Expression profile of HERVs and inflammatory mediators detected in nasal mucosa as a predictive biomarker of COVID-19 severity

Vita Petrone; Marialaura Fanelli; Martina Giudice; Nicola Toschi; Allegra Conti; Christian Maracchioni; Marco Iannetta; Claudia Resta; Chiara Cipriani; Martino Tony Miele; Francesca Amati; Massimo Andreoni; Loredana Sarmati; Paola Rogliani; Giuseppe Novelli; Enrico Garaci; Guido Rasi; Paola Sinibaldi-Vallebona; Antonella Minutolo; Claudia Matteucci; Emanuela Balestrieri; Sandro Grelli

doi:10.3389/fmicb.2023.1155624

Expression profile of HERVs and inflammatory mediators detected in nasal mucosa as a predictive biomarker of COVID-19 severity

Front Microbiol. 2023 May 22:14:1155624. doi: 10.3389/fmicb.2023.1155624. eCollection 2023.

Authors

Vita Petrone¹, Marialaura Fanelli¹, Martina Giudice¹, Nicola Toschi^{2

3}, Allegra Conti², Christian Maracchioni¹, Marco Iannetta⁴, Claudia Resta⁵, Chiara Cipriani¹, Martino Tony Miele¹, Francesca Amati², Massimo Andreoni⁴, Loredana Sarmati⁴, Paola Rogliani⁵, Giuseppe Novelli^{2

6

7}, Enrico Garaci⁸, Guido Rasi¹, Paola Sinibaldi-Vallebona^{1

9}, Antonella Minutolo¹, Claudia Matteucci¹, Emanuela Balestrieri¹, Sandro Grelli^{1

10}

Affiliations

¹ Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
² Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
³ Martinos Center for Biomedical Imaging and Harvard Medical School, Boston, MA, United States.
⁴ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
⁵ Respiratory Medicine Unit, Policlinic of Tor Vergata, Rome, Italy.
⁶ Neuromed IRCCS Institute, Pozzilli, IS, Italy.
⁷ University of Nevada, Department of Pharmacology, Reno, NV, United States.
⁸ IRCCS San Raffaele Pisana, Rome, Italy.
⁹ National Research Council, Institute of Translational Pharmacology, Rome, Italy.
¹⁰ Virology Unit, Policlinic of Tor Vergata, Rome, Italy.

Abstract

Introduction: Our research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome.

Methods: Residuals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR.

Results: The results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1β, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-β, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1β, IL-6, IFN-α, and IFN-β reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation.

Discussion: Overall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

Keywords: COVID-19; HERV; biomarker; human endogenous retroviruses; inflammation; respiratory outcome.

Copyright © 2023 Petrone, Fanelli, Giudice, Toschi, Conti, Maracchioni, Iannetta, Resta, Cipriani, Miele, Amati, Andreoni, Sarmati, Rogliani, Novelli, Garaci, Rasi, Sinibaldi-Vallebona, Minutolo, Matteucci, Balestrieri and Grelli.