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1.
Intern Med J ; 51(11): 1810-1815, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526370

ABSTRACT

BACKGROUND: COVID-19 long-term sequelae are ill-defined since only a few studies have explored the long-term consequences of this disease so far. AIMS: To evaluate the 6-month respiratory outcome and exercise capacity of COVID-19 acute respiratory failure (ARF) patients treated with continuous positive airway pressure (CPAP) during the first wave of the ongoing COVID-19 pandemic. METHODS: A retrospective observational study included COVID-19 patients with ARF. Interventions included CPAP during hospitalisation and 6-month follow up. Frailty assessment was carried out through frailty index (FI), pO2 /FiO2 during hospitalisation and at follow up, respiratory parameters, 6-min walking test (6MWT) and the modified British Medical Research Council (mMRC) and Borg scale at follow up. RESULTS: More than half of the patients had no dyspnoea according to the mMRC scale. Lower in-hospital pO2 /FiO2 correlated with higher Borg scale levels after 6MWT (ρ 0.27; P 0.04) at the follow-up visit. FI was positively correlated with length of hospitalisation (ρ 0.3; P 0.03) and negatively with the 6MWT distance walked (ρ -0.36; P 0.004). CONCLUSIONS: Robust and frail patients with COVID-19 ARF treated with CPAP outside the intensive care unit setting had good respiratory parameters and exercise capacity at 6-month follow up, although more severe patients had slightly poorer respiratory performance compared with patients with higher PaO2 /FiO2 and lower FI.


Subject(s)
COVID-19 , Respiratory Insufficiency , Continuous Positive Airway Pressure , Exercise Tolerance , Humans , Pandemics , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
2.
J Psychiatr Res ; 145: 118-124, 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1525861

ABSTRACT

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.

3.
Front Med (Lausanne) ; 8: 766486, 2021.
Article in English | MEDLINE | ID: covidwho-1518500

ABSTRACT

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.

4.
Acta Anaesthesiol Scand ; 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1511269

ABSTRACT

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.

5.
Brain, behavior, & immunity - health ; 2021.
Article in English | EuropePMC | ID: covidwho-1498647

ABSTRACT

Psychiatric sequelae substantially contribute to the post-acute burden of disease associated with COVID-19, persisting months after clearance of the virus. Brain imaging shows white matter (WM) hypodensities/hyperintensities, and the involvement of grey matter (GM) in prefrontal, anterior cingulate (ACC) and insular cortex after COVID, but little is known about brain correlates of persistent psychopathology. With a multimodal approach, we studied whole brain voxel-based morphometry, diffusion-tensor imaging, and resting-state connectivity, to correlate MRI measures with depression and post-traumatic distress (PTSD) in 42 COVID-19 survivors without brain lesions, at 90.59 ± 54.66 days after COVID. Systemic immune-inflammation index (SII) measured in the emergency department, which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted worse self-rated depression and PTSD, widespread lower diffusivity along the main axis of WM tracts, and abnormal functional connectivity (FC) among resting state networks. Self-rated depression and PTSD inversely correlated with GM volumes in ACC and insula, axial diffusivity, and associated with FC. We observed overlapping associations between severity of inflammation during acute COVID-19, brain structure and function, and severity of depression and post-traumatic distress in survivors, thus warranting interest for further study of brain correlates of the post-acute COVID-19 syndrome. Beyond COVID-19, these findings support the hypothesis that regional GM, WM microstructure, and FC could mediate the relationship between a medical illness and its psychopathological sequelae, and are in agreement with current perspectives on the brain structural and functional underpinnings of depressive psychopathology.

6.
J Thromb Haemost ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1488230

ABSTRACT

BACKGROUND: Platelet activation and thrombotic events characterizes COVID-19. OBJECTIVES: To characterize platelet activation and determine if SARS-CoV-2 induces platelet activation. PATIENTS/METHODS: We investigated platelet activation in 119 COVID-19 patients at admission in a university hospital in Milan, Italy, between March 18 and May 5, 2020. Sixty-nine subjects (36 healthy donors, 26 patients with coronary artery disease, coronary artery disease, and seven patients with sepsis) served as controls. RESULTS: COVID-19 patients had activated platelets, as assessed by the expression and distribution of HMGB1 and von Willebrand factor, and by the accumulation of platelet-derived (plt) extracellular vesicles (EVs) and HMGB1+ plt-EVs in the plasma. P-selectin upregulation was not detectable on the platelet surface in a fraction of patients (55%) and the concentration of soluble P-selectin in the plasma was conversely increased. The plasma concentration of HMGB1+ plt-EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a 6-point ordinal scale (from 1 = discharged to 6 = death). Platelets interacting in vitro with SARS-CoV-2 underwent activation, which was replicated using SARS-CoV-2 pseudo-viral particles and purified recombinant SARS-CoV-2 spike protein S1 subunits. Human platelets express CD147, a putative coreceptor for SARS-CoV-2, and Spike-dependent platelet activation, aggregation and granule release, release of soluble P-selectin and HMGB1+ plt-EVs abated in the presence of anti-CD147 antibodies. CONCLUSIONS: Hence, an early and intense platelet activation, which is reproduced by stimulating platelets in vitro with SARS-CoV-2, characterizes COVID-19 and could contribute to the inflammatory and hemostatic manifestations of the disease.

7.
Eur Arch Psychiatry Clin Neurosci ; 2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1482211

ABSTRACT

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.

8.
Mol Med ; 27(1): 129, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1477255

ABSTRACT

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.


Subject(s)
COVID-19/diagnosis , Chemokine CXCL10/blood , Coronary Artery Disease/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/immunology , COVID-19/mortality , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/immunology , Coronary Artery Disease/mortality , Creatine/blood , Diabetes Mellitus/blood , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Female , Hospitalization , Humans , Hypertension/blood , Hypertension/immunology , Hypertension/mortality , Immunity, Humoral , Immunity, Innate , Inflammation , Intensive Care Units , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lymphocytes/immunology , Lymphocytes/pathology , Male , Middle Aged , Neutrophils/immunology , Neutrophils/pathology , Prognosis , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
9.
Diabetes Metab ; 47(6): 101268, 2021 11.
Article in English | MEDLINE | ID: covidwho-1330744

ABSTRACT

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 (ß 0.291, P = 0.022), while female gender (ß -0.289, P = 0.016), diabetes (ß -0.257, P = 0.028), and hypertension (ß -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.

10.
Pharmacol Res ; 161: 105114, 2020 11.
Article in English | MEDLINE | ID: covidwho-1318944

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical spectrum of COVID-19 is broad and varies from mild to severe forms complicated by acute respiratory distress and death. This heterogeneity might reflect the ability of the host immune system to interact with SARS-CoV2 or the characteristics of the virus itself in terms of loads or persistence. Information on this issue might derive from interventional studies. However, results from high-quality trials are scarce. Here we evaluate the level of evidence of available published interventional studies, with a focus on randomised controlled trials and the efficacy of therapies on clinical outcomes. Moreover, we present data on a large cohort of well-characterized patients hospitalized at a single University Hospital in Milano (Italy), correlating viral clearance with clinical and biochemical features of patients.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , SARS-CoV-2 , Antiviral Agents/pharmacology , Humans , Viral Load
11.
Minerva Med ; 2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1267020

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterised by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalised patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19. METHODS: We prospectively followed up 180 hospitalised COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results. RESULTS: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalisation. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major haemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, p<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, p=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed. CONCLUSIONS: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based lower Pao2/FiO2 ratio, higher D-dimer levels and history of major haemorrhages.

12.
Panminerva Med ; 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-1249754

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) may leave behind an altered health status early after recovery. We evaluated the clinical status of COVID-19 survivors at three months after hospital discharge. METHODS: In this prospective observational cohort study, hospitalized patients aged ≥18 years, evaluated at one (M1) and three (M3) months post-discharge were enrolled. 251 patients (71.3% males, median [IQR] age 61.8 [53.5-70.7] years) were included. Median (IQR) time from discharge to M3 was 89 (79.5-101) days. Primary outcome was residual respiratory dysfunction (RRD), defined by tachypnea, moderate to very severe dyspnea, or peripheral oxygen saturation ≤95% on room air at M3. RESULTS: RRD was found in 30.4% of patients, with no significant difference compared with M1. Chronic obstructive pulmonary disease and length of stay were independent predictors of RRD at multivariable logistic regression (odds ratio, OR, [95% confidence interval, CI] 4.13 [1.17-16.88], p 0.033; OR [95% CI] 1.02 [1.00-1.04], p 0.047, respectively). Obesity and C-reactive protein levels upon admission were additional predictors at regression tree analysis. Impaired quality of life (QoL) was reported by 53.2% of patients. Anxiety and insomnia were each present in 25.5% of patients, and PTSD in 22.4%. No difference was found between M1 and M3 in QoL, anxiety or PTSD. Insomnia decreased at M3. Current major psychiatric disorder as well as anxiety, insomnia and PSTD at M1 independently predicted PTSD at M3. CONCLUSIONS: Clinical damage may persist at three months after discharge in COVID-19 survivors. Post-recovery follow-up is an essential component of patient management.

13.
Nutr Metab Cardiovasc Dis ; 31(7): 2156-2164, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1249046

ABSTRACT

BACKGROUND AND AIMS: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. METHODS AND RESULTS: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001). CONCLUSION: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19. TRIAL REGISTRATION: NCT04318366.


Subject(s)
Adiposity , COVID-19/diagnostic imaging , Intra-Abdominal Fat/diagnostic imaging , Obesity/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed , Aged , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Female , Hospital Mortality , Humans , Intra-Abdominal Fat/physiopathology , Italy , Male , Middle Aged , Obesity/mortality , Obesity/physiopathology , Pericardium , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Risk Factors
14.
Cell Death Differ ; 28(11): 3125-3139, 2021 11.
Article in English | MEDLINE | ID: covidwho-1241944

ABSTRACT

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.


Subject(s)
COVID-19/pathology , Extracellular Traps/metabolism , Neutrophils/immunology , COVID-19/complications , COVID-19/immunology , Citrullination , Complement Activation , Humans , Neutrophils/metabolism , Platelet Activation , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombosis/etiology
15.
Int J Obes (Lond) ; 45(9): 1986-1994, 2021 09.
Article in English | MEDLINE | ID: covidwho-1232062

ABSTRACT

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.


Subject(s)
Body-Weight Trajectory , COVID-19/physiopathology , Obesity, Abdominal/physiopathology , Overweight/physiopathology , Survivors , Adiposity , Aged , Anthropometry , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Obesity, Abdominal/virology , Overweight/virology , Prospective Studies , Waist Circumference
16.
Front Immunol ; 12: 675678, 2021.
Article in English | MEDLINE | ID: covidwho-1231339

ABSTRACT

Background: Restraining maladaptive inflammation is considered a rationale strategy to treat severe coronavirus disease-19 (COVID-19) but available studies with selective inhibitors of pro-inflammatory cytokines have not provided unequivocal evidence of survival advantage. Late administration is commonly regarded as a major cause of treatment failure but the optimal timing for anti-cytokine therapy initiation in COVID-19 patients has never been clearly established. Objectives: To identify a window of therapeutic opportunity for maximizing the efficacy of interleukin (IL)-1 and IL-6 blockade in COVID-19. Methods: Survival at the longest available follow-up was assessed in severe hyper-inflamed COVID-19 patients treated with anakinra, tocilizumab, sarilumab, or standard of care, stratified according to respiratory impairment at the time of treatment initiation. Results: 107 patients treated with biologics and 103 contemporary patients treated with standard of care were studied. After a median of 106 days of follow-up (range 3-186), treatment with biologics was associated with a significantly higher survival rate compared to standard therapy when initiated in patients with a PaO2/FiO2 ≥ 100 mmHg (p < 0.001). Anakinra reduced mortality also in patients with PaO2/FiO2 < 100 mmHg (p = 0.04). Conclusions: IL-1 and IL-6 blocking therapies are more likely to provide survival advantage in hyper-inflamed COVID-19 patients when initiated before the establishment of severe respiratory failure.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19 , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , SARS-CoV-2/immunology , Aged , COVID-19/drug therapy , COVID-19/immunology , COVID-19/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Interleukin-1/immunology , Interleukin-6/immunology , Male , Middle Aged , Severity of Illness Index , Survival Rate
17.
J Neurol ; 268(12): 4436-4442, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1222771

ABSTRACT

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.


Subject(s)
COVID-19 , Intermediate Filaments , Neurofilament Proteins/blood , tau Proteins/blood , Biomarkers , COVID-19/mortality , Glial Fibrillary Acidic Protein/blood , Humans , Ubiquitin Thiolesterase/blood
18.
Phys Med ; 85: 63-71, 2021 May.
Article in English | MEDLINE | ID: covidwho-1220831

ABSTRACT

PURPOSE: To train and validate a predictive model of mortality for hospitalized COVID-19 patients based on lung densitometry. METHODS: Two-hundred-fifty-one patients with respiratory symptoms underwent CT few days after hospitalization. "Aerated" (AV), "consolidated" (CV) and "intermediate" (IV) lung sub-volumes were quantified by an operator-independent method based on individual HU maximum gradient recognition. AV, CV, IV, CV/AV, IV/AV, and HU of the first peak position were extracted. Relevant clinical parameters were prospectively collected. The population was composed by training (n = 166) and validation (n = 85) consecutive cohorts, and backward multi-variate logistic regression was applied on the training group to build a CT_model. Similarly, models including only clinical parameters (CLIN_model) and both CT/clinical parameters (COMB_model) were developed. Model's performances were assessed by goodness-of-fit (H&L-test), calibration and discrimination. Model's performances were tested in the validation group. RESULTS: Forty-three patients died (25/18 in training/validation). CT_model included AVmax (i.e. maximum AV between lungs), CV and CV/AE, while CLIN_model included random glycemia, C-reactive protein and biological drugs (protective). Goodness-of-fit and discrimination were similar (H&L:0.70 vs 0.80; AUC:0.80 vs 0.80). COMB_model including AVmax, CV, CV/AE, random glycemia, biological drugs and active cancer, outperformed both models (H&L:0.91; AUC:0.89, 95%CI:0.82-0.93). All models showed good calibration (R2:0.77-0.97). Despite several patient's characteristics were different between training and validation cohorts, performances in the validation cohort confirmed good calibration (R2:0-70-0.81) and discrimination for CT_model/COMB_model (AUC:0.72/0.76), while CLIN_model performed worse (AUC:0.64). CONCLUSIONS: Few automatically extracted densitometry parameters with clear functional meaning predicted mortality of COVID-19 patients. Combined with clinical features, the resulting predictive model showed higher discrimination/calibration.


Subject(s)
COVID-19 , Densitometry , Humans , Lung , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
19.
Acta Anaesthesiol Scand ; 65(7): 912-920, 2021 08.
Article in English | MEDLINE | ID: covidwho-1114984

ABSTRACT

BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.


Subject(s)
COVID-19/therapy , Quality of Life , Recovery of Function , Respiration, Artificial/statistics & numerical data , Survivors/statistics & numerical data , COVID-19/complications , Critical Care/methods , Female , Follow-Up Studies , Humans , Italy , Male , Malnutrition/complications , Middle Aged , Prospective Studies , Surveys and Questionnaires
20.
Brain Behav Immun ; 94: 138-147, 2021 05.
Article in English | MEDLINE | ID: covidwho-1103720

ABSTRACT

COVID-19 outbreak is associated with mental health implications during viral infection and at short-term follow-up. Data on psychiatric and cognitive sequelae at medium-term follow-up are still lacking. During an ongoing prospective cohort study, the psychopathological and cognitive status of 226 COVID-19 pneumonia survivors (149 male, mean age 58) were prospectively evaluated one and three months after hospital discharge. Psychiatric clinical interview, self-report questionnaires, and neuropsychological profiling of verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency were performed. Three months after discharge from the hospital, 35.8% still self-rated symptoms in the clinical range in at least one psychopathological dimension. We observed persistent depressive symptomatology, while PTSD, anxiety, and insomnia decreased during follow-up. Sex, previous psychiatric history, and the presence of depression at one month affected the depressive symptomatology at three months. Regardless of clinical physical severity, 78% of the sample showed poor performances in at least one cognitive domain, with executive functions and psychomotor coordination being impaired in 50% and 57% of the sample. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted self-rated depressive symptomatology and cognitive impairment at three-months follow-up; and changes of SII predicted changes of depression during follow-up. Neurocognitive impairments associated with severity of depressive psychopathology, and processing speed, verbal memory and fluency, and psychomotor coordination were predicted by baseline SII. We hypothesize that COVID-19 could result in prolonged systemic inflammation that predisposes patients to persistent depression and associated neurocognitive dysfunction. The linkage between inflammation, depression, and neurocognition in patients with COVID-19 should be investigated in long-term longitudinal studies, to better personalize treatment options for COVID-19 survivors.


Subject(s)
COVID-19 , Cognition Disorders , Mental Disorders , Biomarkers , Child, Preschool , Follow-Up Studies , Humans , Male , Neuropsychological Tests , Prospective Studies , SARS-CoV-2 , Survivors
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