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      Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort

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          Abstract

          Aim

          To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes.

          Materials And Methods

          Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20–5/1/21.

          Results

          There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of “high” and “low”, with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001).

          Conclusion

          There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

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          Most cited references23

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          Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia

          Background Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. Purpose To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. Results Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. Conclusion In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.
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            Viral dynamics in mild and severe cases of COVID-19

            Coronavirus disease 2019 (COVID-19) is a new pandemic disease. We previously reported that the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peaks within the first week of disease onset.1, 2 Findings from Feb, 2020, indicated that the clinical spectrum of this disease can be very heterogeneous. 3 Here, we report the viral RNA shedding patterns observed in patients with mild and severe COVID-19. 76 patients admitted to the First Affiliated Hospital of Nanchang University (Nanchang, China) from Jan 21 to Feb 4, 2020, were included in the study. All patients were confirmed to have COVID-19 at the time of admission by RT-PCR. The viral loads of their nasopharyngeal swab samples were estimated with the DCt method (Ctsample – Ctref). Patients who had any of the following features at the time of, or after, admission were classified as severe cases: (1) respiratory distress (≥30 breaths per min); (2) oxygen saturation at rest ≤93%; (3) ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air ≤300 mm Hg; or (4) severe disease complications (eg, respiratory failure, requirement of mechanical ventilation, septic shock, or non-respiratory organ failure). 46 (61%) individuals were classified as mild cases and 30 (39%) were classified as severe cases. The basic demographic data and initial clinical symptoms of these patients are shown in the appendix. Parameters did not differ significantly between the groups, except that patients in the severe group were significantly older than those in the mild group, as expected. 4 No patient died from the infection. 23 (77%) of 30 severe cases received intensive care unit (ICU) treatment, whereas none of the mild cases required ICU treatment. We noted that the DCt values of severe cases were significantly lower than those of mild cases at the time of admission (appendix). Nasopharyngeal swabs from both the left and right nasal cavities of the same patient were kept in a sample collection tube containing 3 mL of standard viral transport medium. All samples were collected according to WHO guidelines. 5 The mean viral load of severe cases was around 60 times higher than that of mild cases, suggesting that higher viral loads might be associated with severe clinical outcomes. We further stratified these data according to the day of disease onset at the time of sampling. The DCt values of severe cases remained significantly lower for the first 12 days after onset than those of corresponding mild cases (figure A ). We also studied serial samples from 21 mild and ten severe cases (figure B). Mild cases were found to have an early viral clearance, with 90% of these patients repeatedly testing negative on RT-PCR by day 10 post-onset. By contrast, all severe cases still tested positive at or beyond day 10 post-onset. Overall, our data indicate that, similar to SARS in 2002–03, 6 patients with severe COVID-19 tend to have a high viral load and a long virus-shedding period. This finding suggests that the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis. Figure Viral dynamics in patients with mild and severe COVID-19 (A) DCT values (Ctsample-Ctref) from patients with mild and severe COVID-19 at different stages of disease onset. Median, quartile 1, and quartile 3 are shown. (B) DCT values of serial samples from patients with mild and severe COVID-19. COVID-19=coronavirus disease 2019. *p<0·005.
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              A minimal common outcome measure set for COVID-19 clinical research

              Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.
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                Author and article information

                Journal
                Clin Radiol
                Clin Radiol
                Clinical Radiology
                Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
                0009-9260
                1365-229X
                23 November 2021
                23 November 2021
                Affiliations
                [7 ]Department of Clinical Medicine, University of Oxford Nuffield Oxford, Oxfordshire, UK
                [8 ]NIHR Oxford Biomedical Research Centre, Oxford, Oxfordshire, UK
                [1 ]Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, UK
                [2 ]Weatherall Institute of Molecular Medicine, Oxford, Oxfordshire, UK
                [3 ]Department of Clinical Medicine, University of Oxford Nuffield Oxford, Oxfordshire, UK
                [4 ]NIHR Oxford Biomedical Research Centre, Oxford, Oxfordshire, UK
                [5 ]National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, London, London, UK
                [6 ]Oxford Medical School, Oxford, Oxfordshire, UK
                Author notes
                []Corresponding author. John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire OX3 9DU, UK. Tel.: ????.
                [†]

                Modernising Medical Microbiology Group: G. Rodger 3, B. Constantinides 3, N. Sanderson 3,4, K. K. Chau 3.

                Article
                S0009-9260(21)00531-6
                10.1016/j.crad.2021.11.002
                8608596
                34895912
                6e227545-23d2-4778-ae56-4e09e1bda6c7
                © 2021 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 24 August 2021
                : 12 November 2021
                Categories
                Article

                Radiology & Imaging
                Radiology & Imaging

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