Correlation between Serum Biomarkers and Lung Ultrasound in COVID-19: An Observational Study.

Serum biomarkers and lung ultrasound are important measures for prognostication and treatment allocation in patients with COVID-19. Currently, there is a paucity of studies investigating relationships between serum biomarkers and ultrasonographic biomarkers derived from lung ultrasound. This study aims to assess correlations between serum biomarkers and lung ultrasound findings. This study is a secondary analysis of four prospective observational studies in adult patients with COVID-19. Serum biomarkers included markers of epithelial injury, endothelial dysfunction and immune activation. The primary outcome was the correlation between biomarker concentrations and lung ultrasound score assessed with Pearson's (r) or Spearman's (rs) correlations. Forty-four patients (67 [41-88] years old, 25% female, 52% ICU patients) were included. GAS6 (rs = 0.39), CRP (rs = 0.42) and SP-D (rs = 0.36) were correlated with lung ultrasound scores. ANG-1 (rs = -0.39) was inversely correlated with lung ultrasound scores. No correlations were found between lung ultrasound score and several other serum biomarkers. In patients with COVID-19, several serum biomarkers of epithelial injury, endothelial dysfunction and immune activation correlated with lung ultrasound findings. The lack of correlations with certain biomarkers could offer opportunities for precise prognostication and targeted therapeutic interventions by integrating these unlinked biomarkers.

Monitoring of pulmonary involvement in critically ill COVID-19 patients - should lung ultrasound be preferred over CT?

BACKGROUND: It is unclear if relevant changes in pulmonary involvement in critically ill COVID-19 patients can be reliably detected by the CT severity score (CTSS) and lung ultrasound score (LUSS), or if these changes have prognostic implications. In addition, it has been argued that adding pleural abnormalities to the LUSS could improve its prognostic value. The objective of this study was to compare LUSS and CTSS for the monitoring of COVID-19 pulmonary involvement through: first, establishing the correlation of LUSS (± pleural abnormalities) and CTSS throughout admission; second, assessing agreement and measurement error between raters for LUSS, pleural abnormalities, and CTSS; third, evaluating the association of the LUSS (± pleural abnormalities) and CTSS with mortality at different timepoints. METHODS: This is a prospective, observational study, conducted during the second COVID-19 wave at the AmsterdamUMC, location VUmc. Adult COVID-19 ICU patients were prospectively included when a CT or a 12-zone LUS was performed at admission or at weekly intervals according to local protocol. Patients were followed 90 days or until death. We calculated the: (1) Correlation of the LUSS (± pleural abnormalities) and CTSS throughout admission with mixed models; (2) Intra-class correlation coefficients (ICCs) and smallest detectable changes (SDCs) between raters; (3) Association between the LUSS (± pleural abnormalities) and CTSS with mixed models. RESULTS: 82 consecutive patients were included. Correlation between LUSS and CTSS was 0.45 (95% CI 0.31-0.59). ICCs for LUSS, pleural abnormalities, and CTSS were 0.88 (95% CI 0.73-0.95), 0.94 (95% CI 0.90-0.96), and 0.84 (95% CI 0.65-0.93), with SDCs of 4.8, 1.4, and 3.9. The LUSS was associated with mortality in week 2, with a score difference between patients who survived or died greater than its SDC. Addition of pleural abnormalities was not beneficial. The CTSS was associated with mortality only in week 1, but with a score difference less than its SDC. CONCLUSIONS: LUSS correlated with CTSS throughout ICU admission but performed similar or better at agreement between raters and mortality prognostication. Given the benefits of LUS over CT, it should be preferred as initial monitoring tool.

Optimal use of procalcitonin to rule out bacteremia in patients with possible viral infections.

Objective: During the winter, many patients present with suspected infection that could be a viral or a bacterial (co)infection. The aim of this study is to investigate whether the optimal use of procalcitonin (PCT) is different in patients with and without proven viral infections for the purpose of excluding bacteremia. We hypothesize that when a viral infection is confirmed, this lowers the probability of bacteremia and, therefore, influences the appropriate cutoff of procalcitonin. Methods: This study was conducted in the emergency department of an academic medical center in The Netherlands in the winter seasons of 2019 and 2020. Adults (>18 years) with suspected infection, in whom a blood culture and a rapid polymerase chain reaction test for influenza was performed were included. Results: A total of 546 patients were included of whom 47 (8.6%) had a positive blood culture. PCT had an area under the curve of 0.85, 95% confidence interval (95% CI) 0.80-0.91, for prediction of bacteremia. In patients with a proven viral infection (N = 212) PCT < 0.5 µg/L had a sensitivity of 100% (95% CI 63.1-100) and specificity of 81.2% (95% CI 75.1-86.3) to exclude bacteremia. In patients without a viral infection, the procalcitonin cutoff point of < 0.25 µg/L showed a sensitivity of 87.2% (95% CI 72.6-95.7) and specificity of 64.1 % (95% CI 58.3-69.6). Conclusion: In patients with a viral infection, our findings suggest that a PCT concentration of <0.50 µg/L makes bacteremia unlikely. However, this finding needs to be confirmed in a larger population of patients with viral infections, especially because the rate of coinfection in our cohort was low.

Assessing COVID-19 pneumonia-Clinical extension and risk with point-of-care ultrasound: A multicenter, prospective, observational study.

BACKGROUND: Assessing the extent of lung involvement is important for the triage and care of COVID-19 pneumonia. We sought to determine the utility of point-of-care ultrasound (POCUS) for characterizing lung involvement and, thereby, clinical risk determination in COVID-19 pneumonia. METHODS: This multicenter, prospective, observational study included patients with COVID-19 who received 12-zone lung ultrasound and chest computed tomography (CT) scanning in the emergency department (ED). We defined lung disease severity using the lung ultrasound score (LUS) and chest CT severity score (CTSS). We assessed the association between the LUS and poor outcome (ICU admission or 30-day all-cause mortality). We also assessed the association between the LUS and hospital length of stay. We examined the ability of the LUS to differentiate between disease severity groups. Lastly, we estimated the correlation between the LUS and CTSS and the interrater agreement for the LUS. We handled missing data by multiple imputation with chained equations and predictive mean matching. RESULTS: We included 114 patients treated between March 19, 2020, and May 4, 2020. An LUS ≥12 was associated with a poor outcome within 30 days (hazard ratio [HR], 5.59; 95% confidence interval [CI], 1.26-24.80; P = 0.02). Admission duration was shorter in patients with an LUS <12 (adjusted HR, 2.24; 95% CI, 1.47-3.40; P < 0.001). Mean LUS differed between disease severity groups: no admission, 6.3 (standard deviation [SD], 4.4); hospital/ward, 13.1 (SD, 6.4); and ICU, 18.0 (SD, 5.0). The LUS was able to discriminate between ED discharge and hospital admission excellently, with an area under the curve of 0.83 (95% CI, 0.75-0.91). Interrater agreement for the LUS was strong: κ = 0.88 (95% CI, 0.77-0.95). Correlation between the LUS and CTSS was strong: κ = 0.60 (95% CI, 0.48-0.71). CONCLUSIONS: We showed that baseline lung ultrasound - is associated with poor outcomes, admission duration, and disease severity. The LUS also correlates well with CTSS. Point-of-care lung ultrasound may aid the risk stratification and triage of patients with COVID-19 at the ED.

[Lung ultrasound in patients with symptoms of covid-19]. / Longechografie bij patiënten met symptomen van covid-19.

The SARS-CoV-2 pandemic presents a challenge for healthcare worldwide. In this context, rapid, correct diagnosis and early isolation of infected persons is of great importance. Pneumonia as an expression of COVID-19 is responsible for the most part of morbidity and mortality. Lung ultrasound can provide valuable information about the diagnosis of a COVID-19 pneumonia in daily practice. A normal ultrasound excludes COVID-19 pneumonia. Conversely, finding abnormalities matching with a COVID-19 pneumonia can be useful for isolation policy. Follow up lung ultrasound visualizes the development of the pneumonia and a possible alternative diagnosis can thereby be determined in the event of a deviating clinical course.

Chest CT in COVID-19 at the ED: Validation of the COVID-19 Reporting and Data System (CO-RADS) and CT Severity Score: A Prospective, Multicenter, Observational Study.

BACKGROUND: CT is thought to play a key role in coronavirus disease 2019 (COVID-19) diagnostic workup. The possibility of comparing data across different settings depends on the systematic and reproducible manner in which the scans are analyzed and reported. The COVID-19 Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) introduced by the Radiological Society of the Netherlands (NVvR) attempt to do so. However, this system has not been externally validated. RESEARCH QUESTION: We aimed to prospectively validate the CO-RADS as a COVID-19 diagnostic tool at the ED and to evaluate whether the CTSS is associated with prognosis. STUDY DESIGN AND METHODS: We conducted a prospective, observational study in two tertiary centers in The Netherlands, between March 19 and May 28, 2020. We consecutively included 741 adult patients at the ED with suspected COVID-19, who received a chest CT and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR (PCR). Diagnostic accuracy measures were calculated for CO-RADS, using PCR as reference. Logistic regression was performed for CTSS in relation to hospital admission, ICU admission, and 30-day mortality. RESULTS: Seven hundred forty-one patients were included. We found an area under the curve (AUC) of 0.91 (CI, 0.89-0.94) for CO-RADS using PCR as reference. The optimal CO-RADS cutoff was 4, with a sensitivity of 89.4% (CI, 84.7-93.0) and specificity of 87.2% (CI, 83.9-89.9). We found a significant association between CTSS and hospital admission, ICU admission, and 30-day mortality; adjusted ORs per point increase in CTSS were 1.19 (CI, 1.09-1.28), 1.23 (1.15-1.32), 1.14 (1.07-1.22), respectively. Intraclass correlation coefficients for CO-RADS and CTSS were 0.94 (0.91-0.96) and 0.82 (0.70-0.90). INTERPRETATION: Our findings support the use of CO-RADS and CTSS in triage, diagnosis, and management decisions for patients presenting with possible COVID-19 at the ED.

Diagnosing COVID-19 pneumonia in a pandemic setting: Lung Ultrasound versus CT (LUVCT) - a multicentre, prospective, observational study.

BACKGROUND: In this coronavirus disease 2019 (COVID-19) pandemic, fast and accurate testing is needed to profile patients at the emergency department (ED) and efficiently allocate resources. Chest imaging has been considered in COVID-19 workup, but evidence on lung ultrasound (LUS) is sparse. We therefore aimed to assess and compare the diagnostic accuracy of LUS and computed tomography (CT) in suspected COVID-19 patients. METHODS: This multicentre, prospective, observational study included adult patients with suspected COVID-19 referred to internal medicine at the ED. We calculated diagnostic accuracy measures for LUS and CT using both PCR and multidisciplinary team (MDT) diagnosis as reference. We also assessed agreement between LUS and CT, and between sonographers. RESULTS: One hundred and eighty-seven patients were recruited between March 19 and May 4, 2020. Area under the receiver operating characteristic (AUROC) was 0.81 (95% CI 0.75-0.88) for LUS and 0.89 (95% CI 0.84-0.94) for CT. Sensitivity and specificity for LUS were 91.9% (95% CI 84.0-96.7) and 71.0% (95% CI 61.1-79.6), respectively, versus 88.4% (95% CI 79.7-94.3) and 82.0% (95% CI 73.1-89.0) for CT. Negative likelihood ratio was 0.1 (95% CI 0.06-0.24) for LUS and 0.14 (95% CI 0.08-0.3) for CT. No patient with a false negative LUS required supplemental oxygen or admission. LUS specificity increased to 80% (95% CI 69.9-87.9) compared to MDT diagnosis, with an AUROC of 0.85 (95% CI 0.79-0.91). Agreement between LUS and CT was 0.65. Interobserver agreement for LUS was good: 0.89 (95% CI 0.83-0.93). CONCLUSION: LUS and CT have comparable diagnostic accuracy for COVID-19 pneumonia. LUS can safely exclude clinically relevant COVID-19 pneumonia and may aid COVID-19 diagnosis in high prevalence situations.