Maureen Masha

Introduction The Omicron BA.1/BA.2 wave in South Africa had lower hospitalisation and mortality than previous SARS-CoV-2 variants and was followed by an Omicron BA.4/BA.5 wave. This study compared admission incidence risk across waves, and the risk of mortality in the Omicron BA.4/BA.5 wave, to the Omicron BA.1/BA.2 and Delta waves. Methods Data from South Africa’s national hospital surveillance system, SARS-CoV-2 case linelist and Electronic Vaccine Data System were linked and analysed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100,000 people. Mortality rates in the Delta, Omicron BA.1/BA.2 and Omicron BA.4/BA.5 wave periods were compared by post-imputation random effect multivariable logistic regression models. Results In-hospital deaths declined 6-fold from 37,537 in the Delta wave to 6,074 in the Omicron BA.1/BA.2 wave and a further 7-fold to 837 in the Omicron BA.4/BA.5 wave. The case fatality ratio (CFR) was 25.9% (N=144,798), 10.9% (N=55,966) and 7.1% (N=11,860) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves respectively. After adjusting for age, sex, race, comorbidities, health sector and province, compared to the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.32-1.56) and Delta (aOR 3.22; 95% CI 2.98-3.49) wave. Being partially vaccinated (aOR 0.89, CI 0.86-0.93), fully vaccinated (aOR 0.63, CI 0.60-0.66) and boosted (aOR 0.31, CI 0.24-0.41); and prior laboratory-confirmed infection (aOR 0.38, CI 0.35-0.42) were associated with reduced risks of mortality. Conclusion Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa’s first three waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased.

Background: South Africa reported a notable increase in COVID-19 cases from mid-November 2021 onwards, starting in Tshwane District, linked to rapid community spread of the Omicron variant. This coincided with a rapid rise in paediatric COVID-19-associated hospitalisations. Methods: We synthesized data from five sources to describe the impact of Omicron on clinical manifestations and outcomes of hospitalized children (≤19 years) with positive SARS-CoV-2 tests in Tshwane District from 31 October to 11 December 2021, including: 1) COVID-19 line lists; 2) collated SARS-CoV-2 testing data; 3) SARS-CoV-2 genomic sequencing data; 4) COVID-19 hospitalisation surveillance; and 5) clinical data of public sector paediatric (≤13 years) COVID-19 hospitalisations. Findings: During the six-week period 6,287 paediatric (≤19 years) COVID-19 cases were recorded in Tshwane District, of these 462 (7.2%) were hospitalized in 42 hospitals (18% of overall admissions). The number of paediatric cases was higher than in the prior 3 waves, uncharacteristically preceding adult hospitalisations. Of the 75 viral specimens sequenced from the district, 99% were Omicron. Detailed clinical information obtained from 139 of 183 (76%) admitted children (≤13 years; including all public sector hospitalisations) indicated that young children (0-4 years) were most affected (62%). Symptoms included fever (47%), cough (40%), vomiting (24%), difficulty breathing (23%), diarrhoea (20%) and convulsions (20%). Length of hospital stay was short (mean 3.2 days), and in 44% COVID-19 was the primary diagnosis. Most children received standard ward care (92%), with 31 (25%) receiving oxygen therapy. Seven children (6%) were ventilated; four children died, all related to complex underlying co-pathologies. All children and majority of parents for whom data were available were unvaccinated. Interpretation: Rapid increases in paediatric COVID-19 cases and hospitalisations mirror high community transmission of SARS-CoV-2 (Omicron variant) in Tshwane District, South Africa. Continued monitoring is needed to understand the long-term impact of the Omicron variant on children. Research in context: Evidence before the study: The announcement of the new Omicron (B.1.1.529) variant of the SARS-CoV-2 virus was made on 24 November 2021. Clinical characteristics, and disease profiles of children with COVID-19 before the arrival of Omicron have been described in the literature. Added value of the study: This study describes the rapid rise in paediatric COVID-19-associated hospitalisations in Tshwane District in the Gauteng Province of South Africa – one of the first known epicentres of the new Omicron variant of the SARS-CoV-2 virus. The clinical picture as well as the steep increase in paediatric positivity rates and hospitalizations are described in detail from the perspective of a large South African health district, providing a broad overview on how the Omicron variant affects the paediatric population. Implication of all available evidence: This study describes the clinical picture and outcomes in children in the current wave of SARS-CoV-2 Omicron variant infections by incorporating data from 42 hospitals at all levels of care in a large district within the South African health system. This provides novel paediatric data to assist global preparation for the impact of the Omicron variant in the paediatric setting.

Background: The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis (TB) are unclear, particularly in low- and middle-income countries in Africa. South Africa has a national adult HIV prevalence of 19% and TB prevalence of 0.7%. Using a nationally representative hospital surveillance system in South Africa, we investigated the factors associated with in-hospital mortality among individuals with COVID-19. Methods: Using data from national active hospital surveillance, we describe the demographic characteristics, clinical features, and in-hospital mortality among hospitalised individuals testing positive for SARS-CoV-2, during 5 March 2020 to 27 March 2021. Chained equation multiple imputation was used to account for missing data and random effect multivariable logistic regression models were used to assess the role of HIV-status and underlying comorbidities on in-hospital COVID-19 mortality. Findings: Among the 219,265 individuals admitted with laboratory confirmed SARS-Cov-2, 51,037 (23.3%) died. Most commonly observed comorbidities among individuals with available data were hypertension (61,098/163,350; 37.4%), diabetes (43,885/159,932; 27.4%), and HIV (13,793/151,779; 9.1%), while TB was reported in 3.6% (5,282/146,381) of individuals. While age was the most important predictor, other factors associated with in-hospital COVID-19 mortality were HIV infection [aOR 1.34, 95% CI: 1.27-1.43), past TB [aOR 1.26, 95% CI: 1.15-1.38), current TB [aOR 1.42, 95% CI: 1.22-1.64) and both past and current TB [aOR 1.48, 95% CI: 1.32-1.67) compared to never TB, as well as other described risk factors for COVID-19, such as male sex, non-white race, and chronic underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy. After adjusting for other factors, PLWH not on ART [aOR 1.45, 95% CI: 1.22-1.72] were more likely to die in-hospital compared to PLWH on ART. Among PLWH, the prevalence of other comorbidities was 29.2% compared to 30.8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased mortality risk in both PLWH and HIV-uninfected individuals. Interpretation: Identified high risk individuals (older individuals and those with chronic comorbidities and PLWH, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation, as well as early referral and treatment. Funding: South African National Government