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1.
Mycoses ; 65(4): 411-418, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1685386

ABSTRACT

BACKGROUND: The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is challenging, and the role of Aspergillus-PCR in bronchoalveolar lavage (BAL) is unknown. OBJECTIVES: This study evaluated diagnostic accuracy of Aspergillus-PCR in BAL in IPA in three different cohorts: ICU-admitted patients with COVID-19, ICU-admitted patients without COVID-19 and immunocompromised patients. METHODS: All stored available BAL samples collected from three patient groups were tested with Aspergillus-PCR (AsperGenius® ). IPA was diagnosed according to appropriate criteria for each patient group. RESULTS: We included 111 BAL samples from 101 patients: 52 (51%) patients admitted to ICU for COVID-19, 24 (24%) admitted to ICU for other reasons and 25 (25%) immunocompromised. There were 31 cases of IPA (28%). Aspergillus-PCR sensitivity was 64% (95% CI 47-79) and specificity 99% (95% CI 93-100). Aspergillus-PCR sensitivity was 40% (95%CI 19-64) in ICU COVID-19, 67% (95% CI 21-93) in non-COVID-19 ICU patients and 92% (95%CI 67-98) in the immunocompromised. The concordance between positive BAL-GM and BAL-PCR in patients with and without IPA was significantly lower in ICU patients (32%; 43% in COVID-19, 18% in non-COVID-19) than in the immunocompromised (92%), p < .001. CONCLUSIONS: Aspergillus-PCR in BAL improves the diagnostic accuracy of BAL-GM in ICU patients.


Subject(s)
COVID-19 , Invasive Pulmonary Aspergillosis , Aspergillus/genetics , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid , COVID-19/diagnosis , Critical Illness , Galactose , Humans , Invasive Pulmonary Aspergillosis/diagnosis , Mannans/analysis , Polymerase Chain Reaction , Sensitivity and Specificity
2.
Nat Commun ; 13(1): 679, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1671560

ABSTRACT

Emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor SARS-CoV-2 while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery.


Subject(s)
COVID-19/immunology , Interferons/pharmacology , Myeloid Cells/immunology , SARS-CoV-2/drug effects , Animals , Antiviral Agents , Bronchoalveolar Lavage , Disease Models, Animal , Humans , Immunity, Innate , Inflammation , Interferon Type I/genetics , Interferon Type I/pharmacology , Interferons/genetics , Lung/immunology , Lung/pathology , Macaca mulatta , Macrophages/immunology , T-Lymphocytes/immunology
3.
Chest ; 161(2): e97-e101, 2022 02.
Article in English | MEDLINE | ID: covidwho-1664781

ABSTRACT

CASE PRESENTATION: An 84-year-old man with an active smoking habit presented to the ED with dyspnea, hemoptysis, and thick phlegm that was difficult to clear. He reported no weight loss, no fever, and no chest pain or dysphonia. He denied both international travel and previous contact with confirmed cases of TB or SARS-CoV-2. He had no known occupational exposures. The patient's personal history included a resolved complete atrioventricular block that required a permanent pacemaker, moderate-to-severe COPD, rheumatoid arthritis (treated with oral prednisone, 2.5 mg/d) and B-chronic lymphocytic leukemia (treated with methotrexate and prophylactic oral supplements of ferrous sulfate). Moreover, he was in medical follow up because of a peptic ulcer, atrophic gastritis, and colonic diverticulosis. The patient also had a history of thoracic surgery after an episode of acute mediastinitis from an odontogenic infection, which required ICU management and temporal tracheostomy.


Subject(s)
Bronchoscopy/methods , COVID-19/diagnosis , Ferrous Compounds , Lung Diseases , Multiple Chronic Conditions/therapy , Respiratory Aspiration , Aged, 80 and over , Biopsy/methods , Bronchoalveolar Lavage/methods , COVID-19/epidemiology , Diagnosis, Differential , Ferrous Compounds/administration & dosage , Ferrous Compounds/adverse effects , Hematinics/administration & dosage , Hematinics/adverse effects , Hemoptysis/diagnosis , Hemoptysis/etiology , Humans , Lung Diseases/chemically induced , Lung Diseases/diagnostic imaging , Lung Diseases/physiopathology , Lung Diseases/therapy , Male , Respiratory Aspiration/complications , Respiratory Aspiration/diagnosis , Respiratory Aspiration/physiopathology , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Withholding Treatment
4.
Adv Sci (Weinh) ; 8(23): e2102593, 2021 12.
Article in English | MEDLINE | ID: covidwho-1559092

ABSTRACT

Fast and accurate identification of microbial pathogens is critical for the proper treatment of infections. Traditional culture-based diagnosis in clinics is increasingly supplemented by metagenomic next-generation-sequencing (mNGS). Here, RNA/cDNA-targeted sequencing (meta-transcriptomics using NGS (mtNGS)) is established to reduce the host nucleotide percentage in clinic samples and by combining with Oxford Nanopore Technology (ONT) platforms (meta-transcriptomics using third-generation sequencing, mtTGS) to improve the sequencing time. It shows that mtNGS improves the ratio of microbial reads, facilitates bacterial identification using multiple-strategies, and discovers fungi, viruses, and antibiotic resistance genes, and displaying agreement with clinical findings. Furthermore, longer reads in mtTGS lead to additional improvement in pathogen identification and also accelerate the clinical diagnosis. Additionally, primary tests utilizing direct-RNA sequencing and targeted sequencing of ONT show that ONT displays important potential but must be further developed. This study presents the potential of RNA-targeted pathogen identification in clinical samples, especially when combined with the newest developments in ONT.


Subject(s)
Bronchoalveolar Lavage Fluid/microbiology , High-Throughput Nucleotide Sequencing/methods , Infections/genetics , Metagenomics/methods , RNA/genetics , Sequence Analysis, RNA/methods , Aged , Bronchoalveolar Lavage/methods , Female , Humans , Male , Metagenome/genetics , Middle Aged
5.
Heart Lung ; 52: 95-105, 2022.
Article in English | MEDLINE | ID: covidwho-1562417

ABSTRACT

BACKGROUND: The gold standard for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is microbiological confirmation by reverse transcriptase-polymerase chain reaction (RT-PCR)1 most commonly done using oropharyngeal (OP) and nasopharyngeal swabs (NP). But in suspected cases, where these samples are false-negative, bronchoalveolar lavage (BAL) may prove diagnostic. OBJECTIVES: Hence, the diagnostic yield of BAL for detection of SARS-CoV-2 in cases of non-diagnostic upper respiratory tract samples is reviewed. METHODS: Databases such as MEDLINE, Scopus, and Google Scholar were searched using a systematic search strategy. The current study has been in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and has been registered with the International Prospective Registry of Systematic Reviews (CRD42020224088). RESULTS: 911 records were identified at initial database extraction, of which 317 duplicates were removed and, 596 records were screened for inclusion eligibility. We included total 19 studies in the systematic review, and 17 were included in metanalysis. The pooled estimate of SARS-CoV-2 positivity in BAL was 11% (95%CI: 0.01-0.24). A sensitivity analysis also showed that the results appear to be robust and minimal risk of bias amongst the studies. CONCLUSION: The current study demonstrates that BAL can be used to diagnose additional cases primary disease and superadded infections in patients with severe COVID-19 lower respiratory tract infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Bronchoalveolar Lavage , COVID-19/diagnosis , Humans
6.
Respir Investig ; 60(1): 68-81, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1382762

ABSTRACT

BACKGROUND: This review aimed to investigate whether bronchoalveolar lavage (BAL) is safe in patients with severe acute respiratory failure (ARF). METHODS: We searched the MEDLINE, CENTRAL, and other databases up to June 2, 2021 for studies that examined BAL for severe ARF. We included all cohort studies and randomized or non-randomized trials, while we excluded case-control studies, case reports, and case series. We evaluated the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: We included 17 studies (1085 patients) in the meta-analysis. The integrated frequency of death was 0.000% (95% confidence interval [CI]: 0.000-0.045%, I2 = 0.0%). The pooled risk of severe complications of respiratory system, cardiovascular system, and major bleeding was 1.32% (95% CI: 0.000-4.41%, I2 = 84.8%), 0.040% (95% CI: 0.000-0.71%, I2 = 9.3%), and 0.000% (95% CI: 0.000-0.27%, I2 = 0.0%), respectively. In the subgroup analysis with mechanical ventilation during BAL, there were few severe complications of the respiratory system (3/717 patients in 13 studies) and almost no heterogeneity (I2 = 0.0%). CONCLUSIONS: Our study suggests that severe complications of BAL for severe ARF are probably rare, particularly in patients receiving mechanical ventilation. After considering the risks and benefits, it would be worthwhile to consider performing BAL in patients with severe ARF of unknown etiology to pursue its cause. TRIAL REGISTRATION: The protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000040600).


Subject(s)
Respiratory Distress Syndrome , Respiratory Insufficiency , Bronchoalveolar Lavage , Cohort Studies , Humans , Respiration, Artificial , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
7.
BMC Pulm Med ; 21(1): 278, 2021 Aug 31.
Article in English | MEDLINE | ID: covidwho-1381257

ABSTRACT

BACKGROUND: There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report. CASE PRESENTATION: A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive. CONCLUSION: Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Delayed Diagnosis , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Asthma/complications , Asthma/drug therapy , Asthma/pathology , Bronchoalveolar Lavage , COVID-19/complications , COVID-19/therapy , Fatal Outcome , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Reverse Transcriptase Polymerase Chain Reaction
8.
J Breath Res ; 15(4)2021 09 13.
Article in English | MEDLINE | ID: covidwho-1379422

ABSTRACT

The evidence that severe coronavirus disease 2019 (COVID-19) is a risk factor for development of mycotic respiratory infection with an increased mortality is rising. Immunosuppressed are among the most susceptible patients andAspergillusspecies is the most feared superinfection. In this study we evaluated mycotic isolation prevalence on bronchoalveolar lavage (BAL) of patients who underwent bronchoscopy in search of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA. Moreover, we described the clinical characteristics and main outcomes of these patients. We included 118 patients, 35.9% of them were immunosuppressed for different reasons: in 23.7% we isolated SARS-CoV-2 RNA, in 33.1% we identified at least one mycotic agent and both in 15.4%. On BAL we observed in three casesAspergillusspp, in six casesPneumocystisand in 32Candidaspp. The prevalence of significant mold infection was 29.3% and 70.7% of cases were false positive or clinically irrelevant infections. In-hospital mortality of patients with fungal infection was 15.3%. The most frequent computed tomography (CT) pattern, evaluated with the Radiological Society of North America consensus statement, among patients with a mycotic pulmonary infection was the atypical one (p< 0.0001). Mycotic isolation on BAL may be interpreted as an innocent bystander, but its identification could influence the prognosis of patients, especially in those who need invasive investigations during the COVID-19 pandemic; BAL plays a fundamental role in resolving clinical complex cases, especially in immunosuppressed patients independently from radiological features, without limiting its role in ruling out SARS-CoV-2 infection.


Subject(s)
Bronchoalveolar Lavage , COVID-19/diagnosis , COVID-19/epidemiology , Mycoses/diagnosis , Mycoses/epidemiology , Nasopharynx/microbiology , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/virology , Female , Humans , Immunocompromised Host , Male , Middle Aged , Mycoses/microbiology , Nasopharynx/virology , Pandemics , Prevalence , Prognosis , RNA, Viral/analysis , RNA, Viral/genetics , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
9.
BMJ Case Rep ; 14(8)2021 Aug 09.
Article in English | MEDLINE | ID: covidwho-1350010

ABSTRACT

Diffuse alveolar haemorrhage (DAH) has been reported as a rare complication of clopidogrel use and is usually a diagnosis of exclusion. We describe the case of an 88-year-old Native American woman who presented with acute hypoxic respiratory failure with CT scan of the chest showing diffuse bilateral ground-glass opacities. She had been on clopidogrel for 6 months for a carotid artery stent. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies revealed DAH. Infectious and autoimmune work-up were all negative. Clopidogrel was stopped and high-dose steroids were started. Her symptoms gradually improved until she was discharged from the hospital. The differential DAH is broad. Anticoagulant-induced DAH should be part of the differential diagnosis, and is usually a diagnosis of exclusion.


Subject(s)
Lung Diseases , Aged, 80 and over , Bronchoalveolar Lavage , Bronchoscopy , Clopidogrel/adverse effects , Female , Hemorrhage/chemically induced , Humans , Lung Diseases/diagnosis , Lung Diseases/diagnostic imaging
12.
Cells ; 10(4)2021 03 24.
Article in English | MEDLINE | ID: covidwho-1232574

ABSTRACT

Despite vaccination and antivirals, influenza remains a communicable disease of high burden, with limited therapeutic options available to patients that develop complications. Here, we report the development and preclinical characterization of Adipose Stromal Cell (ASC) concentrated secretome (CS), generated by process adaptable to current Good Manufacturing Practices (cGMP) standards. We demonstrate that ASC-CS limits pulmonary histopathological changes, infiltration of inflammatory cells, protein leak, water accumulation, and arterial oxygen saturation (spO2) reduction in murine model of lung infection with influenza A virus (IAV) when first administered six days post-infection. The ability to limit lung injury is sustained in ASC-CS preparations stored at -80 °C for three years. Priming of the ASC with inflammatory factors TNFα and IFNγ enhances ASC-CS ability to suppress lung injury. IAV infection is associated with dramatic increases in programmed cell death ligand (PDL1) and angiopoietin 2 (Angpt2) levels. ASC-CS application significantly reduces both PDL1 and Angpt2 levels. Neutralization of PDL1 with anti-mouse PDL1 antibody starting Day6 onward effectively ablates lung PDL1, but only non-significantly reduces Angpt2 release. Most importantly, late-phase PDL1 neutralization results in negligible suppression of protein leakage and inflammatory cell infiltration, suggesting that suppression of PDL1 does not play a critical role in ASC-CS therapeutic effects.


Subject(s)
Adipose Tissue/cytology , Influenza A virus/physiology , Lung Injury/therapy , Lung Injury/virology , Orthomyxoviridae Infections/therapy , Orthomyxoviridae Infections/virology , Angiopoietin-2/metabolism , Animals , B7-H1 Antigen/metabolism , Bronchoalveolar Lavage , Cryopreservation , Culture Media, Conditioned/pharmacology , Cytokines/metabolism , Disease Models, Animal , Female , Humans , Inflammation/complications , Inflammation/pathology , Lung Injury/complications , Lung Injury/pathology , Male , Mice , Orthomyxoviridae Infections/complications , Orthomyxoviridae Infections/pathology , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Sex Characteristics , Stromal Cells/metabolism
13.
J Med Virol ; 93(4): 2374-2384, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217387

ABSTRACT

OBJECTIVES: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures. METHODS: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively. RESULTS: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively. CONCLUSION: Manual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/methods , SARS-CoV-2/isolation & purification , Adult , Bronchoalveolar Lavage , COVID-19/prevention & control , COVID-19/transmission , COVID-19/virology , COVID-19 Testing , Disease Transmission, Infectious/prevention & control , Female , Genome, Viral , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Pandemics , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , Switzerland/epidemiology , Viral Load
14.
J Exp Med ; 218(7)2021 07 05.
Article in English | MEDLINE | ID: covidwho-1205513

ABSTRACT

Safe and effective coronavirus disease-19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged nonhuman primates (NHPs). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared with a single dose. In one-dose regimens, neutralizing antibody responses were stable for at least 14 wk, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and T helper cell (Th cell) 1-skewed cellular responses in aged NHPs that were comparable to those in adult animals. Aged Ad26.COV2.S-vaccinated animals challenged 3 mo after dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. Neutralization of variants of concern by NHP sera was reduced for B.1.351 lineages while maintained for the B.1.1.7 lineage independent of Ad26.COV2.S vaccine regimen.


Subject(s)
Adenoviridae/immunology , Aging/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Body Temperature , Bronchoalveolar Lavage , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/prevention & control , COVID-19/virology , Dose-Response Relationship, Immunologic , Female , Immunity, Humoral , Kinetics , Lung/pathology , Lung/virology , Macaca mulatta , Male , Spike Glycoprotein, Coronavirus/metabolism , Treatment Outcome , Vaccination , Viral Load
15.
Rev Bras Ter Intensiva ; 33(1): 68-74, 2021.
Article in Portuguese, English | MEDLINE | ID: covidwho-1197641

ABSTRACT

OBJECTIVE: To analyze whether changes in medical care due to the application of COVID-19 protocols affected clinical outcomes in patients without COVID-19 during the pandemic. METHODS: This was a retrospective, observational cohort study carried out in a thirty-eight-bed surgical and medical intensive care unit of a high complexity private hospital. Patients with respiratory failure admitted to the intensive care unit during March and April 2020 and the same months in 2019 were selected. We compared interventions and outcomes of patients without COVID-19 during the pandemic with patients admitted in 2019. The main variables analyzed were intensive care unit respiratory management, number of chest tomography scans and bronchoalveolar lavages, intensive care unit complications, and status at hospital discharge. RESULTS: In 2020, a significant reduction in the use of a high-flow nasal cannula was observed: 14 (42%) in 2019 compared to 1 (3%) in 2020. Additionally, in 2020, a significant increase was observed in the number of patients under mechanical ventilation admitted to the intensive care unit from the emergency department, 23 (69%) compared to 11 (31%) in 2019. Nevertheless, the number of patients with mechanical ventilation after 5 days of admission was similar in both years: 24 (69%) in 2019 and 26 (79%) in 2020. CONCLUSION: Intensive care unit protocols based on international recommendations for the COVID-19 pandemic have produced a change in non-COVID-19 patient management. We observed a reduction in the use of a high-flow nasal cannula and an increased number of tracheal intubations in the emergency department. However, no changes in the percentage of intubated patients in the intensive care unit, the number of mechanical ventilation days or the length of stay in intensive care unit.


OBJETIVO: Analisar se as modificações na atenção médica em razão da aplicação dos protocolos para COVID-19 afetaram os desfechos clínicos de pacientes sem a doença durante a pandemia. MÉTODOS: Este foi um estudo observacional de coorte retrospectiva conduzido em uma unidade de terapia intensiva clínica e cirúrgica com 38 leitos, localizada em hospital privado de alta complexidade na cidade de Buenos Aires, Argentina, e envolveu os pacientes com insuficiência respiratória admitidos à unidade de terapia intensiva no período compreendido entre março e abril de 2020 em comparação com o mesmo período no ano de 2019. Compararam-se as intervenções e os desfechos dos pacientes sem COVID-19 tratados durante a pandemia em 2020 e os pacientes admitidos em 2019. As principais variáveis avaliadas foram os cuidados respiratórios na unidade de terapia intensiva, o número de exames de tomografia computadorizada do tórax e lavados broncoalveolares, complicações na unidade de terapia intensiva e condições quando da alta hospitalar. RESULTADOS: Observou-se, em 2020, uma redução significante do uso de cânula nasal de alto fluxo: 14 (42%), em 2019, em comparação com 1 (3%), em 2020. Além disso, em 2020, observou-se aumento significante no número de pacientes sob ventilação mecânica admitidos à unidade de terapia intensiva a partir do pronto-socorro, de 23 (69%) em comparação com 11 (31%) em 2019. Contudo, o número de pacientes com ventilação mecânica 5 dias após a admissão foi semelhante em ambos os anos: 24 (69%), em 2019, e 26 (79%) em 2020. CONCLUSÃO: Os protocolos para unidades de terapia intensiva com base em recomendações internacionais para a pandemia de COVID-19 modificaram o manejo de pacientes sem COVID-19. Observamos redução do uso da cânula nasal de alto fluxo e aumento no número de intubações traqueais no pronto-socorro. Entretanto, não se identificaram alterações na percentagem de pacientes intubados na unidade de terapia intensiva, número de dias sob ventilação mecânica ou número de dias na unidade de terapia intensiva.


Subject(s)
COVID-19/epidemiology , Critical Illness/therapy , Disease Management , Pandemics , Aged , Argentina/epidemiology , Bronchoalveolar Lavage/statistics & numerical data , Female , Health Care Surveys , Humans , Intensive Care Units , Intubation, Intratracheal/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Treatment Outcome
17.
J Transl Med ; 18(1): 427, 2020 11 11.
Article in English | MEDLINE | ID: covidwho-916978

ABSTRACT

BACKGROUND: Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. METHODS: We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. RESULTS: The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. CONCLUSION: Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.


Subject(s)
Respiratory Distress Syndrome , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid , Humans , Respiration, Artificial , Respiratory Distress Syndrome/therapy , T-Lymphocytes, Regulatory
19.
A A Pract ; 15(4): e01432, 2021 Mar 30.
Article in English | MEDLINE | ID: covidwho-1158241

ABSTRACT

The role of concurrent illness in coronavirus disease 2019 (COVID-19) is unknown. Patients with leukemia may display altered thromboinflammatory responses. We report a 53-year-old man presenting with acute leukemia and COVID-19 who developed thrombotic complications and acute respiratory distress syndrome. Multiple analyses, including rotational thromboelastometry and flow cytometry on blood and bronchoalveolar lavage, are reported to characterize coagulation and immune profiles. The patient developed chemotherapy-induced neutropenia that may have protected his lungs from granulocyte-driven hyperinflammatory acute lung injury. However, neutropenia also alters viral clearing, potentially enabling ongoing viral propagation. This case depicts a precarious equilibrium between leukemia and COVID-19.


Subject(s)
Acute Lung Injury/complications , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/pathology , COVID-19/complications , COVID-19/pathology , Leukemia, Myeloid, Acute/complications , Acute Lung Injury/diagnosis , Acute Lung Injury/pathology , Blood Coagulation Disorders/diagnosis , Bronchoalveolar Lavage , COVID-19/diagnosis , Flow Cytometry , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Neutropenia/complications , Neutropenia/diagnosis , Neutropenia/pathology , SARS-CoV-2 , Thrombelastography , Virulence Factors
20.
Respiration ; 100(6): 510-514, 2021.
Article in English | MEDLINE | ID: covidwho-1158153

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has drastically affected hospital and operating room (OR) workflow around the world as well as trainee education. Many institutions have instituted mandatory preoperative SARS-CoV-2 PCR nasopharyngeal swab (NS) testing in patients who are low risk for COVID-19 prior to elective cases. This method, however, is challenging as the sensitivity, specificity, and overall reliability of testing remains unclear. OBJECTIVES: The objective of this study was to assess the concordance of a negative NS in low risk preoperative patients with lower airway bronchoalveolar lavage (BAL) specimens obtained from the same patients. METHODS: We prospectively sent intraoperative lower airway BAL samples collected within 48 h of a negative mandatory preoperative NS for SARS-CoV-2 PCR testing. All adult patients undergoing a scheduled bronchoscopic procedure for any reason were enrolled, including elective and nonelective cases. RESULTS: One-hundred eighty-nine patients were included. All BAL specimens were negative for SARS-CoV-2 indicative of 100% concordance between testing modalities. CONCLUSIONS: These results are promising and suggest that preoperative nasopharyngeal SARS-CoV-2 testing provides adequate screening to rule out active COVID-19 infection prior to OR cases in a population characterized as low risk by negative symptom screening. This information can be used for both pre-procedural screening and when reintroducing trainees into the workforce.


Subject(s)
Bronchoalveolar Lavage Fluid , COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Carrier State/diagnosis , Nasopharynx , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage , Bronchoscopy , Female , Humans , Male , Mass Screening , Middle Aged , Preoperative Care , Prospective Studies , Risk , Sensitivity and Specificity , Young Adult
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