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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316935

ABSTRACT

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

2.
J Antimicrob Chemother ; 77(4): 1140-1145, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1632142

ABSTRACT

OBJECTIVES: To report an outbreak of hypervirulent Klebsiella pneumoniae (hvKp) in COVID-19 patients. METHODS: Prospective, observational study including consecutive COVID-19 patients with hvKp infections admitted to the University Hospital of Pisa (Italy). Clinical data and outcome of patients were collected. All patients were followed-up to 30 days from the diagnosis of infection. Mortality within 30 days of the diagnosis of hvKp infection was reported. The hypermucoviscous phenotype was determined by the 'string test'. Molecular typing was performed on three strains collected during different periods of the outbreak. The strains underwent whole genome sequencing using the Illumina MiSeq instrument. The complete circular assemblies were also obtained for the chromosome and a large plasmid using the Unicycler tool. RESULTS: From November 2020 to March 2021, hvKp has been isolated from 36 COVID-19 patients: 29/36 (80.6%) had infections (15 bloodstream infections, 8 ventilator-associated pneumonias and 6 complicated urinary tract infections), while 7/36 (19.4%) had colonization (3 urine, 2 rectal and 2 skin). The isolates belonged to ST147 and their plasmid carried three replicons of the IncFIB (Mar), IncR and IncHI1B types and several resistance genes, including the rmpADC genes encoding enhancers of capsular synthesis. The hvKp isolates displayed an ESBL phenotype, with resistance to piperacillin/tazobactam and ceftolozane/tazobactam and susceptibility only to meropenem and ceftazidime/avibactam. The majority of patients were treated with meropenem alone or in combination with fosfomycin. Thirty-day mortality was 48.3% (14/29). CONCLUSIONS: ST147 ESBL-producing hvKp is associated with high mortality in COVID-19 patients. Strict microbiological surveillance and infection control measures are needed in this population.


Subject(s)
COVID-19 , Klebsiella Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Humans , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae , Prospective Studies
3.
Clin Ther ; 44(3): 364-373, 2022 03.
Article in English | MEDLINE | ID: covidwho-1632141

ABSTRACT

PURPOSE: Preliminary data suggest that remdesivir may influence the course of COVID-19 according to the duration of pre-admission symptoms. We aim to evaluate whether early use of remdesivir is associated with a reduced COVID-19 progression in a homogeneous cohort of patients with mild to moderate COVID-19. METHODS: This prospective, observational study included patients with COVID-19 pneumonia treated with remdesivir at the University Hospital of Pisa (Italy) from September 2020 to January 2021. According to national recommendations, remdesivir was prescribed in patients with pneumonia who required oxygen supplementation by nasal cannula or mask but without the need for high-flow nasal cannula, non-invasive or invasive mechanical ventilation and had symptoms from no more than 10 days. Patients who received early (≤5 days from onset of symptoms) versus late (>5 days from onset of symptoms) remdesivir were compared. The primary outcome was a composite of high-flow nasal cannula, non-invasive or invasive mechanical ventilation, or death. A multivariate logistic regression analysis was performed to identify factors independently associated with the composite endpoint. FINDINGS: Among 312 consecutive patients with COVID-19 pneumonia who received remdesivir, 90 (28.8%) received early remdesivir, whereas 222 (71.2%) received late remdesivir. Twenty-nine patients (32.2%) in the early-remdesivir group versus 104 patients (46.8%) in the late-remdesivir group met the primary end point (P = 0.018). On multivariate analysis, a history of dyspnea at home (odds ratio = 2.53; 95% CI, 1.55-4.12; P < 0.001) was the strongest factor independently associated with the progression to severe COVID-19, whereas early-remdesivir use was a protective factor (odds ratio = 0.49; 95% CI, 0.27-0.87; P = 0.015). The delayed admission to the hospital was associated with a delayed administration of remdesivir. IMPLICATIONS: The early use of remdesivir (<5 days from symptoms onset) may reduce COVID-19 progression. The identification of patients who need early hospitalization and early remdesivir may provide clinical benefit in patients with COVID-19.


Subject(s)
COVID-19 , Pneumonia , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Disease Progression , Humans , Prospective Studies
4.
Eur J Intern Med ; 95: 13-16, 2022 01.
Article in English | MEDLINE | ID: covidwho-1616475

ABSTRACT

Immunotherapy with convalescent plasma (CP) has been used in the past in several different infectious diseases and proposed as a potential therapeutic option in patients with COVID-19. However, a clear benefit was never demonstrated and randomized clinical trials (RCTs) conducted in different populations of COVID-19 patients showed contrasting results. In general, current evidences suggest that CP in patients with moderate to severe COVID-19 does not reduce the progression to severe respiratory failure or death within 30 days. However, currently published RCTs have several limitations. The administration of plasma with low titer of neutralizing antibodies (NAbs), the use of suboptimal surrogate serological tests to determine NAbs titer, the delayed administration of CP from the onset of COVID-19 symptoms and the lack of information about antibody titer of recipients before CP infusion, are all limiting factors that may have affected the study results. Thus, a potential benefit of early (within the first 72 h from onset of symptoms), high titer CP in patients with mild COVID-19 (pO2/FiO2>300) cannot be definitively excluded. However, immunotherapy with monoclonal antibodies developed from CP demonstrated efficacy in reducing progression to severe COVID-19 and hospitalization and are today recommended in the early phase of COVID-19.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Plasma , SARS-CoV-2
5.
Thromb Haemost ; 122(2): 257-266, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1592074

ABSTRACT

BACKGROUND: It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival. METHODS: In this multicenter observational cohort study, 1,138 patients, hospitalized for CAP (n = 559) or COVID-19 (n = 579) from seven clinical centers in Italy, were included in the study. Consecutive adult patients (age ≥ 18 years) with confirmed COVID-19-related pneumonia, with or without mechanical ventilation, hospitalized from March 1, 2020 to April 30, 2020, were enrolled. COVID-19 was diagnosed based on the World Health Organization interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events. RESULTS: During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p = 0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses.During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p < 0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6 vs. 13.4% in thrombotic-event-free patients; p < 0.001). In CAP, 13.8% of patients experiencing thrombotic events died versus 1.8% of thrombotic event-free ones (p < 0.001). A multivariable Cox-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (hazard ratio: 2.1; 95% confidence interval: 1.4-3.3; p < 0.001). CONCLUSION: Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.


Subject(s)
COVID-19/epidemiology , Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , SARS-CoV-2/physiology , Thrombosis/epidemiology , Aged , COVID-19/mortality , Cohort Studies , Community-Acquired Infections/mortality , Female , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Pneumonia/mortality , Risk Factors , Survival Analysis , Thrombosis/mortality
6.
Epilepsy Behav ; 126: 108470, 2022 01.
Article in English | MEDLINE | ID: covidwho-1560506

ABSTRACT

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


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Pneumonia, Viral , Humans , Influenza A Virus, H3N2 Subtype , Retrospective Studies , SARS-CoV-2 , Seizures
7.
JAMA Netw Open ; 4(11): e2136246, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1540039

ABSTRACT

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.


Subject(s)
COVID-19/therapy , Hospital Mortality , Hospitalization , Immunization, Passive , Plasma , Respiratory Insufficiency , Aged , COVID-19/complications , COVID-19/mortality , Disease Progression , Female , Humans , Italy , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Standard of Care
8.
Infect Dis Ther ; 10(4): 2479-2488, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1505925

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the risk of hospitalization or death in patients infected by SARS-CoV2 variants of concern (VOCs) receiving combinations of monoclonal antibodies (mAbs), bamlanivimab/etesevimab or casirivimab/imdevimab. METHODS: Observational prospective study conducted in two Italian hospitals (University Hospital of Pisa and San Donato Hospital, Arezzo) including consecutive outpatients with COVID-19 who received bamlanivimab/etesevimab or casirivimab/imdevimab from March 20th to May 10th 2021. All patients were at high risk of COVID-19 progression according to FDA/AIFA recommendations. Patients were divided into two study groups according to the infecting viral strain (VOCs): Alpha and Gamma group. The primary endpoint was a composite of hospitalization or death within 30 days from mAbs infusion. A Cox regression multivariate analysis was performed to identify factors associated with the primary outcome in the overall population. RESULTS: The study included 165 patients: 105 were infected by the VOC Alpha and 43 by the VOC Gamma. In the Alpha group, no differences in the primary endpoint were observed between patients treated with bamlanivimab/etesevimab or casirivimab/imdevimab. Conversely, in the Gamma group, a higher proportion of patients treated with bamlanivimab/etesevimab met the primary endpoint compared to those receiving casirivimab/imdevimab (55% vs. 17.4%, p = 0.013). On multivariate Cox-regression analysis, the Gamma variant and days from symptoms onset to mAbs infusion were factors independently associated with higher risk of hospitalization or death, while casirivimab/imdevimab was protective (HR 0.33, 95% CI 0.13-0.83, p = 0.019). CONCLUSIONS: In patients infected by the SARS-CoV-2 Gamma variant, bamlanivimab/etesevimab should be used with caution because of the high risk of disease progression.

9.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1388432

ABSTRACT

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


Subject(s)
Antiviral Agents/pharmacology , Azetidines/pharmacology , COVID-19/mortality , Enzyme Inhibitors/pharmacology , Janus Kinases/antagonists & inhibitors , Liver/virology , Purines/pharmacology , Pyrazoles/pharmacology , SARS-CoV-2/pathogenicity , Sulfonamides/pharmacology , Adult , Aged , Aged, 80 and over , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Cytokine Release Syndrome , Cytokines/metabolism , Drug Evaluation, Preclinical , Female , Gene Expression Profiling , Humans , Interferon alpha-2/metabolism , Italy , Janus Kinases/metabolism , Liver/drug effects , Male , Middle Aged , Patient Safety , Platelet Activation , Proportional Hazards Models , RNA-Seq , Spain , Virus Internalization/drug effects
10.
Clin Infect Dis ; 72(11): 2021-2024, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1369070

ABSTRACT

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


Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents/therapeutic use , Carbapenems , Cephalosporins , Humans , Intensive Care Units , Microbial Sensitivity Tests , Prospective Studies , beta-Lactamases
11.
Thromb Res ; 204: 88-94, 2021 08.
Article in English | MEDLINE | ID: covidwho-1260871

ABSTRACT

PURPOSE: A derangement of the coagulation process and thromboinflammatory events has emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. CC motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. METHODS: We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO2/FiO2 recorded during hospital stay, P/Fnadir) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/Fnadir. We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). RESULTS: CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/Fnadir. CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CONCLUSIONS: CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease.


Subject(s)
COVID-19 , Thrombosis , Chemokine CCL2 , Chemokines, CC , Humans , Inflammation , Italy , Ligands , Retrospective Studies , SARS-CoV-2
12.
Clin Microbiol Infect ; 27(7): 987-992, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1220813

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is being extensively investigated as a treatment, with mixed results to date. Overall, there has been a generalized lack of appropriateness in prescriptions, which, in the field of transfusion medicine, is termed patient-blood management. OBJECTIVES: We aimed to separate study design variables that could affect clinical outcome after CCP therapy. We focus here on variables such as pretransfusion antibody testing in recipients, dose adjustments and antibody affinity measurements. SOURCES: We searched PubMed and preprint servers for relevant preclinical and clinical studies discussing each of these variables in the field of CCP therapy. CONTENT: We show evidence that neglecting those variables has affected the outcomes of the vast majority of CCP clinical trials to date. IMPLICATIONS: A better understanding of such variables will improve the design of the next generation of CCP clinical trials. This will likely lead to better clinical outcomes and will minimize risks of immune evasion from subneutralizing doses of neutralizing antibodies.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/therapy , Antibodies, Viral/immunology , Blood Donors , Dose-Response Relationship, Immunologic , Economics, Pharmaceutical , Humans , Immunization, Passive/methods , Immunoglobulin G/immunology , Severity of Illness Index , Treatment Outcome
13.
J Clin Virol Plus ; 1(1): 100016, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1213343

ABSTRACT

COVID19 convalescent patient plasma units with high titer neutralizing antibody can be used to treat patients with severe disease. Therefore, in order to select suitable donors, neutralizing antibody titer against SARS CoV-2 needs to be determined. Because the neutralization assay is highly demanding from several points of view, a pre-selection of sera would be desirable to minimize the number of sera to be tested. In this study, a total of 140 serum samples that had been titrated for SARS-CoV-2 neutralizing antibody by microneutralization assay were also tested for the presence of anti-SARS-CoV2 antibody using 5 different tests: Architect® immunoassay (Abbott Diagnostics), detecting IgG against the nucleocapsid protein, LIAISON XL® (Diasorin) detecting IgG against a recombinant form of the S1/S2 subunits of the spike protein, VITROS® (Ortho Clinical Diagnostics), detecting IgG against a recombinant form of the spike protein, and ELISA (Euroimmun AG), detecting IgA or IgG against a recombinant form of the S1 subunit. To determine which immunoassay had the highest chance to detect sera with neutralizing antibodies above a certain threshold, we compared the results obtained from the five immunoassays with the titers obtained by microneutralization assay by linear regression analysis and by using receiver operating characteristic curve and Youden's index. Our results indicate that the most suitable method to predict sera with high Nab titer is Euroimmun® IgG, followed closely by Ortho VITROS® Anti-SARS-CoV-2 IgG.

14.
Sci Rep ; 11(1): 6515, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1147151

ABSTRACT

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


Subject(s)
Blood Coagulation Disorders/diagnosis , COVID-19/pathology , Heart Diseases/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Diseases/etiology , Hemodynamics , Heparin, Low-Molecular-Weight/therapeutic use , Hospital Mortality , Humans , Inflammation , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prospective Studies , Risk , SARS-CoV-2/isolation & purification , Troponin T/blood
15.
J Clin Med ; 10(4)2021 Feb 03.
Article in English | MEDLINE | ID: covidwho-1060487

ABSTRACT

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, p < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.

16.
J Antimicrob Chemother ; 76(4): 1078-1084, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-998365

ABSTRACT

BACKGROUND: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. OBJECTIVES: To identify predictors of superinfections in COVID-19. METHODS: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. RESULTS: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5-39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4-13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2-11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7-7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1-7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). CONCLUSIONS: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.


Subject(s)
COVID-19/complications , Cross Infection/microbiology , Superinfection/microbiology , Superinfection/virology , Aged , Aged, 80 and over , Bacterial Infections , Coinfection , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Mycoses , Prospective Studies , Risk Factors
17.
Open Forum Infect Dis ; 7(12): ofaa563, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-998449

ABSTRACT

BACKGROUND: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable. RESULTS: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6; P < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95; P = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. CONCLUSIONS: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.

18.
Open Forum Infectious Diseases ; 2020.
Article in English | Oxford Academic | ID: covidwho-933881

ABSTRACT

Objectives To evaluate the impact of low molecular weight heparin (LMWH) on the outcome of patients with SARS-CoV-2 pneumonia. Methods Prospective observational study including consecutive patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (4th March-30th April 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe ARDS. LMWH, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox-regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent Propensity-score (PS) was calculated and a PS-matching performed for each treatment variable. Results Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) hydroxychloroquine, 201 (63.8%) proteases inhibitors, 150 (47.6%) doxycycline, 141 (44.8%) steroids, 42 (13.3%) macrolides, 40 (12.7%) baricitinib, 13 (4.1%) tocilizumab, and 13 (4.1%) remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (HR 0.36 [95% CI 0.21-0.6], p<0.001) and composite endpoint (HR 0.61 [95% CI 0.39-0.95], p=0.029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in Covid-19. Randomized controlled trials are warranted to confirm these preliminary findings.

19.
Diabetes Care ; 43(10): 2345-2348, 2020 10.
Article in English | MEDLINE | ID: covidwho-713145

ABSTRACT

OBJECTIVE: To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38-6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67-12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18-10.47]). RESULTS: Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27-3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92-3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03-3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46-8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91-5.96, P = 0.079) vs. Q1. CONCLUSIONS: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Hyperglycemia/complications , Pneumonia, Viral/complications , Blood Glucose , COVID-19 , Coronavirus Infections/diagnosis , Diabetes Complications , Diabetes Mellitus , Female , Hospitalization , Humans , Male , Pandemics , Pneumonia, Viral/diagnosis , Prognosis , SARS-CoV-2 , Severity of Illness Index
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