CT and clinical assessment in asymptomatic and pre-symptomatic patients with early SARS-CoV-2 in outbreak settings

Nicole Varble; Maxime Blain; Michael Kassin; Sheng Xu; Evrim B Turkbey; Amel Amalou; Dilara Long; Stephanie Harmon; Thomas Sanford; Dong Yang; Ziyue Xu; Daguang Xu; Mona Flores; Peng An; Gianpaolo Carrafiello; Hirofumi Obinata; Hitoshi Mori; Kaku Tamura; Ashkan A Malayeri; Steven M Holland; Tara Palmore; Kaiyuan Sun; Baris Turkbey; Bradford J Wood

doi:10.1007/s00330-020-07401-8

CT and clinical assessment in asymptomatic and pre-symptomatic patients with early SARS-CoV-2 in outbreak settings

Eur Radiol. 2021 May;31(5):3165-3176. doi: 10.1007/s00330-020-07401-8. Epub 2020 Nov 4.

Authors

Nicole Varble^#^{1

2}, Maxime Blain^#¹, Michael Kassin^#^{1

3}, Sheng Xu¹, Evrim B Turkbey³, Amel Amalou¹, Dilara Long¹, Stephanie Harmon^{4

5}, Thomas Sanford^{1

4

6}, Dong Yang⁷, Ziyue Xu⁷, Daguang Xu⁷, Mona Flores⁷, Peng An⁸, Gianpaolo Carrafiello^{9

10}, Hirofumi Obinata¹¹, Hitoshi Mori¹¹, Kaku Tamura¹¹, Ashkan A Malayeri³, Steven M Holland¹², Tara Palmore¹³, Kaiyuan Sun¹⁴, Baris Turkbey^#^{3

4}, Bradford J Wood^#^{15

16

17

18}

Affiliations

¹ Center for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
² Philips Research North America, Cambridge, MA, USA.
³ Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, USA.
⁴ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁵ Clinical Research Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA.
⁶ State University of New York Upstate Medical University, Syracuse, NY, USA.
⁷ Nvidia Corporation, Bethesda, MD, USA.
⁸ Department of Radiology, Xiangyang NO. 1 People's Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, China.
⁹ Department of Radiology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
¹⁰ Department of Health Sciences, University of Milano, Milan, Italy.
¹¹ Self-Defense Forces Central Hospital, Tokyo, Japan.
¹² National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹³ Hospital Epidemiology Service, NIH Clinical Center, Bethesda, MD, USA.
¹⁴ Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
¹⁵ Center for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA. bwood@nih.gov.
¹⁶ Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD, USA. bwood@nih.gov.
¹⁷ National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. bwood@nih.gov.
¹⁸ National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD, USA. bwood@nih.gov.

^# Contributed equally.

Abstract

Objectives: The early infection dynamics of patients with SARS-CoV-2 are not well understood. We aimed to investigate and characterize associations between clinical, laboratory, and imaging features of asymptomatic and pre-symptomatic patients with SARS-CoV-2.

Methods: Seventy-four patients with RT-PCR-proven SARS-CoV-2 infection were asymptomatic at presentation. All were retrospectively identified from 825 patients with chest CT scans and positive RT-PCR following exposure or travel risks in outbreak settings in Japan and China. CTs were obtained for every patient within a day of admission and were reviewed for infiltrate subtypes and percent with assistance from a deep learning tool. Correlations of clinical, laboratory, and imaging features were analyzed and comparisons were performed using univariate and multivariate logistic regression.

Results: Forty-eight of 74 (65%) initially asymptomatic patients had CT infiltrates that pre-dated symptom onset by 3.8 days. The most common CT infiltrates were ground glass opacities (45/48; 94%) and consolidation (22/48; 46%). Patient body temperature (p < 0.01), CRP (p < 0.01), and KL-6 (p = 0.02) were associated with the presence of CT infiltrates. Infiltrate volume (p = 0.01), percent lung involvement (p = 0.01), and consolidation (p = 0.043) were associated with subsequent development of symptoms.

Conclusions: COVID-19 CT infiltrates pre-dated symptoms in two-thirds of patients. Body temperature elevation and laboratory evaluations may identify asymptomatic patients with SARS-CoV-2 CT infiltrates at presentation, and the characteristics of CT infiltrates could help identify asymptomatic SARS-CoV-2 patients who subsequently develop symptoms. The role of chest CT in COVID-19 may be illuminated by a better understanding of CT infiltrates in patients with early disease or SARS-CoV-2 exposure.

Key points: • Forty-eight of 74 (65%) pre-selected asymptomatic patients with SARS-CoV-2 had abnormal chest CT findings. • CT infiltrates pre-dated symptom onset by 3.8 days (range 1-5). • KL-6, CRP, and elevated body temperature identified patients with CT infiltrates. Higher infiltrate volume, percent lung involvement, and pulmonary consolidation identified patients who developed symptoms.

Keywords: Asymptomatic infections; Pneumonia; SARS-CoV; Virus shedding.

MeSH terms

COVID-19*
China / epidemiology
Disease Outbreaks
Humans
Japan
Retrospective Studies
SARS-CoV-2*
Tomography, X-Ray Computed

Abstract

MeSH terms

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