The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Extracorporeal Circulatory/Life Support: An Update

The evolution of extracorporeal life support technology has added a new advanced dimension to intensive care management of acute cardiac and/or respiratory failure in neonatal, pediatric, and adult patients who fail conventional treatment. ECMO has been a controversial subject within the intensive care community for many years. Perceptions have, however, changed positively over the past decade due to a need for improved management of these groups of patients, technological advances, and evolving evidence. As is common with many emerging therapies, its optimal use is currently not fully backed by quality evidence

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

BACKGROUND: Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support. METHODS: In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH 30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827. FINDINGS: 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%. INTERPRETATION: We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK. FUNDING: UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health

How does the changing profile of infants referred for ECMO affect the overall respiratory outcome?

Objective: Extracorporeal Membrane Oxygenation (ECMO) has been shown to be effective in full-term neonates with severe but reversible lung disease within the context of randomized controlled trial. Since this trial, ECMO has been open to a wider population of infants in the UK and other treatments have become available. The population referred for ECMO has therefore changed. The aims of this study were (i) to compare respiratory outcomes of infants receiving ECMO in recent years with those from ten years ago, and (ii) to see if respiratory outcome varied with diagnostic group. Methods: All infants referred to a single ECMO centre below the age of 12 months over a 7-year period were eligible. They attended the laboratory one year after ECMO for measurements of lung volume, airways conductance, maximum expiratory flow, and indices of tidal breathing. Results: One hundred and six (77% of those eligible) were tested and results compared with 51 infants referred for ECMO as part of the original UK ECMO trial. The groups were of comparable weight and length. Lung volume was not different but there was a strong trend for the infants seen in more recent years to have better forced expiratory flow and specific airway conductance. Restricting analysis to the major sub-group (Meconium Aspiration) confirmed these findings. When divided into diagnostic subgroups, those infants requiring ECMO for respiratory distress syndrome or who were over 2 weeks when commencing ECMO had a poorer respiratory outcome than others. Conclusions: The respiratory outcome of infants treated beyond the tightly-regulated criteria of the UK trial remains good and even shows a trend towards improvement. Certain subgroups require ECMO for longer and have poorer pulmonary function when followed up. This is important when providing information to parents and may have implications for workload planning of ECMO units and future healthcare provision