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1.
Expert Opin Investig Drugs ; : 1-13, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1541410

ABSTRACT

INTRODUCTION: Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and long-lasting impact on the quality of life of COVID-19 survivors. This is an emerging medical need, and it has been hypothesized that antifibrotic treatments could have a role in ameliorating the fibrotic process in the lungs of these patients. AREAS COVERED: The safety and efficacy of available antifibrotic drugs (nintedanib and pirfenidone) and novel promising agents are being assessed in several ongoing clinical trials that were performed either in critically ill patients admitted to intensive care, or in discharged patients presenting fibrotic sequalae from COVID-19. Literature search was performed using Medline and Clinicaltrials.org databases (2001-2021). EXPERT OPINION: Despite the strong rationale support the use of antifibrotic therapies in COVID-related fibrosis, there are several uncertainties regarding the timing for their introduction and the real risks/benefits ratio of antifibrotic treatment in the acute and the chronic phases of the disease. The findings of ongoing clinical trials and the long-term observation of longitudinal cohorts will eventually clarify the best management approach for these patients.

2.
Sci Rep ; 11(1): 21136, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1493228

ABSTRACT

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the case-fatality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 h after admission (adjusted R-squared = 0.48). We developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients in the Emergency Department, or during hospitalization. Although it is reasonable to assume that the model is also applicable in not-hospitalized persons, only appropriate studies can assess the accuracy of the model also for persons at home.


Subject(s)
COVID-19/mortality , Machine Learning , Pandemics , SARS-CoV-2 , Aged , Aged, 80 and over , Blood Cell Count , Blood Chemical Analysis , COVID-19/blood , Cohort Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Models, Statistical , Multivariate Analysis , Oxygen/blood , Pandemics/statistics & numerical data , ROC Curve , Risk Factors , Rome/epidemiology
3.
Respir Med ; 190: 106674, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1487957

ABSTRACT

Influenza and pneumococcal disease represent a well-known burden on healthcare systems worldwide, as well as they still have an attributed morbidity and mortality, especially in elderly individuals and vulnerable populations. In the context of the ongoing pandemic of COVID-19, a series of considerations in favor of extensive influenza and pneumococcal vaccination campaign are emerging, including a possible reduction of hospital extra burden and saving of sanitary resources. In addition, recent studies have suggested that prior vaccinations towards non SARS-CoV-2 pathogens might confer some protection against COVID-19. In this paper the authors consider all factors in support of these hypotheses and provide a consensus statement to encourage influenza and pneumococcal vaccinations in targeted populations.

4.
EClinicalMedicine ; 27: 100553, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1385448

ABSTRACT

Background: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. Methods: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. Findings: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. Interpretation: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

5.
BMC Pulm Med ; 21(1): 241, 2021 Jul 17.
Article in English | MEDLINE | ID: covidwho-1369491

ABSTRACT

INTRODUCTION: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. METHOD: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). RESULTS: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. CONCLUSION: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization.


Subject(s)
COVID-19/physiopathology , Pneumonia, Viral/physiopathology , Aged , Blood Gas Analysis , COVID-19/complications , Carbon Monoxide , Dyspnea/virology , Exercise Tolerance , Female , Humans , Male , Middle Aged , Oxygen/blood , Partial Pressure , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Pulmonary Diffusing Capacity , Residual Volume , SARS-CoV-2 , Severity of Illness Index , Walk Test
6.
Cells ; 10(5)2021 05 14.
Article in English | MEDLINE | ID: covidwho-1234672

ABSTRACT

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Available antifibrotic therapies, namely nintedanib and pirfenidone, might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection but are not economically sustainable by national health systems and have critical adverse effects. It is our opinion that the mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 fibrotic lungs through its anti-inflammatory and antifibrotic factors.


Subject(s)
Biological Factors/pharmacology , COVID-19/complications , Mesenchymal Stem Cells/metabolism , Pulmonary Fibrosis/drug therapy , Biological Factors/metabolism , Biological Factors/therapeutic use , COVID-19/drug therapy , COVID-19/economics , COVID-19/virology , Humans , Indoles/administration & dosage , Indoles/adverse effects , Indoles/economics , Lung/drug effects , Lung/pathology , Lung/virology , Pulmonary Fibrosis/economics , Pulmonary Fibrosis/virology , Pyridones/administration & dosage , Pyridones/adverse effects , Pyridones/economics , SARS-CoV-2/pathogenicity
7.
Adv Exp Med Biol ; 1318: 469-483, 2021.
Article in English | MEDLINE | ID: covidwho-1222730

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel coronavirus disease 2019 (COVID-19) pandemic, which spread throughout the world. Acute hypoxemic respiratory failure is the most dangerous complication of COVID-19 pneumonia. To date, no specific therapeutic drugs or vaccines have been proven efficacious. Ventilatory support is still a significant challenge for physicians facing COVID-19. The mechanisms underlying hypoxemia in those patients are not fully understood, but a new physiopathology model has been proposed. Oxygen therapy should be delivered to patients with mild to moderate hypoxemia. More severe patients could benefit from other treatments (high-flow nasal cannula, noninvasive ventilation or intubation, and invasive ventilation). Given the rapid evolution of COVID-19, there has been a paucity of the high-quality data that typically inform clinical practice guidelines from professional societies, and a worldwide consensus is still lacking. This chapter aims to illustrate the potentials of ventilatory support as therapeutic options for adult and pediatric patients affected by COVID-19 pneumonia.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Adult , Child , Humans , Pandemics , Respiratory Insufficiency/therapy , SARS-CoV-2
9.
Lung India ; 38(Supplement): S41-S47, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1123958

ABSTRACT

The SARS-CoV-2 pandemic has already infected in excess of 50 million people worldwide and resulted in 1.2 million deaths. While the majority of those infected will not have long-term pulmonary sequelae, 5%-10% will develop severe COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). The natural history of these severely affected patients is unclear at present, but using our knowledge of closely related coronavirus outbreaks like severe acute respiratory distress syndrome (SARS) and middle east respiratory syndrome (MERS), we would hypothesize that the majority will stabilize or improve over time although some patients will progress to advanced lung fibrosis or post-COVID interstitial lung disease (PC-ILD). Unlike the SARS and MERS outbreaks which affected only a few thousands, the sheer scale of the present pandemic suggests that physicians are likely to encounter large numbers of patients (potentially hundreds of thousands) with PC-ILD. In this review, we discuss the pathogenesis, natural history, and radiology of such patients and touch on clinical, laboratory, and radiographic clues at presentation which might help predict the future development of lung fibrosis. Finally, we discuss the responsible use of antifibrotic drugs such as pirfenidone, nintedanib, and some newer antifibrotics, still in the pipeline. The biological rationale of these drugs and the patient groups where they may have a plausible role will be discussed. We conclude by stressing the importance of careful longitudinal follow-up of multiple cohorts of post-COVID survivors with serial lung function and imaging. This will eventually help to determine the natural history, course, and response to therapy of these patients.

10.
Respir Med ; 177: 106292, 2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1003035

ABSTRACT

The 2019 coronavirus disease (COVID-19) pandemic is currently a challenge worldwide. Due to the characteristics of lung function tests, the risk of cross infection may be high between health care workers and patients. The role of lung function testing is well defined for the diagnosis of various diseases and conditions. Lung function tests are also indispensable in evaluating the response to medical treatment, in monitoring patient respiratory and systemic pathologies, and in evaluating preoperative risk in cardiothoracic and major abdominal surgeries. However, lung function testing represents a potential route for COVID-19 transmission, due to the aerosol generated during the procedures and the concentration of patients with pulmonary diseases in lung function laboratories. Currently, the opportunities for COVID-19 transmission remain partially unknown, and data are continuously evolving. This review provides useful information on the risks and recommendations for lung function testing, which have varied according to the phase of the pandemic. This information may support national and regional boards and the health authorities to which they belong. There is a need for rapid re-opening of lung function laboratories, but maximum safety is required in the COVID-19 era.

13.
Radiology ; 296(1): 172-180, 2020 07.
Article in English | MEDLINE | ID: covidwho-38290

ABSTRACT

With more than 900 000 confirmed cases worldwide and nearly 50 000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnostic imaging , Pandemics , Pneumonia, Viral/diagnostic imaging , Radiography, Thoracic/methods , COVID-19 , Consensus , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Disease Progression , Global Health , Guideline Adherence , Humans , Personal Protective Equipment , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Radiography, Thoracic/instrumentation , SARS-CoV-2 , Severity of Illness Index , Societies, Medical , Triage , Video Recording
14.
J Ultrasound ; 23(4): 449-456, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-648722

ABSTRACT

COVID-19 pandemic is representing a serious challenge to worldwide public health. Lung Ultrasonography (LUS) has been signaled as a potential useful tool in this pandemic contest either to intercept viral pneumonia or to foster alternative paths. LUS could be useful in determining early lung involvement suggestive or not of COVID-19 pneumonia and potentially plays a role in managing decisions for hospitalization in isolation or admission in general ward. In order to face pandemic, in a period in which a large number of emergency room accesses with suspicious symptoms are expected, physicians need a standardized ultrasonographic approach, fast educational processes in order to be able to recognize both suggestive and not suggestive echographic signs and shared algorithms for LUS role in early management of patients.


Subject(s)
Clinical Protocols , Coronavirus Infections/diagnostic imaging , Emergency Service, Hospital/organization & administration , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Algorithms , Betacoronavirus , COVID-19 , Clinical Decision-Making , Coronavirus Infections/therapy , Early Diagnosis , Hospitalization , Humans , Inservice Training , Medical Staff, Hospital/education , Pandemics , Patient Isolation , Pneumonia, Viral/therapy , SARS-CoV-2 , Ultrasonography
15.
Chest ; 158(1): 106-116, 2020 07.
Article in English | MEDLINE | ID: covidwho-634902

ABSTRACT

With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19.


Subject(s)
Coronavirus Infections , Lung/diagnostic imaging , Pandemics , Patient Care Management , Pneumonia, Viral , Radiography, Thoracic/methods , Respiratory Tract Diseases , Tomography, X-Ray Computed/methods , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Diagnosis, Differential , Disease Progression , Early Diagnosis , Humans , International Cooperation , Patient Care Management/methods , Patient Care Management/standards , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiratory Tract Diseases/diagnosis , Respiratory Tract Diseases/virology , SARS-CoV-2
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