Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-Infection.

Bruce K Patterson,Monica Herrera,Xaiolan Chang,Dennis Maglinte,Jose Guevara-Coto,Eric Hall,Ram Yogendra,Amruta Pise,Purvi Parikh,Saboor Hekmati,Timothy J Triche,Emily Long,Javier Mora,Rodrigo A Mora-Rodríguez,Paul Scott,Hallison Rodrigues,Edgar B Francisco

doi:10.3389/fimmu.2021.746021

Abstract

The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. That non-classical monocytes may be a source of inflammation in PASC warrants further study.

Highlights

Post-acute sequelae SARS-CoV-2 infection (PASC) is a disabling and sometimes debilitating conditions that occurs in 10%-30% of individuals infected by SARS-CoV-2 and has recently been proposed to cause neurologic symptoms in 30% of those infected [1]
CD14lo, CD16+ non-classical monocytes were significantly elevated in PASC (P=0.01)
Since the reports by our group and others found that monocyte subsets can be infected by human immunodeficiency virus (HIV), hepatitis C virus (HCV), Zika virus and Dengue fever virus [10,11,12], we screened peripheral blood mononuclear cells (PBMCs) from PASC individuals, as well as acute severe COVID-19 as controls, for SARS-CoV-2 RNA (Table 1)

Summary

INTRODUCTION

Post-acute sequelae SARS-CoV-2 infection (PASC) is a disabling and sometimes debilitating conditions that occurs in 10%-30% of individuals infected by SARS-CoV-2 and has recently been proposed to cause neurologic symptoms in 30% of those infected [1]. Classical monocytes exhibit the CD14++, CD16phenotype, intermediate monocytes exhibit a CD14+, CD16+ phenotype, and the non-classical monocytes express CD14lo, CD16+ [6, 7]. Further they express very different cell surface markers as previously described [8]. Classical monocytes express low levels of the chemokine receptors CX3R1 and CCR5. We report kinetic differences in the proportions of monocyte subsets in severe cases and PASC, as well as the presence of SARS-CoV-2 protein unaccompanied by corresponding viral RNA in CD14lo, CD16+ monocytes in PASC patients up to 15 months post-acute SARS-CoV2 infection.

Extending beyond 3 weeks from the initial onset of first symptoms

RESULTS

DISCUSSION

ETHICS STATEMENT