SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.

Background: Severe COVID-19 reflects a multi-layered host response with systemic inflammation, thrombo-inflammation, tissue damage, oxidative stress and altered antiviral interferon biology. We performed an integrated exploratory analysis of first-wave hospitalized patients to identify biomarker patterns associated with adverse clinical evolution during established admission. Methods: We analyzed 60 hospitalized COVID-19 patients and 18 healthy controls for soluble IFNAR2 (sIFNAR2) comparison. Biomarker samples were obtained during hospitalization, approximately seven days after symptom onset. Outcomes were final clinical status, severe respiratory involvement, post-sampling clinical worsening and death. Analyses included non-parametric testing, false-discovery-rate adjustment, effect-size estimation, exploratory ROC curves, parsimonious regression, penalized internal validation, composite scores and molecular-structure analyses. Results: Final status was favorable outcome in 31 patients, severe non-fatal disease in 22 and death in 7. sIFNAR2 was higher in patients than in healthy controls and highest among non-survivors, but did not distinguish favorably from severe non-fatal disease. The most consistent severity-associated signals were IL-6, D-dimer, total thiols, IL-10, LDH, ferritin, leukocytes and IL-1RA. D-dimer, IL-6 and ferritin yielded the largest exploratory univariable AUCs for severe respiratory involvement, whereas ferritin, IL-10, IL-1RA and sIFNAR2 predominated in event-limited mortality analyses, which were based on only seven deaths. Composite multi-axis scores and PLS-DA were tools requiring external validation. Conclusions: Biomarker patterns during admission were associated with adverse evolution. Conventional markers remained the most practical signals, while cytokines, redox markers and sIFNAR2 provided complementary biological information. sIFNAR2 should be interpreted as an exploratory complementary marker of the interferon receptor axis, mainly linked to mortality, not as a stand-alone clinical test or functional measure of IFNAR signaling.