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

Sepsis à "staphylocoque epidermidis" chez les grands prématurés : situation à Genève, entre 1995 et 2002

Les grands prématurés, nés à moins de 32 semaines d'aménorrhée, sont particulièrement à risque de développer une infection systémique nosocomiale, dont le germe le plus fréquent est le "Staphylocoque epidermidis". Cette étude rétrospective, sur une période de huit ans, analyse les facteurs de risques, le tableau clinique et le pronostic de 32 enfants qui ont présenté un sepsis à "Staphylocoque epidermidis". Cette étude retrouve les principaux facteurs de risques d'un sepsis : âge gestationnel et petit poids de naissance, présence de cathéters, nutritions parentérales. Cliniquement, le sepsis correspond à une péjoration d'un syndrome brady-apnéique survenant après 10 jours de vie, avec un syndrome inflammatoire modéré. La morbidité est légère, mais la mortalité est de 15%, les décès survenant exclusivement chez les enfants avec une défaillance d'au moins un organe. Cette étude démontre l'importance de la prévention primaire du sepsis et de la connaissance du tableau clinique, indispensable au diagnostic précoce

Plasma transfusions in critically ill children

Plasma transfusions are a common treatment in a critical care setting. Physicians mostly prescribe these transfusions to prevent or stop bleeding, as it contains coagulation factors. In massively bleeding patients, plasma transfusions, in association with red blood cells and platelets, have been associated with improved outcome in large observational studies. This indication is currently being assessed by large randomized controlled trials. The evidence is scarcer and less encouraging for the other patients, who are not bleeding massively. In vitro and animal models show that plasma transfusions increase the inflammatory markers. Retrospective studies suggest that plasma transfusions fail to correct mildly abnormal coagulation tests. Furthermore, plasma transfusions are associated with an increased morbidity in critically ill adults and children. However, the majority of plasma is transfused to non-massively bleeding patients. We published a prospective observational study of 831 patients consecutively admitted to a tertiary pediatric intensive care unit over a year. After adjusting for weight, severity at admission, coagulopathy, extracorporeal life support and other transfusions, the odds ratio for increased morbidity was 3.2 (p=0.002). We also published an international survey to evaluate the current practice. Among 187 intensivists from 25 countries, two thirds of pediatric intensivists would prescribe plasma transfusion to non-bleeding patients. We also performed a systematic review, trying to identify randomized controlled trials assessing plasma transfusion strategies. Out of 843 identified records, none evaluated plasma transfusion strategies according to coagulation test thresholds. Finally, we designed a large international observational study, in which we shoed that plasma transfusions only corrected severe coagulopathies. Our next objective is a large randomized controlled trial, evaluating the effect of two different plasma transfusion strategies, one restrictive, the other liberal

Potential pediatric organ donors after cardiac death

More than 50 people die each year on the Swiss transplant waiting list. To increase their organ donors pool, some centers have developed a post-cardiac death organ donation program. Information about its impact in the pediatric population is still scarce. The aim of this work was to determine the potential impact of a program of organ donation after cardiac in a pediatric population

Massive transfusion in children

Massive transfusions occur frequently in pediatric trauma patients, among some children undergoing surgery, or in children with critical illness. Over the last years, many authors have studied different aspects of massive transfusions, starting with an operative definition. Some information is available on transfusion strategies and adjunctive treatments. Areas that require additional investigation include: studies to assess which children benefit from transfusion protocols based on fixed ratios of blood components vs transfusion strategies based on biophysical parameters and laboratory tests; whether goal-directed therapies that are personalized to the recipient will improve outcomes; or which laboratory tests best define the risk of bleeding and what clinical indicators should prompt the start and stop of massive transfusion protocols. In addition, critical issues that require further study include transfusion support with whole blood vs reconstituted whole blood prepared from packed red blood cells, plasma, and platelets; and the generation of high quality evidence that would lead to treatments which decrease adverse consequences of transfusion and improve outcomes

Plasma in the PICU: why and when should we transfuse?

Whereas red blood cell transfusions have been used since the 19th century, plasma has only been available since 1941. It was originally mainly used as volume replacement, mostly during World War II and the Korean War. Over the years, its indication has shifted to correct coagulation factors deficiencies or to prevent bleeding. Currently, it remains a frequent treatment in the intensive care unit, both for critically ill adults and children. However, observational studies have shown that plasma transfusion fail to correct mildly abnormal coagulation tests. Furthermore, recent epidemiological studies have shown that plasma transfusions are associated with an increased morbidity and mortality in critically ill patients. Therefore, plasma, as any other treatment, has to be used when the benefits outweigh the risks. Based on observational data, most experts suggest limiting its use either to massively bleeding patients or bleeding patients who have documented abnormal coagulation tests, and refraining for transfusing plasma to nonbleeding patients whatever their coagulation tests. In this paper, we will review current evidence on plasma transfusions and discuss its indications

New Generation Neonatal High Frequency Ventilators: Effect of Oscillatory Frequency and Working Principles on Performance

Several new generation neonatal ventilators that incorporate conventional as well as high frequency ventilation (HFOV) have appeared on the market. Most of them offer the possibility to use HFOV in a volume-targeted mode, despite absence of any preclinical data. With a bench test, we evaluated the performances of 4 new neonatal HFOV devices and compared them to the SensorMedics HFOV device

VGAM induced high-flow congestive heart failure responsive to PGE1 infusion

Vein of Galen Aneurismal Malformation (VGAM), a rare congenital anomaly, can lead to congestive heart failure (CHF) and persistent pulmonary hypertension (PHT). Inotropic drugs, diuretics, mechanical ventilation or inhaled nitric oxide (iNO) are the main therapeutic strategies but often do not suffice to control the severe diastolic overload, thus other strategies must be sought. A term male infant was admitted on the second day of life with CHF. Echocardiography revealed normal cardiac anatomy but severe suprasystemic PHT and global volume overload. This led to the diagnosis of VGAM. CHF progressed rapidly to intractable cardiac failure refractory to diuretics, inotropics, oxygen supplementation and iNO. Prostaglandin E1 (PGE1) infusion was therefore started on the third day of life, while awaiting percutaneous occlusion of the fistula. With this treatment, cardiogenic shock could be reversed with rapid improvement of the existing lactic acidosis (lactate levels decreased from 17 to 4.5 mmol/L; base excess from -11.9 to -1.1). Unfortunately, during percutaneous embolisation sudden massive intracerebral hemorrhage occurred leading to death. Patients with refractory cardiac failure and suprasystemic pulmonary hypertension caused by VGAM might benefit of PGE1 infusion to ensure a decompressive right-to-left ductal shunting and thereby maintain an adequate systemic blood flow while awaiting treatment of the aneurismal arteries

Accuracy of Transcutaneous Carbon Dioxide Measurement in Premature Infants

Background. In premature infants, maintaining blood partial pressure of carbon dioxide (pCO2) value within a narrow range is important to avoid cerebral lesions. The aim of this study was to assess the accuracy of a noninvasive transcutaneous method (TcpCO2), compared to blood partial pressure of carbon dioxide (pCO2). Methods. Retrospective observational study in a tertiary neonatal intensive care unit. We analyzed the correlation between blood pCO2 and transcutaneous values and the accuracy between the trends of blood pCO2 and TcpCO2 in all consecutive premature infants born at <33 weeks' gestational age. Results. 248 infants were included (median gestational age: 29 + 5 weeks and median birth weight: 1250 g), providing 1365 pairs of TcpCO2 and blood pCO2 values. Pearson's R correlation between these values was 0.58. The mean bias was -0.93 kPa with a 95% confidence limit of agreement of -4.05 to +2.16 kPa. Correlation between the trends of TcpCO2 and blood pCO2 values was good in only 39.6%. Conclusions. In premature infants, TcpCO2 was poorly correlated to blood pCO2, with a wide limit of agreement. Furthermore, concordance between trends was equally low. We warn about clinical decision-making on TcpCO2 alone when used as continuous monitoring