ABSTRACT
Background: Post-COVID syndrome (PCS) is an increasingly recognised complication of acute SARS-CoV- 2 infection, characterised by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath and cognitive slowing. Acute COVID-19 is strongly linked with increased risk of thrombosis;a prothrombotic state. Elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio is associated with severity of acute COVID-19 infection. Aim(s): We hypothesised that the pro-thrombotic state is implicated in the pathogenesis of PCS. We investigated specialist coagulation parameters associated with reduced exercise capacity in patients with PCS to identify the utility of these parameters to determine ongoing disease activity. We also investigated if an association exists between elevated VWF(Ag):ADAMTS13 ratio and impaired exercise capacity in patients with PCS. Method(s): Retrospective analysis of VWF(Ag):ADAMTS13 ratio in patients with PCS at a dedicated post-COVID clinic. VWF(Ag):ADAMTS13 ratio was correlated with symptoms including exercise capacity as assessed by 1 minute sit-to- stand (STS) test and/or 6 minute walk test (6MWT). Peripheral oxygen desaturation >=3% for 6MWT and STS test, and increase in lactate>1 from baseline during 6MWT were taken as markers of impaired exercise capacity. Result(s): Elevated VWF(Ag):ADAMTS13 ratio (>=1.5) was found to be four times (OR 4.3) more likely in patients with impaired exercise capacity. 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio >=1.5 (p < 0.0001). A higher median VWF(Ag):ADAMTS13 ratio of 1.5 (IQR 1.2-1.7) in patients with abnormal exercise testing compared to 1.1 (IQR 0.9-1.4) in patients with normal exercise testing was found (p < 0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in patients with PCS. Conclusion(s): These findings suggest possible ongoing microvascular/ endothelial dysfunction in the pathogenesis of PCS and highlight the potential role for prophylactic anticoagulation in the management of these patients.
ABSTRACT
Rationale: SARS-CoV-2 infection has been recognised to cause endotheliitis and a pro-thrombotic state during acute illness. Following acute infection, a phenomenon described as 'Long COVID' can cause persisting morbidity with multiple symptoms including exercise intolerance. In recent months preliminary data has proposed persistence of micro-clots as a mechanism for Long COVID. We sought to further understand if a thromboinflammatory processes could be contributing to clinical phenotypes in patients assessed in a UK Post COVID service. Methods: Retrospective analysis of real-world electronic health data relating to patients attending between May 2020 and Jan 2022 (both post hospital and community managed). D-dimer levels, Von Willebrand Factor antigen (vWFAg), date of acute COVID infection and attendance source were available in 1607 patients (1163 community managed and 444 post hospitalisation with acute SARS-CoV-2). vWFAg: ADAMTS13 ratio was reviewed in a subset of 329 patients and correlated with symptoms and functional assessments such as the 6 minute walk test and/or 1 minute sit-tostand test. vWF(Ag):ADAMTS13 ratio was also calculated on 50 voluntary normal controls (Medical Research Ethics Committee Numbers 08/H0810/54 and 08/H0716/72). Results: In the overall cohort D-dimer and vWF(Ag) levels were mostly in the normal range. However, in post-hospitalised patients 21/90 (23.3%) and 65/500(11.5%) community-managed patients had a D-dimer > 550mg/L more than 180 days from acute infection (figure 1). vWF(Ag) levels showed a similar spectrum of abnormalities. In the subgroup with vWF(Ag):ADAMTS13 ratios analysis, 70 (21%) had evidence of abnormal exercise testing as confirmed by desaturation ≥3% and/or an increase in lactate levels >1 above baseline. 43 (61%) of this group had elevated vWF(Ag):ADAMTS13 >1.5. Abnormal exercise testing was associated with a higher vWF(Ag):ADAMTS13 with a median of 1.5 (IQR 1.2-1.7) compared with 1.2 (IQR 0.9-1.4) in those with normal exercise test (p<0.0001), OR 4.955 [2.850-8.612], p<0.0001). Conclusions: This cohort of patients demonstrates a subgroup with persistently elevated D-dimer and vWFAg levels suggesting these markers of thromboinflammatory processes could be of relevance in defining phenotypes within long COVID. The spectrum of abnormality seen, together with the observed correlation of vWF(Ag): ADAMTS13 ratios with impaired exercise tolerance warrants further evaluation of microvascular/ endothelial dysfunction as a mechanism in Long COVID. Further mechanistic studies are in progress.
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P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.
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PurposeTo describe the incidence of pulmonary artery thrombosis in COVID-19 versus influenza pneumonia using CT angiography and to assess whether it may increase the risk of pulmonary hypertension.Materials and MethodsSingle and dual energy CT pulmonary angiography of age- and gender-matched patients with influenza and COVID-19 pneumonia, referred for extra-corporeal membrane oxygenation (ECMO) and/or mechanical ventilation from January 2016 to January 2021, were retrospectively evaluated. Two independent observers qualitatively and quantitively assessed clot burden and Qanadli CT Obstruction Index. Two consensus observers calculated pulmonary artery volume and right to left ventricular diameter ratio (Terarecon, California, USA) to diagnose pulmonary hypertension. Pulmonary infarct volume and perfused blood volume relative enhancement were also calculated (Syngo via, Siemens Healthineers, Forchheim, Germany). All radiologic parameters were correlated with clinical data. To assess if in situ thrombosis could be visualised on CT, isolated segmental and subsegmental filling defects were used as an imaging surrogate. For statistical analyses, Graphpad Prism9 and IBM SPSS v27.0 software were used.ResultsThe incidence of either central PE or DVT was equal between patients with COVID-19 and influenza pneumonia (20%). The incidence of isolated segmental and subsegmental filling defects was higher in COVID-19 but without statistical significance (44% vs 32%;p=0.5607). Right to left ventricular diameter and pulmonary artery to aorta ratios were higher in COVID-19 compared to influenza (1.01 vs 0.866 and 1.04 vs 0.904;p=0.0071 and p=0.0023, respectively).ConclusionIn a comparable group of patients with severe COVID-19 and influenza pneumonia, CT features of pulmonary hypertension are more often present in patients with COVID-19 pneumonia despite an equal clot burden on CT. This is not attributable to pulmonary thrombosis visible on CT and supports the hypothesis that micro- rather than macrovascular obstruction is the cause of severe hypoxia in COVID-19 pneumonia.
ABSTRACT
Air cargo is mostly transported on passenger flights. During the COVID-19 outbreak, there have been worldwide restrictions on passenger transportation. Therefore, airlines experienced a capacity problem for air cargo. Better insight of air cargo demand during COVID-19 could contribute to the better arrangement of capacity by accordingly adapting flight schedules for cargo. The aim of this research was to make short-term predictions of air cargo demand between a major European airport hub and the United States during the COVID-19 pandemic. This was done for the month of May in 2020 by making 14-day predictions. The same was done for the year 2019 to observe whether the models performed well in the absence of the pandemic. The data set was compiled using data provided by a major commercial airline and exogenous features, such as stock market indices, foreign currency exchange rates and healthcare related predictions during COVID-19. To make the predictions, two classes of machine learning models for time series were compared: Autoregressive Integrated Moving Average (ARIMA) and Long Short-Term Memory (LSTM). In the year 2020, the best performing model among the ARIMA-based models is the Seasonal ARIMA including the exogenous feature Schedule . During the year 2019 the Seasonal ARIMA model without exogenous features generates the most accurate predictions. Among the LSTM models, the multivariate LSTM models outperform the univariate LSTM models in both years. Nonetheless, the ARIMA-based models are more accurate than the multivariate LSTM model in this research.Keywords: Air Cargo, COVID-19, Airlines, ARIMA, LSTM