Abstract
The COVID-19 pandemic caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten public health and burden healthcare systems worldwide. Whole ...SARS-CoV-2 genome sequencing has become essential for epidemiological monitoring and identification of new variants, which could represent a risk of increased transmissibility, virulence, or resistance to vaccines or treatment. Different next-generation sequencing approaches are used in SARS-CoV-2 sequencing, although with different ability to provide whole genome coverage without gaps and to reliably detect new variants. In this study, we compared the performance of three target enrichment methods (two multiplex amplification methods and one hybridization capture) using nasopharyngeal swabs from infected individuals. We applied these target enrichment methods to the same set of nasopharyngeal samples (N = 93) in high-throughput mode. SARS-CoV-2 genome was obtained using short-read next-generation sequencing. We observed that each method has some advantages, such as high mapping rate (CleanPlex and COVIDSeq) or absence of systematic variant calling error (SureSelect) as well as their limitations such as suboptimal uniformity of coverage (CleanPlex), high cost (SureSelect) or supply shortages (COVIDSeq). Nevertheless, each of the three target enrichment kits tested in this study yielded acceptable results of whole SARS-CoV-2 genome sequencing and either of them can therefore be used in prospective programs of genomic surveillance of SARS-CoV-2. Genomic surveillance will be crucial to overcoming the ongoing pandemic of COVID-19, despite its successive waves and continually emerging variants.
To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor ...(INI)-based regimen.
This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.
Prevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) <50 copies/mL at initiation and virological suppression was maintained during the first year of follow-up in all but two exhibiting a viral blip. Twenty-four patients had a VL > 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL < 50 copies/mL at week 24 were receiving elvitegravir. The 16 remaining patients were ART experienced in virological failure with drug-resistant viruses displaying several virological outcomes independently of the genotypic susceptibility score. Phenotypic analyses showed a fold change in EC50 of 0.6, 0.9 and 1.9 for raltegravir, dolutegravir and elvitegravir, respectively, in a subtype B context, and 1.1, 1.9 and 2.4 for raltegravir, dolutegravir and elvitegravir, respectively, in a CRF02_AG context.
Assessment of virological response in 39 patients initiating an INI-based regimen with E157Q-mutated virus, in combination with phenotypic analysis, suggests that particular attention should be paid to antiretroviral-naive patients and dolutegravir should be preferentially used in these patients.
Hepatitis E virus (HEV) genotypes 3 and 4 are the major causes of acute hepatitis in industrialized countries. Genotype 3 is mainly found in Europe and America, while genotype 4 is predominant in ...Asia. Several Japanese studies have suggested that genotype 4 is more virulent than genotype 3. We investigated this aspect by analyzing the clinical and biological data for 27 French and Belgian immunocompetent patients infected with HEV genotype 4. Their infections were probably acquired locally, since none of these patients reported traveling outside France or Belgium during the 2-8 weeks before symptoms onset. Each patient was matched for age (±5 years) and gender with two patients infected with HEV genotype 3. Bivariate analysis indicated that the HEV genotype 4-infected patients had significantly higher alanine aminotransferase (ALT) (2067 IU/L) and aspartate aminotransferase (AST) (1581 IU/L) activities and total bilirubin concentrations (92.4 μmol/L) than did those infected with HEV genotype 3 (1566 IU/L,
= 0.016; 657 IU/L,
= 0.003 and 47 μmol/L,
= 0.046) at diagnosis. In contrast, more patients infected with HEV genotype 3 reported dark urine (71% vs. 39%,
= 0.02) and experienced asthenia (89% vs. 58%,
< 0.01) than did those infected with HEV genotype 4. Two HEV genotype 4-infected patients died of multi-organ failure, while none of the genotype 3-infected patients died (
= 0.035). Finally, stepwise regression analysis retained only a greater increase in ALT (odds-ratio: 1.0005, 95% confidence interval: 1.00012-1.00084) and less frequent fever (odds-ratio = 0.1244; 95% confidence interval: 0.01887-0.82020) for patients infected with HEV genotype 4. We conclude that HEV-4 infections are likely to be associated with higher ALT activity than HEV-3 infections. Additional immunological and virological studies are required to confirm these findings and better understand the influence, if any, of genotype on HEV pathophysiology.
Background
The COVID-19 pandemic has altered organ and tissue donations as well as transplantation practices. SARS-CoV-2 serological tests could help in the selection of donors. We assessed COVID-19 ...seroprevalence in a population of tissue donors, at the onset of the outbreak in France, before systematic screening of donors for SARS-CoV-2 RNA.
Methods
235 tissue donors at the Lille Tissue Bank between November 1, 2019 and March 16, 2020 were included. Archived serum samples were tested for SARS-CoV-2 antibodies using two FDA-approved kits.
Results
Most donors were at higher risks for severe COVID-19 illness including age over 65 years (142/235) and/or presence of co-morbidities (141/235). According to the COVID-19 risk assessment of transmission, 183 out of 235 tissue donors presented with a low risk level and 52 donors with an intermediate risk level of donor derived infection. Four out of the 235 (1.7%) tested specimens were positive for anti-SARS-CoV-2 antibodies: 2 donors with anti-N protein IgG and 2 other donors with anti-S protein total Ig. None of them had both type of antibodies.
Conclusion
Regarding the seroprevalence among tissue donors, we concluded that the transmission probability to recipient via tissue products was very low at the beginning of the outbreak.
Transmission of drug-resistant variants is influenced by several factors, including the HIV-1 RNA levels in HIV-1-infected patients. Our study describes the transmitted drug-resistant virus among ...1446 French patients diagnosed at the time of primary infection and included from 1996 to 2006 along with the proportion of chronically infected treated patients in the French Hospital Database on HIV (FHDH).
Genotypic resistance tests were performed at the time of primary infection. The proportion of patients with viral load <500 copies/ml among treated patients, enrolled in the FHDH, was calculated.
Over 1996-2006, the proportion of transmitted resistant viruses to at least one antiretroviral was estimated as 10.9%. When considering class resistance, there was an increase in transmission of nonnucleoside reverse transcriptase inhibitor-resistant virus from 0.6% in 1996-1998 to 4.4% in 1999 (P = 0.034), whereas no change was evidenced for either nucleoside/nucleotide reverse transcriptase inhibitor or protease inhibitor resistance. In the FHDH, the proportion of patients receiving combination antiretroviral therapy (cart) increased from 27.7% in 1996 to 81.4% in 2006 and the proportion of viral load <500 copies/ml in treated patients increased from 17.0% in 1996 to 85.3% in 2006. Phylogenetic analysis revealed that 25.5% of patients harboured HIV-1-non-B virus at the time of primary infection in 2005-2006 compared to 10% in 1996-1998.
In this large study of patients at the time of primary infection, the frequency of acquired resistant virus was stable over time, over 5% for nucleoside/nucleotide reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor. One explanation for this stability may be the increasing number of treated patients in virological success.
The circumstances of prescription of tropism tests clinically relevant in treatment-experienced patients are unclear.
We performed a monocentric retrospective analysis of all tropism tests performed ...between 2006 and 2015 in HIV-infected patients on antiretroviral therapy (ART) without MVC. The motivation of tropism determination was collected. Factors associated with MVC prescription were determined using logistic regression analysis.
Five hundred sixty-three tests were performed in experienced patients not receiving MVC. Reasons for tropism performance were: virological failure (44%), side effects or drug-interactions (37%), simplification or sparing strategies (11%), immunological failure (5%), and improvement of neurological diffusion (3%). MVC was prescribed in 110 cases (20%), though 366 tests (65%) revealed a tropism CCR5. MVC was more often prescribed before 2011 (OR 3.65, 95% CI 2.17-6.13) and in patients with multiple previous ART regimens (less than 4 ART regimens compare to more than 10 ART regimens (OR 0.34, 95% CI 0.15-0.74)).
In experienced patients not receiving MVC, tropism test prescription should be restricted to patients with virological failure and limited therapeutic options such as patients already treated with a wide range of ART regimens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents.
In this monocenter ...prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered).
106 NH residents (median interquartile range age: 86·5 81;91 years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects (p < 0.0001) and a mild transient increase of specific T cells. Before the booster dose, Delta neutralization was detected in 19% (n = 8/43) and 88% (n = 37/42) of COVID-19 naive and COVID-19 recovered subjects, respectively. Three months after the booster dose, all NH residents developed and maintained a higher Delta neutralization (p < 0·0001). Before the booster dose, Omicron neutralization was detected in 5% (n = 2/43) and 55% (n = 23/42) of COVID-19 naive and COVID-19 recovered subjects, respectively, and three months after, in 84% and 95%, respectively. Neutralizing titers to Omicron were lower than to Delta in both groups with a 35-fold reduction compared to Delta.
The booster dose restores high neutralization titers against Delta in all NH residents, and at a lower level against Omicron in a large majority of participants. Future studies are warranted to assess if repeated BNT162b2 booster doses or new specific vaccines might be considered for protecting such fragile patients against Omicron and/or future SARS-CoV-2 variants.
French government through the Programme Investissement d'Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE) and the Label of COVID-19 National Research Priority (National Steering Committee on Therapeutic Trials and Other COVID-19 Research, CAPNET).
A higher proportion of intermittent viremia (to have a HIV-1 RNA viral load>50 copies/mL not confirmed) was reported in the boosted protease inhibitor monotherapy arm in some studies including MONOI ...trial, and that could have an impact on the replenishment of the HIV-1 DNA reservoirs. The HIV-1 DNA level is an interesting marker which reflects the size of cellular HIV reservoir. Our objectives were to study the impact of 96 weeks of Darunavir/ritonavir monotherapy versus a triple standard combination on the HIV-1 blood reservoir and factors associated with HIV-1 plasma DNA at baseline in MONOI trial sub-study.
This sub-study is focused on 160 patients (79 patients in monotherapy arm and 81 in tritherapy arm) for whom blood cells were available both at baseline and at week 96 (W96). Baseline HIV-1 plasma DNA was associated with CD4 nadir, pre therapeutic HIV-1 RNA viral load and baseline HIV-1 RNA measured by ultrasensitive assay. A similar median delta HIV-DNA was observed between D0 and W96 in both arms; 0.35 log copies/10(6) leucocytes in monotherapy arm versus 0.51 log copies/10(6) leucocytes in tritherapy arm.
Despite a higher proportion of intermittent viremia in monotherapy arm, a similar evolution of cellular HIV-1 DNA level was observed between mono and triple therapy arm.
ClinicalTrials. gov NCT00421551.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the prevalence of COVID-19 in people living with HIV (PLWHIV), we performed an epidemiological survey from 1 April through 1 August 2020 in an HIV reference center in Northern France. ...PLWHIV completed a questionnaire about risk exposures and symptoms consistent with COVID-19 and performed a SARS-CoV-2 serology. Among the 600 PLWHIV included, 16 have been infected with SARS-CoV-2. Symptoms consistent with COVID-19 were frequent both in SARS-CoV-2 positive and negative patients (67% vs. 32%,
= 0.02). Among SARS-CoV-2 infected patients, one (6%) has been hospitalized and five (31%) have been asymptomatic. Close contact with a confirmed COVID-19 case was the only factor associated with COVID-19 acquisition (40% vs. 13%,
= 0.01). The prevalence of COVID-19 in PLWHIV was 2.5%, half of the overall population estimate after the first wave of the pandemic in France. In conclusion, proportion of asymptomatic COVID-19 was high in PLWHIV. The prevalence of COVID-19 in PLWHIV was two times lower than in the general population.
Objective
The COVID‐19 pandemic is rapidly spreading worldwide, notably in Europe and North America where obesity is highly prevalent. The relation between obesity and severe acute respiratory ...syndrome coronavirus‐2 (SARS‐CoV‐2) has not been fully documented.
Methods
This retrospective cohort study analyzed the relationship between clinical characteristics, including BMI, and the requirement for invasive mechanical ventilation (IMV) in 124 consecutive patients admitted in intensive care for SARS‐CoV‐2 in a single French center.
Results
Obesity (BMI > 30) and severe obesity (BMI > 35) were present in 47.6% and 28.2% of cases, respectively. Overall, 85 patients (68.6%) required IMV. The proportion of patients who required IMV increased with BMI categories (P < 0.01, χ2 test for trend), and it was greatest in patients with BMI > 35 (85.7%). In multivariate logistic regression, the need for IMV was significantly associated with male sex (P < 0.05) and BMI (P < 0.05), independent of age, diabetes, and hypertension. The odds ratio for IMV in patients with BMI > 35 versus patients with BMI < 25 was 7.36 (1.63‐33.14; P = 0.02).
Conclusions
The present study showed a high frequency of obesity among patients admitted in intensive care for SARS‐CoV‐2. Disease severity increased with BMI. Obesity is a risk factor for SARS‐CoV‐2 severity, requiring increased attention to preventive measures in susceptible individuals.