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

Severe influenza A in a Tunisian ICU sentinel SARI centre: Epidemiological and clinical features.

IntroductionInfluenza A virus infection is a contagious acute respiratory infection which mostly evolves in an epidemic form, less frequently as pandemic outbreaks. It can take a severe clinical form that needs to be managed in intensive care unit (ICU). The aim of this study was to describe the epidemiological and clinical aspects of influenza A, then to determine independent predictive factors of ICU mortality in Abderrahmen Mami hospital, Ariana, Tunisia.MethodsIt was a single-center study, including all hospitalized patients in intensive care, between November 1st, 2009 and October 31st, 2019, with influenza A virus infection. We recorded demographic, clinical and biological data, evolving features; then multivariate analysis of the predictive factors of ICU mortality was realized.ResultsDuring the study period (10 consecutive seasons), 120 patients having severe Influenza A were admitted (Proportion = 2.5%) from all hospitalized patients, with a median age of 48 years and a gender-ratio of 1.14. Among women, 14 were pregnant. Only 7 patients (5.8%) have had seasonal flu vaccine during the year before ICU admission. The median values of the Simplified Acute Physiology Score II, Acute Physiologic and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment were respectively 26, 10 and 3. Virus strains identified with polymerase chain reaction were H1N1 pdm09 (84.2%) and H3N2 (15.8%). Antiviral therapy was prescribed in 88 (73.3%) patients. A co-infection was recorded in 19 cases: bacterial (n = 17) and aspergillaire (n = 2). An acute respiratory distress syndrome (ARDS) was diagnosed in 82 patients. Non-invasive ventilation (NIV) was conducted for 72 (60%) patients with success in 34 cases. Endotracheal intubation was performed in 59 patients with median duration of invasive mechanical ventilation 8 [3.25-13] days. The most frequent complications were acute kidney injury (n = 50, 41.7%), shock (n = 48, 40%), hospital-acquired infections (n = 46, 38.8%) and thromboembolic events (n = 19, 15.8%). The overall ICU mortality rate was of 31.7% (deceased n = 38). Independent predictive factors of ICU mortality identified were: age above 56 years (OR = 7.417; IC95% [1.474-37.317]; p = 0.015), PaO2/FiO2 ≤ 95 mmHg (OR = 9.078; IC95% [1.636-50.363]; p = 0.012) and lymphocytes count ≤ 1.325 109/L (OR = 10.199; IC95% [1.550-67.101]; p = 0.016).ConclusionInfluenza A in ICU is not uncommon, even in A(H1N1) dominant seasons; its management is highly demanding. It is responsible for considerable morbi-mortality especially in elderly patients

Interstitial pneumonia in a glassblower: think to chronic beryllium disease!

Chronic beryllium disease (CBD) is an occupational illness with varying severity. In this report, we describe a 27 year old man, glassblower, who developed a fatal CBD after six months of unknown Beryllium's exposure. The diagnosis was suspected on histological examination and then consolidated by confirmation of Beryllium's exposure at the working area. Physicians should be aware of the potential risk to develop CBD in glassblowers. These workers should benefit from early medical surveillance using the Beryllium lymphocyte proliferation test (BeLPT) and therefore from suitable management

Resource utilization and preparedness within the COVID-19 pandemic in Tunisian medical intensive care units: A nationwide retrospective multicentre observational study

Background: The worldwide SARS-CoV-2 pandemic represents the most recent global healthcare crisis. While all healthcare systems suffered facing the immense burden of critically-ill COVID-19 patients, the levels of preparedness and adaptability differed highly between countries. Aim: to describe resource mobilization throughout the COVID-19 waves in Tunisian University Medical Intensive Care Units (MICUs) and to identify discrepancies in preparedness between the provided and required resource. Methods: This is a longitudinal retrospective multicentre observational study conducted between March 2020 and May 2022 analyzing data from eight University MICUs. Data were collected at baseline and at each bed expansion period in relation to the nation’s four COVID-19 waves. Data collected included epidemiological, organizational and management trends and outcomes of COVID-19 and non-COVID-19 admissions. Results: MICU-beds increased from 66 to a maximum of 117 beds. This was possible thanks to equipping pre-existing non-functional MICU beds (n = 20) and creating surge ICU-beds in medical wards (n = 24). MICU nurses increased from 53 to 200 of which 99 non-ICU nurses, by deployment from other departments and temporary recruitment. The nurse-to-MICU-bed ratio increased from 1:1 to around 1·8:1. Only 55% of beds were single rooms, 80% were equipped with ICU ventilators. These MICUs managed to admit a total of 3368 critically-ill patients (15% of hospital admissions). 33·2% of COVID-19-related intra-hospital deaths occurred within the MICUs. Conclusion: Despite a substantial increase in resource mobilization during the COVID-19 pandemic, the current study identified significant persisting discrepancies between supplied and required resource, at least partially explaining the poor overall prognosis of critically-ill COVID-19 patients

Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol.

One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272)

A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.

During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O, but its impact on clinical outcomes remains unknown. To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations. This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with Pa ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, Pa ≤ 50 mm Hg, and oxygen saturation (arterial [Sa] or measured by pulse oximetry [Sp]) ≤ 90%. A 6-month follow-up was performed. The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, Pa, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality. Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310)

A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.

During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O2, but its impact on clinical outcomes remains unknown. To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O2 in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations. This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with PaCO2 ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, PaO2 ≤ 50 mm Hg, and oxygen saturation (arterial [SaO2] or measured by pulse oximetry [SpO2]) ≤ 90%. A 6-month follow-up was performed. The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O2 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O2 group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, PaCO2, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality. Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O2 but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310)

Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

International audienc

Development and comparative evaluation of SARS-CoV-2 S-RBD and N based ELISA tests in various African endemic settings

International audienceManagement of the COVID-19 pandemic relies on molecular diagnostic methods supported by serological tools. Herein, we developed S-RBD- and N- based ELISA assays useful for infection rate surveillance as well as the follow-up of acquired protective immunity against SARS-CoV-2. ELISA assays were optimized using COVID-19 Tunisian patients' sera and prepandemic controls. Assays were further validated in 3 African countries with variable endemic settings. The receiver operating curve was used to evaluate the assay performances. The N- and S-RBD-based ELISA assays performances, in Tunisia, were very high (AUC: 0.966 and 0.98, respectively, p < 0.0001). Cross-validation analysis showed similar performances in different settings. Cross-reactivity, with malaria infection, against viral antigens, was noticed. In head-to-head comparisons with different commercial assays, the developed assays showed high agreement. This study demonstrates, the added value of the developed serological assays in low-income countries, particularly in ethnically diverse populations with variable exposure to local endemic infectious diseases