Intensive care research最新文献

This editorial is to highlight current issues of heart failure management during COVID-19 pandemic.

Background: Since the end of July 2021, SARS-CoV-2 (Delta variant) invaded Henan Province, China, causing a rapid COVID-19 spread in the province. Among them, the clinical features of COVID-19 (Delta Variant)/HIV co-infection have attracted our attention.

Methods: We included 12 COVID-19 patients living with HIV (human immunodeficiency virus) from July 30, 2021 to September 17, 2021 in Henan Province, China. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were dynamically collected from first nucleic acid positive to hospital discharge. Laboratory findings included SARS-CoV-2 viral load, HIV viral load, IgM, IgG, cytokines, lymphocyte subpopulation, ferritin, etc. Statistical analyses were performed using IBM SPSS version 26·0 and GraphPad Prism version 9·0.

Results: It was founded that the low Ct value persisted for about 21 days, and the viral shedding time (turn negative time) of the patients was 32·36 ± 2·643 days. Furthermore, chest CT imaging revealed that lesions were obviously and rapidly absorbed. It was surprising that IgM levels were statistically higher in patients taking azvudine or convalescent plasma than in patients not taking these drugs (P < 0·001, P = 0·0002, respectively). IgG levels were significantly higher in patients treated with the combined medication of BRII/196 and BRII/198 than in those not treated with these drugs (P = 0·0029). IgM was significantly higher in those with low HIV viral load than those with high HIV viral load (P < 0·001). In addition, as treatment progressed and patients' condition improved, IL-17a showed a decreasing trend.

Conclusions: Based on this study, we found that HIV infection might not exacerbate COVID-19 severity.

Supplementary information: The online version contains supplementary material available at 10.1007/s44231-022-00018-z.

Cases of vaccine breakthrough, especially in variants of concern (VOCs) infections, are emerging in coronavirus disease (COVID-19). Due to mutations of structural proteins (SPs) (e.g., Spike proteins), increased transmissibility and risk of escaping from vaccine-induced immunity have been reported amongst the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir was the first to be granted emergency use authorization but showed little impact on survival in patients with severe COVID-19. Remdesivir is a prodrug of the nucleoside analogue GS-441524 which is converted into the active nucleotide triphosphate to disrupt viral genome of the conserved non-structural proteins (NSPs) and thus block viral replication. GS-441524 exerts a number of pharmacological advantages over Remdesivir: (1) it needs fewer conversions for bioactivation to nucleotide triphosphate; (2) it requires only nucleoside kinase, while Remdesivir requires several hepato-renal enzymes, for bioactivation; (3) it is a smaller molecule and has a potency for aerosol and oral administration; (4) it is less toxic allowing higher pulmonary concentrations; (5) it is easier to be synthesized. The current article will focus on the discussion of interactions between GS-441524 and NSPs of VOCs to suggest potential application of GS-441524 in breakthrough SARS-CoV-2 infections.

Supplementary information: The online version contains supplementary material available at 10.1007/s44231-022-00021-4.

Background: Andrographolide (Andro) has been confirmed to ameliorate alveolar hypercoagulation and fibrinolysis inhibition via NF-κB pathway in acute respiratory distress syndrome (ARDS), but the specific target of Andro is unknown.

Purpose: Our aim is to explore the specific target of Andro through which the drug exerted its effects on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS.

Methods: AECII was treated with different doses of Andro for 1 h, and then stimulated with LPS for 24 h. Expressions of tissue factor (TF), plasminogen activator inhibitor (PAI)-1 and tissue factor pathway inhibitor (TFPI) were detected. Concentrations of thrombin-antithrombin complex (TAT), pro-collagen type III peptide (PIIIP), antithrombin III (ATIII) and activated protein C (APC) in cell supernatant were measured by enzyme linked immunosorbent assay (ELISA). NF-κB signaling pathways activation was simultaneously determined. AECII with p65 down-/over-expression were used as control.

Results: Andro effectively inhibited TF and PAI-1 and promoted TFPI expressions on AECII induced by LPS stimulation. Andro also significantly suppressed the productions of TAT and PIIIP but promoted ATIII and APC secretions from the LPS-treated cell. Furthermore, Andro application obviously inhibited NF-κB signaling pathway activation provoked by LPS, as shown by decreased level of phosphorylation (p‑)-IKKβ/IKKβ, p-p65/p65 and p65 DNA binding activity. The effects of Andro on those factors were obviously strengthened by down- but were weakened by up-regulation of p65 gene in AECII cell.

Conclusions: Our data demonstrates that targeting AECII is the mechanism by which Andro ameliorates alveolar hypercoagulaiton and fibrinolytic inhibition via NF-κB pathway in ARDS. Andro is worth to be clinically further studied in ARDS treatment.