DOI: 10.7272/q62z13rt
title: Post-acute immunological and behavioral sequelae in mice after Omicron infection

description: Progress in understanding long COVID ­­­and developing effective
 therapeutics is hampered in part by the lack of suitable animal models.
 Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection
 to test for pulmonary and behavioral post-acute sequelae. Through in-depth
 phenotyping by CyTOF, we demonstrate that naïve mice experiencing a first
 Omicron infection exhibit profound immune perturbations in the lung after
 resolving acute infection. This is not observed if mice were first
 vaccinated with spike-encoding mRNA. The protective effects of vaccination
 against post-acute sequelae were associated with a highly polyfunctional
 SARS-CoV-2-specific T cell response that was recalled upon BA.1
 breakthrough infection but not seen with BA.1 infection alone. Without
 vaccination, the chemokine receptor CXCR4 was uniquely upregulated on
 multiple pulmonary immune subsets in the BA.1 convalescent mice, a process
 previously connected to severe COVID-19. Taking advantage of recent
 developments in AI-based assessments of murine behaviors, we demonstrate
 that BA.1 convalescent mice respond abnormally to a stimulus
 after repeated presentations (habituation). Collectively, our
 data identify immunological and behavioral post-acute sequelae after
 Omicron infection and uncover a protective effect of vaccination.
    
description: **READ ME FILE** General Information Title: Vaccination protects against
 persistence of pulmonary immunological perturbations in mouse model of
 long COVID Contact: Nadia Roan, PhD Gladstone Institutes University of
 California, San Francisco 
 Dates of collection: 4/1/2022 6/27/2022
 Information about geographic location of data collection: San Francisco
 Bay Area Key Words: COVID-19, SARS-CoV-2, Mouse Model, Long Covid,
 Post-Acute Sequelae of COVID-19 (PASC), T cells, CyTOF, CXCR4 Data and
 File Overview Included are total 40 FCS files corresponding to CyTOF data
 generated from the murine lung. Data were generated from the following
 five groups of mice: 1. Mock-treated (Mock) 2. Vaccinated (Vac) 3. BA.1
 convalescent (BA1) 4. Vaccinated, BA.1 convalescent (Vac_BA1) Each
 experimental group had 5 mice. Each murine sample was analyzed at
 baseline, or following a 6 hour stimulation with SARS-CoV-2 peptides to
 characterize SARS-CoV-2-specific T cells. Each FCS file name begins with
 the treatment group (shorthand names listed above in quotes), followed by
 a number (1-5) to identify the mouse. Of note, numbers identifying mice
 are shared between different experimental groups, but these do not
 correspond to the same mice; rather we arbitrarily numbered each mouse
 within each experimental group from 1-5. The last component of the file
 name was either Baseline or Sti (shorthand for stimulated) to indicate
 whether the sample was analyzed at baseline or after SARS-CoV-2 peptide
 stimulation. All files were pre-gated on live, singlet CD45+ events.
 Sharing and accessing information No licenses or restrictions are placed
 on the data. Methodological Information Methods used for generating and
 analyzing the CyTOF datasets are similar to those recently described: *
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 * Data-specific information Please see above information under data and file overview and methodological information.