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1.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22279197

RESUMEN

IntroductionThe 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. MethodsData from South Africas 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. ResultsIn-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. ConclusionOverall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africas 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.

2.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21268108

RESUMEN

BackgroundSouth 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. MethodsWe 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. FindingsDuring 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. InterpretationRapid 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 contextO_ST_ABSEvidence before the studyC_ST_ABSThe 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 studyThis 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 evidenceThis 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.

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20248409

RESUMEN

BackgroundThe 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. MethodsUsing 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. FindingsAmong 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; %), 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. InterpretationIdentified 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. FundingSouth African National Government Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince the emergence of the COVID-19 pandemic, studies have identified older age, male sex and presence of underlying comorbidities including heart disease and diabetes as risk factors for severe disease and death. There are very few studies, however, carried out in low- and middle-income countries (LMIC) in Africa, many of whom have high poverty rates, limited access to healthcare, and high prevalence of chronic communicable diseases, such as HIV and tuberculosis (TB). Data are also limited from settings with limited access to HIV treatment programmes. Early small cohort studies mainly from high income countries were not conclusive on whether HIV or TB are risk factors for disease severity and death in COVID-19 patients. Large population cohort studies from South Africas Western Cape province and the United Kingdom (UK) have found people living with HIV (PLWH) to have a moderately increased risk of COVID-19 associated mortality. Of these, only the Western Cape study presented data on mortality risk associated with presence of high viral load or immunosuppression, and found similar levels of severity irrespective of these factors. Recent meta-analyses have confirmed the association of HIV with COVID-19 mortality. No studies reported on the interaction between HIV-infection and other non-communicable comorbidities on COVID-19 associated mortality. We performed separate literature searches on PubMed using the following terms: "COVID-19" "risk factors" and "mortality"; "HIV" "COVID-19" and "mortality"; "TB" "COVID-19" and "mortality". All searches included publications from December 1, 2019 until May 5, 2021, without language restrictions. Pooled together, we identified 2,786 published papers. Additionally, we performed two literature searches on MedRxiv using the terms "HIV" "COVID-19" and "mortality", and "TB" "COVID-19" and "mortality" from April 25, 2020 until May 5, 2021, without language restrictions. Pooled together, we identified 7,744 pre-prints. Added value of this studyAmong a large national cohort of almost 220,000 individuals hospitalised with COVID-19 in a setting with 19% adult HIV prevalence and 0.7%TB prevalence, we found that along with age, sex and other comorbidities, HIV and TB were associated with a moderately increased risk of in-hospital mortality. We found increasing risk of in-hospital mortality among PLWH not on ART compared to those on ART. Among PLWH, the prevalence of other comorbidities was high (29%) and the effect of increasing numbers of comorbidities on mortality was similar in PLWH and HIV-uninfected individuals. Our study included 13,793 PLWH from all provinces in the country with varying levels of access to HIV treatment programmes. Implications of all the available evidenceThe evidence suggests that PLWH and TB-infected individuals should be prioritised for COVID-19 prevention and treatment programmes, particularly those with additional comorbidities. Increasing age and presence of chronic underlying illness are important additional factors associated with COVID-19 mortality in a middle-income African setting. The completeness of data is a limitation of this national surveillance system, and additional data are needed to confirm these findings.

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