Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study

Abstract

Background: Despite circumstantial evidence for aerosol and fomite spread of SARS-CoV-2, empirical data linking either pathway with transmission are scarce. Here we aimed to assess whether the presence of SARS-CoV-2 on frequently-touched surfaces and residents' hands was a predictor of SARS-CoV-2 household transmission.

Methods: In this longitudinal cohort study, during the pre-alpha (September to December, 2020) and alpha (B.1.1.7; December, 2020, to April, 2021) SARS-CoV-2 variant waves, we prospectively recruited contacts from households exposed to newly diagnosed COVID-19 primary cases, in London, UK. To maximally capture transmission events, contacts were recruited regardless of symptom status and serially tested for SARS-CoV-2 infection by RT-PCR on upper respiratory tract (URT) samples and, in a subcohort, by serial serology. Contacts' hands, primary cases' hands, and frequently-touched surface-samples from communal areas were tested for SARS-CoV-2 RNA. SARS-CoV-2 URT isolates from 25 primary case-contact pairs underwent whole-genome sequencing (WGS).

Findings: From Aug 1, 2020, until March 31, 2021, 620 contacts of PCR-confirmed SARS-CoV-2-infected primary cases were recruited. 414 household contacts (from 279 households) with available serial URT PCR results were analysed in the full household contacts' cohort, and of those, 134 contacts with available longitudinal serology data and not vaccinated pre-enrolment were analysed in the serology subcohort. Household infection rate was 28·4% (95% CI 20·8-37·5) for pre-alpha-exposed contacts and 51·8% (42·5-61·0) for alpha-exposed contacts (p=0·0047). Primary cases' URT RNA viral load did not correlate with transmission, but was associated with detection of SARS-CoV-2 RNA on their hands (p=0·031). SARS-CoV-2 detected on primary cases' hands, in turn, predicted contacts' risk of infection (adjusted relative risk [aRR]=1·70 [95% CI 1·24-2·31]), as did SARS-CoV-2 RNA presence on household surfaces (aRR=1·66 [1·09-2·55]) and contacts' hands (aRR=2·06 [1·57-2·69]). In six contacts with an initial negative URT PCR result, hand-swab (n=3) and household surface-swab (n=3) PCR positivity preceded URT PCR positivity. WGS corroborated household transmission.

Interpretation: Presence of SARS-CoV-2 RNA on primary cases' and contacts' hands and on frequently-touched household surfaces associates with transmission, identifying these as potential vectors for spread in households.

Funding: National Institute for Health Research Health Protection Research Unit in Respiratory Infections, Medical Research Council.

Figure 1

INSTINCT and ATACCC studies recruitment timelines (A), and inclusion criteria, exposure, and SARS-CoV-2 infection status of contacts included in the analyses (B) ATACCC=Assessment of Transmission And Contagiousness of COVID-19 in Contacts. Ct=cycle threshold. INSTINCT=Integrated Network for Surveillance, Trials and Investigations into COVID-19 Transmission. URT=upper respiratory tract. WGS=whole-genome sequencing. *WGS was possible for 35 of the 152 PCR-positive household contacts, where URT swabs from both the contact and their respective epidemiologically-linked primary case were PCR positive, available, and had a viral load of more than 200 copies per mL. †URT swabs from 21 (36%) of 59 contacts in the serology subcohort deemed infected underwent WGS analysis alongside URT swabs from their primary case (appendix p 12). ‡Insufficient longitudinal serological data among contacts who were PCR positive (no serology after day 7).

Figure 2

Measured SARS-CoV-2 RNA viral load in PCR-positive environmental samples, stratified by contacts' URT PCR status and baseline serological status Only contacts linked to one or more PCR-positive environmental samples are depicted. (A) Primary cases' hand-swab RNA viral load (median 82·09 copies per mL, IQR 46·09–1082·29). (B) Household surface-swab RNA viral load (226·58, 101·38–602·51). (C) Contacts' hand-swab RNA viral load (117·66, 21·75–244·39). The measured environmental viral loads do not differ by contacts' URT PCR status, as shown by the p values in each panel (Mann-Whitney U test). All positive primary case hand swabs and surface swabs were collected on day 0, whereas contacts' hand swabs were positive on day 0 (n=16) and day 7 (n=6). Environmental samples with more than 5 RNA copies per mL were considered PCR positive. URT=upper respiratory tract.

Figure 3

Genomic evidence of SARS-CoV-2 transmission among households Genomic analysis of 25 households (comprising 35 contacts and 25 of their respective epidemiologically linked primary cases) of non-synonymous mutations within the SARS-CoV-2 genome, to assess whether the same or different strains are present within the household. Genomic analyses were performed where upper respiratory tract swabs with viral loads of more than 200 copies per mL were available for both primary cases and contact(s).