The case investigation form (CIF) is a supplemental questionnaire designed by CDC in January 2020 to collect detailed demographic and epidemiologic information about a convenience sample of US COVID-19 case-patients reported by participating states. This purposive nonprobability sample was selected at the state level from persons identified through care-seeking, surveillance, or contact tracing as having COVID-19; infection with severe acute respiratory coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription PCR. CDC provided guidance for selection of case-patients across a range of ages and symptom severities (i.e., hospitalized and nonhospitalized), but states individually controlled sampling. The CIF was completed by state or local health department personnel or by CDC staff through case-patient or proxy interviews, along with medical record reviews (when relevant).

Case-patient demographic information included age, sex, race, ethnicity, and occupation. Workplace settings were classified according to 2012 census industry codes. Clinical information included underlying conditions, symptoms, symptom onset date, dates of medical visits, and outcome (death or survival). For hospitalized case-patients, information was requested about whether the patient had been admitted to an intensive care unit, whether oxygen was received, admission and discharge dates, diagnosis, and location. Questions about exposure included whether in the 14 days before illness onset the case-patient had known exposure to a case-patient with laboratory-confirmed COVID-19 (COVID-19 contact) and, if so, the relationship and setting of the exposure. Case-patients were also asked about their exposure risks (activities and possible exposures in the 14 days before illness onset) including travel; friends, acquaintances, co-workers, or family members with fever or respiratory symptoms; close contact with (e.g., caring for, speaking with, or touching) any ill persons; attendance at a mass gathering (e.g., religious event, concert, sports event); public transportation use; attendance or work at a school or daycare; school or daycare attendance by household members; close contact with a contact of a laboratory-confirmed case-patient; close contact with someone with fever, acute respiratory illness, or both who had traveled internationally in the previous 14 days; and time in a healthcare setting as an employee, patient, or visitor.

The CIF also collected data on the case-patient’s household members, defined as anyone who stayed overnight in the same residence as the case-patient during the 14 days before the case-patient’s illness onset until the date of interview. Case-patients were asked for household members’ age, sex, relationship to the case-patient, and whether each person had “experienced fever or respiratory symptoms (e.g., cough, sore throat, etc.) within 14 days before or after the COVID-19 patient’s illness”; if yes, date of illness onset was collected. When the CIF was designed in January 2020, the most commonly reported COVID-19 signs and symptoms were fever and respiratory symptoms, and guidance for mitigation measures within households had not been widely distributed.

We compared exposures between those reporting known close contact with a COVID-19 case-patient in the 14 days before illness onset and those reporting no known contact. Categorical variables were compared by using χ² or Fisher exact tests, as appropriate. Continuous variables were compared by using t tests for normally distributed data and Wilcoxon rank sum tests otherwise. p<0.05 was considered significant. Analyses were conducted in SAS version 9.4 (https://www.sas.com) and R (https://www.r-project.org).

We separately assessed presumed household transmission by using information about household members provided by the interviewed COVID-19 case-patient (CIF subject). In the absence of SARS-CoV-2 testing data for all household members, we used reported signs and symptoms (i.e., fever or respiratory symptoms) as a proxy for symptomatic COVID-19 infection (i.e., household transmission). We analyzed households of >2 members (including the CIF subject) if the CIF subject had experienced >1 symptom (to enable identification of the first ill person [index case-patient] in the household), and symptom status was provided for >1 other household member. We required that the earliest symptom onset date in the household be >1 calendar day before symptom onset in subsequent case-patients (to limit effect of co-exposures outside the home) and that the earliest onset date in the household be >3 days (our median serial interval) before the interview (to allow time for symptoms to develop in exposed household members). We considered presumed household transmission to have occurred if >1 household member, in addition to the CIF subject, was reported as having fever or respiratory symptoms. The person with the earliest symptom onset date in a household was considered the index case-patient, regardless whether SARS-CoV-2 testing had been performed. Any members of a given household not identified as the index case-patient are hereafter referred to as household contacts.

We calculated the overall household attack rate for symptoms as the number of symptomatic household contacts divided by the total number of household contacts with reported symptom status, with Wilson score 95% CI, and the serial interval as the time from symptom onset in the index case-patient to first symptom onset in a household contact. We investigated age and sex of the index case-patients and their contacts, household size, and relationship of the contact to the index case-patient as possible correlates of contact symptom status by using generalized estimating equation logistic regression with households as the cluster and individual symptom status as the outcome; we used an exchangeable correlation matrix and robust SEs. We excluded household contacts missing symptom status from this analysis. We examined models for collinearity and reduced if necessary. We did not include hospitalization status of the index case-patient in models because of collinearity with index case-patient age. We dichotomized contact age (<18 or >18 years) to avoid collinearity with familial relationship and index case-patient age.

To explore the validity of using reported symptom status to estimate household symptomatic attack rates, we calculated sensitivity and specificity by using a subset of households for which complete reverse transcription PCR and serologic testing data were available (8). We conducted a sensitivity analysis by reclassifying data according to a range of plausible misclassification rates.

Data were collected from 16 states (Alaska, Arizona, California, Connecticut, Georgia, Hawaii, Illinois, Minnesota, Pennsylvania, Rhode Island, Tennessee, Utah, Virginia, Vermont, Washington, and Wisconsin) with 202 laboratory-confirmed COVID-19 case-patients with symptom onset during January 14–April 4, 2020. Age of COVID-19 case-patients in the sample ranged from <1 to 95 years, almost all were symptomatic (195; 97%), and 1 in 3 was hospitalized for management of COVID-19 symptoms. Of the 202 case-patients, 34 (17%) reported having diabetes mellitus and 48 (24%) reported hypertension.

A total of 82 (41%) case-patients reported known contact with a laboratory-confirmed COVID-19 case-patient in the 14 days before symptom onset. The most commonly reported exposure setting was the household (44/82; 54%); within the household setting, the most frequently reported source of COVID-19 exposure was the spouse or partner of the COVID-19 case-patient (16/44; 36%). The second most reported exposure setting was healthcare (20/82; 24%); 14 of the 20 persons exposed in the healthcare setting were healthcare workers, 4 were seeking care for unrelated medical issues, and 2 were visitors.

Among persons reporting no known COVID-19 contact, 20/84 (24%) reported having close contact with an ill person. Persons with no known COVID-19 contact worked in a variety of industries, most commonly healthcare (10/90; 11%); professional/office settings (10/90; 11%); education (9/90; 10%); and accommodation, food, or other services (9/90; 10%) (Table 1). In comparison, 28% (20/72) of persons with known COVID-19 contact reported working in healthcare. Persons with no known COVID-19 contact were significantly less likely than those with known contact to report spending time in a healthcare setting (p = 0.004). However, they were somewhat more likely to report travel (38% vs. 26%) or attendance at a mass gathering (36% vs. 21%) and significantly more likely to report use of public transportation (44% vs. 16%), compared with persons reporting known COVID-19 contact (p = 0.005)

Of the 202 case-patients, 23 (11.3%) reported no known contact with a confirmed case-patient, no travel within 14 days before illness onset, and none of the exposure risks assessed. These persons ranged in age from 21 to 88 years and were significantly older than those reporting >1 possible exposure (median age 52 vs. 49 years; p<0.0001). They required hospitalization more frequently than those reporting >1 possible exposure (52% [12/23] vs. 30% [54/179]; p = 0.10), and were significantly more likely to report >1 underlying medical condition (87% [20/23] vs. 58% [104/179]; p = 0.029). They were much more likely to report having diabetes mellitus (43% [10/23] vs. 14% [24/176]; p = 0.002).

A total of 69 case-patients provided data on the symptom status of >1 household members and were included in our household analysis; in 48 (70%) households, the CIF subject was the first or only symptomatic person in the household (i.e., was identified as the index case-patient; Figure 1). In half (34/69; 49%) of included households, >1 household member, in addition to the CIF subject, was symptomatic (i.e., virus transmission was presumed). Included households ranged in size from 2 to 16 persons (median 4 persons) and comprised a variety of household types (e.g., couples, nuclear families, roommates, multigenerational); household size and members’ ages, sexes, and relationships were interrelated. Presumed transmission was more frequently observed in larger households (78% of households with >5 members vs. 39% of households with <5 members; p = 0.005) (Figure 2). Within households with more members, a larger number of household contacts reported symptoms (Figure 2).

Among 201 household contacts, 193 had data on symptom status, of which 62 (32%; 95% CI 26%–39%) were symptomatic. Sensitivity analysis results showed a similar plausible range of attack rates (21%–39%). The median serial interval was 3 days (range 1–10 days).

Although our sample did not have large numbers of index case-patients at the age extremes, household contacts were more likely to be symptomatic if the index case-patient was <5 (5 households) or >65 years of age (9 households) (Figure 3, panel A); trends were similar, but the point estimates were significant only for index case-patients >45 years of age (vs. index case-patients 18–44 years of age) after adjustment for contact age, contact sex, household size, and relationship of the contact to the index case-patient (Table 2). Adult contacts were symptomatic more often than contacts <18 years of age (Figure 3, panel B), but this association was not significant in adjusted analyses (Table 2). The symptom status of household contacts was also associated with their relationship to the index case-patient (Table 2). Among the contacts of 9 index case-patients <18 years of age, 11/16 (69%) parents, 6/13 (46%) siblings, and 2/5 (40%) other household contacts later became symptomatic. Among contacts of the 60 adult index case-patients, 12/44 (27%) children (range 2–49 years of age), 12/45 (27%) spouses/partners, 7/16 (44%) parents, and 11/42 (26%) other household contacts became symptomatic. When we restricted the analysis to households in which the CIF subject was the index case-patient, overall trends were similar to those reported above, but small sample sizes precluded adjusted analyses.

Illness severity of the index case-patient could not be assessed in multivariable models because of low sample size and correlation with age. However, among 12 household contacts of 10 index case-patients requiring hospitalization (three 18–44, five 45–64, and two index case-patients >65 years of age), only 2 were symptomatic.