Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic Coronavirus Disease 2019 (COVID-19). This virus is highly transmissible among individuals through both droplets and ...aerosol leading to determine severe pneumonia. Among the various factors that can influence both the onset of disease and the severity of its complications, the microbiome composition has also been investigated. Recent evidence showed the possible relationship between gut, lung, nasopharyngeal, or oral microbiome and COVID-19, but very little is known about it. Therefore, we aimed to verify the relationships between nasopharyngeal microbiome and the development of either COVID-19 or the severity of symptoms. To this purpose, we analyzed, by next generation sequencing, the hypervariable V1-V2-V3 regions of the bacterial 16S rRNA in nasopharyngeal swabs from SARS-CoV-2 infected patients (n=18) and control (CO) individuals (n=12) using Microbiota solution A (Arrow Diagnostics). We found a significant lower abundance of Proteobacteria and Fusobacteria in COVID-19 patients in respect to CO (p=0.003 and p<0.0001, respectively) from the phylum up to the genus (p<0.001). The
(
) resulted as the most significantly reduced species in COVID-19 patients respect to CO.
is reported as being able to perform the surface sialylation. Noteworthy, some sialic acids residues on the cell surface could work as additional S protein of SARS-CoV-2 receptors. Consequently, SARS-CoV-2 could use sialic acids as receptors to bind to the epithelium of the respiratory tract, promoting its clustering and the disease development. We can therefore speculate that the significant reduction of
in COVID-19 patients could be directly or indirectly linked to the modulation of sialic acid metabolism. Finally, viral or environmental factors capable of interfering with sialic metabolism could determine a fall in the individual protection from SARS-CoV-2. Further studies are necessary to clarify the precise role of
in COVID-19.
Objective: to describe a single-center experience of Pneumocystis jirovecii pneumonia (PJP) in non-HIV patients recovering from COVID-19. Methods: We report the cases of five non-HIV patients with ...COVID-19 who also developed PJP at a University Hospital. Results: With the exception of one subject, who experienced an atypical and prolonged course of COVID-19, all the patients developed PJP after the clinical resolution of COVID-19 pneumonia. All but one patient had no pre-existing immunosuppressive conditions or other risk factors for PJP development at COVID-19 diagnosis. Nonetheless, following the course of COVID-19 infection, all the patients fulfilled at least one host factor for PJP; indeed, all the patients had received at least 2 weeks of high-dose steroids and three out of five had a CD4+ cell count <200/mm3. Conclusions: The use of corticosteroids for COVID-19 respiratory impairment seems to be the most common risk factor for PJP, together with viral-induced and iatrogenic lymphopenia. The worsening in respiratory function and the characteristic radiological picture during or after COVID-19 pneumonia should raise the suspicion of PJP, even in immunocompetent patients. PJP primary chemoprophylaxis can be considered in selected high-risk COVID-19 patients, but further studies are needed.
Introduction Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are ...at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS. Methods Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations. Results Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of greater than or equal to 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of greater than or equal to 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. greater than or equal to 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS. Conclusions Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols. Keywords: SARS-CoV-2, COVID-19, thymic epithelial tumors, Good's syndrome
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
About 2.3% of the world's population is infected with hepatitis C virus (HCV) and patients have a high risk of developing liver cirrhosis and its complications. Current therapeutic strategies are ...based on a combination of pegylatedinterferon, ribavirin and (only for patients with genotype 1 infection) a protease inhibitor (boceprevir or telaprevir). Consequently, all these combinations have the limitations of interferon. In fact, they are contraindicated in decompensated disease and in subjects with severe comorbidities, and are associated with a high rate of side effects. Moreover, they are poorly effective in advanced disease. As complete viral eradication is associated with improved disease-free survival, several molecules are under clinical development for their potential to overcome the drawbacks of currently available treatments. This review focuses on the pharmacodynamics, pharmacokinetics, safety and tolerability of ABT-450, a potent inhibitor of non-structural 3 protease. ABT-450 is a substrate of cytochrome P450; hence its co-administration with ritonavir, a cytochrome P450 inhibitor, dramatically increases the plasma concentration and half-life of ABT-450 and allows once-daily administration. Given in monotherapy for 3 days at different doses, ABT-450 causes a mean maximum viral decline of about 4 logs. Interestingly, high doses of ABT-450 are associated with a reduced and delayed development of resistance-conferring mutations. Given in combination with other direct antiviral drugs, the sustained response rate reaches 90-95% in both naïve and treatment-experienced genotype 1 patients, and tolerability is good. In conclusion, ABT-450 is an excellent component of interferon-free combinations for the treatment of chronic HCV infection.
Our objective was to evaluate the safety and efficacy of casirivimab/imdevimab therapy in pregnant women with severe coronavirus disease 2019 (COVID-19) requiring oxygen therapy.
This was a ...prospective case series study aimed to evaluate the safety and efficacy of casirivimab/imdevimab therapy in unvaccinated pregnant women with severe COVID-19. Inclusion criteria were severe acute respiratory syndrome coronavirus 2 infection documented with polymerase chain reaction, pregnancy, severe COVID-19 requiring oxygen therapy, duration of symptoms of 10 days or less, and able to provide informed consent. Vaccinated women and those with mild-to-moderate disease were excluded from the study. Included patients received casirivimab and imdevimab as a single intravenous dose of 4,000/4,000 mg. Women were also treated with low molecular weight heparin, steroids, and antibiotics, if necessary. The primary outcome was maternal death. Secondary outcomes were the rate of adverse events during infusion or within 72 hours and the rate of abortion.
Thirteen hospitalized unvaccinated pregnant women with severe COVID-19 requiring oxygen and treated with casirivimab/imdevimab were included in the study. We observed no maternal death, and no patients required intubation or admission to the intensive care unit. No abortion or fetal loss was recorded. Nine pregnancies were still ongoing, and there were three cesarean deliveries and one vaginal delivery. Two were preterm deliveries (at 31 and 34 weeks), and two were term deliveries.
Casirivimab/imdevimab therapy may be considered as a therapy in unvaccinated pregnant women with severe COVID-19.
Background
Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We ...aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine.
Methods
Retrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine.
Results
We included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients’ age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (
p
< 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (
p
= 0.5), pre-or post-therapy vaccination (
p
= 0.2) and number of previous DMTs (
p
= 0.2). Among pOBI patients (
n
= 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis.
Conclusions
Baseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients.
Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have ...confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies.
We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts.
Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials.
Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to "unpackage" current DAA combinations and to develop generic drugs against HCV.
infection (CDI) is associated with substantial morbidity and mortality as well as high propensity of recurrence. Systemic antibiotic therapy (SAT) represents the top inciting factor of CDI, both ...primary and recurrent (rCDI). Among the many strategies aimed to prevent CDI in high-risk subjects undergoing SAT, oral vancomycin prophylaxis (OVP) appears promising under a cost-effectiveness perspective.
A systematic review with meta-analysis and trial sequential analysis (TSA) of studies assessing the efficacy and the safety of OVP to prevent primary CDI and rCDI in persons undergoing SAT was carried out. PubMed and EMBASE were searched until 30 September 2021. The protocol was pre-registered on PROSPERO (CRD42019145543).
Eleven studies met the inclusion criteria, only one being a randomized controlled trial (RCT). Overall, 929 subjects received OVP and 2011 represented the comparator group (no active prophylaxis). OVP exerted a strong protective effect for CDI occurrence: odds ratio 0.14, 95% confidence interval 0.04-0.38. Moderate heterogeneity was observed: I
54%. This effect was confirmed throughout several subgroup analyses, including prevention of primary CDI versus rCDI. TSA results pointed at the conclusive nature of the evidence. Results were robust to a variety of sensitivity and quantitative bias analyses, although the underlying evidence was deemed as low quality. No differences between the two groups were highlighted regarding the onset of vancomycin-resistant
infections.
OVP appears to be an efficacious option for prevention of CDI in high-risk subjects undergoing SAT. Nevertheless, additional data from RCTs are needed to establish OVP as good clinical practice and define optimal dosage and duration.
To evaluate the prevalence of vitamin D deficiency and its impact on infections in HCV-related liver cirrhosis.
We enrolled 291 patients affected by HCV-related liver cirrhosis. Serum vitamin D ...levels were dosed at enrolment. The presence of infection was assessed at baseline and during follow-up based on physical examination and laboratory analyses.
Vitamin D deficiency (<20ng/mL) was diagnosed in 68.3% of patients, and a total of 102 infections were detected. Urinary tract infections were the most common infections diagnosed (41.2%). Vitamin D deficiency rates were higher in patients with decompensated cirrhosis (Child-Pugh B vs A p=0.008, and Child-Pugh C vs A p=0.024). Infection was significantly associated with vitamin D deficiency (p<0.001), MELD score >15 (p=0.003), Child-Pugh class B/C vs A (p<0.001), and active hepatocellular carcinoma (HCC) (p<0.001). At multivariate analysis, vitamin D deficiency (p<0.01), HCC (p<0.05), hospitalization (p<0.001) and exposure to immunosuppressant agents (p<0.05) were independent risk factors for infection at baseline.
Vitamin D may play a role in the development of infections in patients affected by liver cirrhosis, and preventive strategies with vitamin D supplementation are to be evaluated in randomized controlled trials.
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