ABSTRACT
Background: Insomnia, mood decline, anxiety, and cognitive impairment are described following COVID-19, and the mechanisms underlying these symptoms are not fully clarified. Aims of this analysis were to describe prevalence and predictors of impaired neuropsychological performance after COVID-19. Methods: We included patients referred to the post-COVID19 service with and without a previous hospitalization (PH and nPH, respectively) assessed at 3,6 and 12 months (3M,6M,12M) post-COVID19. Patients underwent to a comprehensive neuropsychological assessment using a standardized battery of 10 tests across 4 domains (speed of information processing, /executive, attention/working memory, memory). Neurocognitive impairment (NCI) was defined by: score >1 standard deviation (SD) below the mean on at least 2 tests, or >2 SD below 1 test. Change in NPZ-10 (mean, SD) was analyzed as an outcome. In addition, the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI) were administered. Mann-Whitney and Chi-square tests were used for comparisons, and logistic and linear regression were used to identify factors associated with test results. Results: N=302 participants: median age of 55 years (IQR 47-61), 52% female, median education of 13 yrs (13-18), 63% with >1 comorbidity, 58% PH (mainly males, higher age and higher BMI vs nPH). Overall, the prevalence of NCI was 42%, higher in PH vs nPH (46% vs 36%;p=0.07) (Figure 1a) with a not statistically significant mean decrease of NPZ10 [-0.12 (0.49)]. More in detail, we observed a significant decrease of z-score in the speed of information processing domain in PH vs nPH [-0.29(0.48) vs-0.12(0.31);p<0.001]. NCI prevalence resulted significantly higher in PH vs nPH only at 3M (Figure 1b). A higher proportion of nPH vs PH complained anxiety (BAI>85%) at 3M [55.6% vs 31.4%);p=0.028], sleep disturbances were more frequent in PH vs nPH at 3 and 12M (Figure 1d,c). Male gender appear to be the only associated factor with a lower alteration of BAI>85% and PSQI>5 [OR 0.28 (0.12-0.65);p=0.003;0.22 (0.09-0.52);p=0.001;respectively]. No predictors of NCI or BDI>85% were found. Conclusion: Our preliminary data show a consistent prevalence of NCI, significantly higher in PH vs nPH. This finding remains quite stable up to 12 months of observation. Also a worse sleep quality in PH was observed. Women seem to be at higher risk of anxiety-depressive and sleep disorders than men.
ABSTRACT
Background: Few data are available about comparison of different monoclonal antibodies (MAbs) for COVID-19 in the real-world setting. We aim to compare effectiveness of bamlanivimab/etesevimab (BAM/ETE) versus (vs) casirivimab/imdevimab (CAS/IMD) and to estimate predictors of hospitalization/death. Methods: Observational analysis of all consecutive outpatients (pts) with mild/moderate COVID-19 enrolled within the AIFA access program in a single center in Rome, from March to October, 2021. At first baseline (BL) visit, RT-PCR from nasopharyngeal swab with cycle thereshold (CT) measurement and viral sequencing was performed. Pts received intravenous BAM/ETE (700/1400 mg) or CAS/IMD (1200/1200 mg) and were followed through day 30. Primary endpoint was hospitalization/death due to severe COVID-19 by day 30. Average treatment effect (ATE) in the multiplicative scale of the odds was the chosen estimand to compare the two treatments, adjusted for age, obesity, time from onset to infusion, median C-reactive protein (CRP), vaccination, variant of concern (VOC) and BL-CT. Predictors of clinical failure were explored by two different models of multivariable logistic regression. Results: 242 pts receiving BAM/ETE (n=76) or CAS/IMD (n=166) were included (male 54%;median age 65 yrs;median SpO2 97%;diabetes 12%;hypertension 40%;CVD 17%;COPD 26%;autoimmune diseases 12%;immunodeficiency 18%). Median time from symptoms onset to infusion was 4 days (IQR 3-6). No differences were observed between the two MAbs for BL characteristics except for BMI>35 (BAM/ETE 24%, CAS/IMD 12%), CRP (BAM/ETE 1.8, CAS/IMD 1.2), vaccination (BAM/ETE 26%, CAS/IMD 46%) and distribution of VOC (Alpha 46% BAM/ETE vs 22% CAS/IMD;Gamma 20% vs 7%;Delta 5% vs 55%). Proportion of patients with COVID-related hospitalization/death by day 30 was 12/76 (15.8%) for BAM/ETE and 6/166 (3.6%) for CAS/IMD. Estimate of causal effect of BAM/ETE exposure compared to CAS/IMD on primary end point by ATE is reported in Table 1a. Factors associated with an increased risk of clinical failure by fitting multivariable logistic regression were BMI >35 and P1/Gamma VOC;higher BL-CT was associated with a reduced risk (Table 1b-1c). Conclusion: In a real-life setting, receiving BAM/ETE was associated with a 4-fold higher risk of COVID-19 progression to hospitalization/death than CAS/IMD. SARS-CoV-2 P.1/Gamma, but not B.1617.2/Delta VOC, obesity and higher BL viral load also predicted an increased risk of clinical worsening.
ABSTRACT
Background: After the acute phase of infection, new, recurring or ongoing symptoms related to COVID19 may persist for weeks or months. Aims of our study were to size the impact of these symptoms on physical (PH) and mental (MH) health status and quality of life (QoL), reported by patients (pts), and to investigate factors influencing the perception of PH, MH, and QoL. Methods: We included pts referred to the post-COVID19 outpatient service, with and without prior hospitalization (PHosp), evaluated at 3,6 and 12 months after the acute infection. Demographic, clinical and pharmacological data were collected in an electronic system. At each visit, the Short-Form 36-item questionnaire (SF-36), assessing the perception of PH and MH, and the Visual Analogue Scale (VAS), ranging from 0 to 100, of the EQ5D, assessing QoL, were administered. Student's T-test was employed for comparisons and linear regression was used to identify factors associated with PH, MH, and QoL. In a subgroup of patients, we assessed the presence of anxiety and depressive symptoms and sleep disturbances through the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI II) and the Pittsburgh Sleep Quality Index (PSQI) questionnaires, respectively. Results: Out of a total of 914 assessments, we considered the first one of each pt (n=572): median (IQR) age of 55 years (47-62), 53% male, 38% with at least 1 comorbidity, 54% with PHosp, median distance from acute infection of 4.8 months (3.6-7.1). The mean of each subscale assessed in SF-36 was significantly lower than the normative values of the Italian population (Figure 1) and it remained stable over time. Female gender, the presence of comorbidities, and the use of corticosteroids during the acute infection were associated with a worse perception of PH, MH, and QoL;pts with PHosp reported a better MH overall (Figure 2). Alterations in BAI, BDI II, and PSQI were associated with worse perceptions of PH, MH, and HRQoL, in the subgroup of 265 patients in whom they were evaluated. Conclusion: In our study, post-COVID19 pts reported a significantly worse perception of PH and MH status compared to the Italian normative group, and a higher risk was demonstrated for female pts, pts with comorbidities and pts treated with corticosteroids. Moreover, the presence of anxious-depressive symptoms and poor sleep quality was correlated to a worse perception of health status and QoL. A systematic monitoring of these aspects is mandatory to properly manage pts in the post-COVID19 period.
ABSTRACT
Background: We aimed to evaluate the efficacy of sarilumab, an IL-6 receptor inhibitor, combined with SOC, in patients (pts) affected by severe COVID-19 pneumonia. Methods: Open-label, Phase III, randomized trial assessing clinical efficacy and safety of intravenous sarilumab in pts with severe COVID-19, at 5 clinical centers in Italy. We included hospitalized pts with SARS-CoV-2 infection and pneumonia, in severe or critical condition (excluding mechanically ventilated). Pts were randomized 2:1 to receive sarilumab 400 mg plus SOC (armA) or to continue SOC (armB). The primary endpoint was time to clinical improvement of 2 points on a 7-point category ordinal scale, ranging from 1 (discharged with resumption of normal activities) to 7 (death). Pts were stratified according to baseline disease severity (PaO2/FiO2 ratio < or ≥ 200 mmHg), C reactive protein (CRP < or ≥ 7 mg/dL) and lymphocytes count (< or ≥ 870/mmc). The key secondary endpoint was time to death. Adverse events (AE) were evaluated as safety outcomes. We used chi square test to compare proportions between arms, and Cox regression stratified by clinical center to estimate the hazard risk (HR) of primary endpoint. Results: Of 191 pts screened, 176 were assigned to armA (121) and B (55). A similar proportion of pts were treated with steroids (44 armA vs 26 armB, p=0.170) and remdesivir (22 armA vs 8 armB, p=0.552). 58/121 (48%) pts underwent to a second dose of sarilumab 12 hours after the first dose. At day 30, no significant differences in the primary endpoint were found between the arms (Figure1). After stratifying for inflammatory parameters, the probability of improvement seemed greater in armA than B, for the strata with CRP <7 mg/dL (88% [95% CI 77-96] vs 79% [63-91], HR 1.55 [0.9-2.6];log-rank p=0.049) and with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7];log-rank p=0.058). Figure2 for interaction tests between strata. There were no significant differences in death probability (armA 5% [2.3-10.9]) and armB 3.6% [0.9-13.8] HR 1.30 [0.41-4.15];log-rank p=0.79) and in the rates of AE (armA 32% [39/121] and armB 23% [14/55], p=0.195) and serious AE (armA 18% [22/121] and armB 11% [7/55], p=0.244). Conclusion: In our population, efficacy of sarilumab in pts with severe COVID-19 was not confirmed, even if some benefits were shown in those treated at an early stage of the disease with lower inflammatory burden. Further trials are needed for identifying targeted subgroups for maximizing benefit of this treatment.