Two distinct immunopathological profiles in autopsy lungs of COVID-19

Ronny Nienhold,Angela Frank,Markus Tolnay,Nathalie Schwab,M Barbareschi ,Thomas Hoyler,Thomas Menter,Alexandar Tzankov,Niels Willi,Maurice Henkel,Jasmin D Haslbauer,Viktor H Koelzer,Gieri Cathomas,Holger Moch,Werner Kempf,Francesca Demichelis,Veronika Zsikla,Yari Ciani,Tobias Junt,Kirsten D Mertz

doi:10.1038/s41467-020-18854-2

Abstract

Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.

Highlights

Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality
Among the 398 genes investigated, we identified 68 upregulated and 30 downregulated genes in COVID-19 infected lungs compared to normal tissue (Fig. 1a, b and Supplementary Table 3), and a PCA analysis showed segregation of COVID-19 patients in two welldefined clusters that showed distinct association with viral load (Fig. 1a, c)
We identified interferon-stimulated genes (ISGs) as a key upregulated pathway in COVID-19 autopsy lungs (Table 2), which was differentially represented in clusters 1 and 2, respectively (Fig. 1d)

Summary

Introduction

Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Lymphopenia, high levels of pro-inflammatory cytokines in the circulation[3], and phenotypic changes of pro-inflammatory macrophages in bronchoalveolar lavages (BALs)[4] in severe patients have led to the notion that the immune response against the causative virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to devastating end-organ damage[5]. Since patients with severe COVID-19 may develop acute respiratory distress syndrome (ARDS) and many patients die from respiratory failure with diffuse alveolar damage[6], it is critical to understand the immunological profiles in the lungs of these patients.

Methods

Results

Conclusion