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

Contradictory results have been reported regarding interferon (IFN) lambda (lambda 1-3) and IFN gamma (gamma) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFN lambda 1-3 and IFN gamma mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (n = 32) and in cells of paired bronchoalveolar lavages (BALs) (n = 12). Lower IFN lambda 1-3 values (p < 0.001 for IFN lambda 1 and 3 and p = 0.013 for IFN lambda 2) in the PBMCs of severely ill patients were found compared to healthy donors (n = 15). Reduced levels of IFN gamma 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 IFN lambda amounts in PBMCs (p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFN lambda 3 (p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFN lambda 1 and 3 (p = 0.003 and p < 0.001) and increased IFN gamma (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 IFN gamma, IFN lambda and TLR3, 7 and 8 production.