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This longitudinal prospective cohort study analyzed sACE2 activity in 1192 participants, aged 4 months to 81 years, 3 and 12 months after SARS\u2010CoV\u20102 household exposure. Following SARS\u2010CoV\u20102 exposure, participants exhibited significantly elevated sACE2 activity, irrespective of confirmed infection, with the highest levels observed in exposed children. Longitudinal analysis revealed a decline in sACE2 levels over time, reaching levels comparable to age\u2010 and sex\u2010matched pre\u2010pandemic controls. An increase in sACE2 activity was also confirmed in vitro in Calu\u20103 (human lung) cells within hours of SARS\u2010CoV\u20102 exposure, providing a direct link between SARS\u2010CoV\u20102 exposure and elevated sACE2. This study, therefore, challenges the dichotomy of categorizing SARS\u2010CoV\u20102 exposed participants as infected or not infected solely on currently established diagnostic assays. It demonstrates lasting host responses independent of B\u2010 and T\u2010cell memory and may help to keep SARS\u2010CoV\u20102 infections in balance and contribute to successful virus clearance in children and adults lacking humoral and cellular immune responses following SARS\u2010CoV\u20102 exposure.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> German Registry for Clinical Studies; Identifier: D 00021521.<\/jats:p>","DOI":"10.1002\/jmv.70098","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T08:44:01Z","timestamp":1733215441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elevated Soluble ACE2 Activity in Children and Adults After SARS\u2010CoV\u20102 Exposure Irrespective of Laboratory\u2010Confirmed 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