Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality.

BACKGROUND: As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality. METHODS: In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0-24 per subject. RESULTS: Among 215 enrolled subjects, 168 with LUS data and no current signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome (n = 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, P < .001) and procalcitonin levels (0.35 µg/L vs 0.13, P = .033) and higher supplemental oxygen requirements (median 4 L/min vs 2, P = .001). However, LUS findings and score did not differ significantly between subjects with the composite outcome and those without, and were not associated with outcomes in unadjusted and adjusted logistic regression analyses. CONCLUSIONS: Pathologic findings on LUS were common a median of 3 d after admission in this cohort of non-ICU hospitalized subjects with COVID-19 and did not differ among subjects who experienced the composite outcome of incident ARDS, ICU admission, and all-cause mortality compared to subjects who did not. These findings should be confirmed in future investigations. The study is registered at Clinicaltrials.gov (NCT04377035).

Focused lung ultrasound to predict respiratory failure in patients with symptoms of COVID-19: a multicentre prospective cohort study.

Background: In this study we aimed to assess if a focused lung ultrasound examination predicts the need for mechanical ventilation, admission to an intensive care unit, high-flow oxygen treatment, death from COVID-19 within 30 days and 30-day all-cause mortality in patients with clinical suspicion of COVID-19 or PCR-verified SARS-CoV-2 infection. Methods: A multicentre prospective cohort trial was performed. Film clips from focused lung ultrasound examinations were recorded and rated by blinded observers using different scoring systems. A prediction model was built and used to test relationship between lung ultrasound scores and clinical outcomes. Diagnostic performance of scoring systems was analysed. Results: A total of 3889 film clips of 398 patients were analysed. Patients who had any of the outcomes of interest had a significantly higher ultrasound score than those who did not. Multivariable logistic regression analyses showed that lung ultrasound predicts mechanical ventilation (relative risk 2.44, 95% CI 1.32-5.52), admission to intensive care (relative risk 2.55, 95% CI 1.41-54.59) and high-flow oxygen treatment (relative risk 1.95, 95% CI 1.5-2.53) but not survival when adjusting for sex, age and relevant comorbidity. There was no diagnostic difference in area under the receiver operating characteristic curve between a scoring system using only anterolateral thorax zones and a scoring system that also included dorsal zones. Conclusion: Focused lung ultrasound in patients with clinical suspicion of COVID-19 predicts respiratory failure requiring mechanical ventilation, admission to intensive care units and the need for high-flow oxygen treatment. Thus, focused lung ultrasound may be used to risk stratify patients with COVID-19 symptoms.

Implementation and findings on a one-minute sit-stand test for prehospital triage in patients with suspected COVID-19-a pilot project.

INTRODUCTION: During the initial Coronavirus Disease 2019 (COVID-19) pandemic wave, sparse personal protection equipment made telephone triage of suscpeted COVID-19 patients for ambulance transport necessary. To spare resources, stable patients were often treated and released on-scene, but reports from Italy suggested that some later detoriated. We implemented a prehospital sit-stand test to identify patients in risk for detoriation. METHODS: The test was implemented as part of a new guideline in stable suspected COVID-19 patients younger than 70 years with no risk factors for serious disease triaged by general practitioners to ambulance response in the Central Denmark Region. Data were collected from April 6th to July 6th 2020. The primary outcome for this study was the proportion of patients treated with oxygen within 7 days among patients decompensating vs patients not decompensating during the test. RESULTS: Data on 156 patients triaged to ambulance response by general practioners were analysed. In total 86/156 (55%) were tested with the sit-stand test. Due to off-guideline use of the test, 30/86 (34.8%) were either older than 70 or had risk factors for serious disease. 10/156 (6%) of patients had a positive COVID-19-test. In total, 17/86 (20%) decompensated during the test and of these, 9/17 (53%) were treated with oxygen compared to 2/69 (3%) in patients who did not decompensate (p < 0.001). CONCLUSION: In a population suspected of COVID-19 but with a low COVD-19 prevalence, decompensation with the sit-stand test was observed in 20% of patients and was associated with oxygen treatment within 7 days. These findings are hypotheses-generating and suggest that physical exercise testing may be usefull for decision making in emergency settings.

Lung ultrasound findings following COVID-19 hospitalization: A prospective longitudinal cohort study.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for diagnosis and monitoring in patients with active COVID-19-infection. However, less is known about the changes in LUS findings after a hospitalization for COVID-19. METHODS: In a prospective, longitudinal study in patients with COVID-19 enrolled from non-ICU hospital units, adult patients underwent 8-zone LUS and blood sampling both during the hospitalization and 2-3 months after discharge. LUS images were analyzed blinded to clinical variables and outcomes. RESULTS: A total of 71 patients with interpretable LUS at baseline and follow up (mean age 64 years, 61% male, 24% with acute respiratory distress syndrome (ARDS)) were included. The follow-up LUS was performed a median of 72 days after the initial LUS performed during hospitalization. At baseline, 87% had pathologic LUS findings in ≥1 zone (e.g. ≥3 B-lines, confluent B-lines or subpleural or lobar consolidation), whereas 30% had pathologic findings at follow-up (p < 0.001). The total number of B-lines and LUS score decreased significantly from hospitalization to follow-up (median 17 vs. 4, p < 0.001 and 4 vs. 0, p < 0.001, respectively). On the follow-up LUS, 28% of all patients had ≥3 B-lines in ≥1 zone, whereas in those with ARDS during the baseline hospitalization (n = 17), 47% had ≥3 B-lines in ≥1 zone. CONCLUSION: LUS findings improved significantly from hospitalization to follow-up 2-3 months after discharge in COVID-19 survivors. However, persistent B-lines were frequent at follow-up, especially among those who initially had ARDS. LUS seems to be a promising method to monitor COVID-19 lung changes over time. GOV ID: NCT04377035.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PURPOSE: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). METHODS: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). RESULTS: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. CONCLUSION: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. GOV ID: NCT04377035.

SARS-CoV-2 evades immune detection in alveolar macrophages.

Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.