Background: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Methods: Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Findings: 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation: The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding: Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration.

ASL discloses personal fees to Sanofi and Roche outside the submitted work. HQM discloses grants from Seqirus outside the submitted work. YM discloses grants from Pfizer outside the submitted work. SR discloses grants from Biofire and consulting fees from Seqirus outside the submitted work. EAB discloses grants from Seqirus outside the submitted work. LS discloses consulting fees from CF foundation outside the submitted work. EA discloses grants from Pfizer and fees from Hillevax and Moderna outside the submitted work. SD discloses grants from Pfizer and Biofizer, and fees from Biofire, Diasorin Molecular, and Karius outside the submitted work. DP discloses grants from Pfizer and Roche outside the submitted work. CL discloses grants from AbbVie, AstraZeneca, bioMeriuex, Endpoint Helath, and Entegrion Inc, and investments in Bioscape Digital outside the submitted work. NH discloses grants from Quidel and Sanofi, and honoraria from Genentech outside the submitted work. CG discloses grants from Campbell Alliance/Syneos Health, Merck, Pfizer, and Sanofi, and fees from Sanofi and Pfizer outside the submitted work. No other authors disclose potential competing interests.

Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration.

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Vanderbilt University Medical Center, Marshfield Clinic Research Institute, or Westat IRBs gave ethical approval for this work. CDC determined these activities were conducted consistent with applicable federal law and CDC policy (see 45 C.F.R. part 46; 21 C.F.R. part 56).

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