Discussion
In this convenience sample of 202 early laboratory-confirmed COVID-19 case-patients, predominantly identified before widespread mitigation measures in the United States, the most commonly reported settings of known exposure were households and healthcare facilities (primarily as a workplace). Within the household, presumed transmission by age of index case-patient followed a U-shaped pattern and was significantly higher among contacts of older (≥65 years of age) index case-patients than among contacts of index case-patients 18–44 years of age. Independent of index case-patient age, parents of index case-patients were significantly more likely than other household members to report development of symptoms consistent with COVID-19.
Previous research has also found healthcare workplaces and households to be commonly reported settings of COVID-19 acquisition in the United States.[9,10] In our analysis, the presumed secondary symptomatic attack rate among household members was 32%, somewhat high but consistent with estimates from previous studies, ranging from 10% to 38% (;[11–16] J.B. Lopez et al., unpub data, https://www.medrxiv.org/content/10.1101/2020.08.19.20177188v1). We found that presumed transmission was highest among contacts of older index case-patients (≥65 years of age), even when controlling for contact age category, relationship, and household size; however, our sample size was insufficient to control for underlying conditions or hospitalization status of the index case-patient or for detailed age category of the household contact, which may have confounded this relationship because evidence suggests that older adults are more susceptible to COVID-19.[17] Although results were not statistically significant in adjusted analyses, we also found that contacts of index case-patients <18 years of age (especially index case-patients <5 years of age) were more likely than contacts of index case-patients 18–44 years of age to be symptomatic. Further, symptoms were significantly more likely to develop in parents of index case-patients than in other household members. This relationship was independent of index case-patient age; however, in 8 households of adult case-patients with parental household members, 6 index case-patients were <30 years of age. Higher secondary transmission to the household contacts of younger versus adult or older COVID-19 case-patients has also been reported in analyses from the United Kingdom, South Korea, and Canada (;[16] B.J. Lopez et al., unpub. data, https://www.medrxiv.org/content/10.1101/2020.08.19.20177188v1; L.A. Paul, unpub. data, https://www.medrxiv.org/content/10.1101/2021.03.29.21254565v1). These findings may be explained by the fact that SARS-CoV-2–infected children may have similar or higher viral loads than adults[18] and that they may have closer interaction with family members, especially parents. Parents, compared with other household members, may also play a greater role in caregiving to index case-patients, even for young adults. Conversely, in multigenerational households, adult children may act as caregivers for elderly parents, possibly exposing them before symptom onset.
A substantial proportion (60%) of case-patients in our sample did not report contact with a laboratory-confirmed COVID-19 case-patient in the 14 days before illness onset. Among case-patients without known COVID-19 contact, travel and public activities were more common, although only public transportation use was significantly higher when this group was compared with case-patients with known COVID-19 contact. Public transportation has not been identified as a major source of SARS-CoV-2 transmission,[19–21] although transmission on buses, trains, and commercial flights has been reported.[19,22–26] However, in our analysis, public transportation use might also have been more common among essential workers, those living in densely populated areas, or those with a history of travel—factors that could also increase opportunity for exposure to SARS-CoV-2.[27] Case-patients reporting no known source of infection, travel, or any other exposure risk factor tended to be older and to have more underlying medical conditions—particularly diabetes mellitus. Persons with concurrent conditions may be not only more susceptible to severe outcomes from COVID-19[28,29] but also more susceptible to infection, as suggested by other analyses of SARS-CoV-2[8,30] and Middle East respiratory syndrome coronavirus;[31] however, more investigation is warranted.
The first limitation of our study was that the COVID-19 case-patients for whom the CIF was completed are a convenience sample of case-patients reported by 16 states during January –April 2020. Given restricted testing practices in the United States during January–March 2020, these case-patients are not representative of all US COVID-19 case-patients in terms of demographics, clinical characteristics, or exposures. Furthermore, common exposures have varied in time and geography over the course of the epidemic, and it is not possible to exclude the possibility that persons without known COVID-19 exposure had contact with an asymptomatic friend, co-worker, or family member. Our observed secondary attack rates (symptomatic persons) may also have been affected by the timing of the investigation because public awareness regarding measures to mitigate within-household transmission (e.g., isolation and mask-wearing within the home) was probably lower in the early stages of the US epidemic. Information was not collected on the specifics of known COVID-19 exposure, such as mask wearing or social distancing in the home or other exposure settings, because these were not common practices during survey design. The use of a convenience sample may have also affected findings regarding presumed household transmission, such as if selection were biased toward inclusion of more severe cases or larger investigations.
A second limitation is that SARS-CoV-2 infection in most household members was not laboratory-confirmed, so household members with other causes of illness could have been misclassified as COVID-19 case-patients and those with asymptomatic SARS-CoV-2 infections misclassified as non–case-patients. The possibility of misclassification of children may have been higher, given that young children frequently experience respiratory symptoms[32] and are less likely to show symptoms of SARS-CoV-2 infection.[33–35] However, overall patterns were similar when analysis was restricted to laboratory-confirmed index case-patients, and the point estimate for odds of presumed symptomatic infection among contacts of index case-patients <5 years of age versus contacts of those 18–44 years of age was similar when contacts of unconfirmed index case-patients <5 years of age were excluded. In addition, 4 of 5 households with index case-patients <5 years of age reported that ≥1 household member attended school or daycare in the 14 days before illness onset in the CIF subject, suggesting a possible outside source of infection. Of note, similar methods are frequently used for studies of influenza,[36] and our observed overall symptomatic attack rate and serial interval are consistent with previous knowledge of SARS-CoV-2 transmission.[37,38] It is also possible that symptoms developed in some household members after the date of interview. To limit this possibility, we excluded households in which the interview took place <3 days (median serial interval in our data) after the CIF subject's symptom onset. Similarly, some presumed secondary case-patients may have actually been index case-patients or were co-exposed to the index case-patient; we tested exclusion of contacts with a 1-day lag in symptom onset and found similar trends, although the sample size precluded adjusted models. Previous research showing longer incubation periods for older patients suggests that households with older index patients would be less affected by such misclassification.[39,40]
Last, our sample size was limited by state capacity for participation and data completeness. We did not have sufficient sample size to control for all possible confounders, such as index case-patient signs/symptoms, clinical characteristics, or detailed contact age category, so residual confounding is possible. The lower sample size also limited the precision of our estimates.
Our findings underline the exposure risk associated with work in a healthcare setting and within the household, as previously documented.[9,10] However, most case-patients in the analysis did not have known contact with a laboratory-confirmed COVID-19 case-patient, reflecting unrecognized transmission and highlighting the need for widespread testing in addition to community mitigation measures such as masking, hand hygiene, physical distancing, and limiting nonessential travel, as well as vaccination.[41–43] When going out in public, persons should take preventive actions and consider the risks associated with public activities by taking into account local orders, their ability to maintain physical distance during the activity, and whether they or their household members are at risk for severe illness from COVID-19.[41] Everyday preventive actions also protect at-risk household members. In this analysis, presumed household transmission was common, especially from the oldest index case-patients and from children to their parents. These findings are especially relevant to the context of in-person schooling because children exposed at schools or daycare centers may introduce COVID-19 into the home. Special care must be taken to mitigate exposure risks outside the home and to protect household members at high risk for severe COVID-19, such as older persons and those with concurrent conditions. Persons with COVID-19 should follow recommendations to reduce the risk for within-household transmission, such as staying in a separate room, wearing a mask around others, practicing hand and cough hygiene, and frequently cleaning high-touch surfaces.[44]
Acknowledgment
We thank the Alaska Department of Health and Social Services' Sections of Epidemiology and Public Health Nursing, Kimberly Yousey-Hindes, Danyel Olson, Hazal Kayalioglu, Nicole Torigian, Hawaii Department of Health COVID Investigation and Surveillance Response Team, Austin Bell, Kalyla Bilski, Emma Contestabile, Claire Henrichsen, Katherine Schleiss, Samantha Siebman, Emily Holodick, Lisa Nguyen, Kristen Ehresmann, Anna Kocharian, Lin Zhao, Sharon Balter, Rebecca Fisher, Chelsea Foo, Prabhu Gounder, Jeffrey D. Gunzenhauser, Meredith Haddix, M. Claire Jarashow, Talar Kamali, Moon Kim, Jan King, Dawn Terashita, Elizabeth Traub, Roshan Reporter, Patricia Mottu-Monteon, Anthony Aguiar, Anna Kocharian, Lin Zhao, Richard Crawford, CDC Rhode Island Field Team, CDC Santa Clara County Field Team, CDC Utah Field Team, Holly Biggs, Matt Biggerstaff, Fiona Havers, Amber Haynes, Adriana Lopez, Brian Rha, Katherine Roguski, Mayuko Takamiya, and local and tribal public health agencies.
COVID-19 Case Investigation Form Working Group Members: Neha Balachandran, Rebecca M. Dahl, Mary Dott, Lindsey M. Duca, Zunera Gilani, Aaron Grober, Jessica Leung, John Person, Jessica N. Ricaldi, James J. Sejvar, Tom Shimabukuro, Cuc H. Tran, Hilary Whitham, CDC COVID-19 Response Team; Erica Bye, Kathryn Como-Sabetti, Richard Danila, Ruth Lynfield, Minnesota Department of Health; Howard Chiou, COVID-19 Response Team, Epidemic Intelligence Service, Los Angeles County Department of Public Health; Paula Clogher, Connecticut Emerging Infections Program, Yale School of Public Health; Alissa Dratch, Orange County Healthcare Agency; Amanda Feldpausch, Georgia Department of Public Health; Martin Fenstersheib, Lynn Mello, San Benito County Public Health Services; Mary-Margaret Fill, Tennessee Department of Health; Isaac Ghinai, COVID-19 Response Team, Epidemic Intelligence Service, Chicago Department of Health; Michelle Holshue, COVID-19 Response Team, Epidemic Intelligence Service, Washington Department of Health; Sarah Scott, COVID-19 Response Team, Epidemic Intelligence Service, Maricopa County Public Health.
Emerging Infectious Diseases. 2021;27(9):2323-2332. © 2021 Centers for Disease Control and Prevention (CDC)