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Neurologic and psychiatric symptoms have been reported in the months following the infection with COVID-19. A low-grade inflammation has been associated both with depression and cognitive symptoms, suggesting a link between these disorders. The aim of the study is to investigate cognitive functioning 6 months following hospital discharge for COVID-19, the impact of depression, and the consequences on quality of life. Ninety-two COVID-19 survivors evaluated at 1-month follow-up, 122 evaluated at 3 months and 98 evaluated at 6 months performed neuropsychological and psychiatric evaluations and were compared with a healthy comparison group (HC) of 165 subjects and 165 patients with major depression (MDD). Cognitive performances were adjusted for age, sex, and education. Seventy-nine percent of COVID-19 survivors at 1 month and 75% at 3- and 6-month follow-up showed cognitive impairment in at least one cognitive function. No significant difference in cognitive performances was observed between 1-, 3-, and 6-months follow-up. COVID-19 patients performed worse than HC but better than MDD in psychomotor coordination and speed of information processing. No difference between COVID-19 survivors and MDD was observed for verbal fluency, and executive functions, which were lower than in HC. Finally, COVID-19 survivors performed the same as HC in working memory and verbal memory. The factor that most affected cognitive performance was depressive psychopathology which, in turn, interact with cognitive functions in determining quality of life. Our results confirm that COVID-19 sequelae include signs of cognitive impairment which persist up to 6 months after hospital discharge and affect quality of life. Supplementary Information The online version contains supplementary material available at 10.1007/s00406-021-01346-9.

Background Coronavirus disease 2019 acute respiratory distress syndrome (COVID‐19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID‐19 ARDS sequelae. We assessed the mid‐term lung status of COVID‐19 survivors and investigated factors associated with pulmonary sequelae. Methods All adult COVID‐19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. Results Forty‐nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89–105) days, whilst PFT after 142 (133–160) days. The median age was 58 (52–65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6–16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71–7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9–93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. Conclusions Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID‐19.

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managedin Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO2/FiO2 ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO2/FiO2 ratio

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Aim: Obesity is a risk factor for COVID-19, but the underlying mechanisms are unclear. We investigated the role of adiponectin (an anti-inflammatory adipokine), leptin (a pro-inflammatory adipokine) and their ratio (Adpn/Lep) in this context. Design: Single-centre, prospective observational study. Methods. Adiponectin and leptin were measured in 60 COVID-19 patients with mild (not hospitalised, n=11), moderate (hospitalised but not requiring intensive care, n=25) and severe (admission to the intensive care unit [ICU] or death, n=24) disease. Results: Adiponectin and leptin levels were similar across severity groups, but patients with moderate severity had the highest Adpn/Lep ratio (1.2 [0.5; 2.0], 5.0 [1.6; 11.2], 2.1 [1.0; 3.6] in mild, moderate and severe disease; P = 0.019). Adpn/Lep, but not adiponectin or leptin alone, correlated with systemic inflammation (C reactive protein, CRP: Spearman's rho 0.293, P = 0.023). When dividing patients into Adpn/Lep tertiles, adiponectin was highest, whereas leptin was lowest in the third (highest) tertile. Patients in the highest Adpn/Lep tertile had numerically lower rates of obesity, diabetes and hypertension, and lower rates of death or admission to ICU versus other tertiles. At linear regression in the whole cohort, CRP significantly predicted Adpn/Lep (β 0.291, P = 0.022), while female gender (β -0.289, P = 0.016), diabetes (β -0.257, P = 0.028), and hypertension (β -239, P = 0.043) were negative predictors. Conclusions: We speculate that the rise in Adpn/Lep, due to increased adiponectin and reduced leptin, is a compensatory response to systemic inflammation. In patients with worse cardiometabolic health (e.g. diabetes, hypertension) this mechanism might be blunted, possibly contributing to higher mortality.

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 2/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.

Background and aim of the work: The coronavirus disease-19 (COVID-19) outbreak is posing considerable challenges to healthcare systems and societies worldwide. While the knowledge on the acute phase of the disease has rapidly expanded, little is known on the consequences of COVID-19 following clinical remission. We set up a multidisciplinary COVID-19 follow-up outpatient clinic to identify and address the clinical needs of COVID-19 survivors. Here we describe the features of our follow-up programme. Methods: The multidisciplinary assessment comprises a complete physical examination, respiratory evaluation (peripheral oxygen saturation, respiratory rate, dyspnoea assessment, lung ultrasound and pulmonary function), cardiovascular assessment (electrocardiography, echocardiography), nutritional assessment (anthropometrics, mini Nutritional Assessment screening tool), neurological examination including cognitive tests, and mental health assessment. All data are prospectively collected, and blood is sampled for biobanking. Results: Since 7 April to 5 June, 2020, 453 out of the 1388 COVID-19 survivors managed at our University Hospital have been evaluated at the Outpatient COVID-19 Follow-up Clinic. The characteristics of the follow-up cohort are similar to those of the whole cohort of COVID-19 in terms of demographics, comorbidities, and COVID-19 severity upon ED presentation, indicating that the follow-up cohort is representative of the whole cohort. Conclusions: Continuous patient monitoring might give an answer to the numerous unsolved questions about what comes next in this pandemic and beyond. This will help physicians and researchers establish strategies to face future pandemics and develop preventative and therapeutic strategies for similar hyperinflammatory conditions. (www.actabiomedica.it).

OBJECTIVES: To evaluate the prevalence of diarrhea and its association with drug use in elderly outpatients. METHODS: The study was carried out by 133 general practitioners (GPs) who referred to 24 geriatric units in Italy. The demographic data, disability, gastrointestinal symptoms, and current medications were evaluated using a structured interview, including the evaluation of the activities of daily living (ADL), the instrumental activities of daily living (IADL), and the gastrointestinal symptoms rating scale (GSRS). RESULTS: The study included 5,387 elderly subjects who regularly completed the structured interview. In total, 488 patients (9.1% of the whole population, 210 men and 278 women, mean age 75.6 6.2 yr, range 65–100 yr) reported diarrhea, that is, items 11 and 12 of the GSRS, during the 7-day period before the interview. The prevalence of diarrhea significantly increased with older age (P= 0.025), the severity of ADL (P < 0.0001) and IADL disability (P < 0.0001), and the number of drugs taken (P= 0.0002). A multivariate analysis demonstrated that the presence of diarrhea was significantly associated with the use of antibiotics (odds ratio [OR] 4.58, 95% confidence interval [CI] 1.95–10.73), proton pump inhibitors (OR 2.97, 95% CI 2.03–4.35), allopurinol (OR 2.19, 95% CI 1.26–3.81), psycholeptics (OR 1.82, 95% CI 1.26–2.61), selective serotonin reuptake inhibitors (OR 1.71, 95% CI 1.01–2.89), and angiotensin II receptor blockers (OR 1.46, 95% CI 1.08–1.99), also accounting for sex, age, and the use of antidiarrheal agents and drugs for functional gastrointestinal disorders. CONCLUSION: Diarrhea is a common problem in elderly outpatients. Its prevalence increases with old age, the severity of disability, and the number of drugs. Monitoring the presence of diarrhea and its complications in elderly patients who need treatments with drugs significantly associated with diarrhea may be clinically useful.

COVID-19 survivors are at increased risk of persistent psychopathology after the infection. Despite long-term sequelae are an increasing concern, long-term neuropsychiatric consequences remain largely unclear. This cohort study aimed at investigating the psychopathological impact of COVID-19 in Italy one year after infection, outlining the trajectory of symptomatology at one, six-, and twelve-months follow-up. We evaluated 402, 216, and 192 COVID-19 survivors respectively at one, six, and 12 months. A subgroup of 95 patients was evaluated longitudinally both at one, six, and 12 months. Validated self-report questionnaires were administered to assess depression, fatigue, anxiety, and post-traumatic distress. Socio-demographics and setting of care information were gathered for each participant. At six and twelve months, respectively 94 (44%) and 86 (45%) patients self-rated in the clinical range in at least one psychopathological dimension. Pathological fatigue at twelve months was detected in 63 patients (33%). Considering the longitudinal cohort an interaction effect of sex and time was observed for depression (F = 8.63, p < 0.001) and anxiety (F = 5.42, p = 0.005) with males showing a significant increasing trend of symptoms, whereas an opposite course was observed in females. High prevalence of psychiatric sequelae six and 12 months after COVID-19 was reported for the first time. These findings confirm the need to provide integrated multidisciplinary services to properly address long-lasting mental health sequelae of COVID-19 and to treat them with the aim of reducing the disease burden and related years of life lived with disability.

Background: COVID-19 is associated with unintentional weight loss. Little is known on whether and how patients regain the lost weight. We assessed changes in weight and abdominal adiposity over a three-month follow-up after discharge in COVID-19 survivors. Methods: In this sub-study of a large prospective observational investigation, we collected data from individuals who had been hospitalized for COVID-19 and re-evaluated at one (V1) and three (V2) months after discharge. Patient characteristics upon admission and anthropometrics, waist circumference and hunger levels assessed during follow-up were analyzed across BMI categories. Results: One-hundred-eighty-five COVID-19 survivors (71% male, median age 62.1 [54.3; 72.1] years, 80% with overweight/obesity) were included. Median BMI did not change from admission to V1 in normal weight subjects (−0.5 [−1.2; 0.6] kg/m2, p = 0.08), but significantly decreased in subjects with overweight (−0.8 [−1.8; 0.3] kg/m2, p < 0.001) or obesity (−1.38 [−3.4; −0.3] kg/m2, p < 0.001; p < 0.05 vs. normal weight or obesity). Median BMI did not change from V1 to V2 in normal weight individuals (+0.26 [−0.34; 1.15] kg/m2, p = 0.12), but significantly increased in subjects with overweight (+0.4 [0.0; 1.0] kg/m2, p < 0.001) or obesity (+0.89 [0.0; 1.6] kg/m2, p < 0.001; p = 0.01 vs. normal weight). Waist circumference significantly increased from V1 to V2 in the whole group (p < 0.001), driven by the groups with overweight or obesity. At multivariable regression analyses, male sex, hunger at V1 and initial weight loss predicted weight gain at V2. Conclusions: Patients with overweight or obesity hospitalized for COVID-19 exhibit rapid, wide weight fluctuations that may worsen body composition (abdominal adiposity). ClinicalTrials.gov registration: NCT04318366.

Backgroundacute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients.Methodscross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality.Resultstwo hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 – 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004).Discussionwe described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.

Severe Coronavirus disease 2019 (COVID-19) is characterized by acute respiratory distress syndrome (ARDS) which may lead to long-lasting pulmonary sequelae in the survivors. COVID-19 shares common molecular signatures with interstitial lung diseases (ILDs), including pro-angiogenic and tissue-remodeling mechanisms mediated by vascular endothelial growth factor receptor (VEGF-R), fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R). Nintedanib mainly targets these factors and is approved for ILDs. Therefore, we administered nintedanib through compassionate use to three patients with COVID-19 pneumonia requiring extra-corporeal membrane-oxygenation (ECMO). Here, we describe our experience in an attempt to explore the role of nintedanib in lung recovery in COVID-19. Three obese patients aged between 42 and 52 years were started on nintedanib due to difficulty in obtaining lung function restoration and weaning from ECMO support following the removal of orotracheal intubation (OTI). Soon after the start of the treatment, systemic inflammation and respiratory function rapidly improved and ECMO support was withdrawn. Serial chest CT scans confirmed the progressive lung amelioration, also reflected by functional tests during follow-up. Nintedanib was well-tolerated by all the three patients at the dosage used for ILDs and continued for 2–3 months based on drug availability. Although caution in interpreting events is required; it is tempting to speculate that nintedanib may have contributed to modulate lung inflammation and remodeling and to sustain lung repair. Altogether, nintedanib appears as a promising agent in patients with severe COVID-19 and delayed respiratory function recovery, for whom molecularly targeted therapies are still lacking. Clinical trials are necessary to confirm our observations.

Systemic lupus erythematosus (SLE) preferentially affects women of childbearing age. Miscarriages or fetal death, intrauterine growth restriction (IUGR), preterm delivery, preeclampsia and disease flares complicate pregnancy in SLE patients. Treatment is challenging due to the need to prevent disease exacerbations and limit obstetrical complications, while showing an acceptable safety profile for both the mother and the fetus. We collected data from 74 pregnancies in 53 SLE patients prospectively followed in a dedicated ‘Pregnancy at risk’ outpatient clinic from 2003 to 2019. Out of 74, 45 pregnancies patients were treated with hydroxychloroquine (HCQ). Mothers under HCQ therapy (HCQ+ patients) and those who did not receive HCQ (HCQ−) were homogeneous in terms of age and comorbidities. Disease activity prior to conception was slightly higher in HCQ+ patients. No significant difference was observed in terms of obstetrical history. In patients achieving a viable pregnancy, the rate of IUGR (4/39, 10% in HCQ+ vs 8/25, 32%, in HCQ− patients, p

Background and aims Patients infected with SARS-CoV-2 range from asymptomatic, to mild, moderate or severe disease evolution including fatal outcome. Thus, early predictors of clinical outcome are highly needed. We investigated markers of neural tissue damage as a possible early sign of multisystem involvement to assess their clinical prognostic value on survival or transfer to intensive care unit (ICU). Methods We collected blood from 104 patients infected with SARS-CoV-2 the day of admission to the emergency room and measured blood neurofilament light chair (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and total tau protein levels. Results We found that NfL, GFAP, and tau were significantly increased in patients with fatal outcome, while NfL and UCH-L1 in those needing ICU transfer. ROC and Kaplan–Meier curves indicated that total tau levels at admission accurately predict mortality. Conclusions Blood neural markers may provide additional prognostic value to conventional biomarkers used to predict COVID-19 outcome. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10595-6.