Clinical and molecular characteristics of COVID-19 patients with persistent SARS-CoV-2 infection

Bin Yang,Lixin You,Tian Wang,Si Liu,Jianfeng Zhou,Jia Huang,Tianyu Qin,Xu Qin,Gang Chen,Zizhuo Wang,Junpeng Fan,Yu Fu,Dianxing Hu,Chen Liu,Rourou Xiao,Chao He,Xi Li,Kezhen Li,Ensong Guo,Peng Wu,Fang Lü ,Chaoyang Sun

doi:10.1038/s41467-021-23621-y

Bin Yang, Lixin You + Show 20 more

Open Access

https://doi.org/10.1038/s41467-021-23621-y

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Abstract

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Here, we compare the clinical and molecular features of patients with long duration of viral shedding (LDs) with those from patients with short duration patients (SDs), and healthy donors (HDs). We find that several cytokines and chemokines, such as interleukin (IL)-2, tumor necrosis factor (TNF) and lymphotoxin α (LT-α) are present at lower levels in LDs than SDs. Single-cell RNA sequencing shows that natural killer (NK) cells and CD14+ monocytes are reduced, while regulatory T cells are increased in LDs; moreover, T and NK cells in LDs are less activated than in SDs. Importantly, most cells in LDs show reduced expression of ribosomal protein (RP) genes and related pathways, with this inversed correlation between RP levels and infection duration further validated in 103 independent patients. Our results thus indicate that immunosuppression and low RP expression may be related to the persistence of the viral infection in COVID-19 patients.

Highlights

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described
Inflammatory markers, such as procalcitonin, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP), which have been well reported as high-risk factors of the development of severe COVID-1922–24, were comparable in long duration of viral shedding (LDs) and short duration patients (SDs)
We found that protein targeting to the membrane, endoplasmic reticulum (ER) related pathways, and translation related pathways were consistently downregulated in all cell types in LDs, with the exception of gamma delta T cells, mucosal associated invariant T cells (MAIT), and megakaryocytes (Fig. 3a)

Summary

Introduction

The characteristics of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. Our results indicate that immunosuppression and low RP expression may be related to the persistence of the viral infection in COVID-19 patients. The world is witnessing a major devastating pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus[2] (SARS-CoV-2)[1]. On March 11th 2020, the World Health Organization has declared it a pandemic, which has had a profound impact on the global culture and economy[2]. The duration of viral shedding has been reported to vary dramatically, ranging from 6 to 105 days, with a median duration of 20 days from disease onset[4,5,6,7]. In addition to focus on the severity of the COVID-

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