Abstract
Our knowledge of COVID-19 is changing and evolving rapidly, with novel insights and recommendations, almost on a daily basis. It behooves the medical community to provide updated information ...on a regular basis, on best practice to facilitate optimal care of infected patients and on appropriate advice for the general population. This is particularly important in the case of patients with chronic conditions, such as inflammatory bowel disease IBD. In this review, we have compiled existing evidence on the impact of COVID-19 in IBD patients and provide guidance on the most appropriate care to adopt during the pandemic. Our review highlights that IBD, per se, is not a risk factor for COVID-19. However, all IBD patients with symptoms should be tested for SARS-CoV-2 and the procedures for disease management should be carefully adapted: i in SARS-CoV-2-positive IBD patients, medical treatments should be re-evaluated with a particular focus on corticosteroids always with the purpose of treating active disease and maintaining remission; ii non-urgent surgeries and endoscopic procedures should be postponed for all patients; iii online consultancy should be implemented; and iv hospitalization and surgery should be limited to life-threatening situations.
Because of the increasing use of immunosuppressive and biological drugs, the occurrence of opportunistic infections has become a key safety issue for patients with inflammatory bowel disease (IBD). ...Consequently, improvement of healthcare workers' knowledge of this domain is urgent. In this review, the preventive measures that would help to reduce the rate of opportunistic infections in patients with IBD are listed, and the management of situations frequently confronting doctors is considered. In the absence of national and international recommendations, the information given here should help doctors to optimise patient outcomes.
Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive ...infection in young adults.
Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening.
The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively.
PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.
Human cytomegalovirus (HCMV) resistance to antiviral drugs is a major drawback of repeated or long-duration treatment in immunocompromised patients. Resistance testing is usually performed by ...genotypic assays. For accurate interpretation of these assays, the role of new mutations in HCMV resistance has to be assessed. Two previously unknown UL54 single point mutations (D515Y and V787A) were characterized for phenotypic drug-resistance by marker transfer analysis using bacterial artificial chromosome (BAC) mutagenesis. Increases in 50% inhibitory concentrations of ganciclovir and foscarnet were found for both mutated recombinant strains showing that mutations D515Y and V787A induce resistance to both antivirals. Importantly, none of those impacted the viral growth kinetics. For a better understanding of their molecular resistance mechanisms, a 3D homology model was used to localize the mutated amino-acids in functional domains of UL54 and predict their impact on UL54 function and resistance. However, 3D homology model analysis has limits and phenotypic characterization using BAC-HCMV is still essential to measure the role of unknown mutations.
•We characterized two previously unknown HCMV UL54 single point mutations found in immunocompromised patients.•Both mutations induce resistance to ganciclovir and foscarnet, without impact the viral growth kinetics.•UL54 3D theoretical model allows a better understanding impact of mutations on protein function and resistance mechanism.
OBJECTIVE: To evaluate the cost-effectiveness of the tuberculin skin test (TST), the QuantiFERON®-TB Gold test (QFT) and a combination of TST and QFT (TST+QFT) for diagnosing latent tuberculosis ...infection (LTBI) in France in a bacille Calmette-Guérin (BCG) vaccinated
population.METHODS: A decision analysis model evaluated three strategies among simulated adults in close contact with tuberculosis (TB). We calculated direct lifetime medical costs, life expectancies and incremental cost-effectiveness ratios (ICERs).RESULTS: The discounted direct medical
costs of care per patient of no testing, TST, QFT and TST+QFT were respectively €417, €476, €443 and €435, while discounted life expectancies were respectively 25.030, 25.071, 25.073 and 25.062 years. TST had higher costs and lower efficacy than QFT; TST+QFT was
associated with an ICER of €560 per year of life gained (YLG) compared to no testing, and QFT was associated with an ICER of €730/YLG compared to TST+QFT. The only scenario where QFT was associated with an ICER of >€75 000/YLG was when the prevalence of LTBI around
TB was low (<5%) and TST specificity high (>90%).CONCLUSIONS: In France, for the diagnosis of LTBI after close contact with TB, the TST is more expensive and less effective than QFT. Although it is more expensive, QFT is more effective and cost-effective than TST+QFT under a
wide range of realistic test performance scenarios.
Determinants of persistent low-level viraemia PLLV, a viral load (VL) of between 50 and 500 copies/mL have not been elucidated. In a case–control study, we evaluated the influence of micronutrients ...on PLLV in a population of 454 HIV-1 adults having initiated antiretroviral therapy (ART) between January 2007 and December 2011. Plasma levels of retinol (vitamin A), 25-OH vitamin D
2
+ D
3
, vitamin E and zinc were measured at ART initiation in cases (PLLV after 6 months of ART) and in controls (VL <50 copies/mL after 6 months). Cases and controls were matched for the CD4 cell count (±50/mm
3
) and ethnic origin. Intergroup differences in demographic, biological and treatment parameters and sunshine intensity at ART initiation were adjusted using a propensity score. A receiver operating characteristic (ROC) curve was used to assess intergroup differences in plasma micronutrient levels. Thirty-three of the 454 patients (7.3%) displayed PLLV (median VL: 92 copies/mL). Patients were predominantly male (89%), Caucasian (64%) and CDC stage C (25%). The median age was 38 years, the median initial VL was 5.2 log
10
copies/mL and the median CD4 count was 74/mm
3
. The 22 cases and matched controls were balanced in these respects, and had similar vitamin A/E levels. Two cases (9%) and 9 controls (41%) had a vitamin D level <10.3 ng/mL (
p
= 0.0015), and 2 cases (9%) and 10 controls (48%) had a zinc level <74.6 μg/dL (
p
= 0.04). Our results support in vitro studies suggesting that vitamin D favours HIV-1 replication and that HIV-1 is zinc-dependent. Wide-scale, prospective studies are required.
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