Severe Adaptive Immune Suppression May Be Why Patients With Severe COVID-19 Cannot Be Discharged From the ICU Even After Negative Viral Tests.

Yue Zhou,Xiangrong Song,Xiaoqi Xie,Chenliang Zhou,Xiaodong Jin,Min He,Wei Zhang,Xuelian Liao,Yan Kang,Fei Xiao,Zhongwei Zhang,Bo Wang

doi:10.3389/fimmu.2021.755579

Abstract

During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. To explore the underlying mechanism, we collected blood samples from these patients and analyzed the gene expression profiles of peripheral immune cells. We found that all enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. In addition, no significant change was found in the expression of classic immunosuppression molecules including PD-1, PD-L1, and CTLA-4, suggesting that the adaptive immune suppression may not be due to the change of these genes. According to the published literatures and our data, this adaptive immunosuppression is likely to be caused by the “dysregulated host response” to severe infection, similar to the immunosuppression that exists in other severely infected patients with sepsis.

Highlights

Coronavirus disease 2019 (COVID-19), caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2], has spread throughout the world, causing a devastating medical and social crisis [3, 4]
To obtain a comprehensive understanding of the impact of SARS-CoV-2 infection on patients with severe COVID-19 with at least 3 negative virus tests, we analyzed the transcriptional profiles of whole blood cells via RNA-Seq analysis
To investigate why some severe COVID-19 patients with negative virus tests were still critically ill and could not be discharged from the intensive care unit (ICU), we analyzed the changes in the transcription level of all genes using whole blood cells

Summary

Introduction

Coronavirus disease 2019 (COVID-19), caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2], has spread throughout the world, causing a devastating medical and social crisis [3, 4]. A small proportion (~5%) of patients with COVID-19 progress to a severe condition [6, 9, 10] These patients often require intensive medical treatment because of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), or multiorgan dysfunction (MODS) with a considerable risk of mortality. Continuous negative viral tests are thought to indicate that the virus has been cleared from the body and that the patients can be considered “recovered”. Because these patients were still critically ill, they obviously had not truly recovered from the disease. To determine why these patients were still critically ill even though they exhibited negative viral tests, we collected blood samples and analyzed the gene expression profiles of the peripheral immune cells

Methods

Results

Conclusion