Interleukin-6, procalcitonin and neutrophil-to-lymphocyte ratio: Potential immune-inflammatory parameters to identify severe and fatal forms of COVID-19.

Accumulating evidence supports that the viral-induced hyper-inflammatory immune response plays a central role in COVID-19 pathogenesis. It might be involved in the progression to acute respiratory distress syndrome (ARDS), multi-organ failure leading to death. In this study, we aimed to evaluate the prognostic value of the immune-inflammatory biomarkers in COVID-19, then determine optimal thresholds for assessing severe and fatal forms of this disease.153 patients with confirmed COVID-19 were included in this study, and classified into non-severe and severe groups. Plasmatic levels of interleukin 6 (IL6), C-reactive protein (CRP), soluble-IL2 receptor (IL2Rα), procalcitonin (PCT) and ferritin were measured using chemiluminescence assay. Complete blood count was performed by Convergys 3X® hematology analyzer. Our results demonstrated that the peripheral blood levels of IL6, PCT, CRP, ferritin, IL2Rα, white blood cell count (WBC), neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) were significantly higher in severe forms of COVID-19. The ROC curve analysis showed that IL6 was the most accurate inflammatory biomarker. The calculated cutoff of IL6 (42 pg/ml) could correctly classify > 90% of patients regarding their risk of severity (area under ROC curve (AUROC) = 0.972) and the threshold value of 83 pg/ml was highly predictive of the progression to death (AUROC = 0.94, OR = 184) after a median of 3 days. Besides, IL-6 was positively correlated with other inflammatory markers and the kinetic analysis highlighted its value for monitoring COVID-19 patients. PCT and NLR had also a high prognostic relevance to assess severe forms of COVID-19 with corresponding AUROC of 0.856, 0.831 respectively. Furthermore the cut-off values of PCT (0.16 ng/ml) and NLR (7.4) allowed to predict mortality with high accuracy (se = 96.3%, sp = 70.5%,OR = 61.2)' (se = 75%, sp = 84%, OR = 14.6).The levels of these parameters were not influenced by corticosteroid treatment, which make them potential prognostic markers when patients are already undergoing steroid therapy.

Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020.

Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.

Influenza surveillance during the 2009-2010, 2010-2011, 2011-2012, and 2012-2013 seasons in Algeria.

We report the activity and circulation of influenza viruses in Algeria during four influenza seasons, from a national surveillance study carried out from 2009-2010 to 2012-2013. A total of 2766 samples from in- and outpatients, with no age restriction, were collected. The overall proportion of specimens that tested influenza positive was 46.0%. Overall, 96.6% of influenza A viruses were subtyped, and A/H1 subtypes accounted for 57.3% of influenza A viruses. Influenza A/H1 and A/H3 virus subtypes cocirculated in 2009-2010. In 2010-2011, a high proportion of type B viruses (66.2%) was observed. The subtype H3N2 was identified in 99% of cases typed in 2011-2012. Influenza A/H3N2 and B virus cocirculated in 2012-2013. A remarkably low influenza vaccination rate of 2.4% was observed among all age groups. Antibiotics were prescribed for 926 (41.3%) patients, and no difference was observed between patients with confirmed influenza and patients with influenza-like illness not related to influenza. The burden of influenza is largely undocumented in Algeria and strategies to expand this surveillance across the country are needed. Strategies to increase vaccination coverage are warranted to control and prevent influenza in individuals at risk of complications as well as in the general population.

Surveillance for antiviral resistance among influenza viruses circulating in Algeria during five consecutive influenza seasons (2009-2014).

Influenza season 2007/2008 was marked by a worldwide emergence of oseltamivir-resistant A(H1N1) viruses possessing a mutation in the neuraminidase gene causing His-to-Tyr substitution at amino acid position 275 (H275Y). These strains were isolated in Algeria where 30% of seasonal A(H1N1) viruses harbored the H275Y mutation. Emergence of resistant viruses to currently approved antiviral drug determined the need for antiviral susceptibility monitoring in Algeria especially that oseltamivir is currently used in hospitals of some provinces of the country for treatment of influenza in populations at risk. The aim of the present study is to investigate the sensitivity of circulating influenza viruses in Algeria to oseltamivir. We present 5-year local surveillance results from 2009/2010 influenza season to 2013/2014 influenza season. We tested the sensitivity to oseltamivir of 387 human influenza A and B viruses isolated in Algeria. Determination of IC50 values were performed using the fluorogenic MUNANA substrate. To detect the H275Y mutation in the neuraminidase of the A(H1N1) strains we performed a real-time RT-PCR allelic discrimination analysis. The obtained results showed that all influenza A(H1N1)pdm09, A(H3N2), and B viruses studied remained susceptible to oseltamivir. This is the first study on influenza antiviral susceptibility surveillance in Algeria. Obtained results allow establishing a baseline data for future studies on antiviral resistance emergence worldwide. Our report highlights the importance of a continued and active monitoring of circulating viruses in Algeria for strengthens collaboration within the Global Influenza Surveillance and Response System.

Evaluation of the immunoprotective power of a multiple antigenic peptide against Aah II toxin of Androctonus australis hector scorpion.

Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease. This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of Androctonus australis hector scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin. The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD50 of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the in vitro neutralization test, the immune sera of mice having received the immunogen with incomplete Freund's adjuvant neutralized a challenge dose of 2 LD50. Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.

Serological evidence of Rift Valley fever viral infection among camels imported into Southern Algeria.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV). The present work aims to investigate the epidemiological status and identify the risk factors associated with RVFV infection in dromedary camels (Camelus dromedarius) from southern Algeria. A total of 269 sera of apparently healthy camels was collected and tested using a competitive Enzyme-Linked Immunosorbent Assay (ELISA). Overall, 72 camels (26.7 %, 95 % CI: 21.4-32) were seropositive to RVFV. IgG antibodies were found to be most prevalent in camels from south-western areas, particularly in Tindouf wilaya (52.38 %, p < 0.0001), and in camels introduced from bordering Sahelian countries (35.8 %) (OR = 8.75, 95 %CI: 2.14-35.81). No anti-RVFV antibodies were detected in sera collected from local camels (0 %). Adult (5-10 years) and aged (>10 years) camels have a significantly higher risk of being infected by RVFV (OR = 2.15; 95 %CI = 1.21-3.81, OR = 2.05; 95 %CI = 1.03-4.11, respectively). This report indicated that dromedaries imported to the south-western areas are exposed to RVFV and may contribute to its spread in Algerian territories.

SARS-CoV-2 Lineage A.27: New Data from African Countries and Dynamics in the Context of the COVID-19 Pandemic.

SARS-CoV-2 is constantly evolving with lineages emerging and others eclipsing. Some lineages have an important epidemiological impact and are known as variants of interest (VOIs), variants under monitoring (VUMs) or variants of concern (VOCs). Lineage A.27 was first defined as a VUM since it holds mutations of concern. Here, we report additional lineage A.27 data and sequences from five African countries and describe the molecular characteristics, and the genetic history of this lineage worldwide. Based on the new sequences investigated, the most recent ancestor (tMRCA) of lineage A.27 was estimated to be from April 2020 from Niger. It then spread to Europe and other parts of the world with a peak observed between February and April 2021. The detection rate of A.27 then decreased with only a few cases reported during summer 2021. The phylogenetic analysis revealed many sub-lineages. Among them, one was defined by the substitution Q677H in the spike (S) gene, one was defined by the substitution D358N in the nucleoprotein (N) gene and one was defined by the substitution A2143V in the ORF1b gene. This work highlights the importance of molecular characterization and the timely submission of sequences to correctly describe the circulation of particular strains in order to be proactive in monitoring the pandemic.

T cell counts and IL-6 concentration in blood of North African COVID-19 patients are two independent prognostic factors for severe disease and death.

The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID-19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID-19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID-19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL-6 and IL-10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL-6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927-1.000, P < 0.0001). In addition, the preoperative IL-6 concentration of 77.38 pg/ml was the optimal cutoff value (sensitivity: 84.6%, specificity: 100%). Using multivariate logistic regression analysis and ROC curves, IL-6 > 106.44 pg/ml and CD8+ T cell counts <150 cells/µl were found to be associated with mortality. Measuring the immune parameters and defining a risk threshold can segregate patients who develop a severe disease from those with a mild pathology. The identification of these parameters may help clinicians to predict the outcome of the patients with high risk of unfavorable progress of the disease.

RETRACTED: Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa.

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

The Algerian Chapter of SARS-CoV-2 Pandemic: An Evolutionary, Genetic, and Epidemiological Prospect.

To explore the SARS-CoV-2 pandemic in Algeria, a dataset comprising ninety-five genomes originating from SARS-CoV-2 sampled from Algeria and other countries worldwide, from 24 December 2019, through 4 March 2021, was thoroughly examined. While performing a multi-component analysis regarding the Algerian outbreak, the toolkit of phylogenetic, phylogeographic, haplotype, and genomic analysis were effectively implemented. We estimated the Time to the Most Recent Common Ancestor (TMRCA) in reference to the Algerian pandemic and highlighted the multiple introductions of the disease and the missing data depicted in the transmission loop. In addition, we emphasized the significant role played by local and international travels in disease dissemination. Most importantly, we unveiled mutational patterns, the effect of unique mutations on corresponding proteins, and the relatedness regarding the Algerian sequences to other sequences worldwide. Our results revealed individual amino-acid replacements such as the deleterious replacement A23T in the orf3a gene in Algeria_EPI_ISL_418241. Additionally, a connection between Algeria_EPI_ISL_420037 and sequences originating from the USA was observed through a USA characteristic amino-acid replacement T1004I in the nsp3 gene, found in the aforementioned Algerian sequence. Similarly, successful tracing could be established, such as Algeria/G37318-8849/2020|EPI_ISL_766863, which was imported from Saudi Arabia during the pilgrimage. Lastly, we assessed the Algerian mitigation measures regarding disease containment using statistical analyses.

GTS-21, an α7nAChR agonist, suppressed the production of key inflammatory mediators by PBMCs that are elevated in COPD patients and associated with impaired lung function.

Chronic obstructive pulmonary disease (COPD) is a lung inflammatory disease characterized by progressive airflow limitation, chronic respiratory symptoms and frequent exacerbations. There is an unmet need to identify novel therapeutic alternatives beside bronchodilators that prevent disease progression. Levels of both Nitric Oxide (NO) and IL-6 were significantly increased in the plasma of patients in the exacerbation phase (ECOPD, n = 13) when compared to patients in the stable phase (SCOPD, n = 38). Levels of both NO and IL-6 were also found to inversely correlate with impaired lung function (%FEV1 predicted). In addition, there was a strong positive correlation between levels of IL-6 and NO found in the plasma of patients and those spontaneously produced by their peripheral blood mononuclear cells (PBMCs), identifying these cells as a major source of these key inflammatory mediators in COPD. GTS-21, an agonist for the alpha 7 nicotinic receptors (α7nAChR), was found to exert immune-modulatory actions in PBMCs of COPD patients by suppressing the production of IL-6 and NO. This study provides the first evidence supporting the therapeutic potential of α7nAChR agonists in COPD due to their ability to suppress the production of key inflammatory markers associated with disease severity.

A(H9N2) influenza viruses associated with chicken mortality in outbreaks in Algeria 2017.

In late 2017, increased mortality was detected in chicken farms in Algeria undergoing A(H9N2) influenza outbreaks. Analysis of viruses isolated from affected farms showed that they were monophyletic, were of the G1 hemagglutinin (HA) lineage, and were antigenically and genetically similar to viruses detected contemporaneously in other countries in Northern Africa and the Middle East. The virus was able to spread via contact transmission between ferrets but did not cause disease in intravenously inoculated chickens.

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

The Middle-East and Africa Influenza Surveillance Network (MENA-ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA-ISN countries. Data were presented at the 8th MENA-ISN meeting, organized by the Mérieux Foundation that was held on 10-11 April 2018 in Cairo, Egypt. The meeting included MENA-ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high-risk groups (children under-5, elderly, pregnant women and immunosuppressed individuals) in the MENA-ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza-related morbidity and mortality especially among the most vulnerable groups of the population.