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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.
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ObjectivesWe 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. MethodsIn 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. ResultsWe 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). ConclusionsIn 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.
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Fewer COVID-19 deaths have been reported in this fourth wave, with clinicians reporting less admissions due to severe COVID-19 pneumonia when compared to previous waves. We therefore aimed to rapidly compare the profile of deaths in wave 4 with wave 3 using routinely collected data on admissions to public sector hospitals in the Western Cape province of South Africa. Findings show that there have been fewer COVID-19 pneumonia deaths in the Omicron-driven fourth wave compared to the third wave, which confirms anecdotal reports and lower bulk oxygen consumption by hospitals in the province.
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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.
