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1.
Front Med (Lausanne) ; 9: 877391, 2022.
Article in English | MEDLINE | ID: covidwho-1875417

ABSTRACT

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 viral dynamics in Africa have been less documented than on other continents. In Gabon, a Central African country, a total number of 37,511 cases of COVID-19 and 281 deaths have been reported as of December 8, 2021. After the first COVID-19 case was reported on March 12, 2020, in the capital Libreville, the country experienced two successive waves. The first one, occurred in March 2020 to August 2020, and the second one in January 2021 to May 2021. The third wave began in September 2021 and ended in November 2021. In order to reduce the data gap regarding the dynamics of SARS-CoV-2 in Central Africa, we performed a retrospective genotyping study using 1,006 samples collected from COVID-19 patients in Gabon from 2020 to 2021. Using SARS-CoV-2 variant screening by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and whole genome sequencing (WGS), we genotyped 809 SARS-CoV-2 samples through qRT-PCR and identified to generated 291 new genomes. It allowed us to describe specific mutations and changes in the SARS-CoV-2 variants in Gabon. The qRT-PCR screening of 809 positive samples from March 2020 to September 2021 showed that 119 SARS-CoV-2 samples (14.7%) were classified as VOC Alpha (Pangolin lineage B.1.1.7), one (0.1%) was a VOC Beta (B.1.351), and 198 (24.5 %) were VOC Delta (B.1.617.2), while 491 samples (60.7%) remained negative for the variants sought. The B1.1 variant was predominant during the first wave while the VOC Alpha dominated the second wave. The B1.617.2 Delta variant is currently the dominant variant of the third wave. Similarly, the analysis of the 291 genome sequences indicated that the dominant variant during the first wave was lineage B.1.1, while the dominant variants of the second wave were lineages B.1.1.7 (50.6%) and B.1.1.318 (36.4%). The third wave started with the circulation of the Delta variant (B.1.617). Finally, we compared these results to the SARS-CoV-2 sequences reported in other African, European, American and Asian countries. Sequences of Gabonese SARS-CoV-2 strains presented the highest similarities with those of France, Belgium and neighboring countries of Central Africa, as well as West Africa.

2.
Front Cell Infect Microbiol ; 12: 798767, 2022.
Article in English | MEDLINE | ID: covidwho-1862592

ABSTRACT

COVID-19 is the biggest pandemic the world has seen this century. Alongside the respiratory damage observed in patients with severe forms of the disease, gastrointestinal symptoms have been frequently reported. These symptoms (e.g., diarrhoea), sometimes precede the development of respiratory tract illnesses, as if the digestive tract was a major target during early SARS-CoV-2 dissemination. We hypothesize that in patients carrying intestinal SARS-CoV-2, the virus may trigger epithelial barrier damage through the disruption of E-cadherin (E-cad) adherens junctions, thereby contributing to the overall gastrointestinal symptoms of COVID-19. Here, we use an intestinal Caco-2 cell line of human origin which expresses the viral receptor/co-receptor as well as the membrane anchored cell surface adhesion protein E-cad to investigate the expression of E-cad after exposure to SARS-CoV-2. We found that the expression of CDH1/E-cad mRNA was significantly lower in cells infected with SARS-CoV-2 at 24 hours post-infection, compared to virus-free Caco-2 cells. The viral receptor ACE2 mRNA expression was specifically down-regulated in SARS-CoV-2-infected Caco-2 cells, while it remained stable in HCoV-OC43-infected Caco-2 cells, a virus which uses HLA class I instead of ACE2 to enter cells. It is worth noting that SARS-CoV-2 induces lower transcription of TMPRSS2 (involved in viral entry) and higher expression of B0AT1 mRNA (that encodes a protein known to co-express with ACE2 on intestinal cells). At 48 hours post-exposure to the virus, we also detected a small but significant increase of soluble E-cad protein (sE-cad) in the culture supernatant of SARS-CoV-2-infected Caco-2 cells. The increase of sE-cad release was also found in the intestinal HT29 cell line when infected by SARS-CoV-2. Beside the dysregulation of E-cad, SARS-CoV-2 infection of Caco-2 cells also leads to the dysregulation of other cell adhesion proteins (occludin, JAMA-A, zonulin, connexin-43 and PECAM-1). Taken together, these results shed light on the fact that infection of Caco-2 cells with SARS-CoV-2 affects tight-, adherens-, and gap-junctions. Moreover, intestinal tissues damage was associated to the intranasal SARS-CoV-2 infection in human ACE2 transgenic mice.


Subject(s)
COVID-19 , Cadherins , Gastrointestinal Diseases , Angiotensin-Converting Enzyme 2/genetics , Animals , Antigens, CD/genetics , Caco-2 Cells , Cadherins/genetics , Gene Expression , Humans , Mice , RNA, Messenger , Receptors, Virus/genetics , SARS-CoV-2/genetics
3.
J Clin Virol ; 150-151: 105163, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1804469

ABSTRACT

BACKGROUND: We systematically survey respiratory and gastrointestinal infections of viral origin in samples sent to our university hospital institute in Marseille, southern France. Here, we evaluated whether the measures implemented to fight COVID-19 had an effect on the dynamics of viral respiratory or gastrointestinal infections. METHODS: We analysed PCR performed and positive for the diagnoses of viral respiratory and gastrointestinal infections over five years (January 2017-February 2021). Data were collected from our epidemiological surveillance system (MIDaS). Dates and contents of French measures against SARS-CoV-2 were collected from: https://www.gouvernement.fr/info-coronavirus/les-actions-du-gouvernement. RESULTS: Over the 2017-2021 period, 990,364 analyses were carried out for respiratory infections not including SARS-CoV-2, 510,671 for SARS-CoV-2 and 27,719 for gastrointestinal infections. During winter 2020-2021, when the most restrictive lockdown measures were in place in France, a marked decrease of infections with influenza viruses (one case versus 1,839-1,850 cases during 2017-2020 cold seasons) and with the RSV (56 cases versus 988-1,196 cases during 2017-2020 cold seasons) was observed, demonstrating the relative effectiveness of these measures on their occurrence. SARS-CoV-2 incidence seemed far less affected. Rhinoviruses, parainfluenza 3 virus, and the coronavirus NL63 remained at comparable levels. Also, the norovirus winter season positivity rates decreased continuously and significantly over time from 9.3% in 2017-2018 to 2.0% in 2020-2021. CONCLUSION: The measures taken to control COVID-19 were effective against lower respiratory tract infections viruses and gastroenteritis agents, but not on the agents of the common winter cold and SARS-CoV-2. This suggests that more specific measures to prevent COVID-19 and upper respiratory tract infections need to be discovered to limit the spread of this epidemic.


Subject(s)
COVID-19 , Epidemics , Respiratory Tract Infections , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Humans , Hygiene , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , SARS-CoV-2
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309405

ABSTRACT

A novel severe acute respiratory syndrome coronavirus named SARS-CoV-2, emerged in China in December 2019 and recently spread worldwide causing more than 144,987 deaths from COVID-19 disease. Similar to SARS-CoV that was related to a bat-borne coronavirus, this new virus originated from Rhinolophus affinis bats. Because bats usually transmit their coronaviruses to intermediate animal hosts that in turn represent a source of virus able to cross the species barrier to finally infect humans, the identification of an intermediate animal reservoir was recently the subject of intense researches. At the very beginning it was claimed that a reptile ( Ophiophagus hannah ) was the intermediate host. This hypothesis was quickly eliminated to be replaced by the pangolin ( Manis javanica ) hypothesis. Yet, several other animal species were recently reported as possible intermediate hosts in between bats and humans. To determine which intermediate animal host could have infected the index case patient with SARS-CoV-2, we used multi-sequence alignment, 3-D structure analysis and electrostatic potential surface generation of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2. We report evidence that such in silico investigation is a powerful tool that may help identification of potential SARS-CoV-2 susceptible species and that positions K31and Y41 in the a1 ridge, N82 and N90 in the loop and a3 and K353 in loop and b5 play a major role for SARS-CoV-2 binding to ACE2.

6.
Environ Res ; 207: 112173, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1661835

ABSTRACT

Since the beginning of the COVID-19 pandemic in 2020 caused by SARS-CoV-2, the question of the origin of this virus has been a highly debated issue. Debates have been, and are still, very disputed and often violent between the two main hypotheses: a natural origin through the "spillover" model or a laboratory-leak origin. Tenants of these two options are building arguments often based on the discrepancies of the other theory. The main problem is that it is the initial question of the origin itself which is biased. Charles Darwin demonstrated in 1859 that all species are appearing through a process of evolution, adaptation and selection. There is no determined origin to any animal or plant species, simply an evolutionary and selective process in which chance and environment play a key role. The very same is true for viruses. There is no determined origin to viruses, simply also an evolutionary and selective process in which chance and environment play a key role. However, in the case of viruses the process is slightly more complex because the "environment" is another living organism. Pandemic viruses already circulate in humans prior to the emergence of a disease. They are simply not capable of triggering an epidemic yet. They must evolve in-host, i.e. in-humans, for that. The evolutionary process which gave rise to SARS-CoV-2 is still ongoing with regular emergence of novel variants more adapted than the previous ones. The real relevant question is how these viruses can emerge as pandemic viruses and what the society can do to prevent the future emergence of pandemic viruses.


Subject(s)
COVID-19 , Viruses , Animals , Humans , Pandemics , SARS-CoV-2
7.
Viruses ; 14(1)2021 12 23.
Article in English | MEDLINE | ID: covidwho-1580411

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quickly spread worldwide following its emergence in Wuhan, China, and hit pandemic levels. Its tremendous incidence favoured the emergence of viral variants. The current genome diversity of SARS-CoV-2 has a clear impact on epidemiology and clinical practice, especially regarding transmission rates and the effectiveness of vaccines. In this study, we evaluated the replication of different SARS-CoV-2 isolates representing different virus genotypes which have been isolated throughout the pandemic. We used three distinct cell lines, including Vero E6 cells originating from monkeys; Caco-2 cells, an intestinal epithelium cell line originating from humans; and Calu-3 cells, a pulmonary epithelium cell line also originating from humans. We used RT-qPCR to replicate different SARS-CoV-2 genotypes by quantifying the virus released in the culture supernatant of infected cells. We found that the different viral isolates replicate similarly in Caco-2 cells, but show very different replicative capacities in Calu-3 cells. This was especially highlighted for the lineages B.1.1.7, B.1.351 and P.1, which are considered to be variants of concern. These results underscore the importance of the evaluation and characterisation of each SARS-CoV-2 isolate in order to establish the replication patterns before performing tests, and of the consideration of the ideal SARS-CoV-2 genotype-cell type pair for each assay.


Subject(s)
Epithelial Cells/virology , SARS-CoV-2/physiology , Virus Replication/physiology , Animals , Caco-2 Cells , Cell Line , Chlorocebus aethiops , Genotype , Humans , Intestines/cytology , Lung/cytology , Mutation , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/genetics , Vero Cells , Viral Tropism/physiology
8.
Future Microbiol ; 16: 1341-1370, 2021 11.
Article in English | MEDLINE | ID: covidwho-1555047

ABSTRACT

Since the beginning of the COVID-19 pandemic, large in silico screening studies and numerous in vitro studies have assessed the antiviral activity of various drugs on SARS-CoV-2. In the context of health emergency, drug repurposing represents the most relevant strategy because of the reduced time for approval by international medicines agencies, the low cost of development and the well-known toxicity profile of such drugs. Herein, we aim to review drugs with in vitro antiviral activity against SARS-CoV-2, combined with molecular docking data and results from preliminary clinical studies. Finally, when considering all these previous findings, as well as the possibility of oral administration, 11 molecules consisting of nelfinavir, favipiravir, azithromycin, clofoctol, clofazimine, ivermectin, nitazoxanide, amodiaquine, heparin, chloroquine and hydroxychloroquine, show an interesting antiviral activity that could be exploited as possible drug candidates for COVID-19 treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Middle East Respiratory Syndrome Coronavirus/drug effects , SARS-CoV-2/drug effects , Animals , COVID-19/virology , Cell Line , Chlorocebus aethiops , Drug Repositioning/methods , Humans , Molecular Docking Simulation , Pandemics/prevention & control , Vero Cells
9.
Infect Genet Evol ; 95: 104812, 2021 11.
Article in English | MEDLINE | ID: covidwho-1461688

ABSTRACT

While the COVID-19 pandemic continues to spread with currently more than 117 million cumulated cases and 2.6 million deaths worldwide as per March 2021, its origin is still debated. Although several hypotheses have been proposed, there is still no clear explanation about how its causative agent, SARS-CoV-2, emerged in human populations. Today, scientifically-valid facts that deserve to be debated still coexist with unverified statements blurring thus the knowledge on the origin of COVID-19. Our retrospective analysis of scientific data supports the hypothesis that SARS-CoV-2 is indeed a naturally occurring virus. However, the spillover model considered today as the main explanation to zoonotic emergence does not match the virus dynamics and somehow misguided the way researches were conducted. We conclude this review by proposing a change of paradigm and model and introduce the circulation model for explaining the various aspects of the dynamic of SARS-CoV-2 emergence in humans.


Subject(s)
COVID-19/epidemiology , Genome, Viral , Models, Statistical , Pandemics , SARS-CoV-2/genetics , Zoonoses/epidemiology , Animals , COVID-19/transmission , COVID-19/virology , Chiroptera/virology , Eutheria/virology , Humans , Models, Genetic , Retrospective Studies , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Stochastic Processes , Zoonoses/transmission , Zoonoses/virology
10.
Front Microbiol ; 12: 675528, 2021.
Article in English | MEDLINE | ID: covidwho-1456295

ABSTRACT

The rapid spread of SARS-CoV-2 variants has quickly spanned doubts and the fear about their ability escape vaccine protection. Some of these variants initially identified in caged were also found in humans. The claim that these variants exhibited lower susceptibility to antibody neutralization led to the slaughter of 17 million minks in Denmark. SARS-CoV-2 prevalence tests led to the discovery of infected farmed minks worldwide. In this study, we revisit the issue of the circulation of SARS-CoV-2 variants in minks as a model of sarbecovirus interspecies evolution by: (1) comparing human and mink angiotensin I converting enzyme 2 (ACE2) and neuropilin 1 (NRP-1) receptors; (2) comparing SARS-CoV-2 sequences from humans and minks; (3) analyzing the impact of mutations on the 3D structure of the spike protein; and (4) predicting linear epitope targets for immune response. Mink-selected SARS-CoV-2 variants carrying the Y453F/D614G mutations display an increased affinity for human ACE2 and can escape neutralization by one monoclonal antibody. However, they are unlikely to lose most of the major epitopes predicted to be targets for neutralizing antibodies. We discuss the consequences of these results for the rational use of SARS-CoV-2 vaccines.

11.
Environ Res ; 204(Pt B): 112141, 2022 03.
Article in English | MEDLINE | ID: covidwho-1440019

ABSTRACT

The origin of SARS-CoV-2 is still the subject of a controversial debate. The natural origin theory is confronted to the laboratory leak theory. The latter is composite and comprises contradictory theories, one being the leak of a naturally occurring virus and the other the leak of a genetically engineered virus. The laboratory leak theory is essentially based on a publication by Rahalkar and Bahulikar in 2020 linking SARS-CoV-2 to the Mojiang mine incident in 2012 during which six miners fell sick and three died. We analyzed the clinical reports. The diagnosis is not that of COVID-19 or SARS. SARS-CoV-2 was not present in the Mojiang mine. We also bring arguments against the laboratory leak narrative.


Subject(s)
COVID-19 , Accidents , Humans , Laboratories , SARS-CoV-2
12.
Front Med (Lausanne) ; 8: 663708, 2021.
Article in English | MEDLINE | ID: covidwho-1435999

ABSTRACT

Coronavirus disease 2019 (COVID-19) is now at the forefront of major health challenge faced globally, creating an urgent need for safe and efficient therapeutic strategies. Given the high attrition rates, high costs, and quite slow development of drug discovery, repurposing of known FDA-approved molecules is increasingly becoming an attractive issue in order to quickly find molecules capable of preventing and/or curing COVID-19 patients. Cyclosporin A (CsA), a common anti-rejection drug widely used in transplantation, has recently been shown to exhibit substantial anti-SARS-CoV-2 antiviral activity and anti-COVID-19 effect. Here, we review the molecular mechanisms of action of CsA in order to highlight why this molecule seems to be an interesting candidate for the therapeutic management of COVID-19 patients. We conclude that CsA could have at least three major targets in COVID-19 patients: (i) an anti-inflammatory effect reducing the production of proinflammatory cytokines, (ii) an antiviral effect preventing the formation of the viral RNA synthesis complex, and (iii) an effect on tissue damage and thrombosis by acting against the deleterious action of angiotensin II. Several preliminary CsA clinical trials performed on COVID-19 patients report lower incidence of death and suggest that this strategy should be investigated further in order to assess in which context the benefit/risk ratio of repurposing CsA as first-line therapy in COVID-19 is the most favorable.

13.
Front Med (Lausanne) ; 8: 737602, 2021.
Article in English | MEDLINE | ID: covidwho-1430710

ABSTRACT

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.

14.
Front Cell Infect Microbiol ; 11: 639177, 2021.
Article in English | MEDLINE | ID: covidwho-1389152

ABSTRACT

Several comorbidities, including hypertension, have been associated with an increased risk of developing severe disease during SARS-CoV-2 infection. Angiotensin II receptor blockers (ARBs) are currently some of the most widely-used drugs to control blood pressure by acting on the angiotensin II type 1 receptor (AT1R). ARBs have been reported to trigger the modulation of the angiotensin I converting enzyme 2 (ACE2), the receptor used by the virus to penetrate susceptible cells, raising concern that such treatments may promote virus capture and increase their viral load in patients receiving ARBs therapy. In this in vitro study, we reviewed the effect of ARBs on ACE2 and AT1R expression and investigated whether treatment of permissive ACE2+/AT1R+ Vero E6 cells with ARBs alters SARS-CoV-2 replication in vitro in an angiotensin II-free system. After treating the cells with the ARBs, we observed an approximate 50% relative increase in SARS-CoV-2 production in infected Vero E6 cells that correlates with the ARBs-induced up-regulation of ACE2 expression. From this data, we believe that the use of ARBs in hypertensive patients infected by SARS-CoV-2 should be carefully evaluated.


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , Humans , Renin-Angiotensin System , SARS-CoV-2
15.
Front Immunol ; 12: 698121, 2021.
Article in English | MEDLINE | ID: covidwho-1362325

ABSTRACT

Epidemiological studies and clinical observations show evidence of sexual dimorphism in infectious diseases. Women are at less risk than men when it comes to developing most infectious diseases. However, understanding these observations requires a gender approach that takes into account an analysis of both biological and social factors. The host's response to infection differs in males and females because sex differences have an impact on hormonal and chromosomal control of immunity. Estradiol appears to confer protective immunity, while progesterone and testosterone suppress anti-infectious responses. In addition, genetic factors, including those associated with sex chromosomes, also affect susceptibility to infections. Finally, differences in occupational activities, lifestyle, and comorbidities play major roles in exposure to pathogens and management of diseases. Hence, considering sexual dimorphism as a critical variable for infectious diseases should be one of the steps taken toward developing personalized therapeutic approaches.


Subject(s)
Communicable Diseases , Sex Characteristics , Female , Humans , Male
16.
J Clin Med ; 10(15)2021 Jul 24.
Article in English | MEDLINE | ID: covidwho-1325716

ABSTRACT

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or vaccine immunization. The usual coronavirus mutation rate through genetic drift alone cannot account for such rapid changes. Recent reports of the occurrence of such mutations in immunocompromised patients who received remdesivir and/or convalescent plasma or monoclonal antibodies to treat prolonged SARS-CoV-2 infections led us to hypothesize that experimental therapies that fail to cure the patients from COVID-19 could favor the emergence of immune escape SARS-CoV-2 variants. We review here the data that support this hypothesis and urge physicians and clinical trial promoters to systematically monitor viral mutations by whole-genome sequencing for patients who are administered these treatments.

17.
Environ Res ; 202: 111676, 2021 11.
Article in English | MEDLINE | ID: covidwho-1305234

ABSTRACT

The whole human society was caught unprepared by the emergence of SARS-CoV-2 and the related COVID-19 pandemic. This should have not been. We already had on hand all information to organize properly and prevent this emergence. However, this information was never translated into preparedness because the current system of sanitary crises management is not adapted. We keep implementing a medical, symptomatic, post-emergence approach which cannot stop an emerging pandemic. The only preventive action considered is the screening for viruses in the wild but it is not efficient since pandemic viruses do not exist in the wild, and indeed, have never been found. The emergence of a viral pandemic is the result of a double accident: the in-host evolution of the causative virus and its amplification to the epidemic threshold by societal factors. To be prepared the society should target this societal dimension of emerging diseases and organize accordingly. Unfortunately, the society is not organized that way and is still unprepared and vulnerable.


Subject(s)
COVID-19 , Communicable Diseases, Emerging , Communicable Diseases, Emerging/epidemiology , Humans , Pandemics , SARS-CoV-2
18.
Front Immunol ; 12: 625732, 2021.
Article in English | MEDLINE | ID: covidwho-1291351

ABSTRACT

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this ACE2 gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.


Subject(s)
Angiotensin II/blood , Angiotensin I/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , Peptide Fragments/blood , Adult , Angiotensin-Converting Enzyme 2/genetics , COVID-19/virology , Female , Gene Expression Profiling , HLA-DR Antigens , Humans , Lipopolysaccharide Receptors , Male , Middle Aged , Monocytes/immunology , Monocytes/metabolism , Pilot Projects , Prospective Studies , RNA, Messenger , Virus Shedding
19.
Clin Microbiol Infect ; 27(9): 1352.e1-1352.e5, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1225181

ABSTRACT

OBJECTIVES: Surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic epidemiology led us to detect several variants since summer 2020. We report the recent spread of a new SARS-CoV-2 spike 501Y variant. METHODS: SARS-CoV-2 sequences obtained from human nasopharyngeal samples by Illumina next-generation sequencing were analysed using Nextclade and an in-house Python script and were compared using BLASTn to the GISAID database. Phylogeny was investigated using the IQ-TREE software. RESULTS: We identified that SARS-CoV-2 genomes from four patients diagnosed in our institute harboured a new set of amino acid substitutions including L18F, L452R, N501Y, A653V, H655Y, D796Y, G1219V ± Q677H. These spike N501Y genomes are the first of Nextstrain clade 19B. We obtained partial spike gene sequences of this genotype for an additional 43 patients. All patients infected with this genotype were diagnosed since mid-January 2021. We detected 42 other genomes of this genotype in GISAID, which were obtained from samples collected in December 2020 in four individuals and in 2021 in 38 individuals. The 89 sequences obtained in our institute or other laboratories originated from the Comoros archipelago, western European countries (mostly metropolitan France), Turkey and Nigeria. CONCLUSION: These findings warrant further studies to investigate the spread, epidemiological and clinical features, and sensitivity to immune responses of this variant.


Subject(s)
Amino Acid Substitution , COVID-19/diagnosis , SARS-CoV-2/classification , Sequence Analysis, RNA/methods , Spike Glycoprotein, Coronavirus/genetics , France , High-Throughput Nucleotide Sequencing , Humans , Models, Molecular , Nasopharynx/virology , Nigeria , Phylogeny , Protein Conformation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Turkey
20.
Int J Infect Dis ; 106: 228-236, 2021 May.
Article in English | MEDLINE | ID: covidwho-1207034

ABSTRACT

BACKGROUND: In Marseille, France, following a first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in March-May 2020, a second epidemic phase occurred from June, involving 10 new variants. The Marseille-4 variant caused an epidemic that started in August and is still ongoing. METHODS: The 1038 SARS-CoV-2 whole genome sequences obtained in our laboratory by next-generation sequencing with Illumina technology were analysed using Nextclade and nextstrain/ncov pipelines and IQ-TREE. A Marseille-4-specific qPCR assay was implemented. Demographic and clinical features were compared between patients with the Marseille-4 variant and those with earlier strains. RESULTS: Marseille-4 harbours 13 hallmark mutations. One leads to an S477N substitution in the receptor binding domain of the spike protein targeted by current vaccines. Using a specific qPCR, it was observed that Marseille-4 caused 12-100% of SARS-CoV-2 infections in Marseille from September 2020, being involved in 2106 diagnoses. This variant was more frequently associated with hypoxemia than were clade 20A strains before May 2020. It caused a re-infection in 11 patients diagnosed with different SARS-CoV-2 strains before June 2020, suggesting either short-term protective immunity or a lack of cross-immunity. CONCLUSIONS: Marseille-4 should be considered as a major SARS-CoV-2 variant. Its sudden appearance points towards an animal reservoir, possibly mink. The protective role of past exposure and current vaccines against this variant should be evaluated.


Subject(s)
COVID-19/genetics , Genome, Viral , Mutation , SARS-CoV-2/genetics , Whole Genome Sequencing , Animals , COVID-19/virology , Epidemics , France/epidemiology , Humans , Mink/virology , Molecular Epidemiology , Phylogeny , Reinfection/virology
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