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1.
Can Respir J ; 2022: 1499690, 2022.
Article in English | MEDLINE | ID: covidwho-1650370

ABSTRACT

Background: Continuous positive airway pressure (CPAP) can be beneficial in acute respiratory failure (ARF) due to coronavirus (COVID-19) pneumonia, but delaying endotracheal intubation (ETI) in nonresponders may increase mortality. We aimed at investigating the performance of composite respiratory indexes as possible predictors of CPAP failure in ARF due to COVID-19. Methods: This was a multicenter, prospective, observational, and cohort study conducted in the respiratory units of three University hospitals in Milan and in a secondary care hospital in Codogno (Italy), on consecutive adult patients with ARF due to COVID-19 pneumonia that underwent CPAP between March 2020 and March 2021. ETI transfer to the intensive care unit or death is defined CPAP failure. Predictors of CPAP failure were assessed before T0 and 1 hour after T1 CPAP initiation and included mROX index (ratio of PaO2/FiO2 to respiratory rate), alveolar-to-arterial (A-a) O2 gradient, and the HACOR (heart rate, acidosis, consciousness, oxygenation, and respiratory rate) score. Results: Three hundred and fifty four patients (mean age 64 years, 73% males) were included in the study; 136 (38.4%) satisfied criteria for CPAP failure. A-a O2 gradient, mROX, and HACOR scores were worse in patients who failed CPAP, both at T0 and T1 (p < 0.001 for all parameters). The HACOR score was associated with CPAP failure (odds ratio-OR-for every unit increase in HACOR = 1.361; 95%CI: 1.103-1.680; p=0.004; AUROC = 0.742; p < 0.001). CPAP failure was best predicted by a threshold of 4.50 (sensitivity = 53% and specificity = 87%). Conclusions: The HACOR score may be a reliable and early predictor of CPAP failure in patients treated for ARF in COVID-19 pneumonia.


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Adult , Cohort Studies , Continuous Positive Airway Pressure , Female , Humans , Male , Middle Aged , Pneumonia/complications , Pneumonia/epidemiology , Prospective Studies , Respiratory Insufficiency/therapy , SARS-CoV-2
2.
J Clin Med ; 10(24)2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1572519

ABSTRACT

BACKGROUND: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. METHODS: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. RESULTS: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7-4.6) in the PDT group and 5.5 (3.4-7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. CONCLUSIONS: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.

4.
J Clin Med ; 10(22)2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1534114

ABSTRACT

The best noninvasive respiratory strategy in patients with Coronavirus Disease 2019 (COVID-19) pneumonia is still discussed. We aimed at assessing the rate of endotracheal intubation (ETI) in patients treated with continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) if CPAP failed. Secondary outcomes were in-hospital mortality and in-hospital length of stay (LOS). A retrospective, observational, multicenter study was conducted in intermediate-high dependency respiratory units of two Italian university hospitals. Consecutive patients with COVID-19 treated with CPAP were enrolled. Thoraco-abdominal asynchrony or hemodynamic instability led to ETI. Patients showing SpO2 ≤ 94%, respiratory rate ≥ 30 bpm or accessory muscle activation on CPAP received NIV. Respiratory distress and desaturation despite NIV eventually led to ETI. 156 patients were included. The overall rate of ETI was 30%, mortality 18% and median LOS 24 (17-32) days. Among patients that failed CPAP (n = 63), 28% were intubated, while the remaining 72% received NIV, of which 65% were intubated. Patients intubated after CPAP showed lower baseline PaO2/FiO2, lower lymphocyte counts and higher D-dimer values compared with patients intubated after CPAP + NIV. Mortality was 22% with CPAP + ETI, and 20% with CPAP + NIV + ETI. In the case of CPAP failure, a NIV trial appears feasible, does not deteriorate respiratory status and may reduce the need for ETI in COVID-19 patients.

5.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1518198

ABSTRACT

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1ß, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.


Subject(s)
COVID-19/complications , Cytokines/immunology , Immune Checkpoint Inhibitors/pharmacology , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Case-Control Studies , Cytokines/drug effects , DNA Methylation , Female , Humans , Immunophenotyping , In Vitro Techniques , Interleukin 1 Receptor Antagonist Protein/drug effects , Interleukin 1 Receptor Antagonist Protein/immunology , Interleukin-1beta/drug effects , Interleukin-1beta/immunology , Interleukin-8/drug effects , Interleukin-8/immunology , Male , MicroRNAs/metabolism , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Promoter Regions, Genetic
6.
Infect Dis Ther ; 10(4): 1837-1885, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1333141

ABSTRACT

INTRODUCTION: The Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) constituted an expert panel for developing evidence-based guidance for the clinical management of adult patients with coronavirus disease 2019 (COVID-19) outside intensive care units. METHODS: Ten systematic literature searches were performed to answer ten different key questions. The retrieved evidence was graded according to the Grading of Recommendations Assessment, Development, and Evaluation methodology (GRADE). RESULTS AND CONCLUSION: The literature searches mostly assessed the available evidence on the management of COVID-19 patients in terms of antiviral, anticoagulant, anti-inflammatory, immunomodulatory, and continuous positive airway pressure (CPAP)/non-invasive ventilation (NIV) treatment. Most evidence was deemed as of low certainty, and in some cases, recommendations could not be developed according to the GRADE system (best practice recommendations were provided in similar situations). The use of neutralizing monoclonal antibodies may be considered for outpatients at risk of disease progression. For inpatients, favorable recommendations were provided for anticoagulant prophylaxis and systemic steroids administration, although with low certainty of evidence. Favorable recommendations, with very low/low certainty of evidence, were also provided for, in specific situations, remdesivir, alone or in combination with baricitinib, and tocilizumab. The presence of many best practice recommendations testified to the need for further investigations by means of randomized controlled trials, whenever possible, with some possible future research directions stemming from the results of the ten systematic reviews.

7.
Pharmacol Res ; 158: 104950, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318942

ABSTRACT

Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 µg/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 µg/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes' function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Hypoxia/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Thrombophilia/drug therapy , Aged , Aspirin/therapeutic use , COVID-19 , Clopidogrel/therapeutic use , Compassionate Use Trials , Coronavirus Infections/complications , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypoxia/complications , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Proof of Concept Study , SARS-CoV-2 , Thrombophilia/blood , Thrombophilia/complications , Tirofiban/therapeutic use
9.
Minerva Anestesiol ; 87(8): 915-926, 2021 08.
Article in English | MEDLINE | ID: covidwho-1244403

ABSTRACT

INTRODUCTION: To date, a shared international consensus on treatment of Coronavirus disease 2019 (COVID-19) with invasive or non-invasive respiratory support is lacking. Patients' management and outcomes, especially in severe and critical cases, can vary depending on regional standard operating procedures and local guidance. EVIDENCE ACQUISITION: Rapid review methodology was applied to include all the studies published on PubMed and Embase between December 15th, 2019 and February 28th, 2021, reporting in-hospital and respiratory support-related mortality in adult patients hospitalized with COVID-19 that underwent either continuous positive airway pressure (CPAP), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV). Only English language studies with ≥100 patients and reporting data on respiratory failure were included. Data on comorbidities, ventilatory parameters and hospital-related complications were registered. EVIDENCE SYNTHESIS: Fifty-two studies (287,359 patients; 57.5% males, mean age 64 years, range 24-98 years) from 17 different countries were included in the final analysis. 33.3% of patients were hospitalized in intensive care units. 44.2% had hypertension, 26.1% had diabetes, and 7.1% a chronic respiratory disease. 55% of patients underwent respiratory support (36% IMV, 62% NIV and 2% CPAP). Without considering a study with the highest number of patients treated with NIV (N.=96,729), prevalence of NIV and CPAP use was 12.5% and 13.5% respectively. Globally, invasive and non-invasive approaches were heterogeneously applied. In-hospital mortality was 33.7%, and IMV-related mortality was 72.6% (range: 4.3-99%). Specific mortality in patients treated with CPAP or NIV was available for 53% of studies, and was 29% (range: 7.2-100%). The median length of hospital stay was 13 days (range: 6-63). The most frequent hospital-related complication was acute kidney injury being reported in up to 55.7% of enrolled patients. CONCLUSIONS: Global employment of respiratory supports and related outcomes are very heterogeneous. The most frequent respiratory support in patients with COVID-19 pneumonia is IMV, while NIV and CPAP are less frequently and equally applied, the latter especially in Europe, while data on NIV/CPAP-related mortality is often under-reported. Integrated and comprehensive reporting is desirable and needed to construct evidence-based recommendations.


Subject(s)
COVID-19 , Noninvasive Ventilation , Pneumonia , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Respiration, Artificial , SARS-CoV-2 , Young Adult
10.
J Crit Care ; 65: 1-8, 2021 10.
Article in English | MEDLINE | ID: covidwho-1240427

ABSTRACT

INTRODUCTION AND AIM: Non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP) have been widely employed to treat acute respiratory failure secondary to COVID-19 pneumonia, but their role in terms of efficacy and safety are still debated. The aim of this review was to analyse mortality and intubation rates in COVID-19 patients treated with NIV/CPAP. METHODS: Rapid review methodology was applied to include all the studies published since December-2019 until November-2020 with available data on in-hospital mortality in COVID-19 patients treated with NIV or CPAP. RESULTS: 23 manuscripts were included (4776 patients, 66% males, 46% with hypertension). 46% of patients received non-invasive respiratory support, of which 48.4% with CPAP, 46% with NIV, and 4% with either CPAP or NIV. Non-invasive respiratory support failed in 47.7% of patients, of which 26.5% were intubated and 40.9% died. In-hospital mortality was higher in patients treated with NIV compared with CPAP (35.1% vs. 22.2%). Complications were under-reported, but mostly not related to CPAP/NIV treatment. CONCLUSION: CPAP and NIV appear equally and frequently applied in patients with COVID-19 pneumonia, but associated with high mortality. Robust evidence is urgently needed to confirm the clinical efficacy of non-invasive respiratory support in COVID-19-related ARDS.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Distress Syndrome , Continuous Positive Airway Pressure , Female , Humans , Male , SARS-CoV-2
11.
Front Immunol ; 12: 656362, 2021.
Article in English | MEDLINE | ID: covidwho-1211814

ABSTRACT

Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/prevention & control , Immune System Diseases/virology , Vaccination/methods , Diabetes Mellitus/immunology , Diabetes Mellitus/virology , Europe , Expert Testimony , Glomerulonephritis/complications , Glomerulonephritis/immunology , Glomerulonephritis/virology , Humans , Inflammation/immunology , Inflammation/virology , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/virology , Lung Diseases/complications , Lung Diseases/immunology , Lung Diseases/virology , Pandemics/prevention & control , Rheumatic Diseases/complications , Rheumatic Diseases/immunology , Rheumatic Diseases/virology , Skin Diseases/complications , Skin Diseases/immunology , Skin Diseases/virology , Uveitis/complications , Uveitis/immunology , Uveitis/virology
12.
J Clin Med ; 10(5)2021 Mar 02.
Article in English | MEDLINE | ID: covidwho-1125440

ABSTRACT

Radiological and functional sequelae of Coronavirus Disease 2019 (COVID-19) pneumonia are still poorly understood. This was a prospective, observational, physiological, cohort study on consecutive adult patients with COVID-19 pneumonia admitted in April-May 2020 in the high dependency respiratory unit of L. Sacco University Hospital in Milan (Italy). During hospitalization, patients underwent chest computed tomography (CT), blood gas analysis, spirometry, and lung diffusion capacity for carbon monoxide (DLco), which were repeated 6 weeks post-discharge. Chest CTs were individually read by two expert radiologists, that calculated the total severity score (TSS). Twenty patients completed the study (mean age 58.2 years, 70% males). During the acute phase, mean DLco, alveolar volume (VA), and vital capacity (VC) were 56.0 (16.3), 64.8 (14.0), and 71.7 (16.9) % predicted, respectively, and were inversely associated with PaO2/FiO2 ratio. Fifty percent of patients had a restrictive ventilatory pattern; mean TSS was 7.9 (4.0). At follow up, gas exchange parameters were normalized; consolidations persisted in 10% of cases, while DLco was <80% predicted in 65% of patients and was independently predicted by Log10D-dimer at admission (ß -18.675; 95%CI, -28.373--9.076; p = 0.001). In conclusion, functional abnormalities in COVID-19 pneumonia survivors can persist during follow up and are associated with the severity of the disease.

13.
Respir Med ; 178: 106323, 2021 03.
Article in English | MEDLINE | ID: covidwho-1065565

ABSTRACT

BACKGROUND: The therapeutic approach to COVID-19 and healthcare system preparedness improved during 2020. We compared characteristics and outcomes of hospitalized COVID-19 patients during the first 28 days of the March and October pandemic waves in Milan, Italy. MATERIAL AND METHODS: A prospective, observational study enrolling adult patients hospitalized with COVID-19 pneumonia during March 7-April 4 (1st period) and October 15-November 12 (2nd period). During the 1st period hydroxychloroquine, lopinavir/ritonavir and therapeutic enoxaparin when thrombosis was confirmed were administered; systemic corticosteroids were given in case of severe pneumonia. During the 2nd period dexamethasone, methylprednisolone, remdesivir, thromboprophylaxis or anticoagulation were administered according to international recommendations. Patients with respiratory distress on oxygen masks initiated CPAP. Outcomes were: length of hospital stay, all-cause in-hospital mortality and need for intubation. RESULTS: We included 70 patients (75% males) during the 1st and 76 patients (51% males, p = 0.522) during the 2nd period. Prevalence of severe respiratory failure (30% vs. 12%, p = 0.006), and D-dimer >3000 FEU (34% vs. 15%, P = 0.012) were reduced during the 2nd period, while anticoagulation and corticosteroids were more frequently administered (both p < 0.01). Mortality and time to referral were also reduced (39.4% vs. 22.4%, p = 0.019 and 6 vs. 5 days, p = 0.014), while need for intubation didn't change. Hospitalization length was comparable, but the proportion of patients discharged home was higher during the 2nd period (28.2% vs. 55.4%, p = 0.001). CONCLUSIONS: Changing treatment paradigms and early referral might have reduced mortality in COVID-19 patients. The effects of specific therapeutic regimens needs further confirmation in future clinical studies.


Subject(s)
COVID-19/therapy , Hospitalization , Respiratory Therapy , Adult , Aged , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Female , Hospital Mortality , Humans , Italy , Length of Stay , Male , Middle Aged , Prospective Studies , Seasons , Survival Rate
14.
Multidiscip Respir Med ; 15(1): 713, 2020 Jan 28.
Article in English | MEDLINE | ID: covidwho-895437

ABSTRACT

BACKGROUND: To date, the effects of COVID-19 pneumonia on health-related quality of life (HRQoL) and dyspnoea are unknown. METHODS: In a real-life observational study, 20 patients with COVID-19-related pneumonia received usual care plus erdosteine (300 mg twice daily) for 15 days after hospital discharge following local standard operating procedures. At discharge (T0) and on Day 15 (T1), participants completed the St George's Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale of dyspnoea during daily activity, the BORG scale for dyspnoea during exertion, and Visual Analogue Scale (VAS) for dyspnoea at rest. Paired t-tests compared scores at T0 and T1. RESULTS: The mean (SD) SGRQ total score decreased from 25.5 (15.5) at T0 to 16.9 (13.2) at T1 (p<0.01); 65% of patients achieved a clinically important change of ≥4 points. SGRQ domain scores (symptoms, activity, and impact) were also significantly reduced (all p<0.01). The mean (SD) VAS score decreased from 1.6 (1.7) to 1.4 (2.5); p<0.01. The mean mMRC score decreased significantly (p=0.031) and 30% of patients achieved a clinically important change of ≥1 point. The mean (SD) Borg score increased from 12.8 (4.2) to 14.3 (2.4); p<0.01. CONCLUSION: The present proof of concept study is the first to report HRQoL in patients with COVID-19. During 15 days after hospital discharge, patients reported significant improvements in HRQoL and dyspnoea at rest and during daily activities.

16.
BMJ Open ; 10(10): e043651, 2020 10 10.
Article in English | MEDLINE | ID: covidwho-845975

ABSTRACT

OBJECTIVES: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients' outcomes is still poorly understood. DESIGN: Observational, prospective, multicentre study. SETTING: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards. PARTICIPANTS: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded. INTERVENTIONS: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101-200 mm Hg); mild (PaO2/FiO2 201-300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay. RESULTS: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55-76) years with a PaO2/FiO2 at admission of 262 (140-343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04). CONCLUSIONS: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality. TRIAL REGISTRATION NUMBER: NCT04307459.


Subject(s)
Coronavirus Infections/pathology , Hospital Mortality , Hospitalization , Oxygen/blood , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/etiology , Severe Acute Respiratory Syndrome/etiology , Severity of Illness Index , Aged , Betacoronavirus , Blood Gas Analysis , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/mortality , Coronavirus Infections/virology , Female , Hospitals , Humans , Hypoxia , Intensive Care Units , Italy/epidemiology , Lung/metabolism , Lung/pathology , Lung/virology , Male , Middle Aged , Pandemics , Partial Pressure , Pneumonia, Viral/metabolism , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Prospective Studies , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/virology
17.
Open Forum Infect Dis ; 7(10): ofaa421, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-756944

ABSTRACT

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.

18.
J Clin Med ; 9(4)2020 Apr 22.
Article in English | MEDLINE | ID: covidwho-102095

ABSTRACT

Since the beginning of March 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 13,000 deaths in Europe, almost 54% of which has occurred in Italy. The Italian healthcare system is experiencing a stressful burden, especially in terms of intensive care assistance. In fact, the main clinical manifestation of COVID-19 patients is represented by an acute hypoxic respiratory failure secondary to bilateral pulmonary infiltrates, that in many cases, results in an acute respiratory distress syndrome and requires an invasive ventilator support. A precocious respiratory support with non-invasive ventilation or high flow oxygen should be avoided to limit the droplets' air-dispersion and the healthcare workers' contamination. The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia. It can also limit the room contamination, improve comfort for the patients, and allow for better clinical assistance with long-term tolerability. However, the initiation of a CPAP is not free from pitfalls. It requires a careful titration and monitoring to avoid a delayed intubation. Here, we discuss the rationale and some important considerations about timing, criteria, and monitoring requirements for patients with COVID-19 respiratory failure requiring a CPAP treatment.

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