COVID-19 vaccine uptake and effectiveness by time since vaccination in the Western Cape province, South Africa: An observational cohort study during 2020-2022 (preprint)

Background: There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced high levels of SARS-CoV-2 infection in a mostly vaccine-naive population, and has limited vaccine coverage and competing health service priorities. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa. Methods We performed an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalisation and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies and healthcare utilisation. Results By end 2022, only 41% of surviving adults had completed vaccination and 8% a booster dose, despite several waves of severe COVID-19. Recent vaccination was associated with notable reductions in severe COVID-19 during distinct analysis periods dominated by Delta, Omicron BA.1/2 and BA.4/5 (sub)lineages: within 6 months of completing vaccination or boosting, vaccine effectiveness was 46-92% for death (range across periods), 45-92% for admission with severe disease or death, and 25-90% for any admission or death. During the Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, there were distinct reductions of VE at larger times post completing or boosting vaccination. Conclusions Continued emphasis on regular COVID-19 vaccination including boosting is important for those at high risk of severe COVID-19 even in settings with widespread infection-induced immunity.

Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors, the impact of the COVID-19 pandemic and possible opportunities for intervention (preprint)

In recent years, hospital managers have reported increasing numbers of psychiatric hospital admissions in the Western Cape Province of South Africa, driven by poverty and substance use. We aimed to examine this trend, and the impact of the COVID-19 pandemic, as well as assess factors associated with linkage to ambulatory services following hospital discharge and repeat psychiatric admissions. Using electronic health data from the Provincial Health Data Centre, a consolidated routine service database, all psychiatric hospital admissions in the Western Cape public sector from 2015 to 2022 were analyzed, stratified by hospital level. Mixed effects logistic regression was used in this cohort study to determine the factors associated with successful linkage to ambulatory services within 30 days following hospital discharge, and repeat psychiatric admission within 30 and 90 days. We found that psychiatric hospital admissions, particularly at the district/acute level, were increasing prior to 2020 and an increasing proportion of diagnoses were substance related. 40% of admissions at the district level had not been seen at a primary health care facility in the year before the admission. Male patients and those with substance use disorders were less likely to be successfully linked to outpatient services following discharge. Successful linkage was one of the most protective factors against readmission within 90 days with an adjusted odds ratio of 0.76 (95%CI 0.73-0.79) and 0.45 (95%CI 0.42-0.49) at district/acute and specialized hospitals respectively. Improving linkage to ambulatory services by mental health patients post-discharge is likely to avert hospital readmissions.

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

Abstract 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.

Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa (preprint)

ObjectiveWe aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. MethodsWe included public sector patients aged [≥]20 years with laboratory-confirmed COVID-19 between 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination and prior infection. ResultsAmong 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had lower risk of severe outcomes than previous waves. Prior infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for boosted vs. no vaccine) were protective. ConclusionDisease severity was similar amongst diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, both of which were strongly protective.

Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa (preprint)

Objectives: We aimed to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection, and whether protection against severe disease conferred by prior infection and/or vaccination was maintained. Methods: In this cohort study, we included public sector patients aged [≥]20 years with a laboratory confirmed COVID-19 diagnosis between 14 November-11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalization or death and any hospitalization or death (all [≤]14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection. Results: We included 5,144 patients from wave four and 11,609 from prior waves. Risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted Hazard Ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR:0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58). Conclusions: In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25% reduced risk of severe hospitalization or death compared to Delta.

Estimating vaccine confidence levels among healthcare staff and students of a tertiary institution in South Africa (preprint)

ABSTRACT Introduction In South Africa, healthcare workers were the first group scheduled to receive a COVID-19 vaccine when it became available. Therefore, estimating their vaccine confidence levels and gauging their intention to vaccinate ahead of the COVID-19 vaccination roll-out was imperative. Methods An online survey was conducted among current staff and students of the Faculty of Medicine and Health Sciences of Stellenbosch University in South Africa using a succinct questionnaire. Sentiments about vaccines were estimated using five validated statements. The intention to receive a COVID-19 vaccine was also investigated. Results The response rate was 21.8%, giving a sample size of 1015. Females were 70.0% in the source population and 74.7% in the study sample. The proportion of participants who agreed that vaccines are important for children and for self was 97.4% (95% confidence interval [CI] 96.1% to 98.3%) and 95.4% (95% CI 93.9 to 96.6) respectively. In addition, 95.4% (95% CI 93.8 to 96.6) agreed that vaccines are safe, 97.4% (95% CI 96.15 to 98.28) that vaccines are effective, and 96.1% (95% CI 94.6 to 97.2) that vaccines are compatible with their religious beliefs. The proportion of participants who were willing to receive a COVID-19 vaccine was 89.5% (95% CI 87.2 to 91.4). Log binomial regression revealed statistically significant positive associations between the intention to receive a COVID-19 vaccine and the belief that vaccines are safe (relative risk [RR] =32.2, CI 4.67 to 221.89); effective (RR=21.4, CI 3.16 to 145.82); important for children (RR=3.5, CI 1.78 to 6.99); important for self (RR=18.5, CI 4.78 to 71.12) or compatible with their religious beliefs (RR=2.2, CI 1.46 to 3.78). Conclusion Vaccine confidence levels of the study respondents were highly positive. Nevertheless, this could be further enhanced by targeted interventions. SUMMARY BOX What is already known? ➢ The fast-tracked development and roll out of COVID-19 vaccines has increased general concerns about vaccines ➢ Healthcare workers are critical to the success of any vaccination endeavor. What are the new findings? ➢ Vaccine sentiments in the study population of healthcare staff and students of Stellenbosch University are highly positive. ➢ The study population has minimal variation in vaccine sentiments and vaccination intention across a range of demographic and social variables. ➢ Log binomial regression identified positive sentiments for all five vaccine sentiments investigated as likely predictors of intention to receive a COVID-19 vaccine when one becomes available. What do the new findings imply? ➢ Similar interventions can be applied to enhance vaccine confidence among the healthcare staff and students of the study population as both groups share comparable characteristics across socio-demographic spheres. ➢ Strengthening confidence in vaccine importance, safety and effectiveness among healthcare workers and students holds the promise of a potential positive impact on COVID-19 vaccination uptake in the general population in the near and far future.

Estimating vaccine confidence levels among future healthcare workers and their trainers: A quantitative study protocol (preprint)

ABSTRACT Introduction The outbreak of novel coronavirus disease 2019 (COVID-19) caught the world off guard in the first quarter of the year 2020. To stem the tide of this pandemic, the development, testing, and pre-licensure approval for emergency use of some COVID 19 vaccine candidates were accelerated. This led to raised public concern about their safety and efficacy, compounding the challenges of vaccine hesitancy which was already declared one of the top ten threats to global health in the year 2019. The onus of managing and administering these vaccines to a skeptical populace when they do become available rests mostly on the shoulders of healthcare workers (HCWs). Therefore, the vaccine confidence levels of HCWs becomes critical to the success of vaccination endeavors, especially COVID 19 vaccination. This proposed study aims to estimate the level of vaccine confidence and the intention to receive a COVID 19 vaccine among future HCWs and their trainers at a specific university in Cape Town, South Africa, and to identify any vaccination concerns early for targeted intervention. Methods and analysis An online survey will be distributed to current staff and students of an academic institution for HCWs. The survey questionnaire will consist of a demographic questions section consisting of six items and a vaccine confidence section comprising six items in Likert scale format. A multinomial logistic regression model will be employed to identify factors associated with vaccine confidence and intention. The strength of association will be assessed using odds ratio and its 95% confidence interval. Statistical significance will be defined at a p-value <0.05. Ethics and dissemination Ethics approval has been obtained for the study from Stellenbosch University (HREC Reference # S19/01/014 (PhD)). The results will be shared with relevant health authorities, presented at conferences, and published in a peer-reviewed journal. ARTICLE SUMMARY Strengths and limitations of this study ▸ The proposed study will generate baseline knowledge of the vaccine confidence among future healthcare workers and their trainers in its specific context. ▸ It will contribute to addressing the knowledge gap about the intention to receive a COVID 19 vaccine among health care workers in Africa. ▸ It will enable the early identification of vaccine concerns of healthcare workers while they are still in training and assist in informing tailored measures to address them. ▸ A limitation of the study is the possibility of a low response rate which is an inherent challenge of online surveys.