Elevated Soluble ACE2 Activity in Children and Adults After SARS‐CoV‐2 Exposure Irrespective of Laboratory‐Confirmed Infection
The pivotal role of the cell entry receptor ACE2 for SARS-CoV-2 infection is well-established. When ACE2 is shed from cell surface into plasma as soluble ACE2 (sACE2), it can effectively neutralize SARS-CoV-2. This longitudinal prospective cohort study analyzed sACE2 activity in 1192 participants, aged 4 months to 81 years, 3 and 12 months after SARS-CoV-2 household exposure. Following SARS-CoV-2 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- and sex-matched pre-pandemic controls. An increase in sACE2 activity was also confirmed in vitro in Calu-3 (human lung) cells within hours of SARS-CoV-2 exposure, providing a direct link between SARS-CoV-2 exposure and elevated sACE2. This study, therefore, challenges the dichotomy of categorizing SARS-CoV-2 exposed participants as infected or not infected solely on currently established diagnostic assays. It demonstrates lasting host responses independent of B- and T-cell memory and may help to keep SARS-CoV-2 infections in balance and contribute to successful virus clearance in children and adults lacking humoral and cellular immune responses following SARS-CoV-2 exposure. Trial Registration: German Registry for Clinical Studies; Identifier: D 00021521.
Authors
- Sebastian F. N. Bode (ORCID: https://orcid.org/0000-0001-7217-3312)
- Burkhard Tönshoff (ORCID: https://orcid.org/0000-0002-6598-6910)
- Hanna Renk (ORCID: https://orcid.org/0000-0001-7793-0968)
- Ralf F. W. Bartenschlager (ORCID: https://orcid.org/0000-0001-5601-9307)
- Roland Elling (ORCID: https://orcid.org/0000-0002-2209-4154)
- Aleš Janda (ORCID: https://orcid.org/0000-0001-5604-8378)
- Eva‐Maria Jacobsen (ORCID: https://orcid.org/0000-0003-4750-0136)
- Maximilian Stich (ORCID: https://orcid.org/0000-0002-6237-9058)
- Hans‐Georg Kräusslich (ORCID: https://orcid.org/0000-0002-8756-329X)
- Marco Binder (ORCID: https://orcid.org/0000-0002-5805-6109)
- Anneke Haddad (ORCID: https://orcid.org/0000-0003-3429-0475)
- Kathrin Jeltsch
- Peter Lang (ORCID: https://orcid.org/0000-0001-7737-2142)
- Vladimir Gonçalves Magalhães
- Sven F. Garbade (ORCID: https://orcid.org/0000-0002-7420-4757)
- Armin Rabsteyn (ORCID: https://orcid.org/0000-0002-0553-2693)
- Kerstin Möhr
- Georg F. Hoffmann (ORCID: https://orcid.org/0000-0002-6593-896X)
- Bárbara Müller (ORCID: https://orcid.org/0000-0001-5726-5585)
- Jürgen G. Okun (ORCID: https://orcid.org/0000-0003-2975-1054)
- Friederike Bürger
Institutions
- University of Freiburg (DE)
- German Cancer Research Center (DE)
- Universität Ulm (DE)
- Heidelberg University (DE)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- German Center for Infection Research (DE)
- University Children's Hospital Tübingen (DE)
- University of Tübingen (DE)
Publication Details
- Journal
- Journal of Medical Virology
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/jmv.70098
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.78
Funders
- Deutsches Zentrum für Infektionsforschung