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.
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.
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.
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.
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.
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.
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.
Graphic abstract
Infectious and inflammatory stimuli elicit the generation of chitinase-3-like protein-1 (CHI3L1), involved in tissue damage, repair and remodeling. We evaluated whether plasma CHI3L1 at disease onset ...predicts clinical outcome of patients with Coronavirus 2019 (COVID-19) disease. Blood from 191 prospectively followed COVID-19 patients were collected at hospital admission between March 18th and May 5th, 2020. Plasma from 80 survivors was collected one month post-discharge. Forty age- and sex-matched healthy volunteers served as controls. Primary outcome was transfer to intensive care unit (ICU) or death. CHI3L1 was higher in COVID-19 patients than controls (p < 0.0001). Patients with unfavorable outcome (41 patients admitted to ICU, 47 died) had significantly higher CHI3L1 levels than non-ICU survivors (p < 0.0001). CHI3L1 levels abated in survivors one month post-discharge, regardless of initial disease severity (p < 0.0001), although remaining higher than controls (p < 0.05). Cox regression analysis revealed that CHI3L1 levels predict primary outcome independently of age, sex, comorbidities, degree of respiratory insufficiency and systemic inflammation or time from symptom onset to sampling (p < 0.0001). Kaplan-Meier curve analysis confirmed that patients with CHI3L1 levels above the median (361 ng/mL) had a poorer prognosis (log rank test, p < 0.0001). Plasma CHI3L1 is increased in COVID-19 patients and predicts adverse outcome.
Objective
Toll‐like receptor 7 (TLR‐7), TLR‐8, and interferon (IFN)–induced genes are expressed in patients with idiopathic inflammatory myositis. This study was undertaken to investigate whether ...their activation influences the natural history of the disease.
Methods
Experimental autoimmune myositis was induced in mice by injection of the amino‐terminal portion of the murine histidyl–transfer RNA synthetase (HisRS). Disease was compared in the presence or the absence of the TLR‐7/8 agonist R‐848 in wild‐type mice and in mice that fail to express the IFNα/β receptor (IFNα/βR‐null mice).
Results
Experimental autoimmune myositis induced by a single intramuscular immunization with HisRS spontaneously abated after 7–8 weeks. In contrast, levels of anti‐HisRS autoantibodies, endomysial/perimysial leukocyte infiltration, and myofiber regeneration persisted at the end of the follow‐up period (22 weeks after immunization) in mice immunized with HisRS in the presence of R‐848. Myofiber major histocompatibility complex (MHC) class I molecules were detectable only in mice immunized with both HisRS and R‐848. MHC up‐regulation occurred early and in muscles that were not directly injected with HisRS. Muscle MHC expression paralleled with leukocyte infiltration. MHC class I molecules were selectively up‐regulated in myotubes challenged with R‐848 in vitro. Type I IFN was necessary for the prolonged autoantibody response and for the spreading of the autoimmune response, as demonstrated using IFNα/βR‐null mice. Muscle infiltration was maintained in the injected muscle up to the end of the follow‐up period.
Conclusion
TLR‐7/8 activation is necessary to induce and maintain a systemic autoimmune response targeting the skeletal muscle. This experimental autoimmune myositis model reproduces many characteristics of human idiopathic inflammatory myopathies and may represent a tool for preclinical studies.
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