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Is there an association between the timing of exposure to and severity of COVID-19 disease in close contacts of index patients with COVID-19?
In this cohort study of 730 index patients with a COVID-19 diagnosis and 8852 close contacts, transmission potential was greatest in the first 2 days before and 3 days after onset of symptoms in the index patient. When contacts received a diagnosis of COVID-19 infection, they were more likely to present asymptomatically if they had been exposed to an asymptomatic patient.
These results suggest that the quantity of exposure to a patient with COVID-19 may be associated with clinical presentation among close contacts who develop COVID-19.
Much remains unknown about the transmission dynamics of COVID-19. How the severity of the index case and timing of exposure is associated with disease in close contacts of index patients with COVID-19 and clinical presentation in those developing disease is not well elucidated.
To investigate the association between the timing of exposure and development of disease among close contacts of index patients with COVID-19 and to evaluate whether the severity of the index case is associated with clinical presentation in close contacts who develop COVID-19.
Design, Setting, and Participants
This study used a large, population-based cohort of 730 individuals (index patients) who received a diagnosis of COVID-19 in Zhejiang Province, China, from January 8 to July 30, 2020, along with a contact tracing surveillance program. Field workers visited 8852 close contacts of the index patients and evaluated them for COVID-19 through August 2020. A timeline was constructed to characterize different exposure periods between index patients and their contacts.
Main Outcomes and Measures
The primary outcome was the attack rate of COVID-19, defined as the total number of new COVID-19 cases diagnosed among contacts of index patients divided by the total number of exposed contacts. A secondary outcome was asymptomatic clinical presentation among infected contacts. Relative risks were calculated to investigate risk factors for COVID-19 among contacts and asymptomatic clinical presentation among infected contacts.
Among 8852 close contacts (4679 male contacts [52.9%]; median age, 41 years [interquartile range, 28-54 years]) of 730 index patients (374 male patients [51.2%]; median age, 46 years [interquartile range, 36-56 years]), contacts were at highest risk of COVID-19 if they were exposed between 2 days before and 3 days after the index patient’s symptom onset, peaking at day 0 (adjusted relative risk [ARR], 1.3; 95% CI, 1.2-1.5). Compared with being exposed to an asymptomatic index patient, the risk of COVID-19 among contacts was higher when they were exposed to index patients with mild (ARR, 4.0; 95% CI, 1.8-9.1) and moderate (ARR, 4.3; 95% CI, 1.9-9.7) cases of COVID-19. As index case severity increased, infected contacts were less likely to be asymptomatic (exposed to patient with mild COVID-19: ARR, 0.3; 95% CI, 0.1-0.9; exposed to patient with moderate COVID-19: ARR, 0.3; 95% CI, 0.1-0.8).
Conclusions and Relevance
This cohort study found that individuals with COVID-19 were most infectious a few days before and after symptom onset. Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.
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Accepted for Publication: July 5, 2021.
Published Online: August 23, 2021. doi:10.1001/jamainternmed.2021.4686
Corresponding Authors: Feng Ling, MD, Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Rd, Hangzhou, Zhejiang, China 310051 (email@example.com); Ye Shen, PhD, Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, 211 B.S. Miller Hall, Health Sciences Campus, 101 Buck Rd, Athens, GA 30602 (firstname.lastname@example.org).
Author Contributions: Dr Ling had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Mr Ge and Dr Martinez were co–first authors. Drs Ling and Shen were co–senior authors.
Concept and design: Ge, Martinez, Z. Chen, Zhang, W. Sun, E. Chen, J. Sun, Handel, Ling, Shen.
Acquisition, analysis, or interpretation of data: Ge, Martinez, S. Sun, Zhang, F. Li, W. Sun, Pan, C. Li, J. Sun, Shen.
Drafting of the manuscript: Ge, Martinez, Zhang, F. Li, W. Sun, J. Sun, Ling, Shen.
Critical revision of the manuscript for important intellectual content: Ge, Martinez, S. Sun, Z. Chen, Zhang, F. Li, E. Chen, Pan, C. Li, J. Sun, Handel, Shen.
Statistical analysis: Ge, Martinez, S. Sun, Zhang, W. Sun, E. Chen, J. Sun, Shen.
Obtained funding: Z. Chen, Ling.
Administrative, technical, or material support: Ge, Martinez, S. Sun, Z. Chen, Zhang, F. Li, Pan, C. Li, J. Sun, Ling, Shen.
Supervision: Martinez, Z. Chen, W. Sun, E. Chen, C. Li, Handel, Shen.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by the Zhejiang Basic Public Welfare Research Project (grant LGF21H260003; Dr Ling).
Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank the staff members of all district-level Zhejiang Provincial Centers for Disease Control and Prevention and community health service centers in Zhejiang for their assistance in field investigation and data collection. These individuals were not compensated for their contributions beyond their normal salaries.
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