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SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study.
Lancet Infect Dis. 2021 03; 21(3):333-343.LI

Abstract

BACKGROUND

The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19.

METHODS

This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors.

FINDINGS

Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9-7·1) for 1779 household contacts, 1·3% (0·9-1·9) for 2231 work contacts, and 1·3% (1·0-1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55-69) of COVID-19 diagnoses, and 36% (27-45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82-15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86-16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07-7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21-5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55-6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission.

INTERPRETATION

Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted.

FUNDING

Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China.

Authors+Show Affiliations

National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Electronic address: oon_tek_ng@ncid.sg.National Centre for Infectious Diseases, Singapore; Woodlands Health Campus, National Healthcare Group, Singapore; Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.Communicable Diseases Division, Ministry of Health, Singapore.Communicable Diseases Division, Ministry of Health, Singapore.Communicable Diseases Division, Ministry of Health, Singapore.Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.National Centre for Infectious Diseases, Singapore; Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Communicable Diseases Division, Ministry of Health, Singapore. Electronic address: vernon_lee@moh.gov.sg.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33152271

Citation

Ng, Oon Tek, et al. "SARS-CoV-2 Seroprevalence and Transmission Risk Factors Among High-risk Close Contacts: a Retrospective Cohort Study." The Lancet. Infectious Diseases, vol. 21, no. 3, 2021, pp. 333-343.
Ng OT, Marimuthu K, Koh V, et al. SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study. Lancet Infect Dis. 2021;21(3):333-343.
Ng, O. T., Marimuthu, K., Koh, V., Pang, J., Linn, K. Z., Sun, J., De Wang, L., Chia, W. N., Tiu, C., Chan, M., Ling, L. M., Vasoo, S., Abdad, M. Y., Chia, P. Y., Lee, T. H., Lin, R. J., Sadarangani, S. P., Chen, M. I., Said, Z., ... Lee, V. J. (2021). SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study. The Lancet. Infectious Diseases, 21(3), 333-343. https://doi.org/10.1016/S1473-3099(20)30833-1
Ng OT, et al. SARS-CoV-2 Seroprevalence and Transmission Risk Factors Among High-risk Close Contacts: a Retrospective Cohort Study. Lancet Infect Dis. 2021;21(3):333-343. PubMed PMID: 33152271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: a retrospective cohort study. AU - Ng,Oon Tek, AU - Marimuthu,Kalisvar, AU - Koh,Vanessa, AU - Pang,Junxiong, AU - Linn,Kyaw Zaw, AU - Sun,Jie, AU - De Wang,Liang, AU - Chia,Wan Ni, AU - Tiu,Charles, AU - Chan,Monica, AU - Ling,Li Min, AU - Vasoo,Shawn, AU - Abdad,Mohammad Yazid, AU - Chia,Po Ying, AU - Lee,Tau Hong, AU - Lin,Ray Junhao, AU - Sadarangani,Sapna P, AU - Chen,Mark I-Cheng, AU - Said,Zubaidah, AU - Kurupatham,Lalitha, AU - Pung,Rachael, AU - Wang,Lin-Fa, AU - Cook,Alex R, AU - Leo,Yee-Sin, AU - Lee,Vernon Jm, Y1 - 2020/11/02/ PY - 2020/08/13/received PY - 2020/09/10/revised PY - 2020/09/30/accepted PY - 2020/11/6/pubmed PY - 2021/3/25/medline PY - 2020/11/5/entrez SP - 333 EP - 343 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 21 IS - 3 N2 - BACKGROUND: The proportion of asymptomatic carriers and transmission risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among household and non-household contacts remains unclear. In Singapore, extensive contact tracing by the Ministry of Health for every diagnosed COVID-19 case, and legally enforced quarantine and intensive health surveillance of close contacts provided a rare opportunity to determine asymptomatic attack rates and SARS-CoV-2 transmission risk factors among community close contacts of patients with COVID-19. METHODS: This retrospective cohort study involved all close contacts of confirmed COVID-19 cases in Singapore, identified between Jan 23 and April 3, 2020. Household contacts were defined as individuals who shared a residence with the index COVID-19 case. Non-household close contacts were defined as those who had contact for at least 30 min within 2 m of the index case. All patients with COVID-19 in Singapore received inpatient treatment, with access restricted to health-care staff. All close contacts were quarantined for 14 days with thrice-daily symptom monitoring via telephone. Symptomatic contacts underwent PCR testing for SARS-CoV-2. Secondary clinical attack rates were derived from the prevalence of PCR-confirmed SARS-CoV-2 among close contacts. Consenting contacts underwent serology testing and detailed exposure risk assessment. Bayesian modelling was used to estimate the prevalence of missed diagnoses and asymptomatic SARS-CoV-2-positive cases. Univariable and multivariable logistic regression models were used to determine SARS-CoV-2 transmission risk factors. FINDINGS: Between Jan 23 and April 3, 2020, 7770 close contacts (1863 household contacts, 2319 work contacts, and 3588 social contacts) linked to 1114 PCR-confirmed index cases were identified. Symptom-based PCR testing detected 188 COVID-19 cases, and 7582 close contacts completed quarantine without a positive SARS-CoV-2 PCR test. Among 7518 (96·8%) of the 7770 close contacts with complete data, the secondary clinical attack rate was 5·9% (95% CI 4·9-7·1) for 1779 household contacts, 1·3% (0·9-1·9) for 2231 work contacts, and 1·3% (1·0-1·7) for 3508 social contacts. Bayesian analysis of serology and symptom data obtained from 1150 close contacts (524 household contacts, 207 work contacts, and 419 social contacts) estimated that a symptom-based PCR-testing strategy missed 62% (95% credible interval 55-69) of COVID-19 diagnoses, and 36% (27-45) of individuals with SARS-CoV-2 infection were asymptomatic. Sharing a bedroom (multivariable odds ratio [OR] 5·38 [95% CI 1·82-15·84]; p=0·0023) and being spoken to by an index case for 30 min or longer (7·86 [3·86-16·02]; p<0·0001) were associated with SARS-CoV-2 transmission among household contacts. Among non-household contacts, exposure to more than one case (multivariable OR 3·92 [95% CI 2·07-7·40], p<0·0001), being spoken to by an index case for 30 min or longer (2·67 [1·21-5·88]; p=0·015), and sharing a vehicle with an index case (3·07 [1·55-6·08]; p=0·0013) were associated with SARS-CoV-2 transmission. Among both household and non-household contacts, indirect contact, meal sharing, and lavatory co-usage were not independently associated with SARS-CoV-2 transmission. INTERPRETATION: Targeted community measures should include physical distancing and minimising verbal interactions. Testing of all household contacts, including asymptomatic individuals, is warranted. FUNDING: Ministry of Health of Singapore, National Research Foundation of Singapore, and National Natural Science Foundation of China. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/33152271/SARS_CoV_2_seroprevalence_and_transmission_risk_factors_among_high_risk_close_contacts:_a_retrospective_cohort_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(20)30833-1 DB - PRIME DP - Unbound Medicine ER -