Alterations in the Expression of IFN Lambda, IFN Gamma and Toll-like Receptors in Severe COVID-19 Patients

Author:

Sorrentino Leonardo1ORCID,Fracella Matteo1ORCID,Frasca Federica1,D’Auria Alessandra1,Santinelli Letizia2ORCID,Maddaloni Luca2ORCID,Bugani Ginevra2,Bitossi Camilla1,Gentile Massimo1,Ceccarelli Giancarlo2ORCID,Turriziani Ombretta1ORCID,Mastroianni Claudio Maria2ORCID,Antonelli Guido1,d’Ettorre Gabriella2ORCID,Pierangeli Alessandra1ORCID,Scagnolari Carolina13ORCID

Affiliation:

1. Laboratory of Virology, Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy

2. Department of Public Health and Infectious Diseases, Sapienza University of Rome, Policlinico Umberto I of Rome, 00185 Rome, Italy

3. Istituto Pasteur Italia, 00161 Rome, Italy

Abstract

Contradictory results have been reported regarding interferon (IFN) lambda (λ1–3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1–3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (n = 32) and in cells of paired bronchoalveolar lavages (BALs) (n = 12). Lower IFNλ1–3 values (p < 0.001 for IFNλ1 and 3 and p = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors (n = 15). Reduced levels of IFNγ were also detected in patients’ PBMCs (p < 0.01) and BALs (p = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs (p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFNλ3 (p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 (p = 0.003 and p < 0.001) and increased IFNγ (p = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed (p = 0.033) in patients with bacterial superinfections, while TLR7 and 8 (p = 0.029 and p = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.

Funder

EU funding

Sapienza University of Rome

Publisher

MDPI AG

Subject

Virology,Microbiology (medical),Microbiology

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