Attack rates amongst household members of outpatients with confirmed COVID-19 in Bergen, Norway: A case-ascertained study

Abstract

Background: Households studies reflect the natural spread of SARS-CoV-2 in immunologically naive populations with limited preventive measures to control transmission.We hypothesise that seropositivity provides more accurate household attack rates than RT-PCR. Here, we investigated the importance of age in household transmission dynamics.

Methods: We enroled 112 households (291 participants) in a case-ascertained study in Bergen, Norway from 28th February to 4th April 2020, collecting demographic and clinical data from index patients and household members. SARS-CoV-2-specific antibodies were measured in sera collected 6-8 weeks after index patient nasopharyngeal testing to define household attack rates.

Findings: The overall attack rate was 45% (95% CI 38-53) assessed by serology, and 47% when also including seronegative RT-PCR positives. Serology identified a higher number of infected household members than RT-PCR. Attack rates were equally high in children (48%) and young adults (42%). The attack rate was 16% in asymptomatic household members and 42% in RT-PCR negative contacts. Older adults had higher antibody titres than younger adults. The risk of household transmission was higher when the index patient had fever (aOR 3.31 [95% CI 1.52-7.24]; p = 0.003) or dyspnoea (aOR 2.25 [95% CI 1.80-4.62]; p = 0.027) during acute illness.

Interpretation: Serological assays provide more sensitive and robust estimates of household attack rates than RT-PCR. Children are equally susceptible to infection as young adults. Negative RT-PCR or lack of symptoms are not sufficient to rule out infection in household members.

Funding: Helse Vest (F-11628), Trond Mohn Foundation (TMS2020TMT05).

Fig. 1

Recruitment procedure of study participants. Between 28.02.2020 and 04.04.2020, 223 SARS-CoV-2 cases were identified amongst 3319 SARS-CoV-2 suspected cases that were RT-PCR-tested (1.1% of population tested), out of which 194 were included in the study. There were 245 eligible household members, out of which 148 were included. In households with more than one case, 31 non-primary cases were redefined as household members, giving a total of 179 household members. Possible household clusters of six or nine co-primary cases had symptom onset within 24 or 48 h, respectively, after symptom onset in the index patient. Forty household members did not consent, 3 of whom were RT-PCR positive, 18 were children under 10 years old and 12 were under 20 years old. In total, we included 291 people comprising 112 index patients living with others and their 179 household members. Fifty-one cases were not included in the analyses as they lived alone or were defined as single-person households because they did not have household members who wished to participate in the study.

Fig. 2

The course of the first wave of the pandemic in Bergen and period of recruitment of index patients and household members. (A) The daily number of SARS-CoV-2 RT-PCR positive cases (shown in orange) from the centralised testing centre at Bergen Municipality Emergency Clinic covering a population of 284.000 people and the daily number of COVID-19 deaths (shown in purple) in Bergen, Norway (left Y-axis). The number of hospitalised patients from SARS-CoV-2 infection in Bergen (shown in blue, right Y-axis). Lockdown was initiated in Norway on 12th March, and a gradual reopening starting on 20th April 2020. (B) The number of household members recruited (shown in red) during the recruitment period (grey shaded area). Clinical information was collected from the index patient and their household members at the time of recruitment. Blood samples were collected 6–8 weeks after the date of nasopharyngeal samples (blue dots), at which time there was low transmission in Bergen reducing the likelihood of community infection. Sera from all household members were tested against the receptor-binding domain (RBD) of spike protein in screening ELISA. RBD-specific IgG are shown as the optical density (OD) at 1/100 dilution of sera (shown in blue, right Y-axis). Each symbol represents one subject. The horizontal dotted line indicates OD 0.5 as the cut-off defined by a panel of 128 pre-pandemic sera. Duplicates were performed in ELISA.

Fig. 3

The SARS-CoV-2 antibody responses in seropositive household members. Clinical symptoms of COVID-19 illness and SARS-CoV-2 RT-PCR results were collected from household members at the time of recruitment, blood samples were collected 6–8 weeks later. Only symptomatic household members were tested by RT-PCR depending on the testing capacity at the centralized testing centre, therefore results are not available (NA) from all subjects. Sera from all household members were tested against the receptor-binding domain (RBD) of spike protein by screening ELISA. The positive samples from screening RBD IgG ELISA (OD>0.555) were confirmed by spike ELISA, microneutralisation and virus neutralisation assays with live virus hCoV-19/Norway/Bergen-01/2020 (GISAID accession ID EPI_ISL_541,970) in a certified Biosafety Level 3 Laboratory. Household members with spike-specific IgG endpoint titre ≥100 were defined as seropositive, and were divided into 10-year age cohorts (A-C), clinical symptoms of COVID-19 illness (D-F) and SARS-CoV-2 RT-PCR (G-I). Spike-specific IgG (A, D, G), microneutralisation (B, E, H) and virus neutralisation (C, F, I) titres from all seropositive household members. Clinical symptoms are plotted against symptoms (n = 73 in “Yes”, n = 8 in “No” in d-F and RT-PCR results (n = 28 in “Positive”, n = 16 for “Negative” and n = 37 in “NA” in G-I). The geometric mean titres (GMT) are noted above the graphs for each column, and indicated by a horizontal line. Each symbol represents one subject. Mann-Whitney test was used in comparing antibody titres between household member age cohorts, 21–30 years as the reference group, (A-C) symptomatic and asymptomatic subjects (D-F) and RT-PCR positive and negative subjects (G-I).P<0.05 were considered significant. All P<0.10 are noted. Two or more replicates were performed in all experiments. IC₅₀, 50% inhibitory concentration. CPE, cytopathic effect. No significant difference was found. Two or more replicates were performed in all experiments. IC₅₀, 50% inhibitory concentration. CPE, cytopathic effect.