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1.
EBioMedicine ; 81: 104082, 2022 May 31.
Article in English | MEDLINE | ID: covidwho-1867077

ABSTRACT

BACKGROUND: Community-acquired pneumonia (CAP) can be caused by a variety of pathogens, of which Streptococcus pneumoniae, Influenza and currently SARS-CoV-2 are the most common. We sought to identify shared and pathogen-specific host response features by directly comparing different aetiologies of CAP. METHODS: We measured 72 plasma biomarkers in a cohort of 265 patients hospitalized for CAP, all sampled within 48 hours of admission, and 28 age-and sex matched non-infectious controls. We stratified the biomarkers into several pathophysiological domains- antiviral response, vascular response and function, coagulation, systemic inflammation, and immune checkpoint markers. We directly compared CAP caused by SARS-CoV-2 (COVID-19, n=39), Streptococcus pneumoniae (CAP-strep, n=27), Influenza (CAP-flu, n=22) and other or unknown pathogens (CAP-other, n=177). We adjusted the comparisons for age, sex and disease severity scores. FINDINGS: Biomarkers reflective of a stronger cell-mediated antiviral response clearly separated COVID-19 from other CAPs (most notably granzyme B). Biomarkers reflecting activation and function of the vasculature showed endothelial barrier integrity was least affected in COVID-19, while glycocalyx degradation and angiogenesis were enhanced relative to other CAPs. Notably, markers of coagulation activation, including D-dimer, were not different between the CAP groups. Ferritin was most increased in COVID-19, while other systemic inflammation biomarkers such as IL-6 and procalcitonin were highest in CAP-strep. Immune checkpoint markers showed distinctive patterns in viral and non-viral CAP, with highly elevated levels of Galectin-9 in COVID-19. INTERPRETATION: Our investigation provides insight into shared and distinct pathophysiological mechanisms in different aetiologies of CAP, which may help guide new pathogen-specific therapeutic strategies. FUNDING: This study was financially supported by the Dutch Research Council, the European Commission and the Netherlands Organization for Health Research and Development.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314435

ABSTRACT

Introduction: Clinicians have been struggling with the optimal diagnostic approach of patients with suspected COVID-19. We evaluated the added value of chest CT over RT-PCR alone. Methods: Consecutive adult patients with suspected COVID-19 presenting to the emergency department (Academic Medical Center, Amsterdam University Medical Centers, the Netherlands) from March 16th to April 16th were retrospectively included if they required hospital admission and underwent chest CT and RT-PCR testing for SARS-CoV-2 infection. The CO-RADS classification was used to assess the radiological probability of COVID-19, where a score of 1-2 was considered as negative, 3 as indeterminate, and 4-5 as positive. CT results were stratified by initial RT-PCR results. For patients with a negative RT-PCR but a positive CT, serology or multidisciplinary discussion after clinical follow-up constituted the final diagnosis. Results: 258 patients with suspected COVID-19 were admitted, of which 239 were included because they had both CT and RT-PCR testing upon admission. Overall, 112 patients (46.9%) had a positive initial RT-PCR, and 14 (5.9%) had a positive repeat RT-PCR. Of 127 patients with a negative or indeterminate initial RT-PCR, 38 (29.9% [95%CI 21.3-39.3%]) had a positive CT. Of these, 13 had a positive RT-PCR upon repeat testing, and 5 had positive serology. The remaining 20 patients were assessed in a multidisciplinary consensus meeting, and for 13 it was concluded that COVID-19 was ‘very likely’. Of 112 patients with a positive initial RT-PCR result, CT was positive in 104 (92.9% [95%CI 89.3-97.5%]). Conclusion: In a high-prevalence emergency department setting, chest CT showed high probability of COVID-19 (CO-RADS 4-5) in 29.9% of patients with a negative or indeterminate initial RT-PCR result. As the majority of these patients had proven or ‘very likely’COVID-19 after follow-up, we believe that CT helps in the identification of patients who should be admitted in isolation.

3.
Respirology ; 26(9): 869-877, 2021 09.
Article in English | MEDLINE | ID: covidwho-1280373

ABSTRACT

BACKGROUND AND OBJECTIVE: Patients with coronavirus disease 2019 (COVID-19) pneumonia present with typical findings on chest computed tomography (CT), but the underlying histopathological patterns are unknown. Through direct regional correlation of imaging findings to histopathological patterns, this study aimed to explain typical COVID-19 CT patterns at tissue level. METHODS: Eight autopsy cases were prospectively selected of patients with PCR-proven COVID-19 pneumonia with varying clinical manifestations and causes of death. All had been subjected to chest CT imaging 24-72 h prior to death. Twenty-seven lung areas with typical COVID-19 patterns and two radiologically unaffected pulmonary areas were correlated to histopathological findings in the same lung regions. RESULTS: Two dominant radiological patterns were observed: ground-glass opacity (GGO) (n = 11) and consolidation (n = 16). In seven of 11 sampled areas of GGO, diffuse alveolar damage (DAD) was observed. In four areas of GGO, the histological pattern was vascular damage and thrombosis, with (n = 2) or without DAD (n = 2). DAD was also observed in five of 16 samples derived from areas of radiological consolidation. Seven areas of consolidation were based on a combination of DAD, vascular damage and thrombosis. In four areas of consolidation, bronchopneumonia was found. Unexpectedly, in samples from radiologically unaffected lung parenchyma, evidence was found of vascular damage and thrombosis. CONCLUSION: In COVID-19, radiological findings of GGO and consolidation are mostly explained by DAD or a combination of DAD and vascular damage plus thrombosis. However, the different typical CT patterns in COVID-19 are not related to specific histopathological patterns. Microvascular damage and thrombosis are even encountered in the radiologically normal lung.


Subject(s)
COVID-19 , Lung , Tomography, X-Ray Computed , Autopsy , COVID-19/diagnostic imaging , Humans , Lung/diagnostic imaging , Retrospective Studies
4.
Chest ; 159(3): 1126-1135, 2021 03.
Article in English | MEDLINE | ID: covidwho-1099074

ABSTRACT

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.


Subject(s)
COVID-19 , Emergency Service, Hospital/statistics & numerical data , Patient Admission/statistics & numerical data , Pneumonia, Viral , Radiology Information Systems , Tomography, X-Ray Computed , COVID-19/diagnosis , COVID-19/epidemiology , Clinical Decision-Making , Evaluation Studies as Topic , Female , Humans , Male , Middle Aged , Mortality , Netherlands/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/etiology , Prognosis , Radiology Information Systems/organization & administration , Radiology Information Systems/standards , Research Design/statistics & numerical data , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed/methods , Tomography, X-Ray Computed/statistics & numerical data
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