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

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.

Post COVID-19 Condition in South Africa: 3-month follow-up after hospitalisation with SARS-CoV-2

BackgroundPost COVID-19 Condition (PCC) as defined by WHO refers to a wide range of new, returning, or ongoing health problems experienced by COVID-19 survivors, and represents a rapidly emerging public health priority. We aimed to establish how this developing condition has impacted patients in South Africa and which population groups are at risk. MethodsIn this prospective cohort study, participants [≥]18 years who had been hospitalised with laboratory-confirmed SARS-CoV-2 infection during the second and third wave between December 2020 and August 2021 underwent telephonic follow-up assessment up at one-month and three-months after hospital discharge. Participants were assessed using a standardised questionnaire for the evaluation of symptoms, functional status, health-related quality of life and occupational status. Multivariable logistic regression models were used to determine factors associated with PCC. FindingsIn total, 1,873 of 2,413 (78%) enrolled hospitalised COVID-19 participants were followed up at three-months after hospital discharge. Participants had a median age of 52 years (IQR 41-62) and 960 (51.3%) were women. At three-months follow-up, 1,249 (66.7%) participants reported one or more persistent COVID-related symptom(s), compared to 1,978/2,413 (82.1%) at one-month post-hospital discharge. The most common symptoms reported were fatigue (50.3%), shortness of breath (23.4%), confusion or lack of concentration (17.5%), headaches (13.8%) and problems seeing/blurred vision (10.1%). On multivariable analysis, factors associated with new or persistent symptoms following acute COVID-19 were age [≥]65 years [adjusted odds ratio (aOR) 1.62; 95%confidence interval (CI) 1.00-2.61]; female sex (aOR 2.00; 95% CI 1.51-2.65); mixed ethnicity (aOR 2.15; 95% CI 1.26-3.66) compared to black ethnicity; requiring supplemental oxygen during admission (aOR 1.44; 95% CI 1.06-1.97); ICU admission (aOR 1.87; 95% CI 1.36-2.57); pre-existing obesity (aOR 1.44; 95% CI 1.09-1.91); and the presence of [≥]4 acute symptoms (aOR 1.94; 95% CI 1.19-3.15) compared to no symptoms at onset. InterpretationThe majority of COVID-19 survivors in this cohort of previously hospitalised participants reported persistent symptoms at three-months from hospital discharge, as well as a significant impact of PCC on their functional and occupational status. The large burden of PCC symptoms identified in this study emphasises the need for a national health strategy. This should include the development of clinical guidelines and training of health care workers, in identifying, assessing and caring for patients affected by PCC, establishment of multidisciplinary national health services, and provision of information and support to people who suffer from PCC.

Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections: a survival analysis

BackgroundEmerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear. MethodsRdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene Allplex 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the period of transition to Omicron was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene Allplex assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for. Results150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77). ConclusionOmicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.

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

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.

Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy

A novel proxy for the Delta variant, RNA-dependent RNA polymerase target delay in the Seegene Allplex 2019-nCoV PCR assay, was associated with higher mortality (adjusted Odds Ratio 1.45 [95%CI 1.13-1.86]), compared to presumptive Beta infection, in the Western Cape, South Africa (April-July 2021). Prior diagnosed infection and vaccination were protective.

COVID-19 in-hospital mortality in South Africa: the intersection of communicable and non-communicable chronic diseases in a high HIV prevalence setting

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.

Staff testing for COVID-19 via an online pre-registration form

Structured AbstractO_ST_ABSBackgroundC_ST_ABSHealthcare workers are at increased risk of contracting SARS-CoV-2 and potentially causing institutional outbreaks. Staff testing is critical in identifying and isolating infected individuals while also reducing unnecessary workforce depletion. Tygerberg Hospital implemented an online pre-registration system to expedite staff and cluster testing. ObjectivesWe aimed to identify (1) specific presentations associated with a positive or negative result for SARS-CoV-2 and (2) staff sectors where enhanced strategies for testing might be required. MethodsRetrospective descriptive study involving all clients making use of the hospitals pre-registration system during May 2020. ResultsOf 799 clients, most were young and female with few comorbidities. The most common occupation was nurses followed by administrative staff, doctors and general assistants. Doctors tested earlier compared to other staff (median: 1.5 vs 4 days). The most frequent presenting symptoms were headache, sore throat, cough and myalgia. Amongst those testing positive (n=105), fever, altered smell, altered taste sensation, chills and history of fever were the most common symptoms. Three or more symptoms was more predictive of a positive test, but 12/145 asymptomatic clients also tested positive. ConclusionStaff coronavirus testing using an online pre-registration form is a viable and acceptable strategy. While some presentations are less likely to be associated with SARS-CoV-2 infection, no symptom can completely exclude it. Staff testing should form part of a bundle of strategies to protect staff including wearing masks, regular hand washing, buddy screening, physical distancing, availability of PPE and special dispensation for COVID-19-related leave. Unstructured AbstractHospital staff testing is critical to identify and isolate SARS-CoV-2 infected individuals while reducing unnecessary workforce depletion. Tygerberg Hospital implemented an online pre-registration system to expedite staff testing. In a retrospective descriptive study of all clients registering during May 2020 (N=799), we found rapid and sustained uptake of the system. The most frequent presenting symptoms were headache, sore throat, cough and myalgia. Amongst those testing positive (n=105), fever, altered smell, altered taste sensation and chills were the most likely symptoms, but 12/145 asymptomatic clients also tested positive. Staff testing should form part of a bundle of strategies to protect staff.