Viral clearance after early corticosteroid treatment in patients with moderate or severe covid-19.

The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.

Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients.

OBJECTIVES: To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. METHODS: Heavily pretreated (> 5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. RESULTS: Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25-60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score < -2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between -1 and -2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D) < 18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r = 0.34; P < 0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI) = 1.01-17.6] and 7.2 (95% CI = 1.67-31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. CONCLUSIONS: About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption.

Efficacy of low-dose intermittent subcutaneous interleukin (IL)--2 in antiviral drug--experienced human immunodeficiency virus--infected persons with detectable virus load: a controlled study of 3 il-2 regimens with antiviral drug therapy.

To evaluate the safety and efficacy of 3 regimens of intermittent subcutaneous (sc) interleukin (IL)--2 in a phase 2 study, 61 antiviral drug-experienced human immunodeficiency virus (HIV)--positive patients were randomly assigned to one of the following study arms: antiretroviral therapy (ART) plus IL-2 (12 million IU [MIU] by continuous intravenous infusion, followed by 7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (7.5 MIU twice a day, sc, every 8 weeks); ART plus IL-2 (3 MIU twice a day, sc, every 4 weeks); or ART alone. A significant increase of circulating CD4 cells was observed in IL-2--treated subjects, compared with those given ART alone. Low doses of IL-2 were better tolerated. Despite the incomplete suppression of viral replication, IL-2 with ART did not increase either plasma viremia or cell-associated HIV DNA levels. Low doses of intermittent sc IL-2 induced a stable increase of peripheral CD4 cells that was indistinguishable from those associated with higher, less well-tolerated doses of IL-2.

Cytomegalovirus pneumonia in AIDS patients: value of cytomegalovirus culture from BAL fluid and correlation with lung disease.

OBJECTIVES: To verify the value of cytomegalovirus (CMV) cultures of BAL fluid vs postmortem lung histopathology in detecting CMV pneumonia, and to correlate the BAL viral dose with the number of CMV inclusion bodies (CMV-IB) in the lung tissue of AIDS patients. DESIGN: Retrospective analysis of 434 BALs and 40 autopsies involving 307 AIDS patients; clinical follow-up lasted 10 months. PATIENTS AND METHODS: The 40 patients who died within 20 days of undergoing BAL were divided on the basis of histopathologic findings into subjects with and without CMV-IB in the lung tissue. The relationship between the BAL viral dose and CMV lung infection was evaluated by counting the early antigen (CMV-EA) positive cells/200 microL of BAL and the number of CMV-IB/mm2 of lung tissue. RESULTS: The predictive value of BAL virus isolation for the diagnosis of CMV pneumonia was 61% for positive and 100% for negative results. The patients with the largest number of CMV-IB had CMV-EA counts from 2 to 840; in those with a moderate and small number, the CMV-EA counts were, respectively, from 11 to 700 and 2 to 300. Among the patients surviving up to 10 months after the BAL index sample, the frequency of recurrent extrapulmonary CMV abnormalities was 27% in those with positive and 7% in those with negative cultures. CONCLUSIONS: BAL CMV cultures from AIDS patients have a very high negative and relatively low positive predictive value for CMV pneumonia. The presence and replication of CMV in the lung may lead to systemic dissemination as suggested by the higher probability of CMV extrapulmonary diseases. Viral titers do not seem to be related to the degree of lung damage.

[Polyomavirus infections of the urinary tract. Cytologic and ultrastructural features]. / Infezione da poliomavirus delle vie urinarie. Aspetti citologici ed ultrastrutturali.

The cytopathology of viral infections has some limitations, since the cellular changes provide only an indirect evidence of the underlying disease, and the diagnosis should always be confirmed by virologic methods. We report here one case of Polyomavirus infection in a renal transplant recipient, in which the cellular changes observed in Papanicolaou-stained voided urine specimen were consistent with viral infection. Transmission electron microscopy (TEM) provided a simple and relatively quick identification of viral particles, whose size and morphology were typical for human Polyomavirus. Immunoelectron microscopy (IEM), using colloidal gold technique, confirmed the diagnosis. The morphological criteria used in differential diagnosis and the advantages and limitations of the method are discussed.