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J Med Virol . Elevated Soluble ACE2 Activity in Children and Adults After SARS-CoV-2 Exposure Irrespective of Laboratory-Confirmed Infection

tetano

Editor, Senior Moderator
J Med Virol


. 2024 Dec;96(12):e70098.
doi: 10.1002/jmv.70098. Elevated Soluble ACE2 Activity in Children and Adults After SARS-CoV-2 Exposure Irrespective of Laboratory-Confirmed Infection

Maximilian Stich[SUP] 1 2 3 4 [/SUP], Vladimir Gonçalves Magalhães[SUP] 5 [/SUP], Friederike Bürger[SUP] 1 [/SUP], Sven F Garbade[SUP] 1 [/SUP], Kathrin Jeltsch[SUP] 1 [/SUP], Kerstin Mohr[SUP] 5 [/SUP], Anneke Haddad[SUP] 6 7 [/SUP], Roland Elling[SUP] 7 8 [/SUP], Peter Lang[SUP] 9 10 [/SUP], Armin Rabsteyn[SUP] 9 10 11 [/SUP], Eva-Maria Jacobsen[SUP] 12 [/SUP], Sebastian F N Bode[SUP] 12 [/SUP], Barbara Müller[SUP] 13 [/SUP], Hans-Georg Kräusslich[SUP] 4 13 [/SUP], Georg Friedrich Hoffmann[SUP] 1 [/SUP], Jürgen G Okun[SUP] 1 [/SUP], Ralf Bartenschlager[SUP] 2 3 4 [/SUP], Marco Binder[SUP] 5 [/SUP], Aleš Janda[SUP] 12 [/SUP], Hanna Renk[SUP] 14 [/SUP], Burkhard Tönshoff[SUP] 1 [/SUP]



Affiliations
Abstract

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.

Keywords: ACE2; SARS‐CoV‐2; children; exposure; persistence.

 
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