Abstract Background Households are a major setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but there remains a lack of knowledge regarding the dynamics of viral transmission, particularly in the setting of preexisting SARS-CoV-2 immunity and evolving variants. Methods We conducted a prospective, case-ascertained household transmission study in the greater Boston area in March–July 2022. Anterior nasal swabs, along with clinical and demographic data, were collected for 14 days. Nasal swabs were tested for SARS-CoV-2 by polymerase chain reaction (PCR). Whole genome sequencing was performed on high-titer samples. Results We enrolled 33 households in a primary analysis set, with a median participant age of 25 years (range, 2–66 years), 98% of whom had received at least 2 doses of a coronavirus disease 2019 (COVID-19) vaccine. Fifty-eight percent of households had a secondary case during follow-up and the secondary attack rate (SAR) for contacts was 39%. We further examined a strict analysis set of 21 households that had only 1 PCR-positive case at baseline, finding an SAR of 22.5%. Genomic epidemiology further determined that there were multiple sources of infection for household contacts, including the index case and outside introductions. When limiting estimates to only highly probable transmissions given epidemiologic and genomic data, the SAR was 18.4%. Conclusions Household contacts of a person newly diagnosed with COVID-19 are at high risk for SARS-CoV-2 infection in the following 2 weeks. This is, however, not only due to infection from the household index case, but also because the presence of an infected household member implies increased SARS-CoV-2 community transmission.
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