Predictors of pulmonary sequelae after COVID-19 pneumonia: A 12-month follow-up study.

Background: Since the beginning of the SARS-CoV-2 pandemic, over 550 million people have been infected worldwide. Despite these large numbers, the long-term pulmonary consequences of COVID-19 remain unclear. Aims: The aim of this single-center observational cohort study was to identify and characterize pulmonary sequelae of COVID-19 at 12 months from hospitalization and to reveal possible predictors for the persistence of long-term lung consequences. Methods: Based on the persistence or absence of radiological changes after 12 months from hospitalization, the whole population was categorized into NOT-RECOVERED (NOT-REC) and RECOVERED (REC) groups, respectively. Clinical and pulmonary function data tests and clinical data were also collected and compared in the two groups. In the NOT-REC group, high resolution computed tomography (HRCT) images were semiquantitatively scored analyzing ground-glass opacities (GGO), interstitial thickening (IT), consolidations (CO), linear and curvilinear band opacities, and bronchiectasis for each lung lobe. Logistic regression analyses served to detect the factors associated with 12-month radiological consequences. Results: Out of the 421 patients followed after hospitalization for SARS-CoV-2 pneumonia, 347 met inclusion and exclusion criteria and were enrolled in the study. The NOT-REC patients (n = 24; 6.9%) were significantly older [67 (62-76) years vs. 63 (53-71) years; p = 0.02], more frequently current smokers [4 (17%) vs. 12 (4%); p = 0.02], and with more severe respiratory failure at the time of hospitalization [PaO2/FiO2 at admission: 201 (101-314) vs. 295 (223-343); p = 0.01] compared to REC group (n = 323; 93.1%). On multivariable analysis, being a current smoker resulted in an independent predictor for lung sequelae after 12 months from hospitalization [5.6 OR; 95% CI (1.41-22.12); p = 0.01]. Conclusion: After 12 months from hospital admission, a limited number of patients displayed persistent pulmonary sequelae with minimal extension. Being a current smoker at the time of SARS-CoV-2 infection is an independent predictive factor to lung consequences, regardless of the disease severity.

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

BACKGROUND: Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce. METHODS: We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded. RESULTS: We included 909 patients, 48.3% males and 95.2% vaccinated against SARS-CoV-2. The median age was 73 (IQR: 62-82) years. MOL and NIR were prescribed in 407 (44.8%) and 502 (55.2%) patients, respectively. Overall, 124/909 (13.6%) patients experienced any AEs following antivirals intake: 98/124 (79%) patients reporting adverse events presented grade 1 AEs, 23/124 (18.5%) grade 2 AEs and 3 (2.5%) grade 3 AEs. Treatment discontinuation was recorded in 4.8% of patients. AEs were significantly higher in women, in patients treated with NIR compared to MOL and in people who were not vaccinated. CONCLUSIONS: In our real-life setting, AEs were higher than those reported by clinical trials, and were particularly associated with NIR use and with not being vaccinated. Further analyses are needed to better assess safety of oral antivirals and to define which patient's profile may benefit most from MOL and NIR.

HIV tropism switch in archived DNA of HIV-HCV subjects successfully treated with direct-acting antivirals for HCV infection.

We described short-term HIV tropism changes occurring in peripheral blood mononuclear cells and the correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease and with undetectable HIV viremia or residual viremia (RV). Plasma HIV RNA, cellular HIV DNA and tropism were evaluated pre-HCV treatment (baseline, BL) and at 12(T1) and 24(T2) weeks after HCV treatment start. V3 sequences were interpreted using Geno2pheno and classified as R5 only if all three sequences had an FPR ≥ 10% and as X4 when at least one replicate sequence had an FPR < 10%. Forty-nine patients (21 with X4 and 28 with R5 virus) were enrolled. Five X4 patients and 9 R5 subjects experienced at least one tropism change,11 with RV:1/5 patients with X4 infection at BL switched at T1 versus 8/9 in the R5 group (p = 0.022977) and the difference was confirmed in subjects with RV (p = 0.02);6/9 R5 patients switching at T1 confirmed the tropism change at T2. No significant differences in HIV DNA values between patients with RV starting with a R5 or X4 tropism and experienced tropism switch or not were found. Short-term tropism switch involved almost a third of patients, in all but three cases with HIV RV. Being R5 at BL is associated to a higher instability, expressed as number of tropism changes and confirmed switch at T2.

Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases1. Age represents a key factor in COVID-19 morbidity and mortality2. Understanding age-associated immune signatures of patients are therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.

Clinical Features and Chest Imaging as Predictors of Intensity of Care in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic with lung disease representing the main cause of morbidity and mortality. Conventional chest-X ray (CXR) and ultrasound (US) are valuable instruments to assess the extent of lung involvement. We investigated the relationship between CXR scores on admission and the level of medical care required in patients with COVID-19. Further, we assessed the CXR-US correlation to explore the role of ultrasound in monitoring the course of COVID-19 pneumonia. Clinical features and CXR scores were obtained at admission and correlated with the level of intensity of care required [high- (HIMC) versus low-intensity medical care (LIMC)]. In a subgroup of patients, US findings were correlated with clinical and radiographic parameters. On hospital admission, CXR global score was higher in HIMCs compared to LIMC. Smoking history, pO2 on admission, cardiovascular and oncologic diseases were independent predictors of HIMC. The US score was positively correlated with FiO2 while the correlation with CXR global score only trended towards significance. Our study identifies clinical and radiographic features that strongly correlate with higher levels of medical care. The role of lung ultrasound in this setting remains undetermined and needs to be explored in larger prospective studies.

An Integrated Strategy for the Prevention of SARS-CoV-2 Infection in Healthcare Workers: A Prospective Observational Study.

BACKGROUND: Since the beginning of SARS-CoV-2 outbreak, a large number of infections have been reported among healthcare workers (HCWs). The aim of this study was to investigate the occurrence of SARS-CoV-2 infection among HCWs involved in the first management of infected patients and to describe the measures adopted to prevent the transmission in the hospital. METHODS: This prospective observational study was conducted between February 21 and April 16, 2020, in the Padua University Hospital (north-east Italy). The infection control policy adopted consisted of the following: the creation of the "Advanced Triage" area for the evaluation of SARS-CoV-2 cases, and the implementation of an integrated infection control surveillance system directed to all the healthcare personnel involved in the Advance Triage area. HCWs were regularly tested with nasopharyngeal swabs for SARS-CoV-2; body temperature and suggestive symptoms were evaluated at each duty. Demographic and clinical data of both patients and HCWs were collected and analyzed; HCWs' personal protective equipment (PPE) consumption was also recorded. The efficiency of the control strategy among HCWs was evaluated identifying symptomatic infection (primary endpoint) and asymptomatic infection (secondary endpoint) with confirmed detection of SARS-CoV-2. RESULTS: 7595 patients were evaluated in the Advanced Triage area: 5.2% resulted positive and 72.4% was symptomatic. The HCW team was composed of 60 members. A total of 361 nasopharyngeal swabs were performed on HCWs. All the swabs resulted negative and none of the HCWs reached the primary or the secondary endpoint. CONCLUSIONS: An integrated hospital infection control strategy, consisting of dedicated areas for infected patients, strict measures for PPE use and mass surveillance, is successful to prevent infection among HCWs.

Soluble CD163 and soluble CD14 plasma levels but not cellular HIV-DNA decrease during successful interferon-free anti-HCV therapy in HIV-1-HCV co-infected patients on effective combined anti-HIV treatment.

Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2. Plasma levels of sCD163 and of sCD14 were comparable in patients with UV and in subjects with LVL at T0, T1 and T2. The HIV DNA level was positively correlated with LLV but not with sCD163 and sCD14 levels; these two markers of inflammation were positively correlated (p = 0.017). Soluble CD163 and sCD14 decreased over time from T0 to T2 (p = 0.000 and p = 0.034, respectively). In conclusion, the significant decrease in sCD163 and sCD14 levels in patients cured of HCV infection, regardless of the presence of LLV, suggests a main role for HCV in immune activation in HIV-HCV co-infected patients.

Time course of cellular HIV-DNA and low-level HIV viremia in HIV-HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals.

This longitudinal study described cellular HIV-DNA changes and their correlation with HIV low-level plasma viremia (LLV) in HIV-HCV co-infected patients on successful antiretroviral and anti-HCV therapy by treatment with direct-acting antivirals (DAA). Thirty-nine patients were examined prior to the start of DAA (T0), after week 12 (T1) and 24 weeks (T2) of anti-HCV therapy. Cellular PBMC HIV-DNA was analysed as an absolute value and as the percentage of increase or decrease from T0 to T2. Patients were classified as having undetectable plasma HIV viraemia (UV) or LLV in the year before the start of anti-HCV treatment and within the T0-T2 study period. Thirty-five patients (89.7%) of the 39 subjects enrolled had the same plasma HIV viraemia control in the year before HCV treatment and in the T0-T2 interval. The HIV-DNA value at T0 and at T2 was higher in patients with LLV than in subjects with UV (p = 0.015 and p = 0.014, respectively). A similar proportion of patients with LLV and UV experienced an increase or decrease of HIV-DNA from T0 to T2. The percentage increase in HIV-DNA value (262.8%) from T0 to T2 was higher compared to the decrease (43.5%) in patients with UV (p = 0.012), and it was higher compared to the percentage increase in HIV-DNA value reported in subjects with LLV (262.8 versus 49%, p = 0.026). HIV-HCV co-infected patients experienced a multifaceted perturbation of cellular HIV-DNA levels within a 24-week period during anti-HCV treatment; the extent of the phenomenon was greater in subjects with UV. Fast HCV-RNA clearance seemed to have a greater influence on the cellular reservoir than on plasma HIV-RNA.

Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin.

OBJECTIVES: Effective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV-HCV co-infected patients. METHODS: This study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV-HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing. RESULTS: DCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA <12 IU/ml at week 12 and undetectable at week 16. CONCLUSIONS: Sub-optimal DCV drug levels allow the selection of resistance-associated variants and fail to contribute to antiviral activity. No definite reason for the low DCV level was found. Quantifying the drug is suggested in difficult-to-treat patients.

Nosocomial candidemia in patients admitted to medicine wards compared to other wards: a multicentre study.

PURPOSE: Risk factors for nosocomial candidemia, severity of sepsis, treatment, and outcome were compared between patients admitted to medicine wards and those to surgical and intensive care units (ICUs). METHODS: Data were retrospectively collected from patients belonging to six referral hospitals in Italy between January 2011 and December 2013. Risk factors for 30-day mortality were evaluated in the whole patient population. RESULTS: A total of 686 patients (mean age 70 ± 15 years) with candidemia were included. 367 (53.5 %) patients were in medicine wards, and 319 in surgery and ICUs. Host-related risk factors for candidemia were more common in medicine patients whereas healthcare-related factors in surgery/ICU patients. These patients showed severe sepsis and septic shock more commonly (71.7 %) than medicine patients (59.9 %) (p 0.003). The latter underwent central venous catheter (CVC) removal and adequate antifungal therapy less frequently than surgery/ICU patients. 149 (40.6 %) patients died with candidemia in medicine wards and 69 (21.6 %) in other wards (p < 0.001). Overall, the 30-day mortality was 36.3 %. At multivariate analysis, independent risk factors for death were aging, higher Charlson score, severe sepsis and septic shock, and no antifungal therapy, while major surgery and CVC removal were associated with higher probability of survival. CONCLUSIONS: The burden of risk factors for candidemia was different between medicine patients and those in other wards. Despite the lower severity of candidemia in medicine patients, their mortality turned out to be higher than in surgery or ICU patients. Awareness of the best management of candidemia should be pursued, especially in medicine wards.

Epidemiology and outcome of nosocomial candidemia in elderly patients admitted prevalently in medical wards.

BACKGROUND AND AIMS: Candidemia represents an important cause of morbidity and mortality. To-date, the highest rates of candidemia occur in elderly patients, but there are few data on such patient population. The aims of this study were to evaluate the epidemiology, treatment and outcome of candidemia in an elderly patient population. METHODS: Nosocomial candidemia episodes occurring in a university general hospital were included in this study. Demographic, clinical, and Candida susceptibility testing data were retrospectively collected. Potential risk factors for 30-day crude mortality rate including host factors, Candida species, concomitant bacteremia, severity of sepsis, and management of fungemia were assessed by hazard risk (HR) analyses. RESULTS: 145 consecutive episodes of candidemia occurring in 140 patients with a median age of 81 years (interquartile range, 78-86 years) were analyzed. At the onset of candidemia, 98 (67.6 %) cases were hospitalized in medical wards. Candida albicans accounted for 55 % of all candidemia episodes. Overall, resistance to fluconazole was detected in 8.0 % of Candida isolates. Crude hospital mortality at 30 days was 46 %. Failure to receive adequate antifungal therapy was the significant risk factor for death on multivariable analysis (adjusted HR 1.87, 95 % CI 0.94-2.79). DISCUSSION AND CONCLUSIONS: Over two-thirds of elderly patients with candidemia are admitted to medical wards in our series. 30-day crude mortality is high and seems to be related to inadequate antifungal therapy. Increased awareness of the burden of this disease also in medical wards is strongly required to recognize and treat properly this severe infection.

Peripheral and total parenteral nutrition as the strongest risk factors for nosocomial candidemia in elderly patients: a matched case-control study.

Candidemia is an important cause of morbidity and mortality in the healthcare setting. However, there is limited information about risk factors for such infection among elderly patients. A case-control study was conducted during the period 2008-2011. For each case, two controls were selected among patients admitted to the same hospital, and individually matched by sex, age, time of admission, hospital ward and hospitalisation duration. The adjusted odds ratio (OR) was calculated using multiple conditional logistic regression. We identified 145 episodes of candidemia occurring in 140 patients with a median age of 80 years. Candida albicans caused 55% of all candidemia episodes. After adjustment, candidemia was strongly associated with duration of total [duration > 7 days: OR = 20.09; 95% confidence interval (CI): 3.44-117.52] and peripheral parenteral nutrition (duration > 7 days: OR = 26.83; 95% CI: 6.54-110.17), other central vascular catheters (OR = 5.17; 95% CI: 1.24-23.54) and glycopeptide antibiotics (OR = 6.45; 95% CI: 1.90-21.91). Duration of peripheral and total parenteral nutrition and antibiotics predicted over 50% of all candidemias. Intervention studies should be planned to evaluate effectiveness of candidemia prevention by restricting parenteral nutrition, prompting earlier enteral feeding, and reducing use of antibiotics, especially glycopeptides, in elderly patients.