Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta).

Annemiek Maaskant,Dian G M Zijlmans,Jaco Bakker,Babs E Verstrepen,Jan A M Langermans,Marieke A Stammes,Lisette Meijer,Zahra Fagrouch,Ernst J Verschoor,Leo Van Geest,Pierre Roques

doi:10.1371/journal.pone.0252941

Abstract

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after, and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between time points in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not resolved within the first 24 hours. Therefore, it is important to acknowledge the interference between BAL and CT in rhesus macaques.

Highlights

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the development of coronavirus 2019 (COVID-19) was first described in Wuhan, Hubei Province, China at the end of 2019 [1]
In all non-infected animals, an increase in density was visible in the lavaged lung around the opening of the main bronchus at the computed tomography (CT) performed immediately post-Bronchoalveolar lavage (BAL)
The findings in this study demonstrate that, thorax CT alterations due to BAL seem to be resolved within 24 hours in non-infected macaques

Summary

Introduction

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the development of coronavirus 2019 (COVID-19) was first described in Wuhan, Hubei Province, China at the end of 2019 [1]. SARS-CoV-2 spread rapidly across the globe, leading the World Health Organization to officially declare COVID-19 a Public Health Emergency of International Concern by the end of January 2020. Animal models are important to answer several research questions like infection progress, disease development, and to evaluate prophylactic and therapeutic treatment options. Multiple studies compared several NHP models to identify their suitability for COVID-19 research, and demonstrated that Old World monkeys, like macaques, are susceptible to SARS-CoV-2 infection and develop mild-to-moderate disease [5,6,7,8]

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