Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection

Abstract

The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.

Antemortem vs. postmortem histopathological and ultrastructural findings in paired transbronchial biopsies and lung autopsy samples from three patients with confirmed SARS-CoV-2 infection

“…Only 1 of 2 autopsy samples from patient #1 tested positive for SARS-CoV-2 in RT-PCR, and characteristic histopathological changes were very focal, supporting the assumption that the patient died early during the disease before widespread involvement of the lung. Such intrapulmonary heterogeneity of SARS-CoV-2 infection has previously been described 23 . Since the cause of death was pulmonary thromboembolism with high D-dimer levels (>30 mg/l, ref.…”

Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody

“…Following the characterization of MC-specific proteases in SARS-CoV-2 patient serum, we next explored the expression of these mediators in lung tissues obtained from post-mortem COVID-19 patients and control tissues from uninfected patients using publicly available RNA-seq datasets. Due to the small number of patients within each published study, we leveraged three different bulk RNA-seq datasets to generate a combined dataset with ten COVID-19 patient lungs and three lung tissue samples from uninfected individuals ( 36 , 37 ). Transcriptional profiling of these samples revealed 1741 differentially expressed genes between infected lungs and controls ( Supplementary Figure 1B ).…”

A COVID-19 Drug Repurposing Strategy through Quantitative Homological Similarities Using a Topological Data Analysis-Based Framework

“…At the time the searches were carried out, three datasets were identified. Dataset 1 (DS1) was found in the gene expression omnibus (GEO) under ID GSE150316 [ 80 ]. This includes formalin-fixed paraffin-embedded samples from multiple tissues (i.e., lung, jejunum, heart) derived from SARS-CoV-2-infected individuals and uninfected controls obtained in autopsies.…”