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1.
Topics in Antiviral Medicine ; 30(1 SUPPL):300-301, 2022.
Article in English | EMBASE | ID: covidwho-1880872

ABSTRACT

Background: South Africa is one of the African countries most affected by the COVID-19 pandemic. SARS-CoV-2 seroprevalence surveys provide valuable epidemiological information given the existence of asymptomatic cases. We report the findings of the first nationwide household-based population estimates of SARS-CoV-2 seroprevalence among people aged 12 years and older in South Africa. Methods: The survey used a cross-sectional multi-stage stratified cluster design undertaken over two separate time periods (November 2020-February 2021 and April-June 2021) which coincided with the second and third waves of the pandemic in South Africa. The Abbott® and Euroimmun® ani-SARS CoV-2 antibody assays were used to test for SARS-CoV-2 antibodies, the latter being the final result. The survey data was weighted with final individual weights benchmarked against 2020 mid-year population estimates by age, race, sex, and province. Frequencies were used to describe characteristics of the study population and SARS-CoV-2 seroprevalence. Bivariate and multivariate logistics regression analysis were used to identify factors associated with SARS-CoV-2 seropositivity. Results: 13640 participants gave a blood sample. The SARS-CoV-2 seroprevalence using the Euroimmun assay was 19.6% (95% CI 17.9-21.3) over the study period, translating to an estimated 8 675 265 (95% CI 7 508 393-9 842 137) estimated infections among people aged 12 years and older across South Africa by June 2021. Seroprevalence was higher in the Free State (26.8%), and Eastern Cape (26.0%) provinces (Figure). Increased odds of seropositivity were associated with prior PCR testing [aOR=1.29 (95% CI: 0.99-1.66)], being female [aOR=1.28 (95% CI 1.00-1.64), p=0.048] and hypertension, [aOR=1.28 (95% CI 1.00-1.640, p=0.048]. Conclusion: These findings highlight the burden of infection in South Africa by June 2021, and support testing strategies that focus on individuals with known exposure or symptoms since universal testing is not feasible. Females and younger people were more likely to be infected suggesting need for additional strategies targeting these populations. The estimated number of infections was 6.5 times higher than the number of SARS-CoV-2 cases reported nationally, suggesting that the country's testing strategy and capacity partly explain the dynamics of the pandemic. It is therefore essential to bolster testing capacity and to rapidly scale up vaccinations in order to contain the spread of the virus in the country.

2.
Topics in Antiviral Medicine ; 30(1 SUPPL):332, 2022.
Article in English | EMBASE | ID: covidwho-1880610

ABSTRACT

Background: Accurate and reliable serological assays are essential for epidemiological surveillance of SARS-CoV-2. Several commercial anti-SARS assays are available and use cases for serological testing includes surveillance. However, there is growing evidence of varying performance of SARS-CoV-2 assays dependent of their format. We compare the performance of 3 different assays used in a national serosurvey undertaken between April and June 2021, in South Africa before widescale vaccination roll out. Methods: Venous blood samples from participants ≥12 years were transported under cold chain to a central testing laboratory within 24 hours of collection. Samples were tested for SARS CoV-2 antibodies with the Abbott nucleocapsid (NC)-based Architect anti-SARS CoV-2 chemiluminescent microparticle immunoassay (CMIA), the EuroImmun Spike (S)-based assay and the Roche total IgG NC-based Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (ECLIA) on the Cobas e411 platform. We compared antibody detection proportions. Results: 8146 participants (median age 40 years, IQR 26-55) 5.6% of whom reported ≥1 SARS-CoV-2 symptom in the preceding 3 months gave a blood sample. Samples were tested on the Abbott assay with different cut-offs:-15.5% tested positive at the 1.40 cut-off and 26.8% at the 0.49 lower cut-off. 21.6% of the samples tested positive on the Euroimmun and 39.0% tested positive on the Roche assay (Table). 286 samples were from respondents self-reporting a prior positive PCR test, and among them 149(52.1%), 156(54.6%), and 206(72.3%) were positive on the Abbott (1.40 cut-off), Euroimmun and Roche assays respectively. 116/286(40.6%) of these were positive on all three assays and with 21(7.3%) positive on Roche only. 224/286(78.3%) of those reporting prior PCR test positivity were positive at the lower Abbott cut-off, with 47(16.4%) positive on Abbott only. Conclusion: These samples collected before wide scale vaccination roll out in South Africa show variable performance of these assays with the Roche NC assay detecting more infections that both the Abbott NC assay(0.40 cut-off) and the Euroimmun S assay.This could be reflective of seroreversion previously reported with Abbott and Euroimmun, and the greater sensitivity of Roche assay targeting the more abundant NC as an epitope. Use of direct, double Antigen-sandwich-based assays that are stable and have increased sensitivity over time may be optimal to detect both natural and vaccine-induced immunity in serosurveys.

3.
International Journal of Mathematical, Engineering and Management Sciences ; 7(2):243-257, 2022.
Article in English | Scopus | ID: covidwho-1848131

ABSTRACT

Evaluation of E-Learning resources plays a significant role in the context of pedagogic systems. Resource evaluation is important in both conventional ‘talk-and-chalk’ teaching and in blended learning. In on-line (e-learning) teaching [an enforced feature of pedagogic systems in tertiary education during the Covid-19 pandemic] the effective evaluation of teaching resources has obtained importance given the lack of ‘face-to-face’ student-teached interaction. Moreover, the enforced use of e-learning has demonstrated the effectiveness of on-line pedagogic systems, which has been argued in blended learning pedagogic systems. Additionally, in e-learning, the lack of ‘face-to-face’ meetings [between teaching staff and students and in staff meetings] makes feedback (positive and negative) important for all actors in the pedagogic system. In this paper we present a novel approach to enable effective evaluation of teaching resources, which provides effective group decision-support designed to evaluate e-learning resources, enhancing students’ satisfaction. The proposed approach employs Picture Fuzzy Sets to quantify survey responses from actors, including: agree, disagree, neutral, and refuse to answer. In our approach, the system can manage the evaluation of e-learning resources based on both explicit and tacit knowledge using a picture fuzzy rule-based approach in which linguistic semantic terms are used to express rules and preferences. The proposed system has been tested using e-learning case studies with the goal of enhancing the learning experience and increasing students' satisfaction. Experimental results demonstrate that our proposed approach achieves a significant improvement in performance in the evaluation of e-learning resources. Copyright © International Journal of Mathematical, Engineering and Management Sciences.

4.
International Journal of Mathematical Engineering and Management Sciences ; 7(2):243-257, 2022.
Article in English | Web of Science | ID: covidwho-1766357

ABSTRACT

Evaluation of E-Learning resources plays a significant role in the context of pedagogic systems. Resource evaluation is important in both conventional 'talk-and-chalk' teaching and in blended learning. In on-line (e-learning) teaching [an enforced feature of pedagogic systems in tertiary education during the Covid-19 pandemic] the effective evaluation of teaching resources has obtained importance given the lack of 'face-to-face' student-teached interaction. Moreover, the enforced use of e-learning has demonstrated the effectiveness of on-line pedagogic systems, which has been argued in blended learning pedagogic systems. Additionally, in e-learning, the lack of 'face-to-face' meetings [between teaching staff and students and in staff meetings] makes feedback (positive and negative) important for all actors in the pedagogic system. In this paper we present a novel approach to enable effective evaluation of teaching resources, which provides effective group decision-support designed to evaluate e-learning resources, enhancing students' satisfaction. The proposed approach employs Picture Fuzzy Sets to quantify survey responses from actors, including: agree, disagree, neutral, and refuse to answer. In our approach, the system can manage the evaluation of e-learning resources based on both explicit and tacit knowledge using a picture fuzzy rule-based approach in which linguistic semantic terms are used to express rules and preferences. The proposed system has been tested using e-learning case studies with the goal of enhancing the learning experience and increasing students' satisfaction. Experimental results demonstrate that our proposed approach achieves a significant improvement in performance in the evaluation of e-learning resources.

5.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-330496

ABSTRACT

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors, and are cross-reactive against diverse SARS-CoV-2 variants, including the extremely neutralization resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.

7.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327015

ABSTRACT

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

8.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326997

ABSTRACT

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, crossrecognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

9.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-325667

ABSTRACT

Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participants were breakthrough cases vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV2.S. In vaccinated participants, neutralization of Omicron increased from a geometric mean titer (GMT) FRNT50 of 28 to 378 (13.7-fold). Unvaccinated participants had similar Omicron neutralization at baseline but increased from 26 to only 113 (4.4-fold) at follow-up. Delta virus neutralization increased from 129 to 790, (6.1-fold) in vaccinated but only 18 to 46 (2.5-fold, not statistically significant) in unvaccinated participants. Therefore, in Omicron infected vaccinated individuals, Delta neutralization was 2.1-fold higher at follow-up relative to Omicron. In a separate group previously infected with Delta, neutralization of Delta was 22.5-fold higher than Omicron. Based on relative neutralization levels, Omicron re-infection would be expected to be more likely than Delta in Delta infected individuals, and in Omicron infected individuals who are vaccinated. This may give Omicron an advantage over Delta which may lead to decreasing Delta infections in regions with high infection frequencies and high vaccine coverage.

11.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296585

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections. Highlights: A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotypeSerological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunityEvolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination. Graphical abstract:

12.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296584

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only or vaccinated and previously infected. We also investigated whether the virus still requires binding to the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa. We then compared neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation. Neutralization was by blood plasma from South African BNT162b2 vaccinated individuals. We observed that Omicron still required the ACE2 receptor to infect but had extensive escape of Pfizer elicited neutralization. However, 5 out of 6 of the previously infected, Pfizer vaccinated individuals, all of them with high neutralization of D614G virus, showed residual neutralization at levels expected to confer protection from infection and severe disease (2). While vaccine effectiveness against Omicron is still to be determined, these data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly by boosting, could maintain reasonable effectiveness against Omicron. If neutralization capacity is lower or wanes with time, protection against infection is likely to be low. However, protection against severe disease, requiring lower neutralization levels and involving T cell immunity, would likely be maintained.

13.
J Dent Res ; 101(1): 5-10, 2022 01.
Article in English | MEDLINE | ID: covidwho-1484182

ABSTRACT

The emergence of the COVID-19 viral pandemic has generated a renewed interest in pharmacologic agents that target the renin angiotensin system (RAS). Angiotensin-converting enzyme 1 (ACE1) inhibitors decrease the synthesis of angiotensin II (Ang II) from its precursor angiotensin I and inhibit the breakdown of bradykinin, while Ang II receptor blockers antagonize the action of Ang II at the receptor level downstream. The actions of both classes of drugs lead to vasodilation, a blunting of sympathetic drive and a reduction in aldosterone release, all beneficial effects in hypertension and congestive heart failure. ACE2 cleaves the vasoconstrictor Ang II to produce the anti-inflammatory cytoprotective angiotensin 1-7 (Ang 1-7) peptide, which functions through the G protein-coupled receptor MAS to counteract the pathophysiologic effects induced by Ang II via its receptors, including vasoconstriction, inflammation, hypercoagulation, and fibrosis. SARS-CoV-2 enters human cells by binding ACE2 on the cell surface, decreases ACE2 activity, competes for ACE2 receptor-binding sites, and shifts the RAS toward an overexpression of Ang II, accounting for many of the deleterious effects of the virus. Thus, there is great interest in developing recombinant ACE2 as a therapeutic for prevention or treatment of COVID-19. Notably, ACE2 is highly expressed in the oral cavity, and saliva and dorsum of the tongue are major reservoirs of SARS-CoV-2. Cost-effective methods to debulk the virus in the oral cavity may aid in the prevention of viral spread. Here we review the pharmacology of targeted small molecule inhibitors of the RAS and discuss novel approaches to employing ACE2 as a therapeutic for COVID-19.


Subject(s)
COVID-19 , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Humans , Renin-Angiotensin System , SARS-CoV-2
14.
European Journal of Arrhythmia & Electrophysiology ; 6:12, 2020.
Article in English | ProQuest Central | ID: covidwho-1329392

ABSTRACT

Introduction: Device follow up was routinely performed in person pre-March 2020. When the COVID pandemic caused lockdown in the UK this led to new methods of performing the 4-6-week check: utilising remote monitoring and patients sending wound images. We wanted to investigate the patient’s perspective of this experience: comparing traditional follow up vs remote only follow up. We hypothesised that this would have no effect on satisfaction but would show limitations of remote only working in particular patient groups. Methods: Patients who had a device procedure in the months Jan-April 2020 would be asked to complete a telephone survey, excluding ILR devices. This survey consists in 25 questions, which were divided into 5 parts to define the stages of patient journey: pre implant, post implant on the ward, wound management, one-month post implant appointment and overall satisfaction. Each question is rated from 1 to 5 (negative to positive depending in the question). We will compare the results of in person follow up and remote only follow up. Results: A total of 222 patients completed the survey, 88 (40%) in the traditional face to face follow up and 134 (60%) in the remote only group. No difference was seen comparing the sections on pre implant, post implant, wound management and satisfaction of the two groups. For the 134 patients in the 1/12 virtual post implant check group, 92 patients found it very easy to set up their home monitor and 6 patients found it very difficult. Older patients found this slightly more difficult to set up the home monitor, however, patients up to the age of 91 did find this very easy. 60 patients found sending a wound image via email very easy and 60 patients found this very difficult. The age when patients started to struggle more was 71 years old (Fig 1). Of the 134 patients that received remote only follow up a total of £1317.50 was saved not having to pay for travel into clinic. Of these 134 patients 37 would have received free transport. For the 88 patients who visited clinic, £607.50 was spent to travel into clinic, of which 44 received free transport. For the future, 54% of patients would prefer remote only and 46% would prefer in clinic follow up. However, there was no difference in age for these patients. Discussion: Patients appear to be satisfied with both follow up plans. However, this survey highlighted key limitations for remote only 1/12 follow up. The ability to set up a remote monitor did slightly decrease with age. This will be helped by the majority of patients having remote monitoring set up prior to discharge. The difference between patients who were able to send an email with a photo of the wound site highlights a difference in patients’ technical ability at all ages, with older patients finding this more challenging. Centres wanting to adapt this model of care should be knowledgeable of this and consider other options, such as GP/practice nurse wound assessment, or in clinic follow up for these select patients. This difference would allow services to reduce their footfall into device clinics and financial savings to the patient. Unexpectedly patients were split in their option for future follow up which requires further investigation. Due to the COVID 19 pandemic services are socially distancing across the country. Remote only follow up has its limitations, most importantly being receiving the information from the patients. Services can develop pathways from this data to find out which patients would be best suited to this follow up schedule. [Image Omitted]

15.
European Journal of Arrhythmia & Electrophysiology ; 6:11, 2020.
Article in English | ProQuest Central | ID: covidwho-1329358

ABSTRACT

Background: On the 23rd March 2020 the UK went into lockdown due to COVID-19 with vulnerable patients advised to shield at home. Patients with implantable devices still required battery changes and other interventions during this period, both clinically urgent and routine. A new strategy for identifying those needing urgent procedures was introduced at a tertiary cardiac centre to balance the risks of delaying procedures vs coming out of shielding. Method: In normal circumstances, we perform 20-30 device re-intervention procedures per month including box changes, lead revisions, device upgrades and wound revisions. Patients are referred via device clinic or directly by a Consultant. Routinely we aim to box change patients at the time elective replacement indicator (ERI) is triggered. Most elective work was cancelled and patients requiring procedures were identified and booked in first. Working closely with Electrophysiology (EP) Consultants we developed new groups to sort patients (Table 1). An earlier referral threshold of 6 months till ERI was set to plan procedures in advance. Legacy device patients were sent remote monitors (RM) to maintain safety and delay procedures. Regular downloads for patients approaching ERI allowed them to isolate as long as possible. Results: During the months of March-May 2020 the number of requests increased from 25 to 56 requests (Figure 1). A peak in April 2020 of 50 device re-intervention procedures. Five patients hit ERI and had to be upgraded from Urgent to Very Urgent. Three of these had been delayed due to patient/family preference. One Fortify advisory had to be admitted due to prematurely triggering ERI. Three patients had their procedures done locally instead. Ten further patients have been referred for re-intervention locally. Three patients died on the waiting list, all sadly due to contracting COVID-19 in community. Two patients required input from the trust’s safeguarding team due to lack of contact with patient at predicted ERI and non-compliance with RM. From Jan-July 2020 the average referral to treatment time (RTTT) constantly averaged at 50 days. Discussion: Adaptations to this service involved multiple teams working together to maintain patient safety. This involved scheduling, pre admissions and Cardiac Scientists. We also transitioned to a Cardiac Scientist led service empowering the team to risk stratify patients. A further challenge presented itself: a subgroup of patients declined procedures. We compromised with some patients;three patients had procedures at a local centre to avoid travelling into London. Linked trusts referrals to our centre increased during this period, likely due similar measures of lowering thresholds. Linked trusts did not have access to RM, requiring them to directly refer for box changes rather than having the luxury of delaying procedures. Some legacy patients had devices that were incompatible with RM or declined a RM. Since lowering the referral threshold, a rise in referrals was expected, however, the results suggest that a back log of referrals, as the RTTT was indifferent. Collaborating with colleagues internally, local centres and enrolling on RM maintained shielding and device safety towards end of battery. This exemplifies solidarity across cardiac services during the COVID pandemic. [Image Omitted] [Image Omitted]

16.
Br J Surg ; 108(2): e84, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1132436
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