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1.
PLoS One ; 17(7): e0271450, 2022.
Article in English | MEDLINE | ID: covidwho-1951555

ABSTRACT

BACKGROUND: Around 12-20% of patients with community-acquired pneumonia (CAP) require critical care. Ventilator-associated pneumonia (VAP) is the second cause of nosocomial infection in Paediatric Intensive Care Units (PICU). As far as we know, there are no studies comparing both types of pneumonia in children, thus it remains unclear if there are differences between them in terms of severity and outcomes. OBJECTIVE: The aim was to compare clinical and microbiological characteristics and outcomes of patients with severe CAP and VAP. METHODS: A retrospective descriptive study, including patients diagnosed of VAP and CAP, with a positive respiratory culture and under mechanical ventilation, admitted to the PICU from 2015 to 2019. RESULTS: 238 patients were included; 163 (68.4%) with CAP, and 75 (31.5%) with VAP. Patients with VAP needed longer mechanical ventilation (14 vs. 7 days, p<0.001) and more inotropic support (49.3 vs. 30.7%, p = 0.006). Patients with VAP had higher mortality (12 vs. 2.5%, p = 0.005). Enterobacterales were more involved with VAP than with CAP (48 vs. 9%, p<0.001). Taking into account only the non-drug sensitive microorganisms, patients with VAP tended to have more multidrug-resistant bacteria (30 vs. 10.8%, p = 0.141) than patients with CAP. CONCLUSION: Patients with VAP had worse prognosis than patients with CAP, needing longer mechanical ventilation, more inotropic support and had higher mortality. Patients with VAP were mainly infected by Enterobacterales and had more multidrug resistant microorganisms than patients with CAP.


Subject(s)
Community-Acquired Infections , Pneumonia, Bacterial , Pneumonia, Ventilator-Associated , Child , Community-Acquired Infections/microbiology , Community-Acquired Infections/therapy , Humans , Intensive Care Units, Pediatric , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/therapy , Pneumonia, Ventilator-Associated/microbiology , Pneumonia, Ventilator-Associated/therapy , Prognosis , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Retrospective Studies
3.
Sci Rep ; 12(1): 536, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1815583

ABSTRACT

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092-0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.


Subject(s)
COVID-19/diagnosis , Hyperglycemia/drug therapy , Insulin/therapeutic use , Linagliptin/therapeutic use , Blood Glucose/analysis , COVID-19/complications , COVID-19/virology , Drug Therapy, Combination , Female , Hospitalization , Humans , Hyperglycemia/complications , Length of Stay , Male , Middle Aged , Prognosis , Proportional Hazards Models , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/isolation & purification
5.
BMC Anesthesiol ; 22(1): 59, 2022 03 04.
Article in English | MEDLINE | ID: covidwho-1724413

ABSTRACT

BACKGROUND: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. METHODS: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum¼ positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. RESULTS: The «optimum¼ PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). CONCLUSION: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate¼ PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Lung/physiopathology , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/epidemiology , Aged , COVID-19/physiopathology , Critical Care/methods , Female , Humans , Male , Middle Aged , Noninvasive Ventilation/statistics & numerical data , Positive-Pressure Respiration , Prospective Studies , Respiratory Insufficiency/physiopathology , Respiratory Mechanics , Russia/epidemiology , SARS-CoV-2 , Survival Analysis , Tidal Volume , Treatment Failure
6.
CMAJ ; 194(7): E242-E251, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1714791

ABSTRACT

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/administration & dosage , COVID-19/drug therapy , Hospital Mortality , Length of Stay/statistics & numerical data , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Aged , Alanine/administration & dosage , Alanine/adverse effects , Antiviral Agents/adverse effects , COVID-19/epidemiology , COVID-19/mortality , Canada/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Pandemics , Respiration, Artificial/statistics & numerical data , SARS-CoV-2
7.
J Immunol ; 208(2): 321-327, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1708204

ABSTRACT

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.


Subject(s)
8-Hydroxy-2'-Deoxyguanosine/blood , Community-Acquired Infections/pathology , Pneumonia/blood , Pneumonia/mortality , Severity of Illness Index , Aged , Biomarkers/blood , Community-Acquired Infections/blood , Critical Care/statistics & numerical data , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Oxidative Stress/physiology , Pneumonia/pathology , Prognosis , Prospective Studies , Respiration, Artificial/statistics & numerical data
8.
Sci Rep ; 12(1): 2798, 2022 02 18.
Article in English | MEDLINE | ID: covidwho-1707401

ABSTRACT

Brazil is a country of continental dimensions, where many smaller countries would fit. In addition to demographic, socioeconomic, and cultural differences, hospital infrastructure and healthcare varies across all 27 federative units. Therefore, the evolution of COVID-19 pandemic did not manifest itself in a homogeneous and predictable trend across the nation. In late 2020 and early 2021, new waves of the COVID-19 outbreak have caused an unprecedented sanitary collapse in Brazil. Unlike the first COVID-19 wave, in subsequent waves, preliminary evidence has pointed to an increase in the daily reported cases among younger people being hospitalized, overloading the healthcare system. In this comprehensive retrospective cohort study, confirmed cases of hospitalization, ICU admission, IMV requirement and in-hospital death from Brazilian COVID-19 patients throughout 2020 until the beginning of 2021 were analyzed through a spatio-temporal study for patients aged 20-59 years. All Brazilian federative units had their data disaggregated in six periods of ten epidemiological weeks each. We found that there is a wide variation in the waves dynamic due to SARS-CoV-2 infection, both in the first and in subsequent outbreaks in different federative units over the analyzed periods. As a result, atypical waves can be seen in the Brazil data as a whole. The analysis showed that Brazil is experiencing a numerical explosion of hospitalizations and deaths for patients aged 20-59 years, especially in the state of São Paulo, with a similar proportion of hospitalizations for this age group but higher proportion of deaths compared to the first wave.


Subject(s)
COVID-19/mortality , Adult , Brazil/epidemiology , COVID-19/therapy , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Middle Aged , Odds Ratio , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Young Adult
9.
CMAJ Open ; 10(1): E74-E81, 2022.
Article in English | MEDLINE | ID: covidwho-1703594

ABSTRACT

BACKGROUND: During the first wave of the COVID-19 pandemic, a substantial number of Quebec hospitals were hit by hospital-acquired (HA) SARS-CoV-2 infections. Our objective was to assess whether mortality is higher in HA cases than in non-hospital-acquired (NHA) cases and determine the prevalence of HA-SARS-CoV-2 infection in our hospital. METHODS: This retrospective single-centre cohort study included all adults (≥ 18 yr) who had COVID-19, admitted to Hôpital Maisonneuve-Rosemont (Montréal, Canada) from Mar. 1 to June 30, 2020. We collected data on demographic characteristics, comorbidities, treatment, admission to the intensive care unit (ICU) and mechanical ventilation requirements from electronic health records. We adjudicated hospital acquisition based on the timing of symptom onset, and polymerase chain reaction testing for and exposures to SARS-CoV-2. To evaluate the association between HA-SARS-CoV-2 infection and in-hospital mortality, we computed a multivariable logistic regression analysis including known risk factors for death in patients with COVID-19 as covariates. RESULTS: Among 697 patients with SARS-CoV-2 infection, 253 (36.3%) were classified as HA. The mortality rate was higher in the HA group than in the NHA group (38.2% v. 26.4%, p = 0.001), while the rates of ICU admission (8.3% v. 19.1%, p = 0.001) and requirement for mechanical ventilation (3.6% v. 13.0%, p = 0.001) were lower. Multivariable logistic regression analysis showed that HA-SARS-CoV-2 infection in patients younger than 75 years is an independent risk factor for death (odds ratio 2.78, 95% confidence interval 1.44-5.38). INTERPRETATION: Our results show that HA-SARS-CoV-2 infection in younger patients was associated with higher mortality. Future studies need to evaluate relevant patient-centred long-term outcomes in this population.


Subject(s)
COVID-19/mortality , Iatrogenic Disease/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Female , Hospital Mortality , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Pandemics/statistics & numerical data , Quebec/epidemiology , RNA, Viral/isolation & purification , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Treatment Outcome , Young Adult
10.
Lancet ; 397(10289): 2049-2059, 2021 May 29.
Article in English | MEDLINE | ID: covidwho-1671320

ABSTRACT

BACKGROUND: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79). INTERPRETATION: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.


Subject(s)
COVID-19/therapy , Hospital Mortality , Length of Stay/statistics & numerical data , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/mortality , Female , Humans , Immunization, Passive/methods , Immunization, Passive/mortality , Male , Middle Aged , Pandemics , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Treatment Outcome , United Kingdom/epidemiology
11.
JAMA ; 327(3): 227-236, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1669289

ABSTRACT

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Heparin/administration & dosage , Inpatients , Purinergic P2Y Receptor Antagonists/administration & dosage , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/mortality , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Comorbidity , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Hemorrhage/chemically induced , Heparin/adverse effects , Hospital Mortality , Humans , Male , Medical Futility , Middle Aged , Outcome Assessment, Health Care , Oxygen Inhalation Therapy/statistics & numerical data , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/adverse effects , Receptors, Purinergic P2Y12 , Respiration, Artificial/statistics & numerical data , Thrombosis/epidemiology , Ticagrelor/administration & dosage , Ticagrelor/adverse effects , Time Factors , Treatment Outcome
12.
Viruses ; 14(2)2022 01 28.
Article in English | MEDLINE | ID: covidwho-1667344

ABSTRACT

Unselected data of nationwide studies of hospitalized patients with COVID-19 are still sparse, but these data are of outstanding interest to avoid exceeding hospital capacities and overloading national healthcare systems. Thus, we sought to analyze seasonal/regional trends, predictors of in-hospital case-fatality, and mechanical ventilation (MV) in patients with COVID-19 in Germany. We used the German nationwide inpatient samples to analyze all hospitalized patients with a confirmed COVID-19 diagnosis in Germany between 1 January and 31 December in 2020. We analyzed data of 176,137 hospitalizations of patients with confirmed COVID-19-infection. Among those, 31,607 (17.9%) died, whereby in-hospital case-fatality grew exponentially with age. Overall, age ≥ 70 years (OR 5.91, 95%CI 5.70-6.13, p < 0.001), pneumonia (OR 4.58, 95%CI 4.42-4.74, p < 0.001) and acute respiratory distress syndrome (OR 8.51, 95%CI 8.12-8.92, p < 0.001) were strong predictors of in-hospital death. Most COVID-19 patients were treated in hospitals in urban areas (n = 92,971) associated with the lowest case-fatality (17.5%), as compared to hospitals in suburban (18.3%) or rural areas (18.8%). MV demand was highest in November/December 2020 (32.3%, 20.3%) in patients between the 6th and 8th age decade. In the first age decade, 78 of 1861 children (4.2%) with COVID-19-infection were treated with MV, and five of them died (0.3%). The results of our study indicate seasonal and regional variations concerning the number of COVID-19 patients, necessity of MV, and case fatality in Germany. These findings may help to ensure the flexible allocation of intensive care (human) resources, which is essential for managing enormous societal challenges worldwide to avoid overloaded regional healthcare systems.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Inpatients/statistics & numerical data , Aged , Aged, 80 and over , Female , Germany/epidemiology , Hospitalization/trends , Humans , Intensive Care Units/statistics & numerical data , Intensive Care Units/trends , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Respiration, Artificial/trends , Risk Factors , SARS-CoV-2/pathogenicity
13.
Lancet ; 397(10285): 1637-1645, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1655260

ABSTRACT

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , COVID-19/therapy , Hypoxia/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Hypoxia/diagnosis , Hypoxia/virology , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Treatment Outcome , Young Adult
14.
Infect Genet Evol ; 98: 105227, 2022 03.
Article in English | MEDLINE | ID: covidwho-1648267

ABSTRACT

INTRODUCTION: The severity of SARS-CoV-2 induced coronavirus disease 19 (COVID-19) depends on the presence of risk factors and the hosts' gene variability. There are preliminary results that gene polymorphisms of the renin-angiotensin system can influence the susceptibility to and mortality from COVID-19. Angiotensin II type 1 receptor (AT1R) might be a gene candidate that exerts such influence. The aim of this study was to elaborate on the association between A1166C at1r polymorphic variants and the susceptibility to and severity of COVID-19 in the Ukrainian population. METHODS: The study population consisted of the Ukrainian population (Poltava region) with COVID-19, divided into three clinical groups in accordance with oxygen requirement: patients without oxygen therapy (n = 110), with non-invasive (n = 136) and invasive (n = 36) oxygen therapy. The A1166C polymorphism of the at1r was determined by polymerase chain reaction with subsequent restrictase analysis. In an attempt to better explain the role of the A1166C at1r polymorphism we compared its association with COVID-19, essential hypertension (n = 79), renoparenchimal hypertension (n = 30) and dyscirculatory encephalopathy (n = 112). The data for this comparison were obtained by meta-analysis. RESULTS: We observed significant differences in the frequency of AA, AC and CC genotypes in the groups of COVID-19 patients with non-invasive and invasive oxygen therapy in comparison with control subjects as well as in the frequency of combined AC + CC genotype between the groups of COVID-19 patients with any types of oxygen therapy and patients without oxygen therapy. The frequency of the 1166C allele was higher in COVID-19 patients with invasive oxygen therapy (OR = 2.06; CI (1.20-3.53); p = 0.013). We obtained important results indicating that there were no differences between the frequency of at1r polymorphisms in patients with cardiovascular disease and severe COVID-19 with invasive oxygen therapy as well as those who died due to COVID-19. CONCLUSION: Our study indicated the presence of an association between the A1166C at1r polymorphisms and the severity of COVID-19 in the Ukrainian population. It seems that in carriers of 1166C at1r, the severity of COVID-19 and oxygen dependency is higher as compared to the A allele carriers, possibly, due to cardiovascular disorders.


Subject(s)
COVID-19/genetics , COVID-19/therapy , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Receptor, Angiotensin, Type 1/genetics , SARS-CoV-2/genetics , Severity of Illness Index , Adult , Alleles , COVID-19/epidemiology , Female , Genotype , Humans , Male , Middle Aged , Respiration, Artificial/methods , Respiration, Artificial/statistics & numerical data , Risk Factors , Ukraine/epidemiology
15.
PLoS One ; 17(1): e0262522, 2022.
Article in English | MEDLINE | ID: covidwho-1635737

ABSTRACT

BACKGROUND: Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS: We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS: 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS: UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.


Subject(s)
COVID-19/pathology , Upper Extremity Deep Vein Thrombosis/epidemiology , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Comorbidity , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Oxygen Consumption , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Upper Extremity Deep Vein Thrombosis/diagnosis , Upper Extremity Deep Vein Thrombosis/etiology
16.
PLoS One ; 17(1): e0262315, 2022.
Article in English | MEDLINE | ID: covidwho-1622359

ABSTRACT

BACKGROUND: The role of non-invasive ventilation (NIV) in severe COVID-19 remains a matter of debate. Therefore, the utilization and outcome of NIV in COVID-19 in an unbiased cohort was determined. AIM: The aim was to provide a detailed account of hospitalized COVID-19 patients requiring non-invasive ventilation during their hospital stay. Furthermore, differences of patients treated with NIV between the first and second wave are explored. METHODS: Confirmed COVID-19 cases of claims data of the Local Health Care Funds with non-invasive and/or invasive mechanical ventilation (MV) in the spring and autumn pandemic period in 2020 were comparable analysed. RESULTS: Nationwide cohort of 17.023 cases (median/IQR age 71/61-80 years, 64% male) 7235 (42.5%) patients primarily received IMV without NIV, 4469 (26.3%) patients received NIV without subsequent intubation, and 3472 (20.4%) patients had NIV failure (NIV-F), defined by subsequent endotracheal intubation. The proportion of patients who received invasive MV decreased from 75% to 37% during the second period. Accordingly, the proportion of patients with NIV exclusively increased from 9% to 30%, and those failing NIV increased from 9% to 23%. Median length of hospital stay decreased from 26 to 21 days, and duration of MV decreased from 11.9 to 7.3 days. The NIV failure rate decreased from 49% to 43%. Overall mortality increased from 51% versus 54%. Mortality was 44% with NIV-only, 54% with IMV and 66% with NIV-F with mortality rates steadily increasing from 62% in early NIV-F (day 1) to 72% in late NIV-F (>4 days). CONCLUSIONS: Utilization of NIV rapidly increased during the autumn period, which was associated with a reduced duration of MV, but not with overall mortality. High NIV-F rates are associated with increased mortality, particularly in late NIV-F.


Subject(s)
COVID-19/therapy , Noninvasive Ventilation , Respiration, Artificial , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/mortality , Female , Hospital Mortality , Humans , Intubation, Intratracheal/statistics & numerical data , Length of Stay , Male , Middle Aged , Noninvasive Ventilation/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Treatment Outcome , Young Adult
17.
Crit Care ; 25(1): 328, 2021 09 08.
Article in English | MEDLINE | ID: covidwho-1582035

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-Cov2 virus has become the greatest health and controversial issue for worldwide nations. It is associated with different clinical manifestations and a high mortality rate. Predicting mortality and identifying outcome predictors are crucial for COVID patients who are critically ill. Multivariate and machine learning methods may be used for developing prediction models and reduce the complexity of clinical phenotypes. METHODS: Multivariate predictive analysis was applied to 108 out of 250 clinical features, comorbidities, and blood markers captured at the admission time from a hospitalized cohort of patients (N = 250) with COVID-19. Inspired modification of partial least square (SIMPLS)-based model was developed to predict hospital mortality. Prediction accuracy was randomly assigned to training and validation sets. Predictive partition analysis was performed to obtain cutting value for either continuous or categorical variables. Latent class analysis (LCA) was carried to cluster the patients with COVID-19 to identify low- and high-risk patients. Principal component analysis and LCA were used to find a subgroup of survivors that tends to die. RESULTS: SIMPLS-based model was able to predict hospital mortality in patients with COVID-19 with moderate predictive power (Q2 = 0.24) and high accuracy (AUC > 0.85) through separating non-survivors from survivors developed using training and validation sets. This model was obtained by the 18 clinical and comorbidities predictors and 3 blood biochemical markers. Coronary artery disease, diabetes, Altered Mental Status, age > 65, and dementia were the topmost differentiating mortality predictors. CRP, prothrombin, and lactate were the most differentiating biochemical markers in the mortality prediction model. Clustering analysis identified high- and low-risk patients among COVID-19 survivors. CONCLUSIONS: An accurate COVID-19 mortality prediction model among hospitalized patients based on the clinical features and comorbidities may play a beneficial role in the clinical setting to better management of patients with COVID-19. The current study revealed the application of machine-learning-based approaches to predict hospital mortality in patients with COVID-19 and identification of most important predictors from clinical, comorbidities and blood biochemical variables as well as recognizing high- and low-risk COVID-19 survivors.


Subject(s)
COVID-19/mortality , Hospital Mortality/trends , Machine Learning/standards , Severity of Illness Index , COVID-19/epidemiology , Cohort Studies , Female , Humans , Male , Prognosis , Respiration, Artificial/statistics & numerical data , Risk Assessment/methods , Risk Factors
18.
Int J Immunopathol Pharmacol ; 35: 20587384211059675, 2021.
Article in English | MEDLINE | ID: covidwho-1582485

ABSTRACT

INTRODUCTION: The fully-human monoclonal anti-interleukin (IL)-1ß antibody canakinumab may inhibit the production of inflammatory mediators in patients with coronavirus disease 2019 (COVID-19) and the hyperinflammatory response potentially leading to acute respiratory distress syndrome. OBJECTIVES: The goal of our retrospective, observational analysis was to evaluate the safety and efficacy of subcutaneous (s.c.) canakinumab in combination with our standard of care (SOC) treatment of selected patients with COVID-19 with respiratory failure and elevated reactive pro-inflammatory markers. METHODS: Eight participants received two doses of s.c. canakinumab 150 mg (or 2 mg/kg for participants weighing ≤40 kg) in addition to SOC. 12 patients received only SOC treatment. RESULTS: Canakinumab treatment reduced the need for mechanical ventilation and reduced proinflammatory markers, resulting in an amelioration of the final outcome, with respect to the control group who received SOC alone. The treatment was safe and well tolerated; no adverse events were reported. CONCLUSION: The use of canakinumab (300 mg, s.c.) in the early stage of COVID-19 with mild-to-moderate respiratory failure was superior to SOC at preventing clinical deterioration and may warrant further investigation as a treatment option for patients with COVID-19 who experience a hyperinflammatory response in the early stage of the disease.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Interleukin-1beta , Respiration, Artificial , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/immunology , Biomarkers/blood , COVID-19/complications , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Female , Humans , Inflammation Mediators/blood , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/immunology , Italy/epidemiology , Male , Middle Aged , Monitoring, Immunologic/methods , Outcome and Process Assessment, Health Care , Patient Selection , Respiration, Artificial/methods , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Time-to-Treatment
19.
Cytokine ; 150: 155790, 2022 02.
Article in English | MEDLINE | ID: covidwho-1587975

ABSTRACT

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.


Subject(s)
COVID-19/immunology , Cytokines/physiology , Hospitalization , Receptors, Cytokine/physiology , SARS-CoV-2 , Adult , Area Under Curve , Biomarkers , C-Reactive Protein/analysis , COVID-19/physiopathology , COVID-19/therapy , Chemokines/blood , Chemokines/physiology , Cytokines/blood , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Interleukin-6/blood , Length of Stay/statistics & numerical data , Male , Middle Aged , Prognosis , ROC Curve , Receptors, Chemokine/physiology , Respiration, Artificial/statistics & numerical data , Severity of Illness Index , Treatment Outcome
20.
J Med Internet Res ; 23(2): e23026, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1575588

ABSTRACT

BACKGROUND: For the clinical care of patients with well-established diseases, randomized trials, literature, and research are supplemented with clinical judgment to understand disease prognosis and inform treatment choices. In the void created by a lack of clinical experience with COVID-19, artificial intelligence (AI) may be an important tool to bolster clinical judgment and decision making. However, a lack of clinical data restricts the design and development of such AI tools, particularly in preparation for an impending crisis or pandemic. OBJECTIVE: This study aimed to develop and test the feasibility of a "patients-like-me" framework to predict the deterioration of patients with COVID-19 using a retrospective cohort of patients with similar respiratory diseases. METHODS: Our framework used COVID-19-like cohorts to design and train AI models that were then validated on the COVID-19 population. The COVID-19-like cohorts included patients diagnosed with bacterial pneumonia, viral pneumonia, unspecified pneumonia, influenza, and acute respiratory distress syndrome (ARDS) at an academic medical center from 2008 to 2019. In total, 15 training cohorts were created using different combinations of the COVID-19-like cohorts with the ARDS cohort for exploratory purposes. In this study, two machine learning models were developed: one to predict invasive mechanical ventilation (IMV) within 48 hours for each hospitalized day, and one to predict all-cause mortality at the time of admission. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. We established model interpretability by calculating SHapley Additive exPlanations (SHAP) scores to identify important features. RESULTS: Compared to the COVID-19-like cohorts (n=16,509), the patients hospitalized with COVID-19 (n=159) were significantly younger, with a higher proportion of patients of Hispanic ethnicity, a lower proportion of patients with smoking history, and fewer patients with comorbidities (P<.001). Patients with COVID-19 had a lower IMV rate (15.1 versus 23.2, P=.02) and shorter time to IMV (2.9 versus 4.1 days, P<.001) compared to the COVID-19-like patients. In the COVID-19-like training data, the top models achieved excellent performance (AUROC>0.90). Validating in the COVID-19 cohort, the top-performing model for predicting IMV was the XGBoost model (AUROC=0.826) trained on the viral pneumonia cohort. Similarly, the XGBoost model trained on all 4 COVID-19-like cohorts without ARDS achieved the best performance (AUROC=0.928) in predicting mortality. Important predictors included demographic information (age), vital signs (oxygen saturation), and laboratory values (white blood cell count, cardiac troponin, albumin, etc). Our models had class imbalance, which resulted in high negative predictive values and low positive predictive values. CONCLUSIONS: We provided a feasible framework for modeling patient deterioration using existing data and AI technology to address data limitations during the onset of a novel, rapidly changing pandemic.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Machine Learning , Pneumonia, Viral/diagnosis , Aged , Area Under Curve , Cohort Studies , Comorbidity , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Predictive Value of Tests , Prognosis , ROC Curve , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
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