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2.
Open forum infectious diseases ; 8(Suppl 1):S354-S355, 2021.
Article in English | EuropePMC | ID: covidwho-1564848

ABSTRACT

Background Evidence regarding the impact of remdesivir (RDV) on SARS-CoV-2 viral clearance (VC) is scarce. Aim of this study was to compare VC timing in COVID-19 patients who received RDV with those who did not. Methods Matched-cohort study conducted (25 February 2020-15 April 2021) at the IRCSS San Raffaele, Milan, Italy. The study enrolled hospitalized patients with pneumonia and a SARS-CoV-2 positive nasopharyngeal swab (NPS) at admission and at least one NPS during follow-up. Follow-up started at hospital admission and ended at the date of the first negative NPS (within 30 days after discharge). Patients who received RDV (cases) and patients who did not (controls) were matched based on age (±5 years), sex and PaO2/FiO2 (P/F;±10 mmHg) values at admission. NPS were analyzed with RT-PCR. Results described as median (IQR) or frequency (%). Time to VC was estimated with Kaplan-Meier curve and compared with log-rank test. Results 648 patients were enrolled: 216 cases and 432 controls. Patients’ characteristics at admission are reported in Table 1. VC was observed in 490 patients (75.6%) in a median time of 25 (16-34) days. Overall, time to VC was similar in patients receiving or not receiving remdesivir (p=0.519). However, time to VC was different when considering both the use of RDV (yes vs no) and age (≤ or > 63 years), as shown in Figure 1A. A significant finding was also observed considering the use of RDV and P/F values at admission (≤ or > 200 mmHg), as reported in Figure 1B. Among the 490 patients who reached VC during follow-up, overall time to VC was similar in patients receiving or not receiving RDV (p=0.075;Figure 2A);however, RDV use was associated with a higher probability of VC in the subgroup of patients with P/F admission values ≤ 200mmHg (p=0.035;Figure 2B), in the age group 55-65 years (p=0.025;Figure 2C) and in patients with comorbidities (p=0.028). Time to viral clearance among the 490 patients who reached VC during follow-up. Panel A: time to VC according to RDV use. Panel B: time to VC according to RDV and P/F ratio value at admission. Panel C: time to VC according to RDV in the age group 55-65 years. Conclusion Time to viral clearance was similar in patients receiving or not receiving remdesivir;however the use of RDV was associated with a benefit on time to viral clearance in younger patients and in those with a P/F ratio at admission ≤200 mmHg. Disclosures Vincenzo Spagnuolo, MD, ViiV Healthcare (Other Financial or Material Support, Preparation of educational material) Antonella Castagna, MD, Gilead Sciences (Other Financial or Material Support, Speaking fee)Jansenn-Cilag (Other Financial or Material Support, Speaking fee)MSD (Other Financial or Material Support, Speaking fee)Theratechnologies (Other Financial or Material Support, Speaking fee)ViiV Healthcare (Other Financial or Material Support, Speaking fee)

3.
Preprint in English | Other preprints | ID: ppcovidwho-294357

ABSTRACT

A bstract Purpose Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. Methods We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. Results Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p=0.001), fasting blood glucose (HR 4.32, p<0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p=0.01) or fasting blood glucose ≥ 7 mmol/l (HR 3.07, p=0.015). Conclusions Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.

4.
J Cardiothorac Vasc Anesth ; 2021 Nov 27.
Article in English | MEDLINE | ID: covidwho-1537350

ABSTRACT

OBJECTIVES: Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. The authors investigated 1-year survival, quality of life, and functional recovery of patients with COVID-19 ARDS requiring invasive mechanical ventilation. DESIGN: Prospective observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: All patients with COVID-19 ARDS receiving invasive mechanical ventilation and discharged alive from hospital. INTERVENTIONS: Patients were contacted by phone after 1 year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS: The study included all adult (age ≥18 years) patients with COVID-19-related ARDS admitted to an ICU of the authors' institution between February 25, 2020, and April 27, 2020, who received at least 1 day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed 1 year after discharge and 56 completed a battery of tests of cognition, activities of daily living, and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by 5 (8.9%) patients. Comparing 2-month and 1-year data, the authors observed the most significant improvements in the areas of working status and exertional dyspnea. One-year chest CT scans were available for 36 patients; fibrotic-like changes were present in 4 patients. CONCLUSIONS: All patients who survived the acute phase of COVID-19 and were discharged from the hospital were alive at the 1-year follow up, and the vast majority of them had good overall recovery and quality of life.

5.
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
6.
Eur J Clin Invest ; : e13703, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1488194

ABSTRACT

AIMS: Infection by SARS-CoV-2 may result in a systemic disease and a proportion of patients ranging 15%-44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID-19 in order to identify predisposing and/or protective factors of CI and the outcome. METHODS AND RESULTS: This is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID-19 and at least one high-sensitivity cardiac troponin (hs-cTnt) measurement during hospitalization. CI was defined if at least one hs-cTnt value was above the 99th percentile. The primary end-point was the occurrence of CI during hospitalization. We included 750 patients (median age 67, IQR 56-77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34-147 ng/l) were detected in 390 patients (52%) during the hospitalization. At multivariable analysis age, CKD, cancer, C-reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all-cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI. CONCLUSION: This large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID-19, highlighting the leading role of systemic inflammation for the occurrence of CI.

7.
Echocardiography ; 38(10): 1778-1786, 2021 10.
Article in English | MEDLINE | ID: covidwho-1476163

ABSTRACT

BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.

10.
Andrology ; 2021 Aug 18.
Article in English | MEDLINE | ID: covidwho-1379554

ABSTRACT

BACKGROUND: Circulating testosterone levels have been found to be reduced in men with severe acute respiratory syndrome coronavirus 2 infection, COVID-19, with lower levels being associated with more severe clinical outcomes. OBJECTIVES: We aimed to assess total testosterone levels and the prevalence of total testosterone still suggesting for hypogonadism at 7-month follow-up in a cohort of 121 men who recovered from laboratory-confirmed COVID-19. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as total testosterone ≤9.2 nmol/L. The Charlson Comorbidity Index was used to score health-significant comorbidities. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and total testosterone levels at follow-up assessment. RESULTS: Circulating total testosterone levels increased at 7-month follow-up compared to hospital admittance (p < 0.0001), while luteinizing hormone and 17ß-estradiol levels significantly decreased (all p ≤ 0.02). Overall, total testosterone levels increased in 106 (87.6%) patients, but further decreased in 12 (9.9%) patients at follow-up, where a total testosterone level suggestive for hypogonadism was still observed in 66 (55%) patients. Baseline Charlson Comorbidity Index score (OR 0.36; p = 0.03 [0.14, 0.89]) was independently associated with total testosterone levels at 7-month follow-up, after adjusting for age, BMI, and IL-6 at hospital admittance. CONCLUSIONS: Although total testosterone levels increased over time after COVID-19, more than 50% of men who recovered from the disease still had circulating testosterone levels suggestive for a condition of hypogonadism at 7-month follow-up. In as many as 10% of cases, testosterone levels even further decreased. Of clinical relevance, the higher the burden of comorbid conditions at presentation, the lower the probability of testosterone levels recovery over time.

11.
Clin Nutr ; 2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1356177

ABSTRACT

BACKGROUND & AIMS: Sarcopenia, a loss of muscle mass, quality and function, which is particularly evident in respiratory muscles, has been associated with many clinical adverse outcomes. In this study, we aimed at evaluating the role of reduced muscle mass and quality in predicting ventilation weaning, complications, length of intensive care unit (ICU) and of hospital stay and mortality in patients admitted to ICU for SARS-CoV-2-related pneumonia. METHODS: This was an observational study based on a review of medical records of all adult patients admitted to the ICU of a tertiary hospital in Milan and intubated for SARS-CoV-2-related pneumonia during the first wave of the COVID-19 pandemic. Muscle mass and quality measurement were retrieved from routine thoracic CT scans, when sections passing through the first, second or third lumbar vertebra were available. RESULTS: A total of 81 patients were enrolled. Muscle mass was associated with successful extubation (OR 1.02, 95% C.I. 1.00-1.03, p = 0.017), shorter ICU stay (OR 0.97, 95% C.I. 0.95-0.99, p = 0.03) and decreased hospital mortality (HR 0.98, 95% C.I. 0.96-0.99, p = 0.02). Muscle density was associated with successful extubation (OR 1.07, 95% C.I. 1.01-1.14; p = 0.02) and had an inverse association with the number of complications in ICU (Β -0.07, 95% C.I. -0.13 - -0.002, p = 0.03), length of hospitalization (Β -1.36, 95% C.I. -2.21 - -0.51, p = 0.002) and in-hospital mortality (HR 0.88, 95% C.I. 0.78-0.99, p = 0.046). CONCLUSIONS: Leveraging routine CT imaging to measure muscle mass and quality might constitute a simple, inexpensive and powerful tool to predict survival and disease course in patients with COVID-19. Preserving muscle mass during hospitalisation might have an adjuvant role in facilitating remission from COVID-19.

12.
J Crit Care ; 66: 14-19, 2021 12.
Article in English | MEDLINE | ID: covidwho-1351740

ABSTRACT

PURPOSE: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020-December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. RESULTS: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1-18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6-96.9), a specificity of 95.6% (95% CI: 90.6-98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3-92.3), a negative PV of 97.1% (95% CI: 74.6-96.9) and an accuracy of 94.2% (95% CI: 89.6-97.2) in predicting PMD/PNX (AUC:0.924). CONCLUSIONS: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.


Subject(s)
COVID-19 , Mediastinal Emphysema , Pneumothorax , Respiratory Distress Syndrome , Case-Control Studies , Humans , Mediastinal Emphysema/diagnostic imaging , Respiratory Distress Syndrome/diagnostic imaging , SARS-CoV-2
13.
Metabolism ; 123: 154845, 2021 10.
Article in English | MEDLINE | ID: covidwho-1340768

ABSTRACT

PURPOSE: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. METHODS: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. RESULTS: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015). CONCLUSIONS: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hyperglycemia/epidemiology , Thromboembolism/etiology , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/diagnosis , COVID-19/therapy , Diabetes Complications/diagnosis , Diabetes Complications/epidemiology , Diabetes Complications/therapy , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Female , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Hyperglycemia/diagnosis , Hyperglycemia/etiology , Hyperglycemia/therapy , Inflammation/complications , Inflammation/diagnosis , Inflammation/epidemiology , Inflammation/therapy , Italy/epidemiology , Male , Middle Aged , Mortality , Prognosis , Risk Factors , Stress, Psychological/complications , Stress, Psychological/diagnosis , Stress, Psychological/epidemiology , Thromboembolism/diagnosis , Thromboembolism/epidemiology , Treatment Outcome
14.
J Interv Card Electrophysiol ; 2021 Jul 22.
Article in English | MEDLINE | ID: covidwho-1320113

ABSTRACT

PURPOSE: Systemic inflammation has been associated with corrected QT (QTc) interval prolongation. The role of inflammation on QTc prolongation in COVID-19 patients was investigated. METHODS: Patients with a laboratory-confirmed SARS-CoV-2 infection admitted to IRCCS San Raffaele Scientific Institute (Milan, Italy) between March 14, 2020, and March 30, 2020 were included. QTc-I was defined as the QTc interval by Bazett formula in the first ECG performed during the hospitalization, before any new drug treatment; QTc-II was the QTc in the ECG performed after the initiation of hydroxychloroquine drug treatment. RESULTS: QTc-I was long in 45 patients (45%) and normal in 55 patients (55%). Patients with long QTc-I were older and more frequently males. C-Reactive protein (CRP) and white blood cell (WBC) count at hospitalization were higher in patients with long QTc-I and long QTc-II. QTc-I was significantly correlated with CRP levels at hospitalization. After a median follow-up of 83 days, 14 patients (14%) died. There were no deaths attributed to ventricular arrhythmias. Patients with long QTc-I and long QTc-II had a shorter survival, compared with normal QTc-I and QTc-II patients, respectively. In Cox multivariate analysis, independent predictors of mortality were age (HR = 1.1, CI 95% 1.04-1.18, p = 0.002) and CRP at ECG II (HR 1.1, CI 95% 1.0-1.1, p = 0.02). CONCLUSIONS: QTc at hospitalization is a simple risk marker of mortality risk in COVID-19 patients and reflects the myocardial inflammatory status.

15.
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.

16.
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
17.
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
19.
Lancet Rheumatol ; 3(4): e253-e261, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1228198

ABSTRACT

Background: Patients with severe COVID-19 develop a life-threatening hyperinflammatory response to the virus. Interleukin (IL)-1 or IL-6 inhibitors have been used to treat this patient population, but the comparative effectiveness of these different strategies remains undetermined. We aimed to compare IL-1 and IL-6 inhibition in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation. Methods: This cohort study included patients admitted to San Raffaele Hospital (Milan, Italy) with COVID-19, respiratory insufficiency, defined as a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of 300 mm Hg or less, and hyperinflammation, defined as serum C-reactive protein concentration of 100 mg/L or more or ferritin concentration of 900 ng/mL or more. The primary endpoint was survival, and the secondary endpoint was a composite of death or mechanical ventilation (adverse clinical outcome). Multivariable Cox regression analysis was used to compare clinical outcomes of patients receiving IL-1 inhibition (anakinra) or IL-6 inhibition (tocilizumab or sarilumab) with those of patients who did not receive interleukin inhibitors, after accounting for baseline differences. All patients received standard care. Interaction tests were used to assess the probability of survival according to C-reactive protein or lactate dehydrogenase concentrations. Findings: Of 392 patients included between Feb 25 and May 20, 2020, 275 did not receive interleukin inhibitors, 62 received the IL-1 inhibitor anakinra, and 55 received an IL-6 inhibitor (29 received tocilizumab and 26 received sarilumab). In the multivariable analysis, compared with patients who did not receive interleukin inhibitors, patients treated with IL-1 inhibition had a significantly reduced mortality risk (hazard ratio [HR] 0·450, 95% CI 0·204-0·990, p=0·047), but those treated with IL-6 inhibition did not (0·900, 0·412-1·966; p=0·79). In the multivariable analysis, there was no difference in adverse clinical outcome risk in patients treated with IL-1 inhibition (HR 0·866, 95% CI 0·482-1·553; p=0·63) or IL-6 inhibition (0·882, 0·452-1·722; p=0·71) relative to patients who did not receive interleukin inhibitors. For increasing C-reactive protein concentrations, patients treated with IL-6 inhibition had a significantly reduced risk of mortality (HR 0·990, 95% CI 0·981-0·999; p=0·031) and adverse clinical outcome (0·987, 0·979-0·995; p=0·0021) compared with patients who did not receive interleukin inhibitors. For decreasing concentrations of serum lactate dehydrogenase, patients treated with an IL-1 inhibitor and patients treated with IL-6 inhibitors had a reduced risk of mortality; increasing concentrations of lactate dehydrogenase in patients receiving either interleukin inhibitor were associated with an increased risk of mortality (HR 1·009, 95% CI 1·003-1·014, p=0·0011 for IL-1 inhibitors and 1·006, 1·001-1·011, p=0·028 for IL-6 inhibitors) and adverse clinical outcome (1·006, 1·002-1·010, p=0·0031 for IL-1 inhibitors and 1·005, 1·001-1·010, p=0·016 for IL-6 inhibitors) compared with patients who did not receive interleukin inhibitors. Interpretation: IL-1 inhibition, but not IL-6 inhibition, was associated with a significant reduction of mortality in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation. IL-6 inhibition was effective in a subgroup of patients with markedly high C-reactive protein concentrations, whereas both IL-1 and IL-6 inhibition were effective in patients with low lactate dehydrogenase concentrations. Funding: None.

20.
Clin Imaging ; 77: 194-201, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1226279

ABSTRACT

BACKGROUND: The aim of this study was to quantify COVID-19 pneumonia features using CT performed at time of admission to emergency department in order to predict patients' hypoxia during the hospitalization and outcome. METHODS: Consecutive chest CT performed in the emergency department between March 1st and April 7th 2020 for COVID-19 pneumonia were analyzed. The three features of pneumonia (GGO, semi-consolidation and consolidation) and the percentage of well-aerated lung were quantified using a HU threshold based software. ROC curves identified the optimal cut-off values of CT parameters to predict hypoxia worsening and hospital discharge. Multiple Cox proportional hazards regression was used to analyze the capability of CT quantitative features, demographic and clinical variables to predict the time to hospital discharge. RESULTS: Seventy-seven patients (median age 56-years-old, 51 men) with COVID-19 pneumonia at CT were enrolled. The quantitative features of COVID-19 pneumonia were not associated to age, sex and time-from-symptoms onset, whereas higher number of comorbidities was correlated to lower well-aerated parenchyma ratio (rho = -0.234, p = 0.04) and increased semi-consolidation ratio (rho = -0.303, p = 0.008). Well-aerated lung (≤57%), semi-consolidation (≥17%) and consolidation (≥9%) predicted worst hypoxemia during hospitalization, with moderate areas under curves (AUC 0.76, 0.75, 0.77, respectively). Multiple Cox regression identified younger age (p < 0.01), female sex (p < 0.001), longer time-from-symptoms onset (p = 0.049), semi-consolidation ≤17% (p < 0.01) and consolidation ≤13% (p = 0.03) as independent predictors of shorter time to hospital discharge. CONCLUSION: Quantification of pneumonia features on admitting chest CT predicted hypoxia worsening during hospitalization and time to hospital discharge in COVID-19 patients.


Subject(s)
COVID-19 , Female , Hospitalization , Humans , Hypoxia/diagnostic imaging , Lung/diagnostic imaging , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
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