A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT® Technology for Assessing Total Anti-Oxidative Capacity.

BACKGROUND: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility. MATERIALS AND METHODS: In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed. RESULTS: During the recovery phase, plasma levels in antioxidants (γ-tocopherol, ß-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.

Characteristics of Mid-Term Post-Intensive Care Syndrome in Patients Attending a Follow-Up Clinic: A Prospective Comparison Between COVID-19 and Non-COVID-19 Survivors.

At present, it is not clear if critically ill COVID-19 survivors have different needs in terms of follow-up compared with other critically ill survivors, and thus if duplicated post-ICU trajectories are mandatory. OBJECTIVES: To compare the post-intensive care syndrome (PICS) of COVID-19 acute respiratory distress syndrome and non-COVID-19 (NC) survivors referred to a follow-up clinic at 3 months (M3) after ICU discharge. DESIGN SETTING AND PARTICIPANTS: Adults who survived an ICU stay greater than or equal to 7 days and attended the M3 consultation were included in this observational study performed in a post-ICU follow-up clinic of a single tertiary hospital. MAIN OUTCOMES AND MEASURES: Patients underwent a standardized assessment, addressing health-related quality of life (3-level version of EQ-5D), sleep disorders (Pittsburgh Sleep Quality Index [PSQI]), physical status (Barthel index, handgrip and quadriceps strengths), mental health disorders (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised [IES-R]), and cognitive impairment (Montreal Cognitive Assessment [MoCA]). RESULTS: A total of 143 survivors (86 COVID and 57 NC) attended the M3 consultation. Their median age and severity scores were similar. NC patients had a shorter ICU stay (10 d [8-17.2 d]) compared with COVID group (18 d [10.8-30 d]) (p = 0.001). M3 outcomes were similar in the two groups, except for a higher PSQI (p = 0.038) in the COVID group (6 [3-9.5]) versus NC group (4 [2-7]), and a slightly lower Barthel index in the NC group (100 [100-100]) than in the COVID group (100 [85-100]) (p = 0.026). However, the proportion of patients with abnormal values at each score was similar in the two groups. Health-related quality of life was similar in the two groups. The three MoCA (≥ 26), IES-R (<33), and Barthel (=100) were normal in 58 of 143 patients (40.6%). In contrast, 68.5% (98/143) had not returned to their baseline level of daily activities. CONCLUSIONS AND RELEVANCE: In our follow-up clinic at 3 months after discharge, the proportion of patients presenting alterations in the main PICS domains was similar whether they survived a COVID-19 or another critical illness, despite longer ICU stay in COVID group. Cognition and sleep were the two most affected PICS domains.

Characteristics of Mid-Term Post-Intensive Care Syndrome in Patients Attending a Follow-Up Clinic: A Prospective Comparison Between COVID-19 and Non-COVID-19 Survivors

IMPORTANCE: At present, it is not clear if critically ill COVID-19 survivors have different needs in terms of follow-up compared with other critically ill survivors, and thus if duplicated post-ICU trajectories are mandatory. OBJECTIVES: To compare the post-intensive care syndrome (PICS) of COVID-19 acute respiratory distress syndrome and non-COVID-19 (NC) survivors referred to a follow-up clinic at 3 months (M3) after ICU discharge. DESIGN, SETTING, AND PARTICIPANTS: Adults who survived an ICU stay greater than or equal to 7 days and attended the M3 consultation were included in this observational study performed in a post-ICU follow-up clinic of a single tertiary hospital. MAIN OUTCOMES AND MEASURES: Patients underwent a standardized assessment, addressing health-related quality of life (3-level version of EQ-5D), sleep disorders (Pittsburgh Sleep Quality Index [PSQI]), physical status (Barthel index, handgrip and quadriceps strengths), mental health disorders (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised [IES-R]), and cognitive impairment (Montreal Cognitive Assessment [MoCA]). RESULTS: A total of 143 survivors (86 COVID and 57 NC) attended the M3 consultation. Their median age and severity scores were similar. NC patients had a shorter ICU stay (10 d [8–17.2 d]) compared with COVID group (18 d [10.8–30 d]) (p = 0.001). M3 outcomes were similar in the two groups, except for a higher PSQI (p = 0.038) in the COVID group (6 [3–9.5]) versus NC group (4 [2–7]), and a slightly lower Barthel index in the NC group (100 [100–100]) than in the COVID group (100 [85–100]) (p = 0.026). However, the proportion of patients with abnormal values at each score was similar in the two groups. Health-related quality of life was similar in the two groups. The three MoCA (≥ 26), IES-R (<33), and Barthel (=100) were normal in 58 of 143 patients (40.6%). In contrast, 68.5% (98/143) had not returned to their baseline level of daily activities. CONCLUSIONS AND RELEVANCE: In our follow-up clinic at 3 months after discharge, the proportion of patients presenting alterations in the main PICS domains was similar whether they survived a COVID-19 or another critical illness, despite longer ICU stay in COVID group. Cognition and sleep were the two most affected PICS domains.

Increased KL-6 levels in moderate to severe COVID-19 infection.

BACKGROUND: The global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae. METHODS: We retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P <0.00001). ROC curve analysis enabled us to identify that KL-6 > 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69). CONCLUSIONS: KL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection.

One-Year Functional Decline in COVID-19 and Non-COVID-19 Critically Ill Survivors: A Prospective Study Incorporating a Pre-ICU Status Assessment.

We aimed to describe the one-year (1-y) functional status of survivors of COVID-19 critical illness, compared to non-COVID-19 survivors, and compared to their pre-ICU status. Adults who survived a COVID-19 critical illness (COVID group) during the first two waves in 2 hospitals were contacted by phone 1-y after discharge. They were compared to non-COVID-19 ICU survivors. A standardized assessment focused on quality of life (EQ-5D-3L), autonomy for activities of daily living (Barthel Index), and physical activity quantification (IPAQ-SF). Patients rated their 1-y and pre-ICU status. We included 220 survivors (132 COVID and 88 NC). Their age and severity scores were similar. ICU stay was shorter in NC group (3 [3-6] d) than in COVID group (8 [4.2-16.7] d) (p = 0.001). Proportions of organ supports were similar in the two groups. At 1-y, a significant reduction in EQ-5D-3L total score, in Barthel Index and in physical activity was observed in both groups, compared to the respective baseline values. Dependency (Barthel < 100) was observed in at least 35% of survivors at 1-y. Independently of the critical illness, HRQoL, autonomy and physical activities at 1-y were still significantly inferior to the pre-ICU values.

Automatized lung disease quantification in patients with COVID-19 as a predictive tool to assess hospitalization severity.

The pandemic of COVID-19 led to a dramatic situation in hospitals, where staff had to deal with a huge number of patients in respiratory distress. To alleviate the workload of radiologists, we implemented an artificial intelligence (AI) - based analysis named CACOVID-CT, to automatically assess disease severity on chest CT scans obtained from those patients. We retrospectively studied CT scans obtained from 476 patients admitted at the University Hospital of Liege with a COVID-19 disease. We quantified the percentage of COVID-19 affected lung area (% AA) and the CT severity score (total CT-SS). These quantitative measurements were used to investigate the overall prognosis and patient outcome: hospital length of stay (LOS), ICU admission, ICU LOS, mechanical ventilation, and in-hospital death. Both CT-SS and % AA were highly correlated with the hospital LOS, the risk of ICU admission, the risk of mechanical ventilation and the risk of in-hospital death. Thus, CAD4COVID-CT analysis proved to be a useful tool in detecting patients with higher hospitalization severity risk. It will help for management of the patients flow. The software measured the extent of lung damage with great efficiency, thus relieving the workload of radiologists.

Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D.

Exercise Limitation after Critical Versus Mild COVID-19 Infection: A Metabolic Perspective.

Exercise limitation in COVID-19 survivors is poorly explained. In this retrospective study, cardiopulmonary exercise testing (CPET) was coupled with an oxidative stress assessment in COVID-19 critically ill survivors (ICU group). Thirty-one patients were included in this group. At rest, their oxygen uptake (VO2) was elevated (8 [5.6-9.7] mL/min/kg). The maximum effort was reached at low values of workload and VO2 (66 [40.9-79.2]% and 74.5 [62.6-102.8]% of the respective predicted values). The ventilatory equivalent for carbon dioxide remained within normal ranges. Their metabolic efficiency was low: 15.2 [12.9-17.8]%. The 50% decrease in VO2 after maximum effort was delayed, at 130 [120-170] s, with a still-high respiratory exchange ratio (1.13 [1-1.2]). The blood myeloperoxidase was elevated (92 [75.5-106.5] ng/mL), and the OSS was altered. The CPET profile of the ICU group was compared with long COVID patients after mid-disease (MLC group) and obese patients (OB group). The MLC patients (n = 23) reached peak workload and predicted VO2 values, but their resting VO2, metabolic efficiency, and recovery profiles were similar to the ICU group to a lesser extent. In the OB group (n = 15), no hypermetabolism at rest was observed. In conclusion, the exercise limitation after a critical COVID-19 bout resulted from an altered metabolic profile in the context of persistent inflammation and oxidative stress. Altered exercise and metabolic profiles were also observed in the MLC group. The contribution of obesity on the physiopathology of exercise limitation after a critical bout of COVID-19 did not seem relevant.

Prevention of ventilator-associated pneumonia by noble metal coating of endotracheal tubes: a multi-center, randomized, double-blind study

Background Ventilator-associated pneumonia (VAP) causes increased mortality, prolonged hospital stay and increased healthcare costs. Prevention of VAP in intensive care units (ICUs) is currently based on several measures, and application of noble metal coating on medical devices has been shown to inhibit the bacterial adherence of microorganisms to the surface. The objective of this study was to evaluate the potential benefit of noble metal coating of endotracheal tubes for the prevention of VAP. Methods This was a multi-center, randomized, controlled, double-blind, prospective study including ventilated patients from nine ICUs from four hospital sites in Belgium. Patients were randomly intubated with identical appearing noble metal alloy (NMA) coated (NMA-coated group) or non-coated (control group) endotracheal tubes (ETT). Primary endpoint was the incidence of VAP. Secondary endpoints were the proportion of antibiotic days during ICU stay and tracheal colonization by pathogenic bacteria. Results In total, 323 patients were enrolled, 168 in the NMA-coated group and 155 in the control group. During ventilation, VAP occurred in 11 patients (6.5%) in the NMA-coated group and in 18 patients (11.6%) in the control group (p  = 0.11). A higher delay in VAP occurrence was observed in the NMA-coated group compared with the control group by Cox proportional hazards regression analysis (HR 0.41, 95% CI 0.19–0.88, p  = 0.02). The number of antibiotic days was 58.8% of the 1,928 ICU days in the NMA-coated group and 65.4% of the 1774 ICU days in the control group (p  = 0.06). Regarding tracheal colonization, bacteria occurred in 38 of 126 patients in the NMA-coated group (30.2%) and in 37 of 109 patients in the control group (33.9%) (p  = 0.57). Conclusions This study provides preliminary evidence to support the benefit of noble metal coating in the prevention of VAP. A confirmatory study in a larger population would be valuable. Trial registration: Clinical trial number: NCT04242706 (http://www.clinicaltrials.gov)

Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic.

PURPOSE: Many patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3). PATIENTS AND METHODS: All COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine. RESULTS: Among the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 [49-68] years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 [61-80]. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 [6.8-17.7] mg/L). CONCLUSION: The burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.

Cardiopulmonary Exercise Testing in Critically Ill Coronavirus Disease 2019 Survivors: Evidence of a Sustained Exercise Intolerance and Hypermetabolism.

To investigate exercise capacity at 3 and 6 months after a prolonged ICU stay. DESIGN: Observational monocentric study. SETTING: A post-ICU follow-up clinic in a tertiary university hospital in Liège, Belgium. PATIENTS: Patients surviving an ICU stay greater than or equal to 7 days for a severe coronavirus disease 2019 pneumonia and attending our post-ICU follow-up clinic. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary and metabolic variables provided by a cardiopulmonary exercise testing on a cycle ergometer were collected at rest, at peak exercise, and during recovery. Fourteen patients (10 males, 59 yr [52-62 yr], all obese with body mass index > 27 kg/m2) were included after a hospital stay of 40 days (35-53 d). At rest, respiratory quotient was abnormally high at both 3 and 6 months (0.9 [0.83-0.96] and 0.94 [0.86-0.97], respectively). Oxygen uptake was also abnormally increased at 3 months (8.24 mL/min/kg [5.38-10.54 mL/min/kg]) but significantly decreased at 6 months (p = 0.013). At 3 months, at the maximum workload (67% [55-89%] of predicted workload), oxygen uptake peaked at 81% (64-104%) of predicted maximum oxygen uptake, with oxygen pulse and heart rate reaching respectively 110% (76-140%) and 71% (64-81%) of predicted maximum values. Ventilatory equivalent for carbon dioxide remains within normal ranges. The 50% decrease in oxygen uptake after maximum effort was delayed, at 130 seconds (115-142 s). Recovery was incomplete with a persistent anaerobic metabolism. At 6 months, no significant improvement was observed, excepting an increase in heart rate reaching 79% (72-95%) (p = 0.008). CONCLUSIONS: Prolonged reduced exercise capacity was observed up to 6 months in critically ill coronavirus disease 2019 survivors. This disability did not result from residual pulmonary or cardiac dysfunction but rather from a metabolic disorder characterized by a sustained hypermetabolism and an impaired oxygen utilization.

Long-term clinical follow-up of patients suffering from moderate-to-severe COVID-19 infection: a monocentric prospective observational cohort study.

OBJECTIVES: Various symptoms and considerable organ dysfunction persist following infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Uncertainty remains about the potential mid- and long-term health sequelae. This prospective study of patients hospitalized with coronavirus disease 2019 (COVID-19) in Liège University Hospital, Belgium aimed to determine the persistent consequences of COVID-19. METHODS: Patients admitted to the University Hospital of Liège with moderate-to-severe confirmed COVID-19, discharged between 2 March and 1 October 2020, were recruited prospectively. Follow-up at 3 and 6 months after hospital discharge included demographic and clinical data, biological data, pulmonary function tests (PFTs) and high-resolution computed tomography (CT) scans of the chest. RESULTS: In total, 199 individuals were included in the analysis. Most patients received oxygen supplementation (80.4%). Six months after discharge, 47% and 32% of patients still had exertional dyspnoea and fatigue. PFTs at 3-month follow-up revealed a reduced diffusion capacity of carbon monoxide (mean 71.6 ± 18.6%), and this increased significantly at 6-month follow-up (P<0.0001). Chest CT scans showed a high prevalence (68.9% of the cohort) of persistent abnormalities, mainly ground glass opacities. Duration of hospitalization, intensive care unit admission and mechanical ventilation were not associated with the persistence of symptoms 3 months after discharge. CONCLUSION: The prevalence of persistent symptoms following hospitalization with COVID-19 is high and stable for up to 6 months after discharge. However, biological, functional and iconographic abnormalities improved significantly over time.

Outcome Improvement Between the First Two Waves of the Coronavirus Disease 2019 Pandemic in a Single Tertiary-Care Hospital in Belgium.

OBJECTIVES: To compare patient management and outcome during the first and second waves of the coronavirus 2019 pandemic. DESIGN: Single-center prospective cohort study. SETTING: Tertiary-care University Hospital. PATIENTS: All adult patients admitted in either the first (from March 15 to May 15, 2020) or second (from October 1 to November 30, 2020) wave of coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was 30-day mortality. During the second wave of the coronavirus disease 2019 pandemic, 33 patients (4.8%) were transferred due to overcrowding and excluded from analysis. There were 341 (first wave of the coronavirus disease 2019 pandemic) and 695 (second wave of the coronavirus disease 2019 pandemic) coronavirus disease 2019 patients admitted to the hospital, with median age first wave of the coronavirus disease 2019 pandemic as 68 (57-80) and second wave of the coronavirus disease 2019 pandemic as 71 (60-80) (p = 0.15), and similar admission severity. For the first wave of the coronavirus disease 2019 pandemic versus second wave of the coronavirus disease 2019 pandemic, 30-day mortality was 74/341 (22%) and 98/662 (15%) (p = 0.007). In the ward, 11/341 (3.2%) and 404/662 (61%) received dexamethasone (p < 0.001); 6/341 (2%) and 79/662 (12%) received high-flow nasal oxygen (p < 0.0001); 2/341 (0.6%) and 88/662 (13.3%) received remdesivir (p < 0.0001); 249/341 (73%) and 0/662 (0%) received hydroxychloroquine (p < 0.0001); and 87/341 (26%) and 128/662 (19%) (p = 0.024) patients were transferred to ICU. On ICU admission, median Sequential Organ Failure Assessment was 6 (3-7) and 4 (3-6) (p = 0.02). High-flow nasal oxygen was given to 16/87 (18%) and 102/128 (80%) (p < 0.001); 69/87 (79%) and 56/128 (44%) received mechanical ventilation (p < 0.001) with durations 17 days (10-26 d) and 10 days (5-17 d) (p = 0.01). Median ICU length of stay was 14 days (5-27 d) and 6 days (3-11 d) (p < 0.001). Finally, 16/87 (18%) and 8/128 (6%) received renal replacement therapy (p = 0.0055); and 64/87 (74%) and 51/128 (40%) needed vasopressor support (p < 0.001). CONCLUSIONS: The main therapeutic changes between the first wave of the coronavirus disease 2019 pandemic and the second wave of the coronavirus disease 2019 pandemic were use of steroids, unrestrictive use of high-flow nasal oxygen for hypoxemic patients, and transfer of patients to other geographic areas in the case of ICU overcrowding. These changes were associated with a decrease in 30-day mortality, ICU admission, and organ support.

Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study.

BACKGROUND: A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). MATERIAL AND METHODS: Biomarkers of the systemic OSS included antioxidants (9 assays), trace elements (3 assays), inflammation markers (4 assays) and oxidative damage to lipids (3 assays). RESULTS: Blood samples were drawn after 9 (7-11) and 41 (39-43) days of ICU stay, respectively in 3 and 6 patients. Vitamin C, thiol proteins, reduced glutathione, γ-tocopherol, ß-carotene and PAOT® score were significantly decreased compared to laboratory reference values. Selenium concentration was at the limit of the lower reference value. By contrast, the copper/zinc ratio (as a source of oxidative stress) was higher than reference values in 55% of patients while copper was significantly correlated with lipid peroxides (r = 0.95, p < 0.001). Inflammatory biomarkers (C-reactive protein and myeloperoxidase) were significantly increased when compared to normals. CONCLUSIONS: The systemic OSS was strongly altered in critically ill COVID-19 patients as evidenced by increased lipid peroxidation but also by deficits in some antioxidants (vitamin C, glutathione, thiol proteins) and trace elements (selenium).