[Inflammation during COVID-19]

Infection due to SARS-CoV-2 is associated with clinical features of diverse severity. Severe disease includes biological criteria of both inflammation and coagulation activation, and high circulating levels of pro- and anti-inflammatory cytokines. The most critical patients present with acute respiratory distress syndrome and multiple organ failure, resembling bacterial sepsis. Clinical trials have shown that steroids reduce mortality of severe cases, suggesting that inflammation as a mechanism of defense against viral invasion is excessive rather than insufficient. Several molecules targeting more specific pathways than steroids are under evaluation. Those reducing interleukin 6 activity have a certain degree of effectiveness. Anticoagulants and fibrinolytics have moderate impact on the hypercoagulation state. Like for bacterial sepsis, future trials will attempt therapy "individualization" based on biomarkers, but we still lack precision diagnostic tools.

Oxidative Stress Status and its correlation with Redox Status as Measured By An Electrochemical (PAOT®) Methodology: A Pilot Study in Critical COVID-19 Pneumonia Survivors

Background: In most serious COVID-19 forms which required prolonged stay in intensive care unit, pulmonary, cardiovascular, renal, neurological and psychological sequelae have been reported after the infection. All these complications can be sustained by chronic inflammatory problems and/ or increased oxidative stress. Material and Methods: Biomarkers of the systemic oxidative stress status (OSS) including enzymatic and non-enzymatic antioxidants, total antioxidant capacity of plasma (PAOT®-Sore), trace elements, oxidative damage to lipids and inflammation markers, were investigated in 12 patients admitted to a revalidation center for post-19 COVID pneumonia. Results: From blood samples collected two months after hospital discharge and one month after admission to the revalidation center, vitamin C, thiol proteins, reduced glutathione, gamma-tocopherol and beta carotene were significantly decreased compared to reference values. By contrast, lipid peroxides and markers of inflammation (neutrophils, myeloperoxidase) were significantly higher than the norms. Lipid peroxides was strongly correlated with Cu (r = 0.95, P < 0.005) and Cu/Zn ratio (0.66, P = 0.020). Using an electrochemical method (PAOT®), total antioxidant capacity (TAC) evaluated in saliva and urine negatively correlated with copper and lipid peroxides. Similar findings were obtained for PAOT®-skin score. Conclusions: Systemic OSS was strongly altered in patients admitted in revalidation after C0VID-19 infection. This suggests the need for supplementing these patients with antioxidants.

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, β-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).

COVID-19-associated kidney injury is characterized by acute tubular necrosis and capillary congestion with evidence for SARS-CoV-2 in the nephron

BACKGROUND AND AIMS: Kidney damage has been reported in COVID-19 patients. Despite numerous reports about COVID-19-associated nephropathy, the factual presence of the SARS-CoV-2 in the renal parenchyma remains controversial. METHOD: We consecutively performed 16 immediate (≤3h) post-mortem renal biopsies in patients diagnosed with COVID-19. Kidney samples from 5 patients who died from sepsis and were free from COVID-19 were used as controls. Samples were methodically evaluated by 3 pathologists. Virus detection in the renal parenchyma was performed in all samples by bulk RNA RT-PCR (E and N1/N2 genes), immunostaining (nCoV2019 N-Protein), fluorescent in situ hybridization (nCoV2019-S) and electron microscopy. The first (overview) and second (targeted zoom) columns display positive signal for viral RNA in different renal compartments, including proximal and distal tubules, glomeruli and vessels. nCoV2019-S RNA is in green;Lotus tetragonolobus lectin (LTL) is in red;DAPI is in blue. RESULTS: The mean age of our COVID-19 cohort was 68.2±12.8 years, most of whom were males (68.7%). Proteinuria was observed in 53.3% of cases, while acute kidney injury occurred in 60% of cases. Acute tubular necrosis of variable severity was found in all cases, with no tubular or interstitial inflammation. There was no difference in acute tubular necrosis severity between the patients with COVID-19 versus control samples. Congestion in glomerular and peri-tubular capillaries was respectively observed in 56.3 and 87.5% of patients with COVID-19 compared to 20% of controls, with no evidence of thrombi. The nCoV2019 N-Protein was detected in proximal tubules and also at the basolateral pole of scattered cells of the distal tubules in 9/16 cases. In situ hybridization confirmed these findings. RT-PCR of kidney total RNA detected SARS-CoV-2 N gene in one case. Electron microscopy did not show typical viral inclusions. CONCLUSION: Our immediate post-mortem kidney samples from patients with COVID-19 highlight a congestive pattern of acute kidney injury, with no significant glomerular or interstitial inflammation. Immunostaining and in situ hybridization suggest that SARS-CoV-2 is present in various segments of the nephron.

Patients from COVID-19 mostly recover from tubular proteinuria and acute kidney injury after hospital discharge

BACKGROUND AND AIMS: Proteinuria, hematuria and acute kidney injury (AKI) are frequently observed in hospitalized patients with COVID-19. However, few data are available on these parameters after hospital discharge. METHOD: This retrospective, observational and monocentric study included 153 hospitalized patients, in whom urine total proteinuria and a1-microglobulin (a marker of tubular injury) were measured. Thirty patients died. Among the 123 survivors, follow-up urine and creatinine analyses were available for 72 patients (after a median of 51 [19;93] days following hospital discharge). RESULTS: The median proteinuria at hospitalization and follow-up (n=72) was 419 [239;748] and 79 [47;129] mg/g, respectively (p<0.0001). The median concentrations of urinary a1-microglobulin (n=66) were 50 [25;81] and 8 [0;19] mg/g, respectively (p<0.0001). Estimating glomerular filtration rate (eGFR) was lower during the hospitalization compared to the follow-up: 81 [62;92] versus 87 [66;98] mL/min/ 1.73m2 (p=0.0222). At follow-up, a decreased renal function was observed in 10/72 (14%) of patients, with 50% of them presenting decreased renal function before COVID-19 hospitalization and others developing severe AKI and/or proteinuria during hospitalization. CONCLUSION: In most hospitalized patients with COVID-19, proteinuria and eGFR significantly improved after hospital discharge. Only patients who developed severe AKI and/or heavy proteinuria will require a specific follow-up by nephrologists.

Could KL-6 levels in COVID-19 help to predict lung disease?

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. MATERIALS AND METHODS: Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. DISCUSSION AND CONCLUSION: Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary.

[The first wave of COVID-19 in Intensive care]

In December 2019, in Wuhan, a new human infectious pathology was born, COVID-19, consisting above all in pneumoniae, induced by the coronavirus named SARS-CoV-2 because of the respiratory distress it caused (SARS for severe acute respiratory syndrome, and CoV for Coronavirus). A real health and planetary crisis has appeared, much more substantial than that linked to SARS-CoV-1 in 2002-2004 and to MERS-CoV (Middle East Respiratory Syndrome Coronavirus) in 2012. In addition to respiratory damage that can be dramatic, this pathology is complicated by the frequency of cardiovascular, renal and coagulation diseases. Health care systems have had to adapt urgently, in the absence of hindsight from the pathology, and without effective therapeutic weapons. Through this review of the literature, we detail our local practices for the overall management of patients hospitalized in Intensive care.

Correlation anatomoclinique de l'atteinte renale de la COVID-19.

Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2020