SummaryContinued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

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Background The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. Findings From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1–0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3–1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2–0·5), after controlling for factors associated with disease severity. Interpretation Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. Funding The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disea...

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Objectives To determine magnitude and reasons of loss to programme and poor antiretroviral prophylaxis coverage in prevention of mother-to-child transmission (PMTCT) programmes in sub-Saharan Africa. Design Systematic review and meta-analysis. Methods We searched PubMed and Embase databases for PMTCT studies in sub-Saharan Africa published between January 2002 and March 2012. Outcomes were the percentage of pregnant women (i) tested for HIV, (ii) initiating antiretroviral prophylaxis, (iii) having a CD4 cell count measured, and (iv) initiating antiretroviral combination therapy (cART) if eligible. In children outcomes were (v) early infant diagnosis for HIV, and (vi) cART initiation. We combined data using random-effects meta-analysis and identified predictors of uptake of interventions. Results Forty-four studies from 15 countries including 75,172 HIV-infected pregnant women were analyzed. HIV-testing uptake at antenatal care services was 94% (95% confidence intervals [CI] 92-95%) for opt-out and 58% (95% CI 40-75%) for opt-in testing. Coverage with any antiretroviral prophylaxis was 70% (95% CI 64-76%) and 62% (95% CI 50-73%) of pregnant women eligible for cART received treatment. Sixty-four percent (95% CI 48-81%) of HIV exposed infants had early diagnosis performed and 55% (95% CI 36-74%) were tested between 12 and 18 months. Uptake of PMTCT interventions was improved if cART was provided at the antenatal clinic and if the male partner was involved. Conclusions In sub-Saharan Africa, uptake of PMTCT interventions and early infant diagnosis is unsatisfactory. An integrated family-centered approach seems to improve retention.

Background The SARS-CoV-2 Omicron variant of concern (VOC) almost completely replaced other variants in South Africa during November 2021, and was associated with a rapid increase in COVID-19 cases. We aimed to assess clinical severity of individuals infected with Omicron, using S Gene Target Failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We performed data linkages for (i) SARS-CoV-2 laboratory tests, (ii) COVID-19 case data, (iii) genome data, and (iv) the DATCOV national hospital surveillance system for the whole of South Africa. For cases identified using Thermo Fisher TaqPath COVID-19 PCR, infections were designated as SGTF or non-SGTF. Disease severity was assessed using multivariable logistic regression models comparing SGTF-infected individuals diagnosed between 1 October to 30 November to (i) non-SGTF in the same period, and (ii) Delta infections diagnosed between April and November 2021. Results From 1 October through 6 December 2021, 161,328 COVID-19 cases were reported nationally; 38,282 were tested using TaqPath PCR and 29,721 SGTF infections were identified. The proportion of SGTF infections increased from 3% in early October (week 39) to 98% in early December (week 48). On multivariable analysis, after controlling for factors associated with hospitalisation, individuals with SGTF infection had lower odds of being admitted to hospital compared to non-SGTF infections (adjusted odds ratio (aOR) 0.2, 95% confidence interval (CI) 0.1-0.3). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ between SGTF-infected individuals compared to non-SGTF individuals diagnosed during the same time period (aOR 0.7, 95% CI 0.3-1.4). Compared to earlier Delta infections, after controlling for factors associated with severe disease, SGTF-infected individuals had a lower odds of severe disease (aOR 0.3, 95% CI 0.2-0.6). Conclusion Early analyses suggest a reduced risk of hospitalisation among SGTF-infected individuals when compared to non-SGTF infected individuals in the same time period, and a reduced risk of severe disease when compared to earlier Delta-infected individuals. Some of this reducton is likely a result of high population immunity.

Background: The effect of HIV co-infection on COVID-19 outcomes in sub-Saharan Africa is unknown. Methods: We conducted a population cohort study using linked data from adults attending public sector health facilities in the Western Cape, South Africa. We used Cox-proportional hazards models adjusted for age, sex, location and comorbidities to examine the association between HIV and COVID-19 death among (i) public sector 'active patients' (at least 1 health visit in the 3 years before March 2020), (ii) laboratory-diagnosed COVID-19 cases and (iii) hospitalized COVID-19 cases. COVID-19 was diagnosed with SARS-CoV-2 PCR tests. We calculated the standardized mortality ratio (SMR) for COVID-19 comparing HIV positive vs. negative adults using modelled population estimates. Results: Among 3,460,932 public sector patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died. In adjusted analysis, HIV increased risk of COVID-19 mortality (adjusted hazard ratio [aHR]:2.14; 95% confidence interval [CI]:1.70; 2.70), with similar risks across strata of viral load and immunosuppression. increased HIV-associated risk of COVID-19 death remained when restricting to COVID-19 cases (aHR:1.70; 95%CI:132; 2.18) or hospitalized cases (aHR:1.45; 95%CI:1.14; 1.84). Current and previous tuberculosis also increased COVID-19 mortality risk (aHR [95%CI]:2.70 [1.81; 4.04] and 1.51 [1.18; 1.93] respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI:1.96; 2.86); population attributable fraction 8.5% (95%CI:6.1; 11.1). Conclusion: HIV was associated with a doubling of COVID-19 mortality risk. While our findings may over-estimate the HIV-associated risk COVID-19 death due to residual confounding, people with HIV should be considered a high-risk group for COVID-19 management.

Background With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa. Methods Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (two consecutive unsuppressed viral loads with the second being >1,000 copies/ml, after ≥24 weeks of therapy) and switch to second-line. Cox proportional hazards models stratified by program were used to determine predictors of these outcomes. Results The 3-year probability of virologic failure among 5485 children was 19.3% (95%CI: 17.6–21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared to efavirenz), and exposure to prevention of mother to child transmission regimens were independently associated with failure (adjusted hazard ratios (95%CI): 1.77(1.11–2.83), 2.39(1.57–3.64) and 1.40(1.02–1.92) respectively). Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (IQR) months between failure and switch was 5.7(2.9–11.0). Conclusion Triple ART based on nevirapine or ritonavir as a single protease inhibitor appears to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.