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1.
Front Microbiol ; 13: 851460, 2022.
Article in English | MEDLINE | ID: covidwho-1775714

ABSTRACT

Purpose: An increasing number of laryngotracheal complications in mechanically ventilated COVID-19 patients has been reported in the last few months. Many etiopathogenetic hypotheses were proposed but no clear explanation of these complications was identified. In this paper we evaluated the possibility that the tracheal mucosa could be a high viral replication site that could weaken the epithelium itself. Methods: Subjects for the COVID-19 group and the control group were selected retrospectively according to specific criteria. Patients' basic and clinical data were recorded and analyzed. Tracheal samples of both groups were collected during surgical tracheostomies and then analyzed from a histological and genetic-transcriptional point of view. Results: Four COVID-19 patients were enrolled in this study and compared with four non-COVID-19 patients. No laryngotracheal complications were identified in both groups. The SARS-CoV-2 was detected in one out of four COVID-19 samples. A subepithelial inflammatory lymphomonocyte infiltrate was observed in all patients but two cases of the COVID-19 group showed vasculitis of small subepithelial vessels associated with foci of coagulative necrosis. Two gene sets (HALLMARK_INFLAMMATORY_RESPONSE and HALLMARK_ESTROGEN_RESPONSE_LATE) were significantly deregulated in COVID-19 patients compared to the control group. Conclusion: The altered inflammatory response of the COVID-19 patients could be another possible explanation of the increasing number of laryngotracheal complications.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323427

ABSTRACT

Background: The pandemic surge of Coronavirus disease 2019 (COVID-19) is posing the unprecedent challenge of rapidly identifying and isolating probable cases and diagnosing the main respiratory complications. We aimed to describe the application of a lung ultrasound (LUS)-based diagnostic approach, combining the LUS likelihood of COVID-19 pneumonia with patient’s symptoms and clinical history.Methods: This is an international multicenter prospective observational study on patients suspected for COVID-19, presenting to 22 different US and European hospitals. Patients underwent LUS and reverse transcription-polymerase chain reaction (RT-PCR) swab test. We identified 3 different clinical phenotypes based on pre-existing chronic cardiac or respiratory diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to 4 different patterns, characterized by the presence and distribution of typical and atypical LUS signs: high (HPLUS), intermediate (IPLUS), alternative (APLUS) and low (LPLUS) probability patterns. The association between the combination of patterns and phenotypes with RT-PCR results was described and analyzed.Findings: We studied 1462 patients, classified in mild (n=400), severe (n=727) and mixed (n=335) phenotypes. In the overall population, the HPLUS corresponded to a positive RT-PCR in 92.6% of cases, with similarly high percentages in all clinical phenotypes ranging from 87.5% (mild) to 90.3% (mixed) and 96.5% (severe). The IPLUS yielded a lower match with positive RT-PCR (65.7%). In patients with respiratory failure, the LPLUS predicted a negative RT-PCR in 100% of cases. In the overall population, the APLUS indicated an alternative pulmonary condition in 81.1% of patients. At multivariate analysis the HPLUS strongly predicted RT-PCR positivity (odds ratio 4.173, interquartile range 2.595-6.712, p<0.0001), independently from age, low oxygen saturation and dyspnea.Interpretation: Combining LUS patterns of probability for interstitial pneumonia with clinical phenotypes at presentation could facilitate the early diagnosis of COVID-19 or suggest an alternative pulmonary condition. This approach may be useful to rapidly guide and support patient’s allocation for a wiser use of hospital resources during a pandemic surge.Funding: None.Conflict of Interest: The authors declare no conflicts of interest. Ethical Approval: The local Ethical Committee Boards of each center approved the study, and the study was conducted following the ethical standards of the 1964 Helsinki declaration and its later amendments and with local guidelines for good clinical practice.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316935

ABSTRACT

Introduction: High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. Methods: : In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. Results: hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO 2 . Changes of hsTnT, D-dimer and CRP were related but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. Conclusions: : D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308789

ABSTRACT

Purpose: The aim of this study was to evaluate whether measurement of diaphragm thickness by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. Methods: : We retrospectively reviewed the records of consecutive of 77 patients with laboratory-confirmed Covid-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P<0.10 were entered into a multivariate logistic regression model. Cumulative probability for lack of adverse outcomes in patients with or without low baseline diaphragm muscle mass was calculated with the Kaplan–Meier product-limit estimator. Results: : The main findings of this study are that 1) patients who developed adverse outcomes had thinner diaphragm than those who did not (2.0 vs 2.2 mm, p:0.001), 2) DT and lymphocyte count were independent significant predictors of adverse outcomes, with end-expiratory DT being the strongest (-708, OR: 0.492, p: 0.018). Conclusion: Diaphragmatic ultrasound may be a valid tool to evaluate the risk of respiratory failure. Evaluating the need of mechanical ventilation treatment should be based not only on PaO 2 /FiO 2 , but on a more comprehensive assessment including DT because if the lungs become less compliant a thinner diaphragm, albeit free of intrinsic abnormality, may become exhausted, thus contributing to severe respiratory failure.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308708

ABSTRACT

Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID19 and the mechanisms of action of Ig led to consider this adjunctive therapy also in patients with respiratory failure by SARS-CoV2 infection. This manuscript report the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID19. METHODS A panel of multidisciplinary experts defined the clinical phenotypes of COVID19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. RESULTS Three different phenotypes of COVID19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune-paralysis (late phase), and patients with sepsis by hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panellists considered appropriate its use in the late phase and patients with sepsis/septic shock by bacterial superinfection. CONCLUSION As with other immunotherapies, IVIg adjunctive therapy may a potential role in the managing of COVID19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.

6.
Epilepsy Behav ; 126: 108470, 2022 01.
Article in English | MEDLINE | ID: covidwho-1560506

ABSTRACT

Several studies reported acute symptomatic seizures as a possible neurological complication of COVID-19 pneumonia. Apart from metabolic imbalances, hypoxia, and fever, other ictogenic mechanisms are likely related to an immune-mediated damage. The same mechanisms are shared by other respiratory viruses. Since neurotropic properties of SARS-CoV-2 have been questioned, we investigated whether SARS-CoV-2 has a similar ictogenic potential to other respiratory non-neurotropic viruses. We conducted a retrospective study identifying 1141 patients with SARS-CoV-2 pneumonia and 146 patients with H1N1/H3N2 pneumonia. We found a similar prevalence of seizures in the two viral pneumonia (1.05% with SARS-CoV-2 vs 2.05% with influenza; p = 0.26). We detailed clinical, electroencephalographic, and neuroradiological features of each patient, together with the hypothesized pathogenesis of seizures. Previous epilepsy or pre-existing predisposing conditions (i.e., Alzheimer's disease, stroke, cerebral neoplasia) were found in one-third of patients that experienced seizures, while two-thirds of patients had seizures without known risk factors other than pneumonia in both groups. The prevalence of pre-existing predisposing conditions and disease severity indexes was similar in SARS-CoV-2 and H1N1/H3N2 pneumonia, thus excluding they could act as potential confounders. Considering all the patients with viral pneumonia together, previous epilepsy (p < 0.001) and the need for ventilatory support (p < 0.001), but not the presence of pre-existing predisposing conditions (p = 0.290), were associated with seizure risk. Our study showed that SARS-CoV-2 and influenza viruses share a similar ictogenic potential. In both these infections, seizures are rare but serious events, and can manifest without pre-existing predisposing conditions, in particular when pneumonia is severe, thus suggesting an interplay between disease severity and host response as a major mechanism of ictogenesis, rather than a virus-specific mechanism.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Pneumonia, Viral , Humans , Influenza A Virus, H3N2 Subtype , Retrospective Studies , SARS-CoV-2 , Seizures
7.
Montalto, Francesca, Ippolito, Mariachiara, Noto, Alberto, Madotto, Fabiana, Gelardi, Filippa, Savatteri, Paolino, Giarratano, Antonino, Cortegiani, Andrea, Brescia, Fabrizio, Fabiani, Fabio, Zanier, Chiara, Nadalini, Elisa, Gambaretti, Eros, Gabriele, Francesco, Astuto, Marinella, Murabito, Paolo, Sanfilippo, Filippo, Misseri, Giovanni, Moscarelli, Alessandra, Spadaro, Savino, Bussolati, Enrico, Squadrani, Eleonora, Villa, Gianluca, D’Errico, Raffaella, Cocci, Giulia, Lanini, Iacopo, Mirabella, Lucia, Morelli, Alessandra, Tullo, Livio, Caggianelli, Girolamo, Ball, Lorenzo, Iiriti, Margherita, Giordani, Francesca, Giardina, Massimiliano, Mazzeo, Anna Teresa, Grasselli, Giacomo, Cattaneo, Emanuele, Alongi, Salvatore, Marenghi, Cristina, Marmiere, Marilena, Rocchi, Margherita, Turi, Stefano, Landoni, Giovanni, Torrano, Vito, Tinti, Giulia, Giorgi, Antonio, Fumagalli, Roberto, Salvo, Francesco, Blangetti, Ilaria, Cascella, Marco, Forte, Cira Antonietta, Navalesi, Paolo, Montalbano, Marta, Chiarelli, Valentina, Bonanno, Giuseppe, Ferrara, Francesco Paolo, Pernice, Innocenza, Catalisano, Giulia, Marino, Claudia, Presti, Gabriele, Fricano, Dario Calogero, Fucà, Rosa, Palmeri di Villalba, Cesira, Strano, Maria Teresa, Caruso, Sabrina, Scafidi, Antonino, Mazzarese, Vincenzo, Augugliaro, Ettore, Terranova, Valeria, Forfori, Francesco, Corradi, Francesco, Taddei, Erika, Isirdi, Alessandro, Pratesi, Giorgia, Puccini, Francesca, Paternoster, Gianluca, Barile, Alessio, Tescione, Marco, Santacaterina, Irene, Siclari, Eliana Maria, Tripodi, Vincenzo Francesco, Vadalà, Mariacristina, Agrò, Felice Eugenio, Pascarella, Giuseppe, Piliego, Chiara, Aceto, Paola, De Pascale, Gennaro, Dottarelli, Alessandra, Romanò, Bruno, Russo, Andrea, Covotta, Marco, Giorgerini, Valeria, Sardellitti, Federica, Vitelli, Giulia Maria, Coluzzi, Flaminia, Bove, Tiziana, Vetrugno, Luigi.
Journal of Anesthesia, Analgesia and Critical Care ; 1(1):17-17, 2021.
Article in English | BioMed Central | ID: covidwho-1542137
10.
Ultraschall Med ; 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1500782

ABSTRACT

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

11.
Intensive Crit Care Nurs ; 67: 103093, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1469862

ABSTRACT

OBJECTIVES: To evaluate the effects of the reorganisation of an intensive care unit for COVID-19 patients in the context of the SARS-CoV-2 pandemic on wellbeing perceived by nurses. METHODS: An observational cross-sectional study was conducted to evaluate wellbeing perceived by nurses who during the study were on duty in the COVID-19 intensive care unit. The "Covid-19-Nurse Well-being at Work (NWB) scale" questionnaire consisting of 72 items divided into 13 sections, was validated and used to collect data. RESULTS: The level of wellbeing perceived by the nurses was very good (4.77; SD 0.83). Differences in the of level of perceived wellbeing were found for "years of experience" and the various levels of competence. We found a positive correlation between "female gender" and "nurses' togetherness and collaboration", a negative correlation between "male gender" and "satisfactory practical organisation of work, and a negative correlation between "work experience" and the overall "level of wellbeing at work. CONCLUSIONS: The reorganisation had positive effects in terms of wellbeing perceived by the nurses. The factors that contributed mostly to the perception of wellbeing were in the area of "support", "communication, and "socializing with colleagues". It is appropriate to consider "gender differences", "work experience" and "levels of competence" when implementing this type of reorganisation to respond to a pandemic or a health emergency.


Subject(s)
COVID-19 , Nurses , Cross-Sectional Studies , Female , Humans , Intensive Care Units , Job Satisfaction , Male , SARS-CoV-2 , Surveys and Questionnaires
12.
World J Emerg Surg ; 16(1): 46, 2021 09 10.
Article in English | MEDLINE | ID: covidwho-1403246

ABSTRACT

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.


Subject(s)
COVID-19/epidemiology , Global Health , Pandemics , Biomedical Research , COVID-19/diagnosis , COVID-19/therapy , COVID-19 Vaccines , Delivery of Health Care/organization & administration , Health Policy , Health Services Accessibility , Health Status Disparities , Healthcare Disparities , Humans , International Cooperation , Mass Vaccination/organization & administration , Pandemics/prevention & control , Politics , Primary Health Care/organization & administration , Telemedicine/organization & administration
13.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1388432

ABSTRACT

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.


Subject(s)
Antiviral Agents/pharmacology , Azetidines/pharmacology , COVID-19/mortality , Enzyme Inhibitors/pharmacology , Janus Kinases/antagonists & inhibitors , Liver/virology , Purines/pharmacology , Pyrazoles/pharmacology , SARS-CoV-2/pathogenicity , Sulfonamides/pharmacology , Adult , Aged , Aged, 80 and over , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Cytokine Release Syndrome , Cytokines/metabolism , Drug Evaluation, Preclinical , Female , Gene Expression Profiling , Humans , Interferon alpha-2/metabolism , Italy , Janus Kinases/metabolism , Liver/drug effects , Male , Middle Aged , Patient Safety , Platelet Activation , Proportional Hazards Models , RNA-Seq , Spain , Virus Internalization/drug effects
14.
Clin Infect Dis ; 72(11): 2021-2024, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1369070

ABSTRACT

Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 µg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.


Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents/therapeutic use , Carbapenems , Cephalosporins , Humans , Intensive Care Units , Microbial Sensitivity Tests , Prospective Studies , beta-Lactamases
15.
J Clin Med ; 10(16)2021 Aug 08.
Article in English | MEDLINE | ID: covidwho-1348654

ABSTRACT

INTRODUCTION: Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID-19 and the mechanisms of action of Ig led to the consideration of this adjunctive therapy, including in patients with respiratory failure due to the SARS-CoV-2 infection. This manuscript reports the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID-19. METHODS: A panel of multidisciplinary experts defined the clinical phenotypes of COVID-19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. RESULTS: Three different phenotypes of COVID-19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune paralysis (late phase) and patients with sepsis due to a hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panelists considered its use in the late phase and patients with sepsis/septic shock by bacterial superinfection appropriate. CONCLUSION: As with other immunotherapies, IVIg adjunctive therapy may have a potential role in the management of COVID-19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.

16.
A A Pract ; 15(5): e01466, 2021 May 21.
Article in English | MEDLINE | ID: covidwho-1238750

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly infectious virus transmitted by inhalation of infected matter containing live virus or by exposure from contaminated surfaces. Aerosol-generating procedures (AGPs) create an increased risk of airborne transmission of infection. Tracheal extubation of coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is a risky AGP procedure owing to the proximity of the staff members to the patients' mouths and the exposure to airway secretions. We describe the use of a disposable openable mask (Janus Mask, Biomedical Srl, Florence, Italy) that might limit aerosol generation in the periextubation phase of COVID-19 cardiac surgical patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Airway Extubation , Exhalation , Humans , Intensive Care Units
17.
BMJ Open ; 11(2): e036616, 2021 02 11.
Article in English | MEDLINE | ID: covidwho-1228874

ABSTRACT

INTRODUCTION: In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose. METHODS AND ANALYSIS: The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell'Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences. TRIAL REGISTRATION DETAILS: The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.


Subject(s)
COVID-19 , Shock, Septic , Humans , Immunization, Passive , Immunoglobulin M , Prospective Studies , SARS-CoV-2 , Shock, Septic/drug therapy , Treatment Outcome
18.
Minerva Anestesiol ; 87(4): 432-438, 2021 04.
Article in English | MEDLINE | ID: covidwho-1181857

ABSTRACT

BACKGROUND: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. METHODS: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P<0.10 were entered into a multivariate logistic regression model. Cumulative probability for lack of adverse outcomes in patients with or without low baseline diaphragm muscle mass was calculated with the Kaplan-Meier product-limit estimator. RESULTS: The main findings of this study are that: 1) patients who developed adverse outcomes had thinner diaphragm than those who did not (2.0 vs. 2.2 mm, P=0.001); and 2) DT and lymphocyte count were independent significant predictors of adverse outcomes, with end-expiratory DT being the strongest (ß=-708; OR=0.492; P=0.018). CONCLUSIONS: Diaphragmatic ultrasound may be a valid tool to evaluate the risk of respiratory failure. Evaluating the need of mechanical ventilation treatment should be based not only on PaO2/FiO2, but on a more comprehensive assessment including DT because if the lungs become less compliant a thinner diaphragm, albeit free of intrinsic abnormality, may become exhausted, thus contributing to severe respiratory failure.


Subject(s)
COVID-19/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Respiratory Muscles/anatomy & histology , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Cohort Studies , Diaphragm/anatomy & histology , Diaphragm/pathology , Female , Hospital Mortality , Humans , Italy/epidemiology , Kaplan-Meier Estimate , Male , Middle Aged , Pilot Projects , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Predictive Value of Tests , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/diagnostic imaging , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , Respiratory Muscles/diagnostic imaging , Treatment Outcome , Ultrasonography
19.
Sci Rep ; 11(1): 6515, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1147151

ABSTRACT

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.


Subject(s)
Blood Coagulation Disorders/diagnosis , COVID-19/pathology , Heart Diseases/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Diseases/etiology , Hemodynamics , Heparin, Low-Molecular-Weight/therapeutic use , Hospital Mortality , Humans , Inflammation , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prospective Studies , Risk , SARS-CoV-2/isolation & purification , Troponin T/blood
20.
Intensive Care Med ; 47(4): 444-454, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1141400

ABSTRACT

PURPOSE: To analyze the application of a lung ultrasound (LUS)-based diagnostic approach to patients suspected of COVID-19, combining the LUS likelihood of COVID-19 pneumonia with patient's symptoms and clinical history. METHODS: This is an international multicenter observational study in 20 US and European hospitals. Patients suspected of COVID-19 were tested with reverse transcription-polymerase chain reaction (RT-PCR) swab test and had an LUS examination. We identified three clinical phenotypes based on pre-existing chronic diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to four different patterns: high (HighLUS), intermediate (IntLUS), alternative (AltLUS), and low (LowLUS) probability. The combination of patterns and phenotypes with RT-PCR results was described and analyzed. RESULTS: We studied 1462 patients, classified in mild (n = 400), severe (n = 727), and mixed (n = 335) phenotypes. HighLUS and IntLUS showed an overall sensitivity of 90.2% (95% CI 88.23-91.97%) in identifying patients with positive RT-PCR, with higher values in the mixed (94.7%) and severe phenotype (97.1%), and even higher in those patients with objective respiratory failure (99.3%). The HighLUS showed a specificity of 88.8% (CI 85.55-91.65%) that was higher in the mild phenotype (94.4%; CI 90.0-97.0%). At multivariate analysis, the HighLUS was a strong independent predictor of RT-PCR positivity (odds ratio 4.2, confidence interval 2.6-6.7, p < 0.0001). CONCLUSION: Combining LUS patterns of probability with clinical phenotypes at presentation can rapidly identify those patients with or without COVID-19 pneumonia at bedside. This approach could support and expedite patients' management during a pandemic surge.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Ultrasonography , Adult , Aged , Early Diagnosis , Humans , Middle Aged
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