Medical Imaging of Pulmonary Disease in SARS-CoV-2-exposed Non-human Primates

Overview

Journal Trends Mol Med

Specialties General Medicine
Molecular Biology

Date 2021 Dec 27

PMID 34955425

Citations 8

Authors

Marieke A Stammes

Ji Hyun Lee

Lisette Meijer

Thibaut Naninck

Lara A Doyle-Meyers

Alexander G White

H Jacob Borish

Amy L Hartman

Xavier Alvarez

Shashank Ganatra

Deepak Kaushal

Rudolf P Bohm

Roger Le Grand

Charles A Scanga

Jan A M Langermans

Ronald E Bontrop

Courtney L Finch

JoAnne L Flynn

Claudia Calcagno

Ian Crozier

Jens H Kuhn

Affiliations

Soon will be listed here.

Abstract

Chest X-ray (CXR), computed tomography (CT), and positron emission tomography-computed tomography (PET-CT) are noninvasive imaging techniques widely used in human and veterinary pulmonary research and medicine. These techniques have recently been applied in studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed non-human primates (NHPs) to complement virological assessments with meaningful translational readouts of lung disease. Our review of the literature indicates that medical imaging of SARS-CoV-2-exposed NHPs enables high-resolution qualitative and quantitative characterization of disease otherwise clinically invisible and potentially provides user-independent and unbiased evaluation of medical countermeasures (MCMs). However, we also found high variability in image acquisition and analysis protocols among studies. These findings uncover an urgent need to improve standardization and ensure direct comparability across studies.

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References

Pillet S, Arunachalam P, Andreani G, Golden N, Fontenot J, Aye P . Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates. Cell Mol Immunol. 2022; 19(2):222-233. PMC: 8727235. DOI: 10.1038/s41423-021-00809-2. View

Bar-On Y, Flamholz A, Phillips R, Milo R . SARS-CoV-2 (COVID-19) by the numbers. Elife. 2020; 9. PMC: 7224694. DOI: 10.7554/eLife.57309. View

Johnston S, Ricks K, Jay A, Raymond J, Rossi F, Zeng X . Development of a coronavirus disease 2019 nonhuman primate model using airborne exposure. PLoS One. 2021; 16(2):e0246366. PMC: 7853502. DOI: 10.1371/journal.pone.0246366. View

Cleary S, Pitchford S, Amison R, Carrington R, Robaina Cabrera C, Magnen M . Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology. Br J Pharmacol. 2020; 177(21):4851-4865. PMC: 7283621. DOI: 10.1111/bph.15143. View

Hassan A, Feldmann F, Zhao H, Curiel D, Okumura A, Tang-Huau T . A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. Cell Rep Med. 2021; 2(4):100230. PMC: 7969912. DOI: 10.1016/j.xcrm.2021.100230. View

Maaskant A, Meijer L, Fagrouch Z, Bakker J, van Geest L, Zijlmans D . Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta). PLoS One. 2021; 16(7):e0252941. PMC: 8270458. DOI: 10.1371/journal.pone.0252941. View

Iking J, Staniszewska M, Kessler L, Klose J, Luckerath K, Fendler W . Imaging Inflammation with Positron Emission Tomography. Biomedicines. 2021; 9(2). PMC: 7922638. DOI: 10.3390/biomedicines9020212. View

White A, Maiello P, Coleman M, Tomko J, Frye L, Scanga C . Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates. J Vis Exp. 2017; (127). PMC: 5752181. DOI: 10.3791/56375. View

Zeiss C, Compton S, Veenhuis R . Animal Models of COVID-19. I. Comparative Virology and Disease Pathogenesis. ILAR J. 2021; 62(1-2):35-47. PMC: 8083356. DOI: 10.1093/ilar/ilab007. View

10.

Zhu H, Zhang H, Zhou N, Ding J, Jiang J, Liu T . Molecular PET/CT Profiling of ACE2 Expression In Vivo: Implications for Infection and Outcome from SARS-CoV-2. Adv Sci (Weinh). 2021; 8(16):e2100965. PMC: 8373167. DOI: 10.1002/advs.202100965. View

11.

Tarkin J, Joshi F, Evans N, Chowdhury M, Figg N, Shah A . Detection of Atherosclerotic Inflammation by Ga-DOTATATE PET Compared to [F]FDG PET Imaging. J Am Coll Cardiol. 2017; 69(14):1774-1791. PMC: 5381358. DOI: 10.1016/j.jacc.2017.01.060. View

12.

Boszormenyi K, Stammes M, Fagrouch Z, Kiemenyi-Kayere G, Niphuis H, Mortier D . The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues. Viruses. 2021; 13(8). PMC: 8402919. DOI: 10.3390/v13081673. View

13.

Deng W, Bao L, Liu J, Xiao C, Liu J, Xue J . Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Science. 2020; 369(6505):818-823. PMC: 7402625. DOI: 10.1126/science.abc5343. View

14.

Bewley K, Gooch K, Thomas K, Longet S, Wiblin N, Hunter L . Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques. Sci Adv. 2021; 7(37):eabg7996. PMC: 8442907. DOI: 10.1126/sciadv.abg7996. View

15.

Lim S, Sung S, Min K, Jung Y, Cho Y, Lee K . Bronchoalveolar lavage affects computed tomographic and radiographic characteristics of the lungs in healthy dogs. Vet Radiol Ultrasound. 2018; 59(5):564-570. DOI: 10.1111/vru.12656. View

16.

Amani B, Khanijahani A, Amani B . Hydroxychloroquine plus standard of care compared with standard of care alone in COVID-19: a meta-analysis of randomized controlled trials. Sci Rep. 2021; 11(1):11974. PMC: 8184930. DOI: 10.1038/s41598-021-91089-3. View

17.

Wang G, Yang M, Duan Z, Liu F, Jin L, Long C . Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models. Cell Res. 2020; 31(1):17-24. PMC: 7705431. DOI: 10.1038/s41422-020-00450-0. View

18.

van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham J, Port J . ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020; 586(7830):578-582. PMC: 8436420. DOI: 10.1038/s41586-020-2608-y. View

19.

Sulbaran G, Maisonnasse P, Amen A, Effantin G, Guilligay D, Dereuddre-Bosquet N . Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection. Cell Rep Med. 2022; 3(2):100528. PMC: 8784613. DOI: 10.1016/j.xcrm.2022.100528. View

20.

Gabe L, Baker K, van Beek E, Hunninghake G, Reinhardt J, Hoffman E . Effect of segmental bronchoalveolar lavage on quantitative computed tomography of the lung. Acad Radiol. 2011; 18(7):876-84. PMC: 3115559. DOI: 10.1016/j.acra.2011.03.006. View