Clinical and biochemical short-term effects of hyperbaric oxygen therapy on SARS-Cov-2+ hospitalized patients with hypoxemic respiratory failure

Abstract

Background: Hyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known.

Method: 50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets (P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1β, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA.

Results: The average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05).

Conclusion: Patients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).

Keywords: COVID-19; Cell adhesion molecules; Cytokines; Hyperbaric oxygen therapy (HBOT); Hypoxemia.

Fig. 1

Effect of HBOT on oxygen saturation Graphs show the daily oxygen saturation (SatO2) breathing ambient air (FiO2 = 0.21%) pre HBOT session (H) or at equivalent time for the control group (C). Group H shows higher 02 Sat than group C since the second day of HBOT treatment (statistical differences are shown in Table 3). The days needed to reach 02 Sat >90% were: H: 3 + 1 and C: 5 ± 1.

Fig. 2

Variations in plasma concentration of Cardiovascular Disease Markers A: Soluble Vascular Cell Molecule (sVCAM), B: Soluble P selectin (sPselectin), C. Intercellular Adhesion Molecule-1 (sICAM-1), D: Acute Phase Amyloid A (SAA) and E: Myeloperoxidase (MPO). Graphs show the mean variations of each plasma concentration at the end of the study relative to the respective baseline measure for treated patients (AH) or control ones (AC)). Significant differences between AH and AC are shown (AH vs AC, P < 0.05 and P < 0.01).

Fig. 3

Variations in plasma levels of IL-1RA, TNFα and VEGF A: Interleukin 1 receptor antagonist (IL-1RA), B: Tumor Necrosis Factor alpha (TNFα), C. Vascular Endothelial Growth Factor (VEGF). Graphs show the mean variations of each plasma concentration at the end of the study relative to the respective baseline measure for treated patients (AH) or control ones (AC)). Significant differences between AH and AC are shown (AH vs AC, P < 0.05).