ICU Biomarkers in Critical COVID-19

> Research explainer: This briefing examines verified primary research published 59 days before the briefing date. It is not a same-day research update and does not provide medical advice.

This research explainer examines a source published on 2026-06-23 about biomarkers measured at intensive-care admission in people with critical COVID-19. It is an observational account of association, comparison, and prognostic testing within the reported cohort, rather than evidence that a biomarker causes an outcome or should direct care. [pmid:42337728]

Evidence

The study included 96 adults with critical COVID-19 admitted to a Swedish tertiary-hospital ICU between April and October 2020, alongside 10 ICU-admitted post-trauma comparison patients. Blood was collected at ICU admission and plasma concentrations of heparin-binding protein (HBP) and endothelin-1 (ET-1) were measured. [pmid:42337728]

HBP was markedly higher in the critical COVID-19 cohort: the reported median was 150 ng/mL, with an interquartile range of 47–299 ng/mL, versus 13.3 ng/mL, with an interquartile range of 8.8–62.1 ng/mL, in the trauma ICU group. The reported comparison had p<0.0001. [pmid:42337728]

The outcome finding is more constrained than the concentration difference. In the COVID-19 cohort, admission HBP was not associated with 60-day mortality or with need for invasive mechanical ventilation (IMV). The authors therefore concluded that, despite marked elevation, HBP did not predict outcomes at ICU admission in this cohort. [pmid:42337728]

ET-1 did not differ significantly between the two groups in the reported comparison. Median ET-1 was 1.6 pg/mL (IQR 1.2–1.9) in critical COVID-19 and 2.0 pg/mL (IQR 1.2–2.8) in trauma ICU patients, with p=0.25. [pmid:42337728]

Among the COVID-19 patients, those who required IMV had higher ET-1 levels than those who did not. However, that relationship was not present in the logistic-regression analysis adjusted for age, sex, and body-mass index. ET-1 was not linked to mortality or IMV after the reported analyses. [pmid:42337728]

The source also reports no correlation between plasma HBP and ET-1. Several inflammatory parameters—including C-reactive protein, procalcitonin, ferritin, and interleukin-6—were elevated but did not distinguish survivors from non-survivors in this study. [pmid:42337728]

Analysis — What the admission signal means

The clearest result is a group difference, not a prognostic rule. HBP concentration at ICU admission was much higher in participants with critical COVID-19 than in the small trauma ICU comparison group, so the study supports saying that HBP was elevated in this particular critical-COVID-19 cohort. [pmid:42337728] It does not establish that HBP separates critical COVID-19 from every other form of critical illness, because the comparator was limited to 10 trauma ICU patients. [pmid:42337728]

The negative outcome analyses matter because an elevated biomarker can still lack useful outcome discrimination at a particular sampling point. Here, neither the reported HBP analysis nor the adjusted ET-1 analysis established an independent association with the study’s 60-day mortality or IMV endpoints. [pmid:42337728] Thus, the measured admission values should not be reframed as validated prognostic markers on the basis of this source alone. [pmid:42337728]

The HBP and ET-1 results also should not be treated as interchangeable signals: the study found no correlation between their plasma levels. [pmid:42337728] A careful reading is therefore narrower than a general endothelial-injury narrative. The paper documents measured concentrations and their reported relationships to selected outcomes in one ICU cohort; it does not resolve how these biomarkers behave across disease stages, care settings, or treatment eras. [pmid:42337728]

Limitations

This was an observational, single-centre study, so it cannot establish causation. [pmid:42337728] Participants were enrolled at one Swedish tertiary hospital during 2020, which leaves uncertainty about applicability to other places, SARS-CoV-2 variants, and treatment eras. [pmid:42337728] The trauma comparison group was small and was not a non-critically-ill control group. [pmid:42337728] Measurements were taken at ICU admission, so the findings do not establish predictive performance at earlier or later disease stages. [pmid:42337728] Finally, the supplied source does not provide enough information to determine whether the enrolled cohort represented all people with critical COVID-19. [pmid:42337728]