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2.
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
3.
BMJ ; 376: e068407, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1612964

ABSTRACT

OBJECTIVE: To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). DESIGN: INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. SETTING: 11 hospitals in Iran. PARTICIPANTS: Adults aged ≥18 years with covid-19 admitted to the ICU. INTERVENTION: Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. MAIN OUTCOME MEASURES: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. RESULTS: Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). CONCLUSIONS: In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04486508.


Subject(s)
Anticoagulants/therapeutic use , Atorvastatin/therapeutic use , COVID-19/complications , Critical Care/methods , Venous Thromboembolism/epidemiology , Adolescent , Adult , Aged , COVID-19/mortality , Critical Care/statistics & numerical data , Double-Blind Method , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Heparin/therapeutic use , Humans , Intensive Care Units , Iran/epidemiology , Male , Middle Aged , Odds Ratio , SARS-CoV-2 , Treatment Outcome , Venous Thromboembolism/prevention & control , Venous Thromboembolism/virology , Young Adult
5.
Lancet Respir Med ; 9(8): 851-862, 2021 08.
Article in English | MEDLINE | ID: covidwho-1340912

ABSTRACT

BACKGROUND: In the Île-de-France region (henceforth termed Greater Paris), extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) was considered early in the COVID-19 pandemic. We report ECMO network organisation and outcomes during the first wave of the pandemic. METHODS: In this multicentre cohort study, we present an analysis of all adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 Greater Paris intensive care units between March 8 and June 3, 2020. Central regulation for ECMO indications and pooling of resources were organised for the Greater Paris intensive care units, with six mobile ECMO teams available for the region. Details of complications (including ECMO-related complications, renal replacement therapy, and pulmonary embolism), clinical outcomes, survival status at 90 days after ECMO initiation, and causes of death are reported. Multivariable analysis was used to identify pre-ECMO variables independently associated with 90-day survival after ECMO. FINDINGS: The 302 patients included who underwent ECMO had a median age of 52 years (IQR 45-58) and Simplified Acute Physiology Score-II of 40 (31-56), and 235 (78%) of whom were men. 165 (55%) were transferred after cannulation by a mobile ECMO team. Before ECMO, 285 (94%) patients were prone positioned, median driving pressure was 18 cm H2O (14-21), and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg (IQR 54-70). During ECMO, 115 (43%) of 270 patients had a major bleeding event, 27 of whom had intracranial haemorrhage; 130 (43%) of 301 patients received renal replacement therapy; and 53 (18%) of 294 had a pulmonary embolism. 138 (46%) patients were alive 90 days after ECMO. The most common causes of death were multiorgan failure (53 [18%] patients) and septic shock (47 [16%] patients). Shorter time between intubation and ECMO (odds ratio 0·91 [95% CI 0·84-0·99] per day decrease), younger age (2·89 [1·41-5·93] for ≤48 years and 2·01 [1·01-3·99] for 49-56 years vs ≥57 years), lower pre-ECMO renal component of the Sequential Organ Failure Assessment score (0·67, 0·55-0·83 per point increase), and treatment in centres managing at least 30 venovenous ECMO cases annually (2·98 [1·46-6·04]) were independently associated with improved 90-day survival. There was no significant difference in survival between patients who had mobile and on-site ECMO initiation. INTERPRETATION: Beyond associations with similar factors to those reported on ECMO for non-COVID-19 ARDS, 90-day survival among ECMO-assisted patients with COVID-19 was strongly associated with a centre's experience in venovenous ECMO during the previous year. Early ECMO management in centres with a high venovenous ECMO case volume should be advocated, by applying centralisation and regulation of ECMO indications, which should also help to prevent a shortage of resources. FUNDING: None.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Intensive Care Units , Pulmonary Embolism , Renal Insufficiency , Respiratory Distress Syndrome , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , Cohort Studies , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , France/epidemiology , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Renal Insufficiency/epidemiology , Renal Insufficiency/etiology , Renal Insufficiency/therapy , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Survival Analysis
6.
Am J Respir Crit Care Med ; 204(1): 34-43, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1311194

ABSTRACT

Rationale: The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives: To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods: We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results: Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41-55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2-7), the median PaO2/FiO2 ratio was 86.8 (IQR, 64-99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24-69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions: Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/statistics & numerical data , Respiratory Distress Syndrome/therapy , Adult , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Chile/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Needs Assessment , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/virology , Retrospective Studies , Severity of Illness Index , Treatment Outcome
7.
Crit Care ; 25(1): 238, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1300260

ABSTRACT

BACKGROUND: Current practices regarding tracheostomy in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Our objectives were to assess the prevalence and the association between the timing of tracheostomy (during or after ECMO weaning) and related complications, sedative, and analgesic use. METHODS: International, multicenter, retrospective study in four large volume ECMO centers during a 9-year period. RESULTS: Of the 1,168 patients treated with ECMO for severe ARDS (age 48 ± 16 years, 76% male, SAPS II score 51 ± 18) during the enrollment period, 353 (30%) and 177 (15%) underwent tracheostomy placement during or after ECMO, respectively. Severe complications were uncommon in both groups. Local bleeding within 24 h of tracheostomy was four times more frequent during ECMO (25 vs 7% after ECMO, p < 0.01). Cumulative sedative consumption decreased more rapidly after the procedure with sedative doses almost negligible 48-72 h later, when tracheostomy was performed after ECMO decannulation (p < 0.01). A significantly increased level of consciousness was observed within 72 h after tracheostomy in the "after ECMO" group, whereas it was unchanged in the "during-ECMO" group. CONCLUSION: In contrast to patients undergoing tracheostomy after ECMO decannulation, tracheostomy during ECMO was neither associated with a decrease in sedation and analgesia levels nor with an increase in the level of consciousness. This finding together with a higher risk of local bleeding in the days following the procedure reinforces the need for a case-by-case discussion on the balance between risks and benefits of tracheotomy when performed during ECMO.


Subject(s)
Respiratory Distress Syndrome/therapy , Tracheostomy/methods , Adult , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , France/epidemiology , Germany/epidemiology , Humans , Internationality , Italy/epidemiology , Male , Middle Aged , Respiratory Distress Syndrome/epidemiology , Retrospective Studies , Simplified Acute Physiology Score , Tracheostomy/statistics & numerical data , Treatment Outcome , United States/epidemiology
8.
Nutrients ; 13(7)2021 Jun 24.
Article in English | MEDLINE | ID: covidwho-1285399

ABSTRACT

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.


Subject(s)
COVID-19/blood , Vitamin A/blood , Adult , Aged , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/mortality , Chromatography, Liquid/methods , Critical Illness , Cross-Sectional Studies , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Ferritins/blood , Hospitalization , Humans , Inflammation/epidemiology , Lymphocyte Count , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/epidemiology , SARS-CoV-2 , Severity of Illness Index
10.
J Korean Med Sci ; 36(19): e139, 2021 May 17.
Article in English | MEDLINE | ID: covidwho-1232536

ABSTRACT

BACKGROUND: Some coronavirus disease 2019 (COVID-19) patients initially present with early oxygen demand, requiring more medical resources, and some develop severe conditions, while others worsen later in their clinical course. Whether the nature of the two groups is the same but in the spectrum of different diagnostic time points is not certain. METHODS: Hospitalized COVID-19 patients who needed oxygen therapy from February to November 2020 were included in the study. The patients were divided into early and late groups based on the time when the oxygen requirement occurred. Basic and epidemiologic characteristics were compared. Clinical variables were analyzed in both groups. RESULTS: A total of 164 patients needed oxygen therapy, 94 of whom were in the early group and 70 of whom were in the late group. The early and late groups had similar baseline characteristics except age (median age, 73 vs. 67 years), uncertain exposure history (50% vs. 31.4%) and the time from the onset of illness to admission (median, 5 vs. 2 days). Multivariate analysis showed that age > 65 years (OR, 4.65), symptom onset > 5 days (OR, 9.13) and several clinical manifestations, such as febrile sensation (OR, 6.01), dyspnea (OR, 30.0), C-reactive protein > 1 mg/dL (OR, 7.87) and chest X-ray abnormality (OR, 8.15), were predictive factors in the early group. The early group required more intensive care such as mechanical ventilation care, extracorporeal membrane oxygenation and death (29.8% vs. 14.3%, P = 0.002). CONCLUSION: Older age, especially > 65 years, and a delay of over 5 days from the onset of illness to admission were associated with early oxygen demand in COVID-19 patients. Interventions for earlier diagnosis of elderly people may benefit clinical outcomes.


Subject(s)
COVID-19/therapy , Hospitalization , Oxygen Inhalation Therapy , SARS-CoV-2 , Age Factors , Aged , COVID-19/complications , COVID-19/epidemiology , Critical Care/statistics & numerical data , Dyspnea/etiology , Extracorporeal Membrane Oxygenation/statistics & numerical data , Fever/etiology , Hospital Mortality , Humans , Male , Middle Aged , Oxygen Inhalation Therapy/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Time Factors
11.
Am J Surg ; 223(2): 388-394, 2022 02.
Article in English | MEDLINE | ID: covidwho-1193212

ABSTRACT

BACKGROUND: ECMO is an established supportive adjunct for patients with severe, refractory ARDS from viral pneumonia. However, the exact role and timing of ECMO for COVID-19 patients remains unclear. METHODS: We conducted a retrospective comparison of the first 32 patients with COVID-19-associated ARDS to the last 28 patients with influenza-associated ARDS placed on V-V ECMO. We compared patient factors between the two cohorts and used survival analysis to compare the hazard of mortality over sixty days post-cannulation. RESULTS: COVID-19 patients were older (mean 47.8 vs. 41.2 years, p = 0.033), had more ventilator days before cannulation (mean 4.5 vs. 1.5 days, p < 0.001). Crude in-hospital mortality was significantly higher in the COVID-19 cohort at 65.6% (n = 21/32) versus 36.3% (n = 11/28, p = 0.041). The adjusted hazard ratio over sixty days for COVID-19 patients was 2.81 (95% CI 1.07, 7.35) after adjusting for age, race, ECMO-associated organ failure, and Charlson Comorbidity Index. CONCLUSION: ECMO has a role in severe ARDS associated with COVID-19 but providers should carefully weigh patient factors when utilizing this scarce resource in favor of influenza pneumonia.


Subject(s)
COVID-19/complications , Extracorporeal Membrane Oxygenation/statistics & numerical data , Influenza, Human/complications , Respiratory Distress Syndrome/mortality , Adult , COVID-19/mortality , COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Female , Hospital Mortality , Humans , Influenza, Human/mortality , Influenza, Human/therapy , Male , Middle Aged , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Retrospective Studies , Severity of Illness Index , Treatment Outcome
12.
Transfus Clin Biol ; 28(3): 321-329, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1174514

ABSTRACT

OBJECTIVE: To explore whether convalescent plasma therapy is beneficial to patients with severe acute respiratory infections and gave hints to the management of COVID-19. METHODS: A comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane library was conducted for all eligible studies range from inception to February 29, 2020. Studies with control group were included. Treatment group received convalescent plasma therapy, and control group may receive any therapy other than convalescent plasma therapy. Odds ratios (ORs), mean differences (MDs) and 95% confidence intervals (CIs) were pooled for categorical and continuous outcomes. RESULTS: A total of 1997 patients from 13 studies were included, and seven studies were prospectively designed. Pooled analysis indicated convalescent plasma treatment significantly reduced the mortality by 51% (OR=0.49, 95% CI: 0.36 to 0.67). Subgroup analyses by publication time, study design, and influenza A revealed similar results. Sensitivity analyses suggested that the results were stable. In addition, convalescent plasma therapy reduced mechanical ventilation requirement (OR: 0.35, 95% CI: 0.21 to 0.59), while it was not associated with less use of extracorporeal membrane oxygenation (OR: 2.0, 95% CI: 0.83 to 4.83) and shorter length of hospital stay (MD: -2.20, 95% CI: -4.98 to 0.57days). Pooled estimates showed there was no difference in serious adverse effects between the convalescent plasma treatment and control groups (OR: 0.75, 95% CI: 0.50 to 1.13). CONCLUSION: Convalescent plasma therapy significantly reduced the mortality and mechanical ventilation requirements of patients with virus-induced severe acute respiratory infections, without serious adverse effects. More studies are needed to explore whether this treatment can be extrapolated into COVID-19.


Subject(s)
Blood Component Transfusion , COVID-19/therapy , Convalescence , Immunization, Passive , Plasma , Respiratory Tract Infections/therapy , SARS-CoV-2 , Acute Disease , COVID-19/blood , COVID-19/mortality , Extracorporeal Membrane Oxygenation/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Procedures and Techniques Utilization , Respiration, Artificial/statistics & numerical data , Respiratory Tract Infections/virology
13.
Am J Respir Crit Care Med ; 204(1): 34-43, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1171751

ABSTRACT

Rationale: The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives: To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods: We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results: Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41-55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2-7), the median PaO2/FiO2 ratio was 86.8 (IQR, 64-99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24-69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions: Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/statistics & numerical data , Respiratory Distress Syndrome/therapy , Adult , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Chile/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Needs Assessment , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/virology , Retrospective Studies , Severity of Illness Index , Treatment Outcome
14.
J Surg Res ; 264: 81-89, 2021 08.
Article in English | MEDLINE | ID: covidwho-1164149

ABSTRACT

BACKGROUND: Right ventricular failure is an underrecognized consequence of COVID-19 pneumonia. Those with severe disease are treated with extracorporeal membrane oxygenation (ECMO) but with poor outcomes. Concomitant right ventricular assist device (RVAD) may be beneficial. METHODS: A retrospective analysis of intensive care unit patients admitted with COVID-19 ARDS (Acute Respiratory Distress Syndrome) was performed. Nonintubated patients, those with acute kidney injury, and age > 75 were excluded. Patients who underwent RVAD/ECMO support were compared with those managed via invasive mechanical ventilation (IMV) alone. The primary outcome was in-hospital mortality. Secondary outcomes included 30-d mortality, acute kidney injury, length of ICU stay, and duration of mechanical ventilation. RESULTS: A total of 145 patients were admitted to the ICU with COVID-19. Thirty-nine patients met inclusion criteria. Of these, 21 received IMV, and 18 received RVAD/ECMO. In-hospital (52.4 versus 11.1%, P = 0.008) and 30-d mortality (42.9 versus 5.6%, P= 0.011) were significantly lower in patients treated with RVAD/ECMO. Acute kidney injury occurred in 15 (71.4%) patients in the IMV group and zero RVAD/ECMO patients (P< 0.001). ICU (11.5 versus 21 d, P= 0.067) and hospital (14 versus 25.5 d, P = 0.054) length of stay were not significantly different. There were no RVAD/ECMO device complications. The duration of mechanical ventilation was not significantly different (10 versus 5 d, P = 0.44). CONCLUSIONS: RVAD support at the time of ECMO initiation resulted in the no secondary end-organ damage and higher in-hospital and 30-d survival versus IMV in specially selected patients with severe COVID-19 ARDS. Management of severe COVID-19 ARDS should prioritize right ventricular support.


Subject(s)
COVID-19/complications , Extracorporeal Membrane Oxygenation/methods , Heart Failure/therapy , Heart-Assist Devices , Respiratory Distress Syndrome/therapy , Ventricular Dysfunction, Right/therapy , Adult , COVID-19/diagnosis , COVID-19/therapy , Combined Modality Therapy , Critical Care/methods , Critical Care/statistics & numerical data , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Heart Failure/diagnosis , Heart Failure/etiology , Heart Failure/mortality , Hospital Mortality , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Ventricular Dysfunction, Right/diagnosis , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/mortality
16.
Medicine (Baltimore) ; 100(7): e24437, 2021 Feb 19.
Article in English | MEDLINE | ID: covidwho-1125890

ABSTRACT

ABSTRACT: To describe the clinical and demographic characteristics of critically ill patients with COVID-19 in Daegu, South Korea, and to explore the risk factors for in-hospital mortality in these patients.Retrospective cohort study of 110 critically ill patients with COVID-19 admitted to the ICU in Daegu, South Korea, between February 18 and April 5, 2020. The final date of follow-up was April 20, 2020.A total of 110 patient medical records were reviewed. The median age was 71 years (interquartile range [IQR] = 63-78 years). During the study period, 47 patients (42.7%) died in the hospital. The most common SARS-CoV-2 infection related complication was acute respiratory distress syndrome (ARDS) in 95 patients (86.4%). Of the 79 patients (71.8%) who received invasive mechanical ventilation, 46 (58.2%) received neuromuscular blockade injection, and 19 (24.1%) received ECMO treatment. All patients received antibiotic injection, 99 patients (90%) received hydroxychloroquine, 96 patients (87.3%) received lopinavir-ritonavir antiviral medication, and 14 patients (12.7%) received other antiviral agents, including darunavir-cobicistat and emtricitabine-tenofovir. In the multivariable logistic regression model, the odds ratio of in-hospital death was higher with APACHE II score (OR = 1.126; 95% CI = 1.014-1.252; P  = .027).The in-hospital mortality rate of critically ill patients with COVID-19 was approximately 40%. Higher APACHE II score at admission was an independent risk factor for death in these patients.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Critical Illness/mortality , Critical Illness/therapy , APACHE , Age Factors , Aged , Aged, 80 and over , Comorbidity , Drosophila Proteins , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Hospital Mortality , Humans , Male , Membrane Proteins , Middle Aged , Prognosis , Republic of Korea/epidemiology , Respiration, Artificial/methods , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , SARS-CoV-2
17.
Curr Med Sci ; 41(1): 1-13, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1081528

ABSTRACT

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Adult , Aged , COVID-19/mortality , Case-Control Studies , China , Critical Illness , Extracorporeal Membrane Oxygenation/statistics & numerical data , Humans , Male , Middle Aged , Prognosis , Propensity Score , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome , Young Adult
18.
Crit Care ; 25(1): 38, 2021 01 28.
Article in English | MEDLINE | ID: covidwho-1055829

ABSTRACT

BACKGROUND: Extracorporeal life support (ECLS) has become an integral part of modern intensive therapy. The choice of support mode depends largely on the indication. Patients with respiratory failure are predominantly treated with a venovenous (VV) approach. We hypothesized that mortality in Germany in ECLS therapy did not differ from previously reported literature METHODS: Inpatient data from Germany from 2007 to 2018 provided by the Federal Statistical Office of Germany were analysed. The international statistical classification of diseases and related health problems codes (ICD) and process keys (OPS) for extracorporeal membrane oxygenation (ECMO) types, acute respiratory distress syndrome (ARDS) and hospital mortality were used. RESULTS: In total, 45,647 hospitalized patients treated with ECLS were analysed. In Germany, 231 hospitals provided ECLS therapy, with a median of 4 VV-ECMO and 9 VA-ECMO in 2018. Overall hospital mortality remained higher than predicted in comparison to the values reported in the literature. The number of VV-ECMO cases increased by 236% from 825 in 2007 to 2768 in 2018. ARDS was the main indication for VV-ECMO in only 33% of the patients in the past, but that proportion increased to 60% in 2018. VA-ECMO support is of minor importance in the treatment of ARDS in Germany. The age distribution of patients undergoing ECLS has shifted towards an older population. In 2018, the hospital mortality decreased in VV-ECMO patients and VV-ECMO patients with ARDS to 53.9% (n = 1493) and 54.4% (n = 926), respectively. CONCLUSIONS: ARDS is a severe disease with a high mortality rate despite ECLS therapy. Although endpoints and timing of the evaluations differed from those of the CESAR and EOLIA studies and the Extracorporeal Life Support Organization (ELSO) Registry, the reported mortality in these studies was lower than in the present analysis. Further prospective analyses are necessary to evaluate outcomes in ECMO therapy at the centre volume level.


Subject(s)
Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/standards , Mortality/trends , Respiratory Distress Syndrome/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Germany/epidemiology , Humans , Infant , Male , Middle Aged , Registries/statistics & numerical data , Respiratory Distress Syndrome/epidemiology , Retrospective Studies
19.
Trials ; 22(1): 42, 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1021412

ABSTRACT

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/drug therapy , Ecdysterone/therapeutic use , Respiratory Insufficiency/drug therapy , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/physiopathology , Disease Progression , Double-Blind Method , Extracorporeal Membrane Oxygenation/statistics & numerical data , Hospitalization , Humans , Hypoxia/physiopathology , Middle Aged , Mortality , Oxygen Inhalation Therapy/statistics & numerical data , Proto-Oncogene Proteins/metabolism , Randomized Controlled Trials as Topic , Receptors, Coronavirus/metabolism , Receptors, G-Protein-Coupled/metabolism , Renin-Angiotensin System , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/physiopathology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Tachypnea/physiopathology , Treatment Outcome
20.
Chest ; 159(2): 524-536, 2021 02.
Article in English | MEDLINE | ID: covidwho-996765

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented burden on the delivery of intensive care services worldwide. RESEARCH QUESTION: What is the global point estimate of deaths and risk factors for patients who are admitted to ICUs with severe COVID-19? STUDY DESIGN AND METHODS: In this systematic review and meta-analysis Medline, Embase, and the Cochrane library were searched up to August 1, 2020. Pooled prevalence of participant characteristics, clinical features, and outcome data was calculated with the use of random effects models. Subgroup analyses were based on geographic distribution, study type, quality assessment, sample size, end date, and patient disposition. Studies that reported in-hospital mortality rate of adult patients (age >18 years) with confirmed COVID-19 admitted to an ICU met study eligibility criteria. Critical evaluation was performed with the Newcastle Ottawa Scale for nonrandomized studies. RESULTS: Forty-five studies with 16,561 patients from 17 countries across four continents were included. Patients with COVID-19 who were admitted to ICUs had a mean age of 62.6 years (95% CI, 60.4-64.7). Common comorbidities included hypertension (49.5%; 95% CI, 44.9-54.0) and diabetes mellitus (26.6%; 95% CI, 22.7-30.8). More than three-quarters of cases experienced the development of ARDS (76.1%; 95% CI, 65.7-85.2). Invasive mechanical ventilation was required in 67.7% (95% CI, 59.1-75.7) of case, vasopressor support in 65.9% (95% CI, 52.4-78.4) of cases, renal replacement therapy in 16.9% (95% CI, 12.1-22.2) of cases, and extracorporeal membrane oxygenation in 6.4% (95% CI, 4.1-9.1) of cases. The duration of ICU and hospital admission was 10.8 days (95% CI, 9.3-18.4) and 19.1 days (95% CI, 16.3-21.9), respectively, with in-hospital mortality rate of 28.1% (95% CI, 23.4-33.0; I2 = 96%). No significant subgroup effect was observed. INTERPRETATION: Critically ill patients with COVID-19 who are admitted to the ICU require substantial organ support and prolonged ICU and hospital level care. The pooled estimate of global death from severe COVID-19 is <1 in 3.


Subject(s)
COVID-19/epidemiology , Extracorporeal Membrane Oxygenation/statistics & numerical data , Hospital Mortality , Intensive Care Units , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Vasoconstrictor Agents/therapeutic use , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Coinfection/physiopathology , Coinfection/therapy , Comorbidity , Diabetes Mellitus/epidemiology , Glucocorticoids/therapeutic use , Heart Diseases/physiopathology , Heart Diseases/therapy , Hospitalization , Humans , Hypertension/epidemiology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Length of Stay/statistics & numerical data , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Thrombosis/physiopathology , Thrombosis/therapy
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