate this method on the TREC-COVID challenge, which was organized by the Allen Institute for Artificial Intelligence and the National Institute of Standards and Technology. Our neural model ranked first from 143 competing systems. More importantly, it was able to achieve this result by training on a dataset that was selected using our proposed method. This work highlights the performance gains that may be achieved through careful dataset selection in transfer learning. © 2020, Springer Nature Switzerland AG.
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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.
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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.