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COVID-19 Transmission Dynamics Among Close Contacts of Index Patients With COVID-19A Population-Based Cohort Study in Zhejiang Province, China

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  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?

Findings  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.

Meaning  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.

Abstract

Importance  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.

Objectives  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.

Results  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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Article Information

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 (fengl@cdc.zj.cn); 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 (yeshen@uga.edu).

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.

References
1.
Zhu  N , Zhang  D , Wang  W ,  et al; China Novel Coronavirus Investigating and Research Team.  A novel coronavirus from patients with pneumonia in China, 2019.   N Engl J Med. 2020;382(8):727-733. doi:10.1056/NEJMoa2001017 PubMedGoogle ScholarCrossref
2.
Huang  C , Wang  Y , Li  X ,  et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.   Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5 PubMedGoogle ScholarCrossref
3.
World Health Organization. Weekly epidemiological update—5 January 2021. Accessed July 1, 2021. https://www.who.int/publications/m/item/weekly-epidemiological-update---5-january-2021
4.
Liu  Q , Lu  P , Shen  Y ,  et al.  Collateral impact of the coronavirus disease 2019 (COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.   Clin Infect Dis. Published online August 28, 2020. doi:10.1093/cid/ciaa1289PubMedGoogle Scholar
5.
Hawks  L , Woolhandler  S , McCormick  D .  COVID-19 in prisons and jails in the United States.   JAMA Intern Med. 2020;180(8):1041-1042. doi:10.1001/jamainternmed.2020.1856 PubMedGoogle ScholarCrossref
6.
Shen  Y , Li  C , Dong  H ,  et al.  Community outbreak investigation of SARS-CoV-2 transmission among bus riders in eastern China.   JAMA Intern Med. 2020;180(12):1665-1671. doi:10.1001/jamainternmed.2020.5225 PubMedGoogle ScholarCrossref
7.
Fung  HF , Martinez  L , Alarid-Escudero  F ,  et al.  The household secondary attack rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a rapid review.   Clini Infect Dis. Published online October 12, 2020. Google Scholar
8.
Cevik  M , Kuppalli  K , Kindrachuk  J , Peiris  M .  Virology, transmission, and pathogenesis of SARS-CoV-2.   BMJ. 2020;371:m3862. doi:10.1136/bmj.m3862 PubMedGoogle Scholar
9.
Cevik  M , Marcus  JL , Buckee  C , Smith  TC .  SARS-CoV-2 transmission dynamics should inform policy.   Clin Infect Dis. 2020;ciaa1442. doi:10.1093/cid/ciaa1442 PubMedGoogle Scholar
10.
Cevik  M , Tate  M , Lloyd  O , Maraolo  AE , Schafers  J , Ho  A .  SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.   Lancet Microbe. 2021;2(1):e13-e22. doi:10.1016/S2666-5247(20)30172-5PubMedGoogle ScholarCrossref
11.
He  X , Lau  EHY , Wu  P ,  et al.  Temporal dynamics in viral shedding and transmissibility of COVID-19.   Nat Med. 2020;26(5):672-675. doi:10.1038/s41591-020-0869-5 PubMedGoogle ScholarCrossref
12.
To  KK-W , Tsang  OT-Y , Leung  W-S ,  et al.  Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study.   Lancet Infect Dis. 2020;20(5):565-574. doi:10.1016/S1473-3099(20)30196-1 PubMedGoogle ScholarCrossref
13.
Cheng  HY , Jian  SW , et al; Taiwan COVID-19 Outbreak Investigation Team.  Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset.   JAMA Intern Med. 2020;180(9):1156-1163. doi:10.1001/jamainternmed.2020.2020 PubMedGoogle ScholarCrossref
14.
Dicker  RC , Coronado  F , Koo  D , Parrish  RG .  Principles of Epidemiology in Public Health Practice; an Introduction to Applied Epidemiology and Biostatistics. Centers for Disease Control and Prevention; 2006.
15.
Zou  G .  A modified Poisson regression approach to prospective studies with binary data.   Am J Epidemiol. 2004;159(7):702-706. doi:10.1093/aje/kwh090 PubMedGoogle ScholarCrossref
16.
Zocchetti  C , Consonni  D , Bertazzi  PA .  Relationship between prevalence rate ratios and odds ratios in cross-sectional studies.   Int J Epidemiol. 1997;26(1):220-223. doi:10.1093/ije/26.1.220 PubMedGoogle ScholarCrossref
17.
Gasparrini  A .  Distributed lag linear and non-linear models in R: the package dlnm.   J Stat Softw. 2011;43(8):1-20. doi:10.18637/jss.v043.i08 PubMedGoogle ScholarCrossref
18.
Gasparrini  A , Armstrong  B , Kenward  MG .  Distributed lag non-linear models.   Stat Med. 2010;29(21):2224-2234. doi:10.1002/sim.3940 PubMedGoogle ScholarCrossref
19.
Gasparrini  A , Guo  Y , Hashizume  M ,  et al.  Mortality risk attributable to high and low ambient temperature: a multicountry observational study.   Lancet. 2015;386(9991):369-375. doi:10.1016/S0140-6736(14)62114-0 PubMedGoogle ScholarCrossref
20.
Gasparrini  A , Guo  Y , Sera  F ,  et al.  Projections of temperature-related excess mortality under climate change scenarios.   Lancet Planet Health. 2017;1(9):e360-e367. doi:10.1016/S2542-5196(17)30156-0 PubMedGoogle ScholarCrossref
21.
Lauer  SA , Grantz  KH , Bi  Q ,  et al.  The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application.   Ann Intern Med. 2020;172(9):577-582. doi:10.7326/M20-0504 PubMedGoogle ScholarCrossref
22.
Huang  L , Zhang  X , Zhang  X ,  et al.  Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: a prospective contact-tracing study.   J Infect. 2020;80(6):e1-e13. doi:10.1016/j.jinf.2020.03.006 PubMedGoogle ScholarCrossref
23.
Guan  W-J , Ni  Z-Y , Hu  Y ,  et al; China Medical Treatment Expert Group for Covid-19.  Clinical characteristics of coronavirus disease 2019 in China.   N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032 PubMedGoogle ScholarCrossref
24.
Baden  LR , El Sahly  HM , Essink  B ,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389PubMedGoogle ScholarCrossref
25.
Gandhi  M , Rutherford  GW .  Facial masking for COVID-19—potential for “variolation” as we await a vaccine.   N Engl J Med. 2020;383(18):e101. doi:10.1056/NEJMp2026913 PubMedGoogle Scholar
26.
Chin  ET , Huynh  BQ , Chapman  LAC , Murrill  M , Basu  S , Lo  NC .  Frequency of routine testing for coronavirus disease 2019 (COVID-19) in high-risk healthcare environments to reduce outbreaks.   Clin Infect Dis. 2020;ciaa1383. doi:10.1093/cid/ciaa1383 PubMedGoogle Scholar
27.
Bi  Q , Wu  Y , Mei  S ,  et al.  Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study.   Lancet Infect Dis. 2020;20(8):911-919. doi:10.1016/S1473-3099(20)30287-5 PubMedGoogle ScholarCrossref
28.
Burke  RM , Midgley  CM , Dratch  A ,  et al.  Active monitoring of persons exposed to patients with confirmed COVID-19—United States, January-February 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(9):245-246. doi:10.15585/mmwr.mm6909e1 PubMedGoogle ScholarCrossref
29.
Sun  K , Wang  W , Gao  L ,  et al.  Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2.   Science. 2021;371(6526):eabe2424. doi:10.1126/science.abe2424 PubMedGoogle Scholar
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