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. 2024 Sep 30;25(19):10530.
doi: 10.3390/ijms251910530.

IFN Lambda Deficiency Contributes to Severe COVID-19 Outcomes

Anna Zaleska  1 , Anna Dor-Wojnarowska  1 , Anna Radlińska  1 , Marta Rorat  2 , Wojciech Szymański  3 , Adrian Gajewski  4 , Maciej Chałubiński  4
Affiliations

IFN Lambda Deficiency Contributes to Severe COVID-19 Outcomes

Anna Zaleska et al. Int J Mol Sci. .

Abstract

Interferons (IFNs) produced by airway epithelial cells are crucial in defending against pathogens. Fluctuations in IFN-λ levels may influence coronavirus disease 19 (COVID-19) severity. However, conflicting data have been reported regarding serum IFN-λ concentrations in COVID-19 patients. To address this, we evaluated serum IFN-λ levels over time in moderate and severe COVID-19 patients and their association with cytokine production and clinical parameters using the enzyme-linked immunosorbent assay (ELISA) and the Bio-Plex Pro Human Cytokine 17-plex Assay. Results from testing 51 COVID-19 patients showed that 68% lacked detectable serum IFN-λ. Among non-IFN-λ secretors, severe COVID-19 predominated. In contrast, IFN-λ secretors displayed stable IFN-λ levels in moderate cases, while severe cases showed a decline over time, which persisted even after recovery. A negative correlation was observed between IFN-λ levels and inflammatory markers. This, combined with an increase in tumor necrosis factor alpha (TNF-α) and clinical improvement, suggests a regulatory role for IFN-λ in promoting faster recovery. Despite this, survival rates were similar between the groups, indicating that while IFN-λ influences the course of the disease, it does not directly affect overall survival. In conclusion, IFN-λ is vital, but not unique, for the antiviral response and COVID-19 recovery. Simultaneously, serum IFN-λ deficiency signifies severe COVID-19.

Keywords: COVID-19; SARS-CoV-2; innate immunity; interferon.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(a) IFN-λ concentration in the serum of COVID-19 patients (n = 51) at three time points. (b) IFN-λ concentration in serum of COVID-19 patients (n = 51) regarding disease severity. Results are presented as row data with the average concentration for each group (p—statistical significance). (day 0) the first day of hospitalization, (day 8) the 8th day of hospitalization, (day 40–50) after hospital release between days 40 and 50.
Figure 2
Figure 2
Serum IFN-λ concentration in IFN-λ-secreting individuals with COVID-19 (n = 16) by disease severity. Results are presented as row data with the average concentration for each group (p—statistical significance). (day 0) the first day of hospitalization, (day 8) the 8th day of hospitalization, (day 40–50) after hospital release between days 40 and 50.
Figure 3
Figure 3
Cytokine repertoire in IFN-λ-secreting (n = 16) and non-secreting individuals (n = 35) with COVID-19 at three time points. Results are presented as row data with medians for each group (p—statistical significance).
Figure 3
Figure 3
Cytokine repertoire in IFN-λ-secreting (n = 16) and non-secreting individuals (n = 35) with COVID-19 at three time points. Results are presented as row data with medians for each group (p—statistical significance).
Figure 3
Figure 3
Cytokine repertoire in IFN-λ-secreting (n = 16) and non-secreting individuals (n = 35) with COVID-19 at three time points. Results are presented as row data with medians for each group (p—statistical significance).
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