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1.
Cell Reports Medicine ; : 100898, 2022.
Article in English | ScienceDirect | ID: covidwho-2165956

ABSTRACT

Summary Multiple SARS-CoV-2 exposures, from infection or vaccination, can potently boost spike antibody responses. Less is known about the impact of repeated exposures on T cell responses. Here, we compare the prevalence and frequency of peripheral SARS-CoV-2-specific T cell and IgG responses in 190 individuals with complex SARS-CoV-2 exposure histories. As expected, an increasing number of SARS-CoV-2 spike exposures significantly enhances the magnitude of IgG responses, while repeated exposures improve the number of T cell responders but have less impact on SARS-CoV-2 spike-specific T cell frequencies in the circulation. Moreover, we find that the number and nature of exposures (rather than the order of infection and vaccination) shape the spike immune response, with spike-specific CD4 T cells displaying a greater polyfunctional potential following hybrid immunity compared to vaccination only. Characterizing adaptive immunity from an evolving viral and immunological landscape may inform vaccine strategies to elicit optimal immunity as the pandemic progresses.

3.
Front Reprod Health ; 3: 687677, 2021.
Article in English | MEDLINE | ID: covidwho-2089941

ABSTRACT

Khuluma is a psychosocial and peer-to-peer mHealth intervention that uses text messaging to facilitate support groups for adolescents living with HIV (ALWH) with the aim of contributing toward positive health outcomes. Although use of mobile technology in the form of mHealth interventions has proliferated recently in the field of health, published literature describing methods and processes of its application are limited. We present a set of methods and processes utilised to develop and pilot the Khuluma mHealth intervention amongst young people (15-20 years) in South Africa. We recruited and enrolled 52 adolescents (15-20-year olds) from four clinics in Pretoria and Cape Town to participate in a 6-month pilot of Khuluma. Participants were ALWH, aware of their status, on antiretroviral therapy for more than 12 months, and not suffering from severe depression. We conducted four pre and post intervention focus group discussions (FGDs) with a proportion of ALWH (n = 36) enrolled in the pilot study using participatory methods. Several processes were utilised to then implement this pilot study. These included engaging ALWH for minor study implementation modifications; forming virtual groups; activating the mHealth platform; facilitating and delivering the Khuluma intervention. The acceptability of the intervention was informed by follow-up focus group discussions and text message data. The initial participatory processes helped to tailor the intervention design to participants' needs. The peer-led facilitation of the groups allowed for the provision of sensitive psychosocial support that allowed young people to express themselves freely, develop a sense of self-worth, and interact more. The nature of the mobile technology also allowed participants to build friendships beyond their geographic area and interact with their peers in real time. Within the evolving context of COVID-19, establishing evidence-based processes and methods for intervention design and curation in virtual spaces is critical.

4.
Br J Sports Med ; 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2088779

ABSTRACT

BACKGROUND: Both vaccination and physical activity have been shown to independently decrease the likelihood of severe COVID-19 infection. OBJECTIVE: To assess the association between regular physical activity and vaccination against COVID-19 among healthcare workers. METHODS: A test negative case-control study design was used to estimate the risk of having an associated COVID-19-related hospital admission, among individuals who were unvaccinated compared with those who were fully vaccinated with Ad26.COV2.S (>28 days after a single dose). 196 444 participant tests were stratified into three measured physical activity subgroups with low, moderate and high activity, to test the hypothesis that physical activity is an effect modifier on the relationship between vaccination and hospitalisation. RESULTS: Vaccine effectiveness against a COVID-19-related admission among vaccinated individuals within the low activity group was 60.0% (95% CI 39.0 to 73.8), 72.1% (95% CI 55.2 to 82.6) for the moderate activity group, and 85.8% (95% CI 74.1 to 92.2) for the high activity group. Compared with individuals with low activity levels, vaccinated individuals with moderate and high activity levels had a 1.4 (95% CI 1.36 to 1.51) and 2.8 (95% CI 2.35 to 3.35) times lower risk of COVID-19 admission, respectively (p value <0.001 for both groups). CONCLUSIONS: Regular physical activity was associated with improved vaccine effectiveness against COVID-19 hospitalisation, with higher levels of physical activity associated with greater vaccine effectiveness. Physical activity enhances vaccine effectiveness against severe COVID-19 outcomes and should be encouraged by greater public health messaging.

6.
J Int AIDS Soc ; 25(7): e25968, 2022 07.
Article in English | MEDLINE | ID: covidwho-1958777

ABSTRACT

INTRODUCTION: Community-based delivery of HIV pre-exposure prophylaxis (PrEP) to South African adolescent girls and young women's (AGYW) could increase access but needs evaluation. We integrated PrEP services via home-based services and pop-up tents into existing community-based HIV testing services (CB-HTS) in Eastern Cape Province, South Africa. METHODS: After accessing CB-HTS via a "pop-up" tent or home-based services, HIV-negative AGYW aged 16-25 years were invited to complete a baseline questionnaire and referred for PrEP services at a community-based PrEP site co-located with pop-up HTS tents. A 30-day supply of PrEP was dispensed. PrEP uptake, time-to-initiation, cohort characteristics and first medication refill within 90 days were measured using descriptive statistics. RESULTS: Of the 1164 AGYW who tested for HIV, 825 (74.3%) completed a questionnaire and 806 (97.7%) were referred for community-based PrEP. Of those, 624 (77.4%) presented for PrEP (482/483 [99.8%] from pop-up HTS and 142/323 [44.0%] from home-based HTS), of which 603 (96.6%) initiated PrEP. Of those initiating PrEP following home-based HTS, 59.1% initiated within 0-3 days, 25.6% within 4-14 days and 15.3% took ≥15 days to initiate; 100% of AGYW who used pop-up HTS initiated PrEP the same day. Among AGWY initiating PrEP, 37.5% had a detectable sexually transmitted infection (STI). Although AGYW reported a low self-perception of HIV risk, post-hoc application of HIV risk assessment measures to available data classified most study participants as high risk for HIV acquisition. Cumulatively, 329 (54.6%) AGYW presented for a first medication refill within 90 days of accepting their first bottle of PrEP. CONCLUSIONS: Leveraging CB-HTS platforms to provide same-day PrEP initiation and refill services was acceptable to AGYW. A higher proportion of AGYW initiated PrEP when co-located with CB-HTS sites compared to those referred following home-based HTS, suggesting that proximity of CB-HTS and PrEP services facilitates PrEP uptake among AGYW. The high prevalence of STIs among those initiating PrEP necessitates the integration of STI and HIV prevention programs for AGYW. Eligibility for PrEP initiation should not be required among AHYW in high HIV burden communities. Community-based service delivery will be crucial to maintaining access to PrEP services during the COVID-19 pandemic and future health and humanitarian emergencies.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Pre-Exposure Prophylaxis , Adolescent , Anti-HIV Agents/therapeutic use , Counseling , Feasibility Studies , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Pandemics , South Africa
8.
J Int AIDS Soc ; 25(6): e25938, 2022 06.
Article in English | MEDLINE | ID: covidwho-1905884

ABSTRACT

INTRODUCTION: Conditional cash transfers (CTs) augmented with other interventions are promising interventions for reducing HIV risk in adolescent girls and young women. METHODS: A multi-phase, quasi-experimental study assessed the impact of a CT (ZAR300; $22) conditional on attending a skills building intervention, Women of Worth (WoW), designed to improve sexual and reproductive health (SRH) outcomes in Cape Town, South Africa from May 2017 to December 2019. The intervention entailed 12 sessions with encouragement to attend adolescent and youth-friendly health services. Women aged 19-24 years were randomized 1:1 to receive the intervention with a CT ("cash + care" or C+C) or without a CT ("care"). The study included a pilot phase followed by a post-modification phase with improved uptake and retention without changing programme content or CT. Self-reported HIV prevalence and SRH/HIV vulnerability were assessed via a self-administered questionnaire at baseline, after 11 sessions, and 6-30 months' post-intervention for a subset. Mixed effect logistic regression models were fitted to estimate within-subject changes in outcomes. RESULTS: Of 5116 participants, 904 (452 participants per arm) were in the pilot and 4212 (2039 "care" participants and 2173 "C+C" participants) were in the post modified phase. There were 1867 (85.9%) and 135 (6,6%) participants in the "C+C" group and the "Care," respectively, that were WoW completers (≥ 11 sessions/retention). During the pilot phase, 194 (42.9%) and 18 (4.0%) participants in "C+C" and the "care" groups were retained. Receiving a CT sustained participation nearly 60-fold (OR 60.37; 95% CI: 17.32; 210.50, p <0.001). Three-hundred and thirty women were followed for a median of 15.0 months [IQR: 13.3; 17.8] to assess the durability of impact. Self-reported new employment status increased more than three-fold (p <0.001) at WoW completion and was sustained to the longer time point. Intimate partner violence indicators were reduced immediately after WoW, but this was not durable. CONCLUSIONS: Participants receiving CT had sustained participation in an SRH/HIV prevention skills building with improvement in employment and some SRH outcomes. Layered, "young woman centred" programmes to address HIV and SRH risk in young women may be enhanced with CT.


Subject(s)
HIV Infections , Intimate Partner Violence , Sexual Health , Adolescent , Female , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Sexual Behavior , South Africa/epidemiology
10.
Cell Rep Med ; 3(3): 100535, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1815266

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 antibody 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 convalescent donors who had been hospitalized with severe illness, and are cross-reactive against diverse SARS-CoV-2 variants, including the 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.


Subject(s)
COVID-19 , Viral Vaccines , Ad26COVS1 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , SARS-CoV-2/genetics
12.
Nat Commun ; 13(1): 1976, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1783980

ABSTRACT

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
13.
Lancet ; 399(10332): 1281-1282, 2022 04 02.
Article in English | MEDLINE | ID: covidwho-1768610
14.
Clin Infect Dis ; 75(1): e289-e292, 2022 08 24.
Article in English | MEDLINE | ID: covidwho-1769236

ABSTRACT

We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Polymerase Chain Reaction , South Africa/epidemiology
15.
Lancet ; 399(10330): 1141-1153, 2022 03 19.
Article in English | MEDLINE | ID: covidwho-1747473

ABSTRACT

BACKGROUND: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic. METHODS: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 1010 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual. FINDINGS: Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]). INTERPRETATION: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally. FUNDING: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation.


Subject(s)
COVID-19 , HIV Infections , Vaccines , Ad26COVS1 , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Female , Humans , Male , SARS-CoV-2 , South Africa/epidemiology
16.
S Afr J Infect Dis ; 37(2): 400, 2022.
Article in English | MEDLINE | ID: covidwho-1726253
17.
Nature ; 603(7901): 488-492, 2022 03.
Article in English | MEDLINE | ID: covidwho-1661968

ABSTRACT

The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3-6 and reduce vaccine protection from infection7,8. 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. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 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 for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9-12.


Subject(s)
COVID-19/immunology , COVID-19/virology , Cross Reactions/immunology , Immunity, Cellular , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Adult , Aged , COVID-19 Vaccines/immunology , Convalescence , Hospitalization , Humans , Middle Aged , SARS-CoV-2/chemistry , SARS-CoV-2/classification
18.
Cell Rep Med ; 3(2): 100510, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1636907

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with improved disease outcome and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta and Delta infection trigger responses with significantly improved Fc cross-reactivity against global VOCs compared with D614G-infected or Ad26.COV2.S-vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence affects Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin Fc Fragments/immunology , SARS-CoV-2/immunology , /immunology , Adult , Aged , COVID-19/blood , COVID-19/prevention & control , COVID-19/virology , Cohort Studies , Cross Reactions , Female , HEK293 Cells , Humans , Jurkat Cells , Male , Middle Aged , Neutralization Tests , Protein Binding , Spike Glycoprotein, Coronavirus/immunology , THP-1 Cells , Treatment Outcome , Vaccination/methods
19.
J Int AIDS Soc ; 24(12): e25846, 2021 12.
Article in English | MEDLINE | ID: covidwho-1591262

ABSTRACT

INTRODUCTION: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co-infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy-specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next-generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co-infections research. DISCUSSION: The 26-member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics-centred guidance for advancing timely, responsible HIV/co-infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug-related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post-approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co-infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. CONCLUSIONS: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for - and the promise of - advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and wellbeing of pregnant people and their children.


Subject(s)
Acquired Immunodeficiency Syndrome , Biomedical Research , Coinfection , HIV Infections , Child , Female , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Pregnancy , Stakeholder Participation
20.
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