Histology and cytokine levels in hepatic injury accompanying a case of non-severe COVID-19.

The pathogenesis of liver dysfunction that complicates coronavirus disease 2019 (COVID-19) remains unclear, especially in mild to moderate severity cases. In this case, a novel coronavirus infection was detected by polymerase chain reaction (PCR) in a 76-year-old woman hospitalized after presenting with fever. No other abnormal physical findings were observed, and oxygen administration was not required. Chest computed tomography (CT) showed a ground-glass-like and an infiltrative shadow in the right lung, and moderate COVID-19 was diagnosed. Initially, the fever resolved, and PCR turned negative; however, the fever reappeared on hospitalization day 14, and CT showed pneumonia exacerbation accompanied by new onset of fatty liver. Biochemical testing revealed marked liver dysfunction, accompanied by elevated serum interleukin (IL)-6, IL-10, and tumor necrosis factor-α levels. Physical findings and all laboratory parameters improved after conservative treatment, and she was discharged on day 22. A liver biopsy performed 44 days post-discharge showed T-cell-dominant inflammatory cell infiltration, mainly in the portal region. Some hepatocytes showed fatty degeneration.We report a case of moderate COVID-19 in which histological hepatitis persisted after a substantial period had passed since the initial infection had cleared and associated transaminase elevations had resolved, with a comparison of serum cytokine dynamics.

Randomized placebo-controlled trial of oral tannin supplementation on COVID-19 symptoms, gut dysbiosis and cytokine response.

The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction in the inflammatory state was evident and significantly correlated with microbiota modulation. Among cytokines measured, MIP-1α was significantly decreased with tannin treatment (p=0.03) where it correlated positively with IL-1ß and TNF- α, and negatively with stool Bifidobacterium abundance.

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

Distinct cytokine profiles associated with COVID-19 severity and mortality.

BACKGROUND: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. METHODS: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). RESULTS: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-ß was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. CONCLUSIONS: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.

Immunocytometric analysis of COVID patients: A contribution to personalized therapy?

AIMS: This study aims to cast light on immunocytometric alterations in COVID-19, a potentially fatal viral infection with heterogeneous clinical expression and a not completely defined pathophysiology. METHODS: We studied 35 COVID patients at hospital admission testing by cytofluorimetry a large panel of lymphocyte subpopulations and serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17A and the soluble receptor of IL-17A (IL-17RA). KEY FINDINGS: At hospital admission, total lymphocytes and most T and B subpopulations were reduced in 50-80% of patients, with close relationship to disease severity. While activated T helper 1 (TH1) and TH17 cells resulted normal or higher. Serum IL-6 was increased in all patients, while TNF-α and IL-17A were higher in advanced stages. A patient subset with low severity had very high IL-17RA levels. Tocilizumab treatment caused an increase of IL-17A in 3/6 patients and a reduction in 3 others, while the lymphocyte number increased in 3 patients and did not change in the others. SIGNIFICANCE: Cytofluorimetry revealed a functional exhaustion of most lymphocyte populations in COVID patients not involving activated TH1 and TH17. Consequently, there was a relevant cytokines production that contributes to impair the respiratory inflammation. The increase of TH17 and IL-17 in a subset of cases and the evidence of a significant increase of IL-17RA (that prevents the interaction of IL-17 with the cell receptor) in patients with low severity suggest that some patients could benefit from monoclonal antibodies treatment targeting IL-17 pathway. Immunocytofluorimetric markers may contribute to a personalized therapy in COVID patients.

The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia.

OBJECTIVES: The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. METHODS: Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. RESULTS: 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. CONCLUSIONS: Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.