Radiographic Findings and other Predictors in Adults with Covid-19

As of March 20, 2020, there were 234,073 confirmed cases of coronavirus disease 2019 (Covid-19) and 9,840 deaths worldwide. Older age and elevated d-dimer are reported risk factors for Covid-19. However, whether early radiographic change is a predictor of fatality remains unknown. We retrospectively reviewed records of all laboratory-confirmed patients admitted to a quarantine unit at Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. The Tongji Hospital ethics committee approved this study. A total of 128 patients were admitted. 102 patients were confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using RNA detection. As of March 20, 82 confirmed patients were discharged, 15 died, and 5 remained hospitalized. The median age was 57 years (range, 27 - 85), 59 (58%) were male, and 44 (43%) patients had a comorbidity. The most common symptoms were fever, cough, and dyspnea. When compared with survivors, non-survivors were older and more likely to have lymphopenia, elevated lactate dehydrogenase (LDH), elevated d-dimer, and increased hypersensitive troponin I. In a multivariate regression model that included these predictors, older age and elevated LDH were independent risk factors for fatality. Twenty-one survivors and 11 non-survivors had CT scans within the first week. We used severity score to quantify the extent of lung opacification as described in the Supplementary Appendix. The total severity score and number of involved lung lobes within the first week were significantly greater in non-survivors compared to survivors . Using univariate logistic regression analysis, higher total severity score ([≥]15) (odds ratio 53, 95% CI 3-369; p = 0.003), and more involved lung lobes (5 involved lobes) (9, 2-53; p = 0.016) in CT images within the first week were significantly associated with fatality. Moreover, in this subset of patients with CT data within the first week, higher total severity score was the only independent risk factor in a multivariate analysis incorporated the predictors discussed above (older age, lymphocytopenia, elevated LDH, elevated d-dimer, and increased troponin I). For survivors with serial CT scans performed over four weeks, total severity score peaked in the second week. This report suggests that the extent of lung lesions in early CT images is a potential predictor of poor outcome of Covid-19. This will help clinicians to identify the patients with poor prognosis at early stage.

(LDH), elevated d-dimer, and increased hypersensitive troponin I (Table S1, S2). In a multivariate regression model that included these predictors, older age and elevated LDH were independent risk factors for fatality (Table S3). Twenty-one survivors and 11 non-survivors had CT scans within the first week. We used severity score to quantify the extent of lung opacification as described in the

Study Population and Data Collection
This retrospective study was approved by the institutional ethics board of Tongji Hospital of Huazhong University of Science and Technology. Written informed consent was waived. The study included all patients with laboratory-confirmed COVID-19 admitted to a quarantine unit of Tongji Hospital, a large regional hospital in Wuhan, China, between January 31 and March 5, 2020. COVID-19 patients were diagnosed according to World Health Organization (WHO) interim guideline 1 . Confirmed cases were defined by the positive findings in reverse-transcriptase-polymerase-chainreaction (RT-PCR) assay of throat swab specimens. Clinical characteristics, laboratory test results, and treatment information were extracted from electronic medical records.
All laboratory testing and radiological examination were performed according to the clinical care needs of the patient.

RT-PCR for SARS-CoV-2
Throat swab specimens were tested for SARS-CoV-2 using real-time RT-PCR according to the WHO protocol 3 . The following primers and probes were used for realtime RT-PCR detection of N gene of SARS-CoV-2: N forward primer 5'- Positive results were confirmed in two independent real-time RT-PCR assays.

Chest CT Protocols and Evaluation
High-resolution transverse CT images were obtained using Optima 660 (GE Medical All rights reserved. No reuse allowed without permission.
the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint System, Milwaukee, USA) or Somatom Definition AS+ (Siemens Healthineers, Forchheim, Germany). Tube voltage was 100 or 120 kV, and automatic tube current modulation was 100 -400 mA. All images were reconstructed with a slice thickness of 1.0mm or 1.25mm. The CT images were reviewed by two radiologists (ZW and NW) who were blinded to the final outcome of the patients. Images were reviewed independently. Any disagreements were resolved by discussion and consensus.

Statistical Analysis
Statistical analysis was done with SPSS Statistics Software (version 26; IBM, New York, USA). Continuous variables were presented as median (IQR) and analyzed using Mann-Whitney U test; categorical variables were presented as number (%) and analyzed by χ² test or Fisher's exact test between survivors and non-survivors where appropriate. Univariable and multivariable logistic regression models were used to estimate odds ratios and the 95% confidence intervals of the risk factors associated with fatal outcome. A two-sided α of less than 0.05 was considered statistically significant.
All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint  the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint Data are median (IQR), n (%), or n/N (%), where N is the total number of patients with available data. p values comparing survivor with non-survivor were calculated by χ² test, Fisher's exact test, or Mann-Whitney U test, as appropriate. Covid-19, coronavirus disease 2019.
All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint   the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is OR=odds ratio. *Per 1 unit increase.
All rights reserved. No reuse allowed without permission.
the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is    OR=odds ratio. *Per 1 unit increase.
All rights reserved. No reuse allowed without permission.
the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint  Data are median (IQR), n (%), or n/N (%), where N is the total number of patients with available data. χ² test, Fisher's exact test, or Mann-Whitney U test were used to compare the values between survivors and non-survivors as appropriate.

Table S6. Demographics and baseline characteristics of the subset of patients included in the analysis of CT within the first week after symptom onset
All rights reserved. No reuse allowed without permission.
the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is     All rights reserved. No reuse allowed without permission.
the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.23.20041673 doi: medRxiv preprint Figure S2. Transverse CT images of a 41-year-old woman with Covid-19. A-C, day 6 after symptom onset, multifocal consolidations and ground-glass opacities affecting the bilateral, subpleural lung parenchyma associated with crazy-paving pattern. D-F, day 10 after symptom onset, bilateral extensive ground-glass opacities, involving nearly the entire lower lobes and right middle lobe, and most of the upper lobes, giving a white lung appearance, with air bronchograms and crazy-paving pattern. The patient died 8 days after this scan.
All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Author Contributions
KL and GZ conceptualized the study design. KL, SC, DC, YF, CC collected demographic, clinical, and laboratory data. ZW and NW interpreted the images of CT scans. KL, DC, YF and GZ analysed the data. KL and GZ interpreted the results. GZ wrote the manuscript with all authors providing feedback for revision. All authors read and approved the final report.