Seasonal variation of asymptomatic viral and bacterial nasopharyngeal carriage in rural Senegal.

BACKGROUND: The surveillance of respiratory pathogens in rural areas of West Africa has, to date, largely been focussed on symptoms. In this prospective study conducted prior to the COVID-19 pandemic, we aimed to assess the asymptomatic prevalence of respiratory pathogen carriage in a group of individuals living in a rural area of Senegalese. METHODS: Longitudinal follow up was performed through monthly nasopharyngeal swabbing during the dry season and weekly swabbing during the rainy season. We enrolled 15 individuals from the village of Ndiop. A total of 368 nasopharyngeal swabs were collected over a one-year period. We investigated the prevalence of 18 respiratory viruses and eight respiratory bacteria in different age groups using singleplex and multiplex PCR. RESULTS: In total, 19.56% of the samples (72/368) were positive for respiratory viruses and 13.60% of the samples (50/368) were positive for respiratory bacteria. Coronaviruses (19/72, 26.39%), adenoviruses (17/72, 23.61%), rhinoviruses (14/72, 19.44%), Streptococcus pneumoniae (17/50, 34%), and Moraxella catarrhalis (15/50, 30%) were the most frequently detected viruses. Interestingly, the carriage of respiratory pathogens was shown to be more frequent during the rainy season, as pluviometry was shown to be positively associated with the occurrence of respiratory viruses such as influenza (P = .0078, r2 =.523) and RSV (P = .0055, r2 =.554). CONCLUSIONS: Our results show a non-negligible circulation of respiratory pathogens in a rural area in Senegal (West Africa) with an underestimated proportion of asymptomatic individuals. This study highlights the fact that the circulation of viruses and bacteria in the community has been overlooked.

Description of nasopharyngeal bacterial pathogens associated with different SARS-CoV-2 variants.

The emergence of the coronavirus pandemic facilitated the acquisition of mutations in the SARS-CoV-2 genome, resulting in the appearance of new variants over the past three years. We previously identified several taxa associated with the clinical outcome of COVID-19 disease in a retrospective study involving 120 patients (infected patients and negative subjects). However, little is known about whether the different variants could influence variations in the composition of the nasopharyngeal microbiota. In this study, we used multiplex pathogen-specific PCR to analyse the presence of nasopharyngeal bacterial pathogens from 400 SARS-CoV-2 positive patients (equally distributed in the four SARS-CoV-2 variants studied: B.1.1.7 (Alpha), B.1 0.617.2 (Delta), B.1.160 (Marseille-4), and B.1.1.529 (omicron)). We then compared them to 400 patients who tested negative for all respiratory viruses tested in this study, including SARS-CoV-2. We first observed an enrichment of Staphylococcus aureus (P ≤ .05) and Corynebacterium propinquum (P ≤ .05) in COVID-19-positive patients, regardless of the variant, compared to negative subjects. We specifically highlighted a significantly higher frequency of S. aureus (P ≤ .0001), C. propinquum (P ≤ .0001), and Klebsiella pneumoniae (P ≤ .0001), in patients infected with the omicron variant, whereas that of Haemophilus influenzae was higher in patients infected with Marseille-4 (P ≤ .001) and Alpha (P ≤ .01) variants. Our results suggest that the nasopharyngeal bacterial pathogens have their own specificity according to the SARS-CoV-2 variant and independently of the season. Additional studies are needed to determine the role of these pathogens in the evolution of the clinical outcome of patients.

Influence of Microbiota on Clinical Expressions of Respiratory Viral Infections.

Respiratory infections, mainly due to viruses, are among the leading causes of worldwide morbidity and mortality. We investigated the prevalence of viruses and bacteria in a cross-sectional survey conducted in Dielmo, a village in rural Senegal with a population of 481 inhabitants. Nasopharyngeal sampling was performed in 50 symptomatic subjects and 101 asymptomatic subjects. Symptomatic subjects were defined as individuals presenting with clinical signs of respiratory infection, whereas asymptomatic subjects were recruited in the same households. The identification of pathogens was performed by polymerase chain reaction for 18 respiratory viruses and eight respiratory bacteria. The prevalence results for respiratory viruses detected in each study group demonstrated that 83.6% of symptomatic samples were positive for at least one respiratory virus, and 21.8% were detected in asymptomatic samples. Influenza A (P = 0.0001), metapneumovirus (P = 0.04), and enterovirus (P = 0.001) were significantly more prevalent in symptomatic patients. Overall, 82.0% of symptomatic subjects and 26.9% of asymptomatic subjects were positive for at least one respiratory bacterium. The most frequent pathogenic bacteria detected were Moraxella catarrhalis (56%) and Streptococcus pneumoniae (48.0%) among symptomatic individuals, whereas in asymptomatic subjects Corynebacterium propinquum was more prevalent (18%). A principal component analysis showed that parainfluenzas 2 and 4 were associated with asymptomatic subjects, whereas influenza A was associated with the presence of symptoms. Considering these results, a large epidemiological surveillance of the circulation of these respiratory pathogens in the general population should be conducted to provide a better understanding of their carriage and to potentially prevent epidemics.

The Archaeome's Role in Colorectal Cancer: Unveiling the DPANN Group and Investigating Archaeal Functional Signatures.

BACKGROUND AND AIMS: Gut microbial imbalances are linked to colorectal cancer (CRC), but archaea's role remains underexplored. Here, using previously published metagenomic data from different populations including Austria, Germany, Italy, Japan, China, and India, we performed bioinformatic and statistical analysis to identify archaeal taxonomic and functional signatures related to CRC. METHODS: We analyzed published fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy individuals. We conducted a biostatistical analysis to investigate the relationship between Candidatus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently linking them to CRC and mapping them against UniprotKB and GO databases for specific archaeal gene functions. RESULTS: Our analysis identified enrichment of methanogenic archaea in healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN archaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Functionally, we found a marked association between MvhB-type polyferredoxin and colorectal cancer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine and the galactose metabolism process with the healthy phenotype. CONCLUSIONS: The archaeomes of CRC patients show identifiable alterations, including a decline in methanogens and an increase in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus Mancarchaeum acidiphilum, Natrinema sp. J7-2, and Ferroglobus placidus emerge as potential archaeal biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea's role in CRC dynamics.

How to distinguish mpox from its mimickers: An observational retrospective cohort study.

During the current global outbreak of mpox (formerly monkeypox), atypical features were frequently described outside endemic areas, raising concerns around differential diagnosis. In this study, we included 372 adult patients who had clinical signs consistent with mpox and who were screened using non-variola orthopoxvirus specific quantitative polymerase chain reaction (PCR) between 15 May and 15 November 2022 at the University Hospital Institute Méditerranée Infection, Marseille, France. At least one clinical sample was positive for 143 (38.4%) of these patients and 229 (61.6%) were negative. Clinically, patients who had mpox presented more frequently with systemic signs (69.9% vs. 31.0%, p < 10-6 ) including fever (51.0% vs. 30.1%, p < 10-3 ), myalgia (33.5% vs. 17.9%, p = 0.002), and lymphadenopathy (38.5% vs. 13.1%, p < 10-6 ). Among the patients who were negative for the non-variola orthopoxvirus, an alternative diagnosis was identified in 58 of them (25.3%), including chickenpox (n = 30, 13.1%), syphilis (n = 9, 4%), bacterial skin infection (n = 8, 3.5%), gonococcus (n = 5, 2.2%), HSV infection (n = 5, 2.2%), and histoplasmosis (n = 1, 0.4%). Overall, in the current outbreak, we show that mpox has a poorly specific clinical presentation. This reinforces the importance of microbiological confirmation. In symptomatic patients who are negative for the monkeypox virus by PCR, a broad differential diagnosis should be maintained.

Colorectal Cancer Archaeome: A Metagenomic Exploration, Tunisia.

Colorectal cancer (CRC) is a serious public health problem known to have a multifactorial etiology. The association between gut microbiota and CRC has been widely studied; however, the link between archaea and CRC has not been sufficiently studied. To investigate the involvement of archaea in colorectal carcinogenesis, we performed a metagenomic analysis of 68 formalin-embedded paraffin fixed tissues from tumoral (n = 33) and healthy mucosa (n = 35) collected from 35 CRC Tunisian patients. We used two DNA extraction methods: Generead DNA FFPE kit (Qiagen, Germantown, MD, USA) and Chelex. We then sequenced the samples using Illumina Miseq. Interestingly, DNA extraction exclusively using Chelex generated enough DNA for sequencing of all samples. After data filtering and processing, we reported the presence of archaeal sequences, which represented 0.33% of all the reads generated. In terms of abundance, we highlighted a depletion in methanogens and an enrichment in Halobacteria in the tumor tissues, while the correlation analysis revealed a significant association between the Halobacteria and the tumor mucosa (p < 0.05). We reported a strong correlation between Natrialba magadii, Sulfolobus acidocaldarius, and tumor tissues, and a weak correlation between Methanococcus voltae and healthy adjacent mucosa. Here, we demonstrated the feasibility of archaeome analysis from formol fixed paraffin-embedded (FFPE) tissues using simple protocols ranging from sampling to data analysis, and reported a significant association between Halobacteria and tumor tissues in Tunisian patients with CRC. The importance of our study is that it represents the first metagenomic analysis of Tunisian CRC patients' gut microbiome, which consists of sequencing DNA extracted from paired tumor-adjacent FFPE tissues collected from CRC patients. The detection of archaeal sequences in our samples confirms the feasibility of carrying out an archaeome analysis from FFPE tissues using a simple DNA extraction protocol. Our analysis revealed the enrichment of Halobacteria, especially Natrialba magadii, in tumor mucosa compared to the normal mucosa in CRC Tunisian patients. Other species were also associated with CRC, including Sulfolobus acidocaldarius and Methanococcus voltae, which is a methanogenic archaea; both species were found to be correlated with adjacent healthy tissues.

Description of Streptococcus thalassemiae sp. nov., a Bacterium Isolated from Human Blood.

Blood is a precious biological liquid that is normally sterile. Therefore, bacteria in the bloodstream are shown a priori anomaly. A blood culture is systematically performed to diagnose the cause of the bacteremia. Indeed, a patient received in our service had a thalassemia major and underwent a genoidentical transplant. Then, a blood test was performed to diagnose a four-day fever. In this context, we have isolated strain Marseille-Q2617 from the blood sample. It revealed a new bacterial strain that belongs to the genus Streptococcus. It is a Gram-positive coccus, nonmotile, and nonspore forming. The major fatty acid found is hexadecanoic acid, with 49.5%. A taxonomic method was used to characterize the strain by studying their phenotypic, phylogenetic, and genomic characteristics. In addition, sequence analysis of the 16S rRNA gene shows that the strain Marseille-Q2617 has 99.94% sequence similarity to Streptococcus mitis. Average nucleotide identity (ANI) analysis for strain Marseille-Q2617T showed the highest similarity of 92.9% with S. mitis. The DNA-DNA hybridization value obtained (50.2%) between strain Marseille-Q2607 and S. mitis, its closest related species, was below the recommended threshold (<70%). Strain Marseille-Q2617T has a genome size of 2.02 Mbp with 40.5 mol% of G + C content. Based on these results, we propose a new species of the genus Streptococcus, for which the name Streptococcus thalassemiae sp. nov., Marseille-Q2617T (=CSUR Q2617 = CECT 30109) was proposed.

Preliminary landscape of Candidatus Saccharibacteria in the human microbiome.

Introduction: Candidate Phyla Radiation (CPR) and more specifically Candidatus Saccharibacteria (TM7) have now been established as ubiquitous members of the human oral microbiota. Additionally, CPR have been reported in the gastrointestinal and urogenital tracts. However, the exploration of new human niches has been limited to date. Methods: In this study, we performed a prospective and retrospective screening of TM7 in human samples using standard PCR, real-time PCR, scanning electron microscopy (SEM) and shotgun metagenomics. Results: Using Real-time PCR and standard PCR, oral samples presented the highest TM7 prevalence followed by fecal samples, breast milk samples, vaginal samples and urine samples. Surprisingly, TM7 were also detected in infectious samples, namely cardiac valves and blood cultures at a low prevalence (under 3%). Moreover, we observed CPR-like structures using SEM in all sample types except cardiac valves. The reconstruction of TM7 genomes in oral and fecal samples from shotgun metagenomics reads further confirmed their high prevalence in some samples. Conclusion: This study confirmed, through their detection in multiple human samples, that TM7 are human commensals that can also be found in clinical settings. Their detection in clinical samples warrants further studies to explore their role in a pathological setting.

Sequencing of monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection.

A large outbreak of Monkeypox virus (MPXV) infections has arisen in May 2022 in nonendemic countries. Here, we performed DNA metagenomics using next-generation sequencing with Illumina or Nanopore technologies for clinical samples from MPXV-infected patients diagnosed between June and July 2022. Classification of the MPXV genomes and determination of their mutational patterns were performed using Nextclade. Twenty-five samples from 25 patients were studied. A MPXV genome was obtained for 18 patients, essentially from skin lesions and rectal swabbing. All 18 genomes were classified in clade IIb, lineage B.1, and we identified four B.1 sublineages (B.1.1, B.1.10, B.1.12, B.1.14). We detected a high number of mutations (range, 64-73) relatively to a 2018 Nigerian genome (genome GenBank Accession no. NC_063383.1), which were harbored by a large part of a set of 3184 MPXV genomes of lineage B.1 recovered from GenBank and Nextstrain; and we detected 35 mutations relatively to genome ON563414.3 (a B.1 lineage reference genome). Nonsynonymous mutations occurred in genes encoding central proteins, among which transcription factors and core and envelope proteins, and included two mutations that would truncate a RNA polymerase subunit and a phospholipase d-like protein, suggesting an alternative start codon and gene inactivation, respectively. A large majority (94%) of nucleotide substitutions were G > A or C > U, suggesting the action of human APOBEC3 enzymes. Finally, >1000 reads were identified as from Staphylococcus aureus and Streptococcus pyogenes for 3 and 6 samples, respectively. These findings warrant a close genomic monitoring of MPXV to get a better picture of the genetic micro-evolution and mutational patterns of this virus, and a close clinical monitoring of skin bacterial superinfection in monkeypox patients.

Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients.

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. Ten patients (2.4%) developed QTc prolongation > 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.

Maliibacterium massiliense gen. nov. sp. nov., Isolated from Human Feces and Proposal of Maliibacteriaceae fam. nov.

Bacterial strain Marseille-P3954 was isolated from a stool sample of a 35-year-old male patient living in France. It was a gram-positive, rod-shaped anaerobic, non-motile, and non-spore-forming bacterium. C16:0 and C18:1n9 were the major fatty acid, while its genome measured 2,422,126 bp with 60.8 mol% of G+C content. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain Marseille-P3954 had 85.51% of similarity with Christensenella minuta, its closest related species with standing in nomenclature. As this value is very low compared to the recommended threshold, it suggested that the Marseille-P3954 strain belongs to a new bacterial genus, classified in a new family. On the basis of these genomic, phenotypic, and phylogenetic evidences, we propose that strain Marseille-P3954 should be classified as a new genus and species, Maliibacterium massiliense gen. nov., sp. nov. The type strain of M. massiliense sp. nov. is Marseille-P3954 (CSUR P3954 = CECT 9568).

Unraveling the Underlying Molecular Mechanism of 'Silent Hypoxia' in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway.

A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the renin angiotensin system (RAS) in COVID-19 patients, we propose a model that explains 'silent hypoxia'. The RAS imbalance caused by SARS-CoV-2 results in an accumulation of angiotensin 2 (Ang II), which activates the angiotensin 2 type 1 receptor (AT1R) and triggers a harmful cascade of intracellular signals leading to the nuclear translocation of the hypoxia-inducible factor (HIF)-1α. HIF-1α transactivates many genes including the angiotensin-converting enzyme 1 (ACE1), while at the same time, ACE2 is downregulated. A growing number of cells is maintained in a hypoxic condition that is self-sustained by the presence of the virus and the ACE1/ACE2 ratio imbalance. This is associated with a progressive worsening of the patient's biological parameters including decreased oxygen saturation, without further clinical manifestations. When too many cells activate the Ang II-AT1R-HIF-1α axis, there is a 'hypoxic spillover', which marks the tipping point between 'silent' and symptomatic hypoxia in the patient. Immediate ventilation is required to prevent the 'hypoxic spillover'.

Use of scanning electron microscopy and energy dispersive X-ray for urine analysis: A preliminary investigation.

Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) are powerful tools to study the ultrastructure of numerous specimens and to determine their elemental composition, respectively. However, results have not yet been reported on their application to urine samples in routine clinical laboratory practice. Herein we investigate urine sediment by using SEM and EDX to detect and identify different urine components. A total of 206 urine samples from patients with and without urinary tract infections were analyzed using SEM and EDX. Microorganisms, crystals, epithelial cells, leukocytes, and erythrocytes were targeted in urine sediment samples. The identification of urine components was based on their morphology, size, contrast, and elemental composition. SEM-analysis allowed us to identify and classify microorganisms in urine sediments into the categories of gram-negative bacilli, cluster cocci, chain cocci, gram-negative bacilli, gram-positive bacilli, and yeasts. In addition, various types of epithelial cells such as renal, transitional, and squamous epithelial cells were found. Furthermore, leukocytes and erythrocytes were well identified, with the detection of various morphological forms of erythrocytes, such as dysmorphic and isomorphic erythrocytes. Using SEM-EDX analysis, calcium oxalate was the most frequently-identified crystal (92.0%), with prominent peaks of C, O, and Ca elements, followed by struvite (6%), with peaks of Mg, P, O, and N. These preliminary data suggest that the two complementary SEM-EDX analyses can be used to detect and identify microorganisms and crystals in urine samples. Further studies are still needed to apply SEM-EDX to urine sediment analysis. SEM-EDX analyses provided comparative results with the routine results, with accurate identification, high resolution and deep focus compared to the routine urinalysis SEM-analysis allowed us to identify and classify microorganisms in urine sediments into the categories of gram-negative bacilli, cluster cocci, chain cocci, gram-negative bacilli, gram-positive bacilli and yeasts. SEM-EDX analysis enabled the accurate identification of crystals based on both morphology and elemental composition.

The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule.

The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant ("Marseille-4") for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.

SARS-CoV-2 quasi-species analysis from patients with persistent nasopharyngeal shedding.

At the time of a new and unprecedented viral pandemic, many questions are being asked about the genomic evolution of SARS-CoV-2 and the emergence of different variants, leading to therapeutic and immune evasion and survival of this genetically highly labile RNA virus. The nasopharyngeal persistence of infectious virus beyond 17 days proves its constant interaction with the human immune system and increases the intra-individual mutational possibilities. We performed a prospective high-throughput sequencing study (ARTIC Nanopore) of SARS-CoV-2 from so-called "persistent" patients, comparing them with a non-persistent population, and analyzing the quasi-species present in a single sample at time t. Global intra-individual variability in persistent patients was found to be higher than in controls (mean 5.3%, Standard deviation 0.9 versus 4.6% SD 0.3, respectively, p < 0.001). In the detailed analysis, we found a greater difference between persistent and non-persistent patients with non-severe COVID 19, and between the two groups infected with clade 20A. Furthermore, we found minority N501Y and P681H mutation clouds in all patients, with no significant differences found both groups. The question of the SARS-CoV-2 viral variants' genesis remains to be further investigated, with the need to prevent new viral propagations and their consequences, and quasi-species analysis could be an important key to watch out.

Subcutaneously administered antibiotics: a review.

BACKGROUND: Subcutaneous (SC) administration of antibiotics represents an attractive alternative to the intravenous (IV) route. METHODS: We performed a systematic electronic search of PubMed and the Cochrane Library for all articles published prior to April 2022, using the key terms and MeSH terms 'subcutaneous', 'antibiotic' and the international non-proprietary name of antibiotics. RESULTS: A total of 30 studies were selected including data on the efficacy and tolerability of antibiotics, and seven studies that were conducted in healthy subjects, for relevant information regarding the safety and tolerability of antibiotics. Comparative studies have shown that efficacy is similar for the SC and IV routes for ceftriaxone, teicoplanin and ertapenem. The SC use of other antibiotics such as ampicillin, ceftazidime, cefepime, piperacillin/tazobactam, metronidazole and fosfomycin has also been described. These results have largely been corroborated by pharmacokinetic/pharmacodynamic analyses, especially for time-dependent antibiotics. Complications of SC treatment are rarely severe, with no reports of bacteraemia or other invasive infection related to this route of administration. Therapeutic drug monitoring has been proposed to adapt the dose and avoid toxicity. DISCUSSION: The rationale for using SC administration of ceftriaxone, ertapenem and teicoplanin is strong in patients with non-severe infections. It is already commonly practised in some countries, particularly in France. Other antibiotics could be administered subcutaneously, but further studies are needed to validate their use in clinical practice. Further research is needed to safely generalize and optimize this route of administration whenever possible. This would reduce the risk of catheter-related infections and their complications, together with the length of hospital stay.

Microscopic observations of SARS-CoV-2 like particles in different oral samples.

The emerging coronavirus pneumonia epidemic caused by the SARS-CoV-2 infection has spread rapidly around the world. The main routes of transmission of SARS-CoV-2 are currently recognised as aerosol/droplet inhalation. However, the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly known. The current data indicates the presence of viral RNA in oral samples, suggesting the implication of saliva in SARS-CoV-2 transmission, however, no direct observation of SARS-CoV-2 particles in different oral samples has been reported. In this study, we investigated whether particles of SARS-CoV-2 were present in oral samples collected from three symptomatic COVID-19 patients. Using scanning electron microscopy (SEM), the correlative strategy of light microscopy and electron microscopy and immunofluorescence staining, we showed the presence of SARS-like particles in RT-qPCR SARS-CoV-2-positive saliva, dental plaque and gingival crevicular fluid (GCF) samples. In the saliva samples, we demonstrated the presence of epithelial oral cells with morphogenetic features of SARS-CoV-2 infected cells. Inside those cells, vacuoles filled with nascent particles were observed, suggesting the potential infection and replication of SARS-CoV-2 in oral tissues. Our results corroborate previous studies and confirm that the oral cavity may be a potential niche for SARS-CoV-2 infection and a potential source of transmission.