Early recovery of natural killer cells post T-cell depleted allogeneic stem cell transplantation using alemtuzumab "in the bag".

BACKGROUND: Allogeneic stem cell transplantation (SCT) is a critical therapy for haematological malignancy but may lead to acute and chronic graft versus host disease (GvHD). T-cell depletion with alemtuzumab, either in vivo or ex vivo, reduces the incidence of GvHD but is a risk factor for disease relapse and poor immune reconstitution. Natural killer (NK) cells are the first lymphocytes to recover. Classical NK cells make up >90% of the normal circulating population and can directly kill neoplastic or virally infected cells while the regulatory subset makes up <10%, secretes cytokines and is not cytotoxic. The recovery and balance of these subsets post SCT remains controversial, with most studies analysing patients who received unmanipulated grafts and in vivo immunosuppression. OBJECTIVE: The aim was to assess the early recovery of NK cells in 18 consecutive patients receiving ex vivo T-cell depleted SCT and to compare the results to 25 individuals receiving haploidentical non-T cell depleted grafts. METHODS: All patients received myeloablative conditioning. After stem cell collection, the stem cells of the T cell depleted group were treated "in the bag" with alemtuzumab (CAMPATH 1H) at a concentration of 1mg/108 mononuclear cells and thereafter immediately infused. For those receiving non-T cell depleted grafts, GvHD prophylaxis was with post infusion therapeutic doses of cyclophosphamide. Blood samples were collected at days 21, 28 and 90. Complete blood counts were performed on an automated analyser while lymphocyte and NK subsets were examined using multiparameter flowcytometry. NK cells were defined as lymphocytes which were CD3-/CD56+. The classical subset was recognised as CD56dim/CD16+ while the regulatory population as CD56bright/CD16-. The results for both transplant types were compared at all time points using SPSS v8 statistical software. RESULTS: The recovery of lymphocytes was slow in both groups. Those receiving non-T cell depleted grafts had significantly higher T cell counts at day 21 and 28 when compared to the T cell depleted group (P < 0.05). In contrast, NK cells in the ex vivo T-cell depleted patients recovered rapidly and by day 21 was no different to normal (p > 0.05), while the non-T cell depleted group had significantly decreased numbers (p < 0.001), only recovering at day 90. Both groups had abnormal NK cell subset ratios with significantly elevated percentages of regulatory cells (p < 0.05). However, significant differences were observed between the two groups with those receiving T cell depleted grafts having lower percentages of regulatory cells as well as higher numbers of classical NK cells at day 21 and 28 (p < 0.01). CONCLUSION: This study of ex vivo T-cell depleted SCT's demonstrates that NK cells recover quicker when compared to those receiving unfractionated grafts. These results may have implications for GvHD and the GvL effect which warrants further study.

Outcomes of Best-Practice Guided Digital Mental Health Interventions for Youth and Young Adults with Emerging Symptoms: Part II. A Systematic Review of User Experience Outcomes.

Although many young people demonstrate resilience and strength, research and clinical evidence highlight an upward trend in mental health concerns among those aged 12 to 25 years. Youth-specific digital mental health interventions (DMHIs) aim to address this trend by providing timely access to mental health support for young people (12-25 years). However, there is a considerable gap in understanding young people user experiences with digital interventions. This review, co-designed with Australia's leading mental health organization Beyond Blue, utilizes a systematic methodology to synthesize evidence on user experience in youth-oriented digital mental health interventions that are fully or partially guided. Five relevant online databases were searched for articles published from 2018 to 2023, yielding 22,482 articles for screening and 22 studies were included in the present analysis. User experience outcomes relating to satisfaction and engagement were assessed for each included intervention, with experience indicators relating to usefulness, usability, value, credibility, and desirability being examined. Elements associated with positive/negative outcomes were extracted. Elements shown to positively influence user experience included peer engagement, modern app-based delivery, asynchronous support, and personalized content. In contrast, users disliked static content, homework/log-keeping, the requirement for multiple devices, and social media integration. Asynchronous interventions showed high satisfaction but faced engagement issues, with combined asynchronous/synchronous interventions reporting better completion rates. DMHIs offer a promising platform for youth mental health support and has the potential to dramatically increase the reach of interventions through the adoption of technological and user experience best practices. While young people respond positively to many aspects of intervention modernization, such as interactive, app-based design, other concepts, such as social media integration, they need to be adopted by the field more cautiously to ensure trust and engagement.Trial Registration CRD42023405812.

Hematological Complications of Human Immunodeficiency Virus (HIV) Infection: An Update From an HIV-Endemic Setting.

Medical professionals, particularly in regions with a high burden of human immunodeficiency virus (HIV), should be alert to the hematological complications of HIV, which may include cytopenias, malignancy, and coagulation disturbances. Patients may present with these conditions as the first manifestation of HIV infection. Hematological abnormalities are often multifactorial with opportunistic infections, drugs, malignancy, and HIV infection itself contributing to the clinical presentation, and the diagnosis should consider all these factors. Life-threatening hematological complications requiring urgent diagnosis and management include thrombotic thrombocytopenic purpura, superior mediastinal syndrome, spinal cord compression, and tumor lysis syndrome due to aggressive lymphoma. Antiretroviral therapy is the therapeutic backbone, including for patients with advanced HIV, in addition to specific therapy for the complication. This article reviews the impact of HIV on the hematological system and provides a clinical and diagnostic approach, including the role of a bone marrow biopsy, focusing on perspectives from sub-Saharan Africa.

Outcomes of Best-Practice Guided Digital Mental Health Interventions for Youth and Young Adults with Emerging Symptoms: Part I. A Systematic Review of Socioemotional Outcomes and Recommendations.

Youth-specific digital mental health interventions (DMHI) represent an emerging field of study, and aim to increase access, improve socioemotional outcomes, and, where required, support triage to targeted interventions. However, prior reviews have reported inconsistent findings on the clinical effectiveness of such interventions in young adults (12-25 years). Further, shortfalls remain for the impact of guided interventions based on the mode of delivery and the type of human support personnel (e.g., professional or peer) guiding the intervention. In response, this systematic review, co-designed with Australia's leading mental health organization, aims to assess the effectiveness of guided digital programs in improving youth socioemotional outcomes. Included studies involve young people experiencing mental ill-health, receiving brief (i.e., 1-12 sessions), digitally delivered (at least partially) psychological interventions that were guided or partially guided, tested in a type of experimental study, with a socioemotional outcome. Specific socioemotional outcomes examined were depression, anxiety, stress, wellbeing, mindfulness, and quality of life. A systematic search of the contemporary published and grey literature identified 22,482 records with 32 relevant records published between 2018 and 2023. A narrative synthesis guided integration of findings. Results demonstrated strong evidence for the effectiveness of guided interventions on socioemotional outcomes (i.e., depression, anxiety, stress) yet these effects were short-lived. When factoring in the use of different control groups (i.e., active vs. inactive), inconsistent effects were observed for the socioemotional outcomes of depression, anxiety, and stress. The mode of delivery (i.e., asynchronous, synchronous, combined) and the type of human support personnel did not appear to impact socioemotional outcomes. Results indicate efficacious brief digital interventions for depression and anxiety include refresher/follow-up content, goal setting content, and relapse prevention content. In contrast, poor efficacy is associated with interventions that include homework tasks, self-monitoring, and log-keeping content.PROSPERO, ID CRD42023405812.

Safety of a second homologous Ad26.COV2.S vaccine among healthcare workers in the phase 3b implementation Sisonke study in South Africa.

The Sisonke 2 study provided a homologous boost at least 6 months after administration of the priming dose of Ad26.COV2.S for healthcare workers enrolled on the Sisonke phase 3b implementation study. Safety monitoring was via five reporting sources: (i.) self-report through a web-link; (ii.) paper-based case report forms; (iii.) a toll-free telephonic reporting line; (iv.) healthcare professionals-initiated reports; and (v.) active linkage with National Disease Databases. A total of 2350 adverse events were reported by 2117 of the 240 888 (0.88%) participants enrolled; 1625 of the 2350 reported events are reactogenicity events and 28 adverse events met seriousness criteria. No cases of thrombosis with thrombocytopaenia syndrome were reported; all adverse events including thromboembolic disorders occurred at a rate below the expected population rates apart from one case of Guillain Barre Syndrome and one case of portal vein thrombosis. The Sisonke 2 study demonstrates that two doses of Ad26.COV2.S is safe and well tolerated; and provides a feasible model for national pharmacovigilance strategies for low- and middle-income settings.

Infant and preschool attachment, continuity and relationship to caregiving sensitivity: findings from a new population-based Australian cohort.

BACKGROUND: Here, we report new prevalence and temporal stability data for child attachment and parental caregiving behaviour, from infancy (1 year) to preschool (4 years). METHODS: Attachment (SSP) and caregiving data (MBQS) were from observations of parents and their infants and preschoolers, who represent the third generation of participants within an Australian longitudinal cohort. RESULTS: At 1 year (n = 314 dyads) and at 4 years (n = 368 dyads), proportions assessed secure were 59% and 71%, respectively. Proportions assessed avoidant were 15% and 11%; ambivalent 9% and 6%, and disorganised 17% and 12%, at 1 and 4 years. Continuity of attachment pattern was highest for the infant secure group. Of dyads initially classified disorganised in infancy, 36% remained so at the preschool assessment. Attachment and caregiving continuities across the infancy-preschool period were highest for the stable secure attachment group and lowest for the stable insecure attachment group. Loss of secure attachment to mother by age 4 years correlated with decreased maternal caregiving sensitivity, and acquisition of secure status by age 4 was associated with increased maternal sensitivity. We found no difference in caregiving sensitivity scores for mothers and fathers for female and male preschool children. CONCLUSIONS: The contemporary infant and preschool attachment proportions we report here closely mirror the patterns of those reported in prior decades, with an inclination towards secure base relationships. Our findings alert practitioners anew to the responsiveness of early attachment status to change in caregiving responsiveness and support ongoing investment in early identification of disorganised attachment.

Universal Digital Programs for Promoting Mental and Relational Health for Parents of Young Children: A Systematic Review and Meta-Analysis.

Digital parenting programs aim to increase program access, improve psychosocial outcomes for parents and children, and support triage to targeted interventions where required. This meta-analysis assessed the efficacy of online parenting programs in improving parenting skills and capabilities, and by consequence, the mental health and well-being of parents and children, and the quality of the parent-child relationship. Studies were included if they were: (1) online, (2) self-delivered, (3) designed for universal general population prevention, (4) evaluated experimental or quasi-experimental designs, and (5) assessed parent and child emotional and/or relational health, from pregnancy to 5 years of age. A systematic search of electronic databases and grey literature identified 22 studies that met inclusion criteria, including 24 independent samples, with 5671 unique parents. Meta-analyses were conducted using random effects models and Cohen's d effects. Small-to-moderate improvements in parent depression, anxiety, self-efficacy, and social support were observed. No effects on parent stress, satisfaction, or parent-child relationship quality were observed. Meta-regression and sub-group analysis were conducted to identify sensitivity or moderation effects. Collectively, findings suggest any benefits of online parenting programs mostly occur at the time of the intervention, for parent mental health and well-being outcomes, and that enduring effects are unlikely. However, given the cost effectiveness and accessibility of online programs, further research into ways of sustaining effects on parenting outcomes is warranted. Furthermore, given the centrality of the parent-child bond to child development across the lifecourse, additional investment in new digitally facilitated approaches focusing on this bond are likewise warranted.PROSPERO registration CRD42021275647.

A Mother's Voice: The Construction of Maternal Identity Following Perinatal Loss.

BACKGROUND: Maternal identity, a mother's internalized view of self as mother, has not been studied in relation to perinatal loss. This study aimed to investigate how women construct a sense of maternal identity after the loss of a baby. METHODS: We interviewed 10 mothers who had experienced perinatal loss. A Listening Guide framework for narrative analysis was used to identify patterns of giving voice to the mother's own story. RESULTS: We identified 12 overarching voices which fell within three distinct groupings: voices of motherhood, voices of grief, and voices of growth. Although bereaved mothers grappled with constructing their maternal identity, they also demonstrated how maternal identity is individually and intuitively created through an honouring and remembering of the child that was lost, resulting in significant growth. CONCLUSIONS: There is need for a broader definition of what constitutes motherhood to encapsulate diverse mothering experiences, including perinatal loss.

Multicentre verification of haematology laboratory blood collection tubes during a global blood collection tube shortage.

INTRODUCTION: Verification of blood collection tubes is essential for clinical laboratories. The aim of this study was to assess performance of candidate tubes from four alternative suppliers for routine diagnostic haematology testing during an impending global shortage of blood collection tubes. METHODS: A multicentre verification study was performed in Cape Town, South Africa. Blood from 300 healthy volunteers was collected into K2 EDTA and sodium citrate tubes of BD Vacutainer® comparator tubes and one of four candidate tubes (Vacucare, Vacuette®, V-TUBE™ and Vacutest®). A technical verification was performed, which included tube physical properties and safety. Routine haematology testing was performed for clinical verification. RESULTS: Vacucare tubes did not have a fill-line indicator, Vacuette® tubes had external blood contamination on the caps post-venesection and Vacutest® tubes had hard rubber stoppers. K2 EDTA tubes of Vacuette®, Vacucare and Vacutest® performed similarly to the comparator. Unacceptable constant bias was seen for PT in Vacucare (95% CI -2.38 to -0.10), Vacutest® (95% CI -1.91 to -0.49) and Vacuette® (95% CI 0.10-1.84) tubes and for aPTT in Vacuette® (95% CI 0.22-2.00) and V-TUBE™ (95% CI -2.88 to -0.44). Unacceptable %bias was seen for aPTT in Vacucare (95% CI 2.78-4.59) and Vacutest® tubes (95% CI 2.53-3.82; desirable ±2.30), and in V-TUBE™ for mean cell volume (95% CI 1.15-1.47, desirable ±0.95%) and mean cell haemoglobin concentration (95% CI -1.65 to -0.93, desirable ±0.43%). CONCLUSION: Blood collection tubes introduce variability to routine haematology results. We recommend that laboratories use one brand of tube. Verification of new candidate tubes should be performed to ensure consistency and reliable reporting of results.

Practice, governance, and culture characteristics of lived experience organisations, and evidence of efficacy: A scoping review protocol.

BACKGROUND: Mental health policy and service design is increasingly recognizing the importance of the lived experience voice and its inclusion in all aspects of work. Effective inclusion requires a deeper understanding of how best to support lived experience workforce and community members to meaningfully participate in the system. OBJECTIVES: This scoping review aims to identify key features of organizational practice and governance that facilitate the safe inclusion of lived experience in decision-making and practice within mental health sector contexts. Specifically, the review focuses on mental health organizations devoted to lived experience advocacy or peer support or those in which lived experience membership (paid or voluntary) is central to advocacy and peer support operations. METHODS: This review protocol was prepared with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and registered with the Open Science Framework. The review will be guided by the Joanna Briggs Institute methodology framework and is being conducted by a multidisciplinary team including lived experience research fellows. It will include published and grey literature, including government reports, organizational online documents, and theses. Included studies will be identified through comprehensive searches of five databases: PsycINFO (Ovid), CINAHL (EBSCO), EMBASE (Ovid), MEDLINE (Ovid), and ProQuest Central. Studies published in English from 2000 onwards will be included. Data extraction will be guided by pre-determined extraction instruments. Results will be presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews flow chart. Results will be presented in tabular form and narratively synthesized. The planned commencement and completion dates for this review were July 1, 2022 and April 1, 2023. DISCUSSION: It is anticipated that this scoping review will map the current evidence base underpinning organizational practices in which lived experience workers are involved, specifically in the mental health system. It will also inform future mental health policy and research. TRIAL REGISTRATION: Registration: Open Science Framework (registered: July 26, 2022; registration DOI: 10.17605/OSF.IO/NB3S5).

Point of care ultrasound findings in critically ill SARS-COV2 patients in an HIV endemic, resourced constrained setting.

Objectives: To describe the incidence of venous thromboembolism (VTE) in mechanically ventilated COVID-19 patients in an HIV endemic, resourced constrained setting. To describe the incidence of VTE in relation to HIV status and anticoagulant therapy, and to evaluate VTE-associated cardio-respiratory changes. To establish the contribution of HIV, anticoagulation therapy and other risk factors to mortality. Design: Prospective descriptive study. Setting: Single-center tertiary teaching hospital. Participants: One hundred and one consecutively admitted critically ill adult patients with COVID-19 acute respiratory distress syndrome. Interventions: Point of care ultrasound (POCUS) assessment of the lower limbs and the cardio-respiratory system was performed on intensive care unit (ICU) admission and repeated if clinically indicated. Measurements and main results: DVT was diagnosed by POCUS, whilst pulmonary embolism was diagnosed using a combination of clinical criteria and POCUS (echocardiography and chest wall ultrasound). VTE was diagnosed in 16/101 (16%) patients, despite 14/16 (88%) receiving prior therapeutic dosage of low molecular weight heparin. Clinically significant PE was diagnosed in 5/16 (31%) with 11/16 (69%) having DVT only. The majority of VTE patients, 12/16 (75%), demised 16/101 (16%) patients had HIV co-infection, and 4/16 (25%) with HIV had VTE. Valvular abnormalities were the most common cardiac abnormality with marked tricuspid regurgitation detected in 51/101 (51%). The absence of right atrial enlargement had a 93% negative predictive value for the absence of VTE. Univariate analysis did not demonstrate statistically significant individual risk factors for mortality. Conclusions: Mechanically ventilated COVID- 19 patients at ICU admission had a low incidence of VTE (16%). Therapeutic dose anticoagulation did not reduce mortality compared to prophylactic dosage. In contrast to findings from other studies, no individual risk factor contributed significantly to mortality, likely due to small sample size. POCUS is an ideal screening tool to aid in the assessment of critically ill patients.

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study).

Objective: To assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population. Design: Open label, single arm, phase 3B study. Setting: Sisonke study, South Africa, 17 February to 15 June 2021. Participants: The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine. Main outcome measures: Observed rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software). Results: Most of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population. Conclusions: Vaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates. Trial registration: ClinicalTrials.gov NCT04838795.

My Early Relational Trust-Informed Learning (MERTIL) for Parents: A study protocol for a brief, universal, online, preventative parenting program to enhance relational health.

BACKGROUND: Early relational health is a key determinant of childhood development, while relational trauma in the parent-infant dyad can instigate a cascading pattern of infant risk. Fortunately, early relational trauma is detectable and modifiable. In 2018, Australian Maternal and Child Health (MCH) nurses participated in MERTIL (My Early Relational Trauma-Informed Learning), a program to identify and prevent relational trauma. Program evaluations revealed nurses felt competent and confident to identify and respond to relational trauma; however, response capacity was inhibited by inadequate parent referral options. In response, MERTIL for Parents (My Early Relational Trust-Informed Learning) was developed, which is an online, evidence-based, self-paced parenting program that focuses on enhancing parental knowledge of relational trust and its significance for infant development. This low-cost, accessible prevention resource targets emerging relational concerns to reduce later service system engagement. The potential for universal preventative online programs that target parental and relational wellbeing remains under-explored. This paper reports on a protocol for implementing a MERTIL for Parents pilot study describing practitioners' and parents' perspectives on program feasibility and efficacy. METHODS: This study is a mixed methods, parallel armed, uncontrolled, repeated measures design. We aim to recruit 48 Australian MCH practitioners from the states of Victoria and New South Wales. These professionals will in turn recruit 480 parents with a child aged 0-5 years. All parents will receive MERTIL for Parents, which entails a 40-minute video, tipsheets, posters, and support resources. Parent data will be obtained at three periods: pre-program, program exit, and program follow-up. Practitioner data will be collected at two periods: pre-parent recruitment and program follow-up. Data collection will occur through surveys and focus groups. Primary parent outcomes will be socioemotional assessments of program efficacy. Practitioners and parents will each report on program feasibility. DISCUSSION: This protocol describes the feasibility and efficacy of a new online parenting program, MERTIL for Parents, with pilot field studies commencing in March 2023. We anticipate that this resource will be a valuable addition to various child and family services, for use in individual support and group work.

The International Prognostic Score and HIV status predict red cell concentrate transfusion needs in Hodgkin lymphoma.

Despite the burden of anemia among Hodgkin lymphoma (HL) patients, data evaluating red cell concentrate transfusion are limited. We retrospectively studied 285 newly diagnosed HL patients who received first-line adriamycin, bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD) treatment at Groote Schuur Hospital, Cape Town. HIV prevalence in the cohort was 39.5% and 74.2% of patients had advanced stage HL. Patient prognosis was scored using the HL International Prognostic Score (IPS-7) and HL IPS-3. Seventy (24.6%) patients were transfused with a median of 2 (IQR 1-5) units per patient. Compared to HIV-negative patients, more HIV-positive patients were transfused (14.1% vs. 40.4%, p < .001) and received more units, median 2 (IQR 1-3) vs. 3 (IQR 2-5), p = .035. HL IPS-7 (OR 2.1, p < .001) and HL IPS-3 (OR 2.6, p < .001) were independently associated with transfusion. HL IPS-7, HL IPS-3, and HIV positivity remained associated with transfusion after adjusting for covariates. For patients with newly diagnosed HL, HL IPS-7, HL IPS-3, and HIV status predicted transfusion.

Training of Lived Experience Workforces: A Rapid Review of Content and Outcomes.

Recently, the lived and living experience (LLE) workforce in mental health and alcohol and other drugs (AOD) sectors has expanded. Despite widespread benefit of this inclusion, some LLE practitioners have encountered personal and professional challenges in their workforce roles. An essential avenue to address these challenges is through provision of training to ensure adequate LLE role preparation, and to support integration of LLE workforces within mental health and AOD settings. We aim to understand the primary components applied in LLE training programs (i.e., content and methods), the outcomes from program participation, and to summarize observed patterns between training components and outcomes. This rapid review utilized a systematic methodology following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize existing literature on training programs for service users or carers/family in lived experience roles, in the mental health and AOD workforce. We searched CINAHL, PsycINFO, Medline, and Web of Science databases. We identified 36 relevant studies. Findings indicate short- and long-term impacts of training participation for this emerging workforce, with the most promising outcomes being increased professional knowledge and skills and improved personal psychosocial wellbeing and trauma recovery. Other positive training outcomes included high trainee satisfaction, increased application of training skills, and employment/education opportunities following training completion. Gaps and training limitations were noted in relation to the training content/delivery, trainee reservations, and personal barriers to training participation or completion. In response to program benefits and limitations investigated, we present recommendations for improving training processes for this workforce.

Epidemiology and outcomes of SARS-CoV-2 infection associated with anti-nucleocapsid seropositivity in Cape Town, South Africa.

Background: In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can characterise the scale and determinants of the pandemic, as well as elucidate protection conferred by prior exposure. Methods: We conducted repeated cross-sectional serosurveys (July 2020 - November 2021) using residual plasma from routine convenient blood samples from patients with non-COVID-19 conditions from Cape Town, South Africa. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses, to estimate variant disease severity. Findings: Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.2% in July 2020 to 67.8% in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). Interpretation: The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19. Funding: Wellcome Trust, National Health Laboratory Service, the Division of Intramural Research, NIAID, NIH (ADR) and Western Cape Government Health.

Plasmablastic lymphoma: An update.

Plasmablastic lymphoma (PBL) is a highly aggressive B cell non-Hodgkin lymphoma frequently associated with immunosuppression, particularly human immunodeficiency virus (HIV) infection. Although PBL is rare globally, South Africa has a high burden of HIV infection leading to a higher incidence of PBL in the region. Laboratory features in PBL may overlap with plasmablastic myeloma and other large B cell lymphomas with plasmablastic or immunoblastic morphology leading to diagnostic dilemmas. There are, however, pertinent distinguishing laboratory features in PBL such as a plasma cell immunophenotype with MYC overexpression, expression of Epstein-Barr virus-encoded small RNAs and lack of anaplastic lymphoma kinase (ALK) expression. This review aims to provide a summary of current knowledge in PBL, focusing on the epidemiology, pathophysiology, laboratory diagnosis and clinical management.

Safety evaluation of the single-dose Ad26.COV2.S vaccine among healthcare workers in the Sisonke study in South Africa: A phase 3b implementation trial.

BACKGROUND: Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data. METHODS AND FINDINGS: In this open-label phase 3b implementation study among all eligible HCWs in South Africa registered in the national Electronic Vaccination Data System (EVDS), we monitored adverse events (AEs) at vaccination sites through self-reporting triggered by text messages after vaccination, healthcare provider reports, and active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from the day of first vaccination (17 February 2021) until 28 days after the final vaccination in the study (15 June 2021). COVID-19 breakthrough infections, hospitalisations, and deaths were ascertained via linkage of the electronic vaccination register with existing national databases. Among 477,234 participants, 10,279 AEs were reported, of which 138 (1.3%) were serious AEs (SAEs) or AEs of special interest. Women reported more AEs than men (2.3% versus 1.6%). AE reports decreased with increasing age (3.2% for age 18-30 years, 2.1% for age 31-45 years, 1.8% for age 46-55 years, and 1.5% for age > 55 years). Participants with previous COVID-19 infection reported slightly more AEs (2.6% versus 2.1%). The most common reactogenicity events were headache (n = 4,923) and body aches (n = 4,483), followed by injection site pain (n = 2,767) and fever (n = 2,731), and most occurred within 48 hours of vaccination. Two cases of thrombosis with thrombocytopenia syndrome and 4 cases of Guillain-Barré Syndrome were reported post-vaccination. Most SAEs and AEs of special interest (n = 138) occurred at lower than the expected population rates. Vascular (n = 37; 39.1/100,000 person-years) and nervous system disorders (n = 31; 31.7/100,000 person-years), immune system disorders (n = 24; 24.3/100,000 person-years), and infections and infestations (n = 19; 20.1/100,000 person-years) were the most common reported SAE categories. A limitation of the study was the single-arm design, with limited routinely collected morbidity comparator data in the study setting. CONCLUSIONS: We observed similar patterns of AEs as in phase 3 trials. AEs were mostly expected reactogenicity signs and symptoms. Furthermore, most SAEs occurred below expected rates. The single-dose Ad26.COV2.S vaccine demonstrated an acceptable safety profile, supporting the continued use of this vaccine in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT04838795; Pan African Clinical Trials Registry PACTR202102855526180.