The Delta SARS-CoV-2 variant has a higher viral load than the Beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients
SARS-CoV-2 expresses on its surface the Spike protein responsible for binding with the ACE2 receptor and which carries the majority of immunodominant epitopes. Mutations mainly affect this protein ...and can modify characteristics of the virus, giving each variant a unique profile concerning its transmissibility, virulence, and immune escape. The first lineage selected is the B.1 lineage characterized by the D614G substitution and from which all SARS-CoV-2 variants of concern have emerged. The first three variants of concern
,
, and
spread in early 2021: all shared the N501Y substitution. These variants were replaced by the
variant in summer 2021, carrying unique mutations like the L452R substitution and associated with higher virulence. It was in turn quickly replaced by the
variant at the end of 2021, which has predominated since then, characterized by its large number of mutations. The successive appearance of variants of concern showed a dynamic evolution of SARS-CoV-2 through the selection and accumulation of mutations. This has not only allowed progressive improvement of the transmissibility of SARS-CoV-2, but has also participated in a better immune escape of the virus. This review brings together acquired knowledge about SARS-CoV-2 variants of concern and the impacts of the Spike mutations.
Reliable detection of HIV minority resistant variants (MRVs) requires bioinformatics analysis with specific algorithms to obtain good quality alignments. The aim of this study was to analyze ...ultra-deep sequencing (UDS) data using different analysis pipelines.
HIV-1 protease, reverse transcriptase (RT) and integrase sequences from antiretroviral-naïve patients were obtained using GS-Junior® (Roche) and MiSeq® (Illumina) platforms. MRVs were defined as variants harbouring resistance-mutation present at a frequency of 1%-20%. Reads were analyzed using different alignment algorithms: Amplicon Variant Analyzer®, Geneious® compared to SmartGene® NGS HIV-1 module.
101 protease and 51 RT MRVs identified in 139 protease and 124 RT sequences generated with a GS-Junior® platform were analyzed using AVA® and SmartGene® software. The correlation coefficients for the MRVs were R2 = 0.974 for protease and R2 = 0.972 for RT. Discordances (n = 13 in protease and n = 15 in RT) mainly concerned low-level MRVs (i.e., with frequencies of 1%-2%, n = 18/28) and they were located in homopolymeric regions (n = 10/15). Geneious® and SmartGene® software were used to analyze 143 protease, 45 RT and 26 integrase MRVs identified in 172 protease, 69 RT, and 72 integrase sequences generated with a MiSeq® platform. The correlation coefficients for the MRVs were R2 = 0.987 for protease, R2 = 0.995 for RT and R2 = 0.993 for integrase. Discordances (n = 9 in protease, n = 3 in RT, and n = 3 in integrase) mainly concerned low-level MRVs (n = 13/15).
We found an excellent correlation between the various UDS analysis pipelines that we tested. However, our results indicate that specific attention should be paid to low-level MRVs, for which the use of two different analysis pipelines and visual inspection of sequences alignments might be beneficial. Thus, our results argue for use of a 2% threshold for MRV detection, rather than the 1% threshold, to minimize misalignments and time-consuming sight reading steps essential to ensure accurate results for MRV frequencies below 2%.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high ...risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM.
The ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate.
The ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination.
ClinicalTrials.gov NCT04156945. Registered on November 8, 2019.
•Analysis of pre-treatment resistance-associated substitutions (RASs) among recently HCV-infected MSM with risky behaviours.•Uncommon NS3/NS5A RASs among recently HCV-infected MSM with risky ...behaviour.•High prevalence of subtype-specific polymorphisms in GT4d infections.•Reassurance of the clinical management of HCV infection in this population.
Presence of baseline hepatitis C virus (HCV) resistance-associated substitutions (RASs) can impair treatment outcome of direct-acting antivirals. We investigated the prevalence of pre-treatment HCV resistance among recently HCV-infected men who have sex with men (MSM) with high risk behaviours, either human immunodeficiency virus (HIV) co-infected or at high risk of HIV acquisition and under pre-exposure prophylaxis (PrEP).
NS5A and NS3 fragments were deep sequenced on pre-treatment samples of 72 subjects using Illumina MiSeq paired-end sequencing technology. Ultra-deep sequencing data were analysed by SmartGene® platform. RASs mentioned in the literature were analysed and interpreted depending on genotype (GT) at 10% cut-off.
HCV genotyping showed 36 (50.0%) GT1a, 31 (43.1%) GT4d and 5 (6.9%) GT3a infections. Fifty-five patients (76.4%) were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a viruses, NS3 RASs were found in 4/30 viruses (13.3%; S122 G/N, R155 K and I170 V) and Q80 K polymorphism was present in 14/30 viruses (46.7%). No NS3 RASs were detected in GT4d and GT3a viruses. NS5A RASs were detected in 3/36 GT1a viruses (8.3%; Q30E/R, L31 M and H58 L). NS5A subtype-specific polymorphisms L30R and T58 P were found at high frequencies in 31/31 (100%) and 16/31 (51.6%) GT4d viruses, respectively. One RAS M31 L was also observed along with the polymorphisms L30R and T58 P. No NS5A RASs were detected in GT3a viruses.
A low level of RASs to NS3 and NS5A inhibitors in pre-treatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population.
Human monkeypox virus is spreading in Europe and the USA among individuals who have not travelled to endemic areas.1 On July 23, 2022, monkeypox was declared a Public Health Emergency of ...International Concern by WHO Director-General Tedros Adhanom Ghebreyesus.2 Human-to-human transmission of monkeypox virus usually occurs through close contact with the lesions, body fluids, and respiratory droplets of infected people or animals.3 The possibility of sexual transmission is being investigated, as the current outbreak appears to be concentrated in men who have sex with men and has been associated with unexpected anal and genital lesions.1,4 Whether domesticated cats and dogs could be a vector for monkeypox virus is unknown. Both samples contained virus of the hMPXV-1 clade, lineage B.1, which has been spreading in non-endemic countries since April, 2022, and, as of Aug 4, 2022, has infected more than 1700 people in France, mostly concentrated in Paris, where the dog first developed symptoms. ...the virus that infected patient 1 and the virus that infected the dog showed 100% sequence homology on the 19·5 kilobase pairs sequenced. Given the dog's skin and mucosal lesions as well as the positive monkeypox virus PCR results from anal and oral swabs, we hypothesise a real canine disease, not a simple carriage of the virus by close contact with humans or airborne transmission (or both).
Monkeypox virus (MPXV) is currently spreading among men who have sex with men, outside of sub-Saharan Africa, and close contact during sex seems to be one of the key pathways of viral transmission in ...the current outbreak. Our aim was to describe the distribution of MPXV in the human body, as it might play a role in its dissemination through sexual contact.
The study population in this case series consisted of patients with confirmed MPXV infection attending the Pitié-Salpêtrière Hospital (Paris, France), who had been sampled from multiple anatomical sites, including skin, anus, throat, blood, urine, and semen, at diagnosis and 2 weeks later. We compared the proportion of positive samples and MPXV viral loads (given as PCR cycle thresholds Ct) between anatomical sites, and between day 0 (D0) and D14.
Overall, 356 samples were collected between May 20 and June 13, 2022, from 50 men with a median age of 34 years (IQR 29–40). 22 (44%) of the 50 men were classified as HIV-negative on day (D)0, and 22 (44%) were living with HIV. At D0, MPXV detection was more frequent from skin (44 88% of 50), anus (30 71% of 42), and throat (36 77% of 47) than from blood (13 29% of 45), urine (nine 22% of 41), or semen (13 54% of 24). Viral loads were significantly higher from skin lesions (Ct 19·8) and anal samples (Ct 20·9) than from throat (Ct 27·2), blood (Ct 32·8), urine (31·1), or semen samples (Ct 27·8). When analysing the 107 samples taken from 24 patients at D14, the proportion of positive samples strongly decreased between D0 and D14 at all sites: skin (four 22% of 18), anus (two 9% of 22), throat (none of 21), blood (one 5% of 21), urine (none of 14), and semen (two 9% of 11).
These data contribute to a better understanding of how the virus might spread between sexual partners over a relatively short period of time. High MPXV viral loads from skin and mucosa, including genital and anal sites, suggest that transmission most likely occurs through direct body contact rather than through the respiratory route or contact with body fluids, which should help to refine the prevention messages delivered to individuals most exposed to the virus.
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Abstract
A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 ...(COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.
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