Association of SARS-CoV-2 infection with long-lasting increase in circulating IL-32 levels, 2026, Miano et al.

[Chandelier]

Association of SARS-CoV-2 infection with long-lasting increase in circulating IL-32 levels

Spoiler: Authors

Miano, Lorenzo; Sinopoli, Elena; Cherubini, Alessandro; Suffritti, Chiara; Pelusi, Serena; Rahmeh, Fatima; Lamorte, Giuseppe Enzo; Peyvandi, Flora; Blasi, Francesco; Grasselli, Giacomo; Bandera, Alessandra; Gualtierotti, Roberta; Prati, Daniele; Valenti, Luca Vittorio Carlo

Abstract​

Background & aims: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has a wide spectrum of clinical presentations ranging from asymptomatic viral replication to hyper-inflammatory syndrome and respiratory failure and can trigger immune disorders and long-COVID.
Interleukin-32 (IL-32) is a pro-inflammatory cytokine induced during viral infections and chronic pulmonary disease.

Aim: Aim of this study was to investigate the impact of the SARS-CoV-2 pandemic and severe COVID-19 on circulating IL-32 levels.

Study design: Observational retrospective biomarker study.

Patients & methods: We analyzed 949 healthy blood donors (pre-pandemic and pandemic-era) and 212 patients hospitalized due to severe COVID-19 during the first five infection waves. IL-32 levels were measured by ELISA.

Results: Pandemic-era blood plasma donors showed a +0.78 ± 0.09 log10 pg/ml mean increase in IL-32 (pandemic-era 2.91 ± 0.05 vs. pre-pandemic 2.14 ± 0.07 log10 pg/ml, p<0.0001).
COVID-19 patients exhibited a similar elevated IL-32 compared to unexposed controls (+0.29 ± 0.11 log10 pg/ml, p=0.016; 2.43 ± 0.08 hospital admission vs. pre-pandemic).
Among patients, mean IL-32 was higher in first-wave patients (2.68 ± 0.11 log10 pg/ml) than later waves (2.12 ± 0.11 log10 pg/ml). In setting of severe COVID-19, IL-32 levels were associated with corticosteroids administration (estimate1.99 ± 0.50; p<0.0001), whereas decreased during the later waves of infection (-0.56 ± 0.16; p=0.0005) and with age (estimate -0.01 ± 0.01; p=0.020).
No links were found with sex, Intensive care unit admission, comorbidities, or mortality.
A subset of the COVID patient cohort was tested for pro-inflammatory biomarkers: IL-32 displayed an inverse correlation with patients’ neutrophil-to-lymphocyte ratio (NLR) (estimate -0.23 ± 0.81; p=0.005) and not with IL-6 and biomarkers of endothelial dysfunction (n=42, p=NS). In patients with available follow-up (n=96), IL-32 remained stable up to one-year post-discharge (+0.03 ± 0.12 log10 pg/ml, p=0.970; 2.55 ± 0.15 hospital admission vs. follow-up 3–12 months 2.58 ± 0.15 log10 pg/ml).

Conclusions: IL-32 levels increased following COVID-19, especially during the initial severe wave, and correlated with some markers of inflammation.
IL-32 remained elevated up to one-year post-discharge, suggesting ongoing inflammation and supporting its potential as a biomarker for long-term sequelae.

Web | DOI | Frontiers in Immunology

 

[Amw66]

I know nothing about this - but is not a slight crease after 12 months worth monitoring further over time to see how it pans out ?
Up to one year after discharge is the cut off point for the study - it could suggest at a glance that after 12 months this is not important and everythings going " back to normal"

Are current levels known? the 12 month cut off gets us to 2023. Bolding my own.

from study
We considered as main criteria for the enrolment in the study patients aged over 18 years, admitted between March 2020 and February 2022 to the Infectious Disease Unit and the Intensive Care Unit (ICU) (Registro COVID, nCoV-ICU), with a confirmed COVID-19 diagnosis (positive RT-PCR for SARS-CoV-2 and/or positive nasopharyngeal swab and/or positive BAS/BAL).

A remarkable finding was that we did not observe a significant decline in circulating IL-32 levels in COVID-19 patients who remained in follow-up one year after hospital discharge. In keeping, IL-32 has been reported to be one of the main proteins associated with pulmonary fibrosis, along with IL-8 and IL-10, in post-COVID-19 hospitalized patients, evaluated 6 months after discharge (33).
However, we acknowledge the possibility that patients who continued to experience symptoms after infection may have been more likely to stay in follow-up, which could influence these observations.
Limitations of the present study also include the relatively limited sample size, particularly for follow-up evaluations, constraining the power to identify additional significant associations with clinical outcomes and hindering further stratification for confounding factors.
In conclusion, we found that IL-32 levels increased in apparently healthy individuals concomitantly with a high rate of seroconversion during the first COVID wave, and in patients with severe COVID-19. Among patients, IL-32 was higher in those who were younger and with hyper-inflammation treated with steroids during the first wave. Remarkably, in patients presenting at follow-up with persistent symptoms, IL-32 remained stably elevated.