Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species ( Macaca mulatta ; rhesus macaques; RM, Chlorocebus atheiops ; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques ( Macaca mulatta , RMs) and African green monkeys ( Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.
Article activity feed
-
SciScore for 10.1101/2021.11.28.470250: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Ethical Statement: The Tulane University Institutional Animal Care and Use Committee approved all procedures used during this study. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Detection of Antibodies in Serum: The ability of antibodies in serum to disrupt the binding of the receptor binding domain (RBD) of SARS-CoV-2 spike protein to Angiotensin Converting Enzyme (ACE2) was assessed via the Surrogate Virus Neutralization Test (GenScript# L00847) using the included kit protocol modified per the following: Serum samples were diluted … SciScore for 10.1101/2021.11.28.470250: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Ethical Statement: The Tulane University Institutional Animal Care and Use Committee approved all procedures used during this study. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Detection of Antibodies in Serum: The ability of antibodies in serum to disrupt the binding of the receptor binding domain (RBD) of SARS-CoV-2 spike protein to Angiotensin Converting Enzyme (ACE2) was assessed via the Surrogate Virus Neutralization Test (GenScript# L00847) using the included kit protocol modified per the following: Serum samples were diluted from 1:10 to 1:21,870 to determine an IC50 for RBD/ACE2 binding. Angiotensin Converting Enzyme ( ACE2suggested: NoneFluorescent immunohistochemistry was performed on 5 μm sections of Formalin-fixed, paraffin-embedded lung were incubated for 1 hour with the primary antibodies (SARS, Guinea Pig, (BEI, cat#NR-10361) diluted in NGS at a concentration of 1:1000). cat#NR-10361suggested: NoneExperimental Models: Cell Lines Sentences Resources Positive controls consisted of SARS- CoV-2 infected VeroE6 cell lysate. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources The Tulane National Primate Research Center (TNPRC) is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC no. 000594). TNPRCsuggested: NoneAnalysis of flow cytometry data: FlowJo version 10.7.1 (BD, Oregon, USA) was used to analyze flow cytometry data. FlowJosuggested: (FlowJo, RRID:SCR_008520)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 53. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
