The emergence of new viral pathogens necessitates innovative antiviral therapies and vaccines. Traditional approaches, such as monoclonal antibodies and vaccines, are often hindered by resistance, limited effectiveness, and high costs. Here, we develop an engineered probiotic-based antiviral platform using Escherichia coli Nissle 1917 (EcN), capable of providing both mucosal and systemic immunity via oral administration. EcN was engineered to display anti-spike nanobodies or express the Spike-Receptor Binding Domain on its surface. Our findings reveal that EcN with nanobodies effectively inhibits the interaction between spike protein-expressing pseudoviruses and the ACE2 receptor. Furthermore, we observed the translocation of nanobodies to distant organs, facilitated by outer membrane vesicles (OMVs). The oral administration of EcN expressing spike proteins induced a robust immune response characterized by the production of both IgG and IgA, antibodies that blocked the pseudovirus-ACE2 interaction. While SARS-CoV-2 served as a model, this versatile probiotic platform holds potential for developing customizable biotherapeutics against a wide range of emerging pathogens such as influenza virus or respiratory syncytial virus (RSV) by engineering EcN to express viral surface protein or neutralizing nanobodies demonstrating its versatility as a next-generation mucosal vaccine strategy.

Acute kidney injury (AKI) serves as an independent risk factor for chronic kidney disease (CKD) and hastens its progression. However, effective early diagnosis and treatment methods for AKI are still limited in clinical practice. There is a pressing need to develop fast, effective, and noninvasive diagnostic methods for AKI, as well as treatments that reduce nephrotoxicity. DNA nanotechnology, utilizing the programmable properties of DNA to engineer nanostructures and nanodevices, has achieved significant advancements in disease diagnosis and treatment. The application of DNA nanotechnology for kidney disease, particularly AKI, has been increasingly explored. This review encompasses the advancement of rapid and highly sensitive detection methods for AKI biomarkers, alongside the development of targeted drug delivery systems to the kidneys. These innovations facilitate precise treatment while minimizing adverse drug effects. The review underscores the progress in employing DNA nanotechnology for AKI diagnosis and treatment. Initially, we examine DNA nanotechnology-based strategies for AKI diagnosis, with an emphasis on biomarker detection. Subsequently, we delve into the therapeutic applications of DNA nanotechnology in AKI, highlighting targeted drug delivery and reduced toxicity. Finally, we offer insights into the challenges and opportunities associated with the clinical application of DNA nanotechnology in AKI management.

Hypokalemia is a prevalent complication of COVID-19 patients with acute kidney injury (AKI); however, mechanisms have yet to be fully understood. By single-nucleus RNA sequencing, we found that COVID-19 patients with AKI were associated with a marked upregulation of the epithelial sodium channel (ENaC) in the renal tubular epithelial cells (TECs). By using a mouse model of AKI induced by kidney-specific overexpressing SARS-CoV-2 N protein, we detected that overexpression of renal SARS-CoV-2 N protein could induce hypokalemia and AKI, which was associated with the upregulation of ENaC, ROMK, and BK proteins. Functionally, a patch-clamp study revealed that the overexpression of SARS-CoV-2 N protein largely increased the ENaC current in the TECs. Mechanically, we uncovered that kidney-specific overexpressing SARS-CoV-2 N protein could activate ENaC to cause hypokalemia and AKI directly by binding to the ENaCα and ENaCγ subunits and indirectly by activating the p38 MAPK pathway. Importantly, treatment with an ENaC specific inhibitor could protect against SARS-CoV-2 N-induced hypokalemia and AKI, revealing a regulatory role and therapeutic target of ENaC in SARS-CoV-2 N-induced hypokalemia and AKI. In conclusion, hypokalemia in COVID-19 AKI is induced by SARS-CoV-2 N protein via the ENaC-dependent mechanism. Targeting ENaC may offer a novel therapy for COVID-19 patients with AKI.

Background/Objectives: Vancomycin, a glycopeptide antibiotic used for gram-positive infections, is associated with acute kidney injury (AKI). Therapeutic drug monitoring (TDM) is recommended to minimize this risk while ensuring therapeutic efficacy. This study evaluated whether AUC-guided monitoring improved patient safety compared to traditional trough-guided monitoring. Methods: A retrospective observational cohort study was conducted at the University Medical Centre Maribor, Slovenia, involving patients receiving intravenous vancomycin. One cohort was managed using trough-guided monitoring (n = 85), while the other was monitored using the AUC-guided approach (n = 139). The primary outcome was AKI incidence, and secondary outcomes included renal replacement therapy and mortality. Risk factors for AKI were identified, and pharmacokinetic parameters were evaluated at vancomycin therapy initiation and steady state. Results: The incidence of AKI was 20% in the trough-guided group and 18% in the AUC-guided group (p = 0.727). Secondary outcomes were similar in both cohorts. Risk factors for AKI included older age (OR 1.04; p = 0.042), higher steady-state AUC (OR 1.01; p < 0.001), longer duration of concomitant nephrotoxic therapy (OR 1.06; p = 0.019), and concomitant use of loop diuretics (OR 2.46; p = 0.045). Steady-state AUC values and trough levels (AUC0-24ss, AUC24-48ss, AUC0-48ss, and Cmin48ss) were significantly lower in the AUC-guided group, which was further reflected in the lower percentage of patients exceeding the AUC > 600 mg·h/L threshold at steady state. Conclusions: Although AKI incidence was lower in the AUC-guided group, the difference did not reach statistical significance. However, lower AUC values and trough levels in the AUC-guided group at steady state suggest a trend toward reduced vancomycin exposure and toxicity.

Coronavirus 2019 (COVID-19) is an infectious disease caused by a novel coronavirus, SARS-CoV-2. Acute kidney injury (AKI) affects approximately 20-40% of patients with COVID-19 admitted to the intensive care unit (ICU), and it is a complication that has been linked to increased morbidity and mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury.

Articles were searched from databases such as PubMed, Google Scholar, and Cochrane Library till June 2023. Pooled sensitivity, specificity, area under the curve (AUC), diagnostic odds ratio (DOR), and summery receiver operating curve (SROC) were calculated with 95% confidence interval. I2 statistics and Chi-square test were used to look for the heterogeneity in between studies. Meta-regression was conducted to look for the source of heterogeneity and GRADE analysis was performed to look for the certainty of evidence.

Altogether, eight studies were selected (4 serum/5 urine), out of which one study had both serum and urine NGAL data. The total sample size was 1,067 (349 serum/718 urine). For serum and urine NGAL, the pooled sensitivity was 0.79 (95% CI: 0.72-0.84) and 0.75 (95% CI: 0.68-0.80), pooled specificity was 0.87 (95% CI: 0.81-0.91) and 0.85 (95% CI: 0.77-0.91), DOR was 24 (95% CI: 14-43), and 17 (95% CI: 9-32) and AUC was 0.90 (95% CI: 0.87-0.92) and 0.80 (95% CI: 0.76-0.83), respectively.

Both serum and urine NGAL have favourable pooled sensitivity, specificity, DOR and AUC for the diagnosis of AKI in COVID-19 infection, however, with low certainty of evidence.

Viral mutations and immune dysfunction still lead to recurrent infections of COVID-19 in cancer patients. Our aim in this study was to explore the differences in cumulative risk of COVID-19 death from different cancer types and characterise clinical and demographic factors associated with COVID-19 death.

We conducted a population-based study using the National Cancer Database, which included all cancer types. We calculated age-standardised mortality, cancer mortality, and COVID-19 mortality. Further, we employed a multivariate competing risk analysis to calculate the cumulative risk of COVID-19 death in different cancer types.

5.3% of cancer patients suffered from COVID-19 death. The highest COVID-19 mortality was in chronic lymphocytic leukaemia, while lung and bronchus cancer exhibited lower risk. Notably, years from cancer diagnosis independently predict COVID-19 death. The hazard ratios (HR) in different types of cancers were as follows: lung and bronchus cancer HR = 1.29 (95% confidence interval (CI) = 1.20-1.40, P < 0.001), colon and rectum cancer HR = 1.22 (95% CI = 1.16-1.29, P < 0.001), urinary bladder cancer HR = 1.22 (95% CI = 1.15-1.30, P < 0.001), non-Hodgkin lymphoma HR = 1.17 (95% CI = 1.11-1.23, P < 0.001), kidney cancer HR = 1.15 (95% CI = 1.06-1.24, P < 0.001), and breast cancer HR = 1.11 (95% CI = 1.06-1.16, P < 0.001). Radiotherapy, chemotherapy, and surgical resection did not significantly correlate with COVID-19 death.

We revealed the burden of COVID-19 death across different cancer types. COVID-19 mortality was highest in chronic lymphocytic leukaemia and prostate cancer, while patients with lung and bronchus cancer had a lower risk. Years from diagnosis independently predict COVID-19 death. Based on the results, we support more prompt risk assessment and treatment for various types of cancer.

To assess incidence, risk factors and impact of acute kidney injury(AKI) within 48 h of intensive care unit(ICU) admission on ICU mortality in patients with SARS-CoV-2 pneumonia. To assess ICU mortality and risk factors for continuous renal replacement therapy (CRRT) in AKI I and II patients.

Retrospective observational study.

Sixty-seven ICU from Spain, Andorra, Ireland.

5399 patients March 2020 to April 2022.

Demographic variables, comorbidities, laboratory data (worst values) during the first two days of ICU admission to generate a logistic regression model describing independent risk factors for AKI and ICU mortality. AKI was defined according to current international guidelines (kidney disease improving global outcomes, KDIGO).

Of 5399 patients included 1879 (34.8%) developed AKI. These patients had higher ICU mortality and AKI was independently associated with a higher ICU mortality (HR 1.32 CI 1.17-1.48; p < 0.001). Male gender, hypertension, diabetes, obesity, chronic heart failure, myocardial dysfunction, higher severity scores, and procalcitonine were independently associated with the development of AKI. In AKI I and II patients the need for CRRT was 12.6% (217/1710). In these patients, APACHE II, need for mechanical ventilation in the first 24 h after ICU admission and myocardial dysfunction were associated with risk of needing CRRT. AKI I and II patients had a high ICU mortality (38.5%), especially if CRRT were required (64.1% vs. 34,8%; p < 0.001).

Critically ill patients with SARS-CoV-2 pneumonia and AKI have a high ICU mortality. Even AKI I and II stages are associated with high risk of needing CRRT and ICU mortality.

To investigate the predictive power of the BUN/albumin ratio (BAR) measured in the emergency department (ED) for the requirement of renal replacement therapy (RRT) in patients admitted to the intensive care unit (ICU) with severe COVID-19 pneumonia and acute kidney injury (AKI).

The study included 117 patients with AKI who were admitted to the ICU and had COVID-19 pneumonia detected on chest computed tomography (CT) taken in the ED's pandemic area between November 1, 2020, and June 1, 2021. The predictive power of laboratory values measured at the time of ED admission for the requirement of RRT was analyzed.

Of the patients, 59.8% (n = 70) were male, with an average age of 71.7 ± 14.8 years. The mortality rate of the study was 35% (n = 41). During follow-up, 23.9% (n = 28) of the patients required RRT. Laboratory parameters measured at the time of ED admission showed that patients who required RRT had significantly higher BAR, BUN, and creatinine levels, and significantly lower albumin levels (all p < 0.001). ROC analysis to determine the predictive characteristics for RRT requirement revealed that the BAR had the highest AUC value (AUC, 0.885; 95% CI 0.825-0.945; p < 0.001). According to the study data, for BAR, a cut-off value of 1.7 resulted in a sensitivity of 96.4% and a specificity of 71.9%.

In patients with severe pneumonia who develop acute kidney injury, the BUN/albumin ratio may guide clinicians early in predicting the need for renal replacement therapy.

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.

Recent reports have revealed that nephropathy leading to kidney injury (KI) is a prevalent complication of COVID-19 and is linked to high mortality and morbidity in diabetes mellitus type II (DM-T-II) patients. This systematic literature review and meta-analysis aimed to critically analyze existing studies and evidence on the impact of COVID-19 on nephropathy and kidney injury in diabetes mellitus type II (DM-T-II) patients.

A systematic search was conducted in the Web of Science (WoS), PubMed and Cochrane databases for relevant studies published between March 2020 and July 2023. To ensure the integrity of the systematic literature review and meta-analysis, observational studies that specifically reported post-COVID-19 kidney injury in DM-T2 patients were included, whereas we did not include articles in the press, meta-analyses, case reports, case series, Diabetes Type-I articles or non-English papers. The primary outcome was kidney injury in patients with type II diabetes after contracting COVID-19. The protocol for this study was published on PROSPERO (registration number CRD42023413887).

Initially, 6,339 articles were included in the search, from which only 6 observational studies were selected by following the 2020 PRISMA statement. The quality of the evidence was assessed by a tool provided by the National Institutes of Health (observational studies). The total number of participants included in the studies was 14,723. Our systematic literature review and meta-analysis provide compelling evidence that kidney injury is a prevalent complication of COVID-19 infection in the type II diabetes population, with a pooled odds ratio of 2.27 (95% CI: 2.05-2.51; p < 0.00001), often necessitating hospitalization and hemodialysis in severe cases.

Covid-19 is associated with a two-fold increase in nephropathy and acute kidney injury in diabetes mellitus type 2 patients compared to non-diabetic patients. This implies that kidney injury is more likely to occur in diabetes mellitus type 2 patients post Covid infection.

Pneumothorax is a little known and reported complication of COVID-19. These patients have poorer general outcomes and greater respiratory support requirements, longer hospitalization times, and higher mortality rates. The purpose of this study was to determine which factors predict mortality in patients with tube thoracostomy diagnosed with COVID-19, admitted to the COVID-19 intensive care unit (ICU), and developing pneumothorax.

This respective, observational study was conducted in all COVID-19 ICUs at the Marmara University Pendik Training and Research Hospital, Türkiye. Patients admitted to the ICU with diagnoses of COVID-19 pneumonia and with chest tubes inserted due to pneumothorax were investigated retrospectively.

One hundred patients with tube thoracostomy were included in the study. Their median age was 68 (57-78), and 63% were men. The median follow-up time was 20 [10-29] days, and the median time from initial reverse transcriptase polymerase chain reaction (RT-PCR) results to tube thoracostomy was 17 [9-23] days. Initial RT-PCR results were positive in 90% of the patients, while 8% were negative, and 2% were unknown. Half the patients exhibited pulmonary involvement at thoracic computed tomography (CT) (n = 50), while 22 patients had COVID-19 reporting and data system (CO-RADS) scores of 5 (22%). Sixty-two patients underwent right tube thoracostomy, 24 left side placement, and 14 bilateral placement. The patients' mean positive end expiratory pressure (PEEP) level was 10.31 (4.48) cm H2O, with a mean peak inspiratory pressure (PIP) level of 26.69 (5.95) cm H2O, a mean fraction of inspired oxygen (FiO2) level of 80.06 (21.11) %, a mean respiratory rate of 23.71 (5.62) breaths/min, and a mean high flow nasal cannula (HFNC) flow rate of 70 (8.17) L/min. Eighty-seven patients were intubated (87%), six used non-rebreathable reservoir masks, four HFNC, two non-invasive mechanical ventilation (NIV), and one a simple face mask. Comorbidity was present in 70 patients, 25 had no comorbidity, and the comorbidity status of five was unknown. Comorbidities included hypertension (38%), diabetes mellitus (23%), cardiovascular disease (12%), chronic obstructive pulmonary disease (5%), malignancy (3%), rheumatological diseases (3%), dementia (2%) and other diseases (9%). Twelve of the 100 patients survived. The median survival time was 20 (17.82-22.18) days, and the median 28-day overall survival rate was 29% (20-38%). The multivariate Cox proportional hazards model indicated that age over 68 (HR = 2.23 [95% CI: 1.39-3.56]; p = 0.001), oxygenation status other than by intubation (HR = 2.24 [95% CI: 1.11-4.52]; p = 0.024), and HCO3- below 22 compared with a normal range of 22 to 26 (HR = 1.95 [95% CI: 1.08-3.50]; p = 0.026) were risk factors associated with mortality in patients in the ICU.

Age over 68, receipt of oxygenation other than by intubation, and HCO3- values lower than 22 in patients with COVID-19 pneumonia emerged as prognostic factors associated with mortality in terms of pneumothorax.

The objective of this study was to determine the impact of the timing of KRT, dichotomized by a temporal criterion or by creatinine level, in patients with COVID-19-related AKI. This was a retrospective study involving 512 adult patients admitted to the ICU. All participants had laboratory-confirmed COVID-19 and a confirmed diagnosis of AKI. The potential predictors were the determination of the timing of KRT based on a temporal criterion (days since hospital admission) and that based on a serum creatinine cutoff criterion. Covariates included age, sex, and the SOFA score, as well as the need for mechanical ventilation and vasopressors. The main outcome measure was in-hospital mortality. We evaluated 512 patients, of whom 69.1% were men. The median age was 64 years. Of the 512 patients, 76.6% required dialysis after admission. The overall in-hospital mortality rate was 72.5%. When the timing of KRT was determined by the temporal criterion, the risk of in-hospital mortality was significantly higher for later KRT than for earlier KRT-84% higher in the univariate analysis (OR = 1.84, 95%, [CI]: 1.10-3.09) and 140% higher after adjustment for age, sex, and SOFA score (OR = 2.40, 95% CI: 1.36-4.24). When it was determined by the creatinine cutoff criterion, there was no such difference between high and low creatinine at KRT initiation. In patients with COVID-19-related AKI, earlier KRT might be associated with lower in-hospital mortality.

Magalhães et al. demonstrated that the incidence of acute kidney injury was high in hospitalized patients with COVID-19 and that the second wave was associated with greater severity; however, the mortality rates were similar between the two periods. This may reflect both the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic to provide greater support to their patients.

◼ Renal involvement was frequent in patients with COVID-19 and related to worse outcomes.

◼ Diuretic use, mechanical ventilation, proteinuria, hematuria, age, and creatine phosphokinase and D-dimer levels were risk factors for acute kidney injury.

◼ Acute kidney injury, mechanical ventilation, elevated SOFA Score, and elevated ATN-ISS were associated with mortality.

◼ The second wave was associated with greater severity; however, the mortality rates were similar between the two periods.

◼ This may reflect the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic.

This study aimed to evaluate the incidence of acute kidney injury in hospitalized Brazilian patients with COVID-19 and identify the risk factors associated with its development and prognosis during the two waves of the disease.

We performed a prospective cohort study of hospitalized patients with COVID-19 at a public university hospital in São Paulo from March 2020 to May 2021.

Of 887 patients hospitalized with COVID-19, 54.6% were admitted to the intensive care unit. The incidence of acute kidney injury was 48.1%, and the overall mortality rate was 38.9%. Acute kidney replacement therapy was indicated for 58.8% of the patients. The factors associated with acute kidney injury were diuretic use (odds ratio [OR] 2.2, 95%CI= 1.2-4.1, p=0.01), mechanical ventilation (OR= 12.9, 95%CI= 4.3-38.2, p<0.0001), hematuria(OR= 2.02, 95%CI= 1.1-3.5, p<0.0001), chronic kidney disease (OR= 2.6, 95%CI= 1.2-5.5, p=0.009), age (OR= 1.03, 95%CI= 1.01-1.07, p=0.02), and elevated creatine phosphokinase (OR= 1.02, 95%CI= 1.01-1.07, p=0.02) and D-dimer levels (OR= 1.01, 95%CI= 1.01-1.09, p<0.0001). Mortality was higher among those with acute kidney injury (OR= 1.12, 95%CI= 1.02-2.05, p=0.01), elevated Sequential Organ Failure Assessment Scores (OR= 1.35, 95%CI= 1.1-1.6, p=0.007), elevated Acute Tubular Necrosis-Injury Severity Score (ATN-ISS; (OR= 96.4, 95%CI= 4.8-203.1, p<0.0001), and who received mechanical ventilation (OR= 12.9, 95%CI= 4.3-38.2, p<0.0001). During the second wave, the number of cases requiring mechanical ventilation (OR= 1.57, 95%CI= 1.01-2.3, p=0.026), with proteinuria (OR= 1.44, 95%CI= 1.01-2.1, p=0.04), and with higher ATN-ISS Scores (OR= 40.9, 95%CI= 1.7-48.1, p=0.04) was higher than that during the first wave.

Acute kidney injury was frequent in hospitalized patients with COVID-19, and the second wave was associated with greater severity. However, mortality rates were similar between the two periods, which may reflect both the effectiveness of vaccines and the constant learning that frontline professionals gained throughout the pandemic to provide greater support to their patients.

RBR-62y3h7.

Acute kidney injury (AKI) and the need for Continuous Renal Replacement Therapy (CRRT) are critically important health concerns. This study analyzes global and regional Internet search queries to understand public attention in AKI and CRRT over time.

We used Google Trends™ to analyze search queries for AKI and CRRT from January 2004 to March 2024. The study examined global trends and detailed insights from the United States, including state-by-state breakdowns. We identified patterns, peaks of attention, and temporal trends in public attention, comparing regional variations across the US and top-ranking countries worldwide.

Global attention in AKI peaked in October 2022, with Portugal, Zambia, and Spain showing the highest regional attention. Within the United States, peak attention was in February 2008. Tennessee, Pennsylvania, and West Virginia were the top states that paid attention to AKI. Attention in CRRT peaked globally in March 2024. South Korea, Saudi Arabia, and Bahrain have led the global attention to CRRT. In the United States, peak attention was in April 2020. West Virginia, Tennessee, and Kentucky showed the highest state-specific attention in CRRT.

This study reveals significant temporal and geographical variations in online search patterns for AKI and CRRT, suggesting evolving public attention to these critical health issues. This knowledge can guide the development of targeted public health initiatives, enhance medical education efforts, and help healthcare systems tailor their approach to improving awareness and outcomes in kidney health across diverse populations.

Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages.

Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1β, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD.

There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1β and TNF-α (p < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (p < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway.

Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair.

This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.

The COVID-19 pandemic is well on its way to reaching endemic status across the globe. While the medical community's understanding of the respiratory complications induced by COVID-19 is improving, there is still much to be learned about the neurological manifestations associated with COVID-19 infection. This review aimed to compile relevant, available evidence of COVID-19-induced neurological complications and to provide information for each complication regarding symptomology, progression patterns, demographic risk factors, treatment, and causative mechanism of action when available. Data for this review was collected using a confined search on PubMed using the keywords ["COVID-19" OR "SARS-CoV-2"] AND ["neurological complications" OR "olfactory symptoms" OR "gustatory symptoms" OR "myalgia" OR "headache" OR "dizziness" OR "stroke" OR "seizures" OR "meningoencephalitis" OR "cerebellar ataxia" OR "acute myelitis" OR "Guillain Barré Syndrome" OR "Miller Fisher Syndrome" OR "Posterior Reversible Encephalopathy Syndrome"] between 2019 and 2023. A wide range of neurological manifestations impact a significant percentage of COVID-19 patients, and a deeper understanding of these manifestations is necessary to ensure adequate management. The most common neurological complications identified consist of olfactory and gustatory dysfunctions, myalgia, headache, and dizziness, while the most severe complications include stroke, seizures, meningoencephalitis, Guillain-Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome. While this review effectively provides a roadmap of the neurological risks posed to COVID-19 patients, further research is needed to clarify the precise incidence of these complications and to elucidate the mechanisms responsible for their manifestation.

Acute kidney injury (AKI) is a prevalent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a predictor of disease severity and mortality; furthermore, a prompt diagnosis and treatment of this complication may enhance COVID-19 prognosis. Therefore, we aim to investigate potential risk factors for SARS-CoV-2-associated AKI, including SARS-CoV-2 PCR cycle threshold value (CT value), which correlation with AKI is conflicting.

This case-control study included 110 hospitalized patients with SARS-CoV-2-associated AKI as cases and 110 random SARS-CoV-2 hospitalized patients as controls. Reverse transcription real-time PCR of admission nasopharyngeal swabs evaluated E gene cycle thresholds. Additional clinical and paraclinical information extracted from medical records. The patient's status at discharge, and 14 and 30 days after discharge. Therefore, after adjusting for age and gender, the correlation between variables was assessed.

SARS-CoV-2 AKI is significantly associated with age above 60, hypertension, diabetes mellitus, ischemic heart disease, and underlying kidney diseases. Abnormal admission hemoglobin or alkaline phosphatase, proteinuria or hematuria in urine sediment, and abnormal creatinine during hospitalization were the paraclinical features correlated to SARS-CoV-2 AKI. AKI group demonstrated greater in-hospital, 14- and 30-day mortality. Nevertheless, this study did not evidence a correlation between the admission CT value and mortality or AKI.

Admission CT values provide limited information regarding the dynamic viral load and varying hospitalization time points; thus, they may not be reliable for predicting the prognosis and complications of COVID-19 in all populations. Further studies with serial CT measurements or symptom onset time adjustment are recommended.

BACKGROUND: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. METHODS: We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. RESULTS: A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)‍-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. CONCLUSIONS: Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.

Studies showed that the respiratory is not the only system affected by coronavirus 2, while cardiovascular, digestive, and nervous systems, as well as essential organs such as the kidneys, can be affected by this virus. In this review, we have studied the epidemiology, clinical, and laboratory findings on COVID-19 infection renal involvement, mortality, physiopathology, remaining renal sequels after recovery, underlying renal disease, and renal injury due to its treatment. Also, protective measures for kidney injury are explained in three levels. Evidence of viral particles and genome in the urine and renal tubular cells and signs of damage such as microangiopathy, hypercoagulopathy, and fibrosis are found in COVID-19 patients. The result of this study showed, in hospitalized COVID-19 patients, that the rate of acute kidney injury (AKI) was up to 46%, with a mortality ranging from 11 to 96%. A considerable proportion of patients with AKI would remain on renal replacement therapy. Proteinuria and hematuria are observed in 87 and 75% patients, and increased Cr and glomerular filtration rate (GFR) <60 ml/min per 1.73 m2 are observed in 29.6 and 35.3% of the patients, respectively. Remedsivir is considered to have adverse effects on GFR. COVID-19 patients need special attention to prevent AKI. Those with underlying chronic kidney disease or AKI need proper and explicit evaluation and treatment to improve their prognosis and decrease mortality, which should not be limited to the hospitalization period.

Most patients with COVID-19 report experiencing one or more symptoms after acute infection subsides, known as post-acute sequelae of SARS-CoV-2 infection (PASC). Though research has examined PASC after acute COVID-19, few studies have examined PASC over a longer follow-up duration or accounted for rates of symptoms and diagnoses before COVID-19 infection, and included those not actively seeking treatment for PASC. To determine what symptoms and diagnoses are occurring at higher rates after acute COVID-19 infection from a more inclusive sample, we extracted electronic hospital records (EHR) data from 13,033 adults with previously known diagnoses and symptoms.

The sample was comprised of patients who had a positive PCR test for SARS-CoV-2 between March 1, 2020, and December 31, 2020, and follow-up was conducted through November 29, 2021. All patients in the sample had medical appointments ≥4 weeks before and ≥4 weeks after their positive PCR test. At these appointments, all ICD-10 codes recorded in the EHR were classified into 21 categories based on the literature and expert review. Conditional logistic regression models were used to quantify the odds of these symptoms and diagnostic categories following COVID-19 infection relative to visits occurring before infection. The sample was comprised of 28.0% adults over 65 and was 57.0% female. After the positive PCR test, the most recorded diagnoses and symptoms were dyspnea and respiratory failure, myositis, musculoskeletal pain/stiffness, anxiety, and depression.

Results from regression analyses showed increased odds of diagnosis for 15 of the 21 categories following positive PCR. Relative to pre-COVID, the diagnoses and symptoms with the greatest odds after a positive PCR test were loss of smell or taste [OR (95% CI) = 6.20 (3.18-12.09)], pulmonary fibrosis [3.50 (1.59-7.68)], and dyspnea/respiratory failure [2.14 (1.92-2.40)]. Stratification of these analyses by age, gender, race, and ethnicity showed similar results.

The increased symptoms and diagnoses detected in the current study match prior analyses of PASC diagnosis and treatment-seeking patients. The current research expands upon the literature by showing that these symptoms are more frequently detected following acute COVID-19 than before COVID-19. Further, our analyses provide a broad snapshot of the population as we were able to describe PASC among all patients who tested positive for COVID-19.

The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear.

We selected 342 hospitalized patients with COVID-19 diagnosed via polymerase chain reaction testing between February 2020 and October 2022 and who had at least one urinalysis 14-365 days before admission.

Proteinuria before admission was associated neither with oxygen administration nor developing pneumonia in multivariate analysis (odds ratio [OR] 1.03; 95% confidence interval (CI) 0.44-2.40, p = 0.95 and OR 1.01; 95% CI 0.47-2.17, p = 0.98, respectively). Proteinuria on admission was associated both with oxygen administration and developing pneumonia in multivariate analysis (OR 3.29; 95% CI 1.37-7.88, p < 0.01 and OR 3.81; 95% CI 1.68-8.62, p < 0.01, respectively). The percentage of patients with proteinuria on admission was significantly higher than those before admission (37.4% vs. 17.8%; p < 0.01). In the subgroup analysis, proteinuria on admission among patients with eGFR ≥ 60 mL/min/1.73 m2 was associated with both oxygen administration and developing pneumonia (OR 4.86; 95% CI 1.22-19.38, p = 0.03, OR 3.65; 95% CI 1.06-12.58, p = 0.04, respectively). In contrast, proteinuria on admission among patients with eGFR < 60 mL/min/1.73 m2 was associated with developing pneumonia (OR 6.45; 95%CI 1.78-23.35, p = 0.01), not with oxygen administration (OR 3.28; 95% CI 0.92-11.72, p = 0.07).

Although underlying proteinuria before admission was not associated with COVID-19 severity, proteinuria on admission was associated with oxygen demand and developing pneumonia.

The objective of the study is to determine the association of renal impairment (AKI or CKD) with IL-6 levels on mortality, intubation, and length of hospitalization among COVID-19 positive patients.

This is a retrospective cohort study involving chart review of COVID-19 patients with IL-6 levels and admitted from May 2020 to April 2021. The KDIGO criteria was used for determining renal impairment. The subsequent data processing and analysis was carried out using the statistical software, Stata 13.

A total of 1,120 charts were included with patients classified as having AKI (33%), CKD (14%), and no renal impairment (58%). Overall mortality and need for intubation were 27% and 30%, respectively, with average length of stay at 12 days. The IL-6 values were divided into low (0 to less than 51 pg/mL), intermediate (51 to 251 pg/mL), and high (greater than 251 pg/mL) tertiles, which showed acceptable sensitivity and specificity for mortality and need for intubation.

The presence of renal impairment (CKD or AKI) with increasing IL-6 levels had an effect of increasing risk of adverse outcomes; however, within tertile groups, the presence of renal impairment did not significantly change the risk of adverse outcomes. The tertile groups have acceptable sensitivity and specificity for clinical use.

The effects of coronavirus disease 2019 (COVID-19) primarily concern the respiratory tract and lungs; however, studies have shown that all organs are susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may involve multiorgan damage from direct viral invasion through angiotensin-converting enzyme 2 (ACE2), through inflammatory cytokine storms, or through other secondary pathways. This study involved the analysis of publicly accessible transcriptome data from the Gene Expression Omnibus (GEO) database for identifying significant differentially expressed genes related to COVID-19 and an investigation relating to the pathways associated with mitochondrial, cardiac, hepatic, and renal toxicity in COVID-19. Significant differentially expressed genes were identified and ranked by statistical approaches, and the genes derived by biological meaning were ranked by feature importance; both were utilized as machine learning features for verification. Sample set selection for machine learning was based on the performance, sample size, imbalanced data state, and overfitting assessment. Machine learning served as a verification tool by facilitating the testing of biological hypotheses by incorporating gene list adjustment. A subsequent in-depth study for gene and pathway network analysis was conducted to explore whether COVID-19 is associated with cardiac, hepatic, and renal impairments via mitochondrial infection. The analysis showed that potential cardiac, hepatic, and renal impairments in COVID-19 are associated with ACE2, inflammatory cytokine storms, and mitochondrial pathways, suggesting potential medical interventions for COVID-19-induced multiorgan damage.

The Omicron variant has rapidly spread throughout the world compared to the Delta variant and poses a great threat to global healthcare systems due to its immune evasion and rapid spread. Sex has been identified as a factor significantly associated with COVID-19 mortality, but it remains unclear which clinical indicators could be identified as risk factors in each sex group and which sex-specific risk factors might shape the worse clinical outcome, especially for Omicrons. This study aimed to confirm the relationship between sex and the progression of the Omicron variant and to explore its sex-biased risk factors.

We conducted a retrospective study including 1,132 hospitalized patients with the COVID-19 Omicron variant from 5 December 2022 to 25 January 2023 at Shanghai General Hospital, and the medical history data and clinical index data of the inpatients for possible sex differences were compared and analyzed. Then, a sex-specific Lasso regression was performed to select the variables significantly associated with critical illness, including intensive care unit admission, invasive mechanical ventilation, or death. A logistic regression was used to construct a sex-specific predictive model distinctively for the critical illness outcome using selected covariates.

Among the collected 115 clinical indicators, up to 72 showed significant sex differences, including the difference in merit and the proportion of people with abnormalities. More importantly, males had greater critical illness (28.4% vs. 19.9%) and a significantly higher intensive care unit occupancy (20.96% vs. 14.49%) and mortality (13.2% vs. 4.9%), and males over 80 showed worse outcomes than females. Predictive models (AUC: 0.861 for males and 0.898 for females) showed 12 risk factors for males and 10 for females. Through a comprehensive sex-stratified analysis of a large cohort of hospitalized Omicron-infected patients, we identified the specific risk factors for critical illness by developing prediction models.

Sex disparities and the identified risk factors should be considered, especially in the personalized prevention and treatment of the COVID-19 Omicron variant.

COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49-83.87%), GI bleeding/hemorrhage (IR: 0.47-10.6%), hepatic ischemia (IR: 1.0-7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5-90.9%), anosmia (IR: 4.9-79.6%), dysgeusia (IR: 2.8-83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19-35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5-68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2-55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9-16.7%), and coagulopathy/venous thromboembolism (IR: 19-34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications.

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.

To construct and validate nomogram models that predict the incidence of delirium in elderly patients with non-severe SARS-CoV-2 infection.

Elderly patients (≥65y) tested positive for SARS-CoV-2 infection at the hospital were included. We used the 3-min diagnostic Confusion Assessment Method for delirium diagnosis. Least absolute shrinkage and selection operator (LASSO) logistical regression analysis was performed to explore potential independent influencing factors of delirium. A predict model visualized by nomogram was constructed based on the confirmed variables. The predictive accuracy and clinical value of the model were evaluated using receiver operating characteristic (ROC) curves.

The data of 311 elderly patients were analyzed, of whom 73 (23.47%) patients were diagnosed with delirium. Three independent influencing factors of delirium were confirmed: age (OR1.16,1.11-1.22), Glomerular filtration rate (OR 0.98,0.97-0.99), platelet-large cell ratio (1.06,1.02-1.10). These parameters were used to create a nomogram to predict the development of delirium, which showed good predictive accuracy confirmed by the ROC curves (AUC 0.82,0.76-0.88).

We construct a credible nomogram to predict the development of delirium in elderly patients with Non-severe SARS-CoV-2 infection. Our finding may be useful to physicians in early prevention and treatment of delirium.

The purpose of this study is to evaluate the interference of the continuous use of drug classes in the expression of biomarkers during the first week of hospitalization and in the prognosis of patients with COVID-19.

The patients diagnosed with COVID-19 and confirmed with SARS-CoV-2 by RT-qPCR assay underwent the collection of fasting whole blood samples for further analysis. Other data also extracted for this study included age, sex, clinical symptoms, related comorbidities, smoking status, and classes of continuous use. Routine serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, N-terminal fragment of B-type natriuretic peptide, and cardiac troponin, were measured.

In this cross-sectional study, a total of 176 patients with COVID-19 hospitalizations were included. Among them, 155 patients were discharged (88.5%), and 21 patients died (12%). Among the drug classes evaluated, we verified that the continuous use of diuretic 4.800 (1.853-11.67) (p = 0.0007) and antihypercholesterolemic 3.188 (1.215-7.997) (p = 0.0171) drug classes presented a significant relative risk of death as an outcome when compared to the group of patients who were discharged. We evaluated biomarkers in patients who used continuous antihypercholesterolemic and diuretic drug classes in the first week of hospitalization. We observed significant positive correlations between the levels of CRP with cardiac troponin (r = 0.714), IL-6 (r = 0.600), and IL-10 (r = 0.900) in patients who used continuous anticholesterolemic and diuretic drug classes and were deceased. In these patients, we also evaluated the possible correlations between the biomarkers AST, NT-ProBNP, cardiac troponin, IL-6, IL-8, and IL-10. We observed a significantly negative correlations in AST levels with NT-ProBNP (r = -0.500), cardiac troponin (r = -1.00), IL-6 (r = -1.00), and IL-10 (r = -1.00) and a positive correlation with IL-8 (r = 0.500). We also observed significant negative correlation in the levels of NT-ProBNP with IL-10 (r = -0.800) and a positive correlation with cardiac troponin (r = 0.800). IL-6 levels exhibited positive correlations with cardiac troponin (r = 0.800) and IL-10 (r = 0.700).

In this study, we observed that hospitalized COVID-19 patients who continued using anticholesterolemic and diuretic medications showed a higher number of correlations between biomarkers, indicating a poorer clinical prognosis. These correlations suggest an imbalanced immune response to injuries caused by SARS-CoV-2.

Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19. Methods: This was a pilot randomized, double-blind, placebo-controlled trial. Severe COVID-19 patients were randomly assigned to receive intravenous 50 μg/kg (low dose, n = 3), 100 μg/kg (high dose, n = 5) of SY-005 or placebo (n = 5) every 12 h for 7 days. Plasma SY-005 levels were assessed using enzyme-linked immunosorbent assay (ELISA) and the PK parameters were determined using non-compartmental analysis. Results: All patients treated with SY-005 had a normal baseline estimated glomerular filtration rate (eGFR, 104-125 mL/min/1.73 m2). Both low and high doses of SY-005 were cleared within 6 h after intravenous administration. Plasma maximum concentrations (Cmax), half-life, clearance and volume distribution of low and high doses of SY-005 were 402.4 and 848.9 ng/mL, 0.92 and 0.96 h, 7.52 and 15.19 L/h, and 9.98 and 20.79 L, respectively. Daily pre-dose circulating annexin A5 levels were not significantly different when SY-005 was administered at the low or the high dose 12-h intervals. There was no significant effect on activated partial thromboplastin time (aPTT) or INR (international normalized ratio of prothrombin time) during 7 days of SY-005 treatment. Conclusion: SY-005 doses of 50 and 100 μg/kg were detectable and subsequently cleared from the plasma in severe COVID-19 patients with normal baseline renal function. There was no significant plasma SY-005 accumulation 6 h after drug administration and coagulation was not altered during 7 days of treatment. Clinical trials Registration: This study was registered with ClinicalTrials.gov (NCT04748757, first posted on 10 February 2021).

The health crisis due to Covid-19 led to the search for therapeutics that could improve the evolution of the disease. Remdesivir, an antiviral that interferes with viral replication, was one of the first to be used for the treatment of this pathology.

To determine clinical course and mortality of patients with severe SARS-CoV-2 pneumonia treated with remdesivir, in comparison of those who didn't receive the medication.

Retrospective cohort study, with medical records review of COVID-19 patients, between August 2020 and August 2021. The subjects were divided into two groups, those who received remdesivir before or after admission to intensive care and those who didn't. The primary outcome variable was mortality in intensive care.

Of 214 subjects included, 109 (50,9%) received remdesivir. The median of days for the drug administration was 8 (2-20), IQR: 3. The bivariate analysis prove that the use of remdesivir was related with lower risk of develop Acute Respiratory Distress Syndrome (ARDS) (p = 0,019; OR: 0,521) and lower requirement of mechanical ventilation (p = 0,006; OR:0,450). Additionally, patients treated with remdesivir develop less kidney injury (p = 0,009; OR: 0,441). There was a total of 82 deaths, 29 (26,6%) in the remdesivir group and 53 (50,5%) in the control group [p < 0,001; OR: 0,356 (0,201-0,630)]. All the risk factors associated with mortality in the bivariate analysis were entered into the multivariate analysis by logistic regression, the use of remdesivir remained associated as an independent protective factor to mortality (p = 0.034; OR: 0.429).

Critically ill patients with SARS-CoV-2 pneumonia treated with remdesivir had a lower risk of death and need for mechanical ventilation and develop less ARDS as compared to the control group. No differences were found in the presentation of adverse effects.

Aim: To identify patients at risk of AKI with severe COVID-19 and to guide management strategies according to national and global scientific data for improving kidney-related outcomes.

Materials and Methods: We conducted retrospective study case-control analysing cases of hospitalisation patients with COVID-19 with or without AKI during hospital stay.

Results: In the study, we found that there was a positive correlation between AKI and respiratory insufficiency (0,513 - moderate, p<0,0001), moderate in the case of AKI grade 2 (0.301, <0,001) and mild in the case of AKI grade 1 and 3 correspondingly (0.252, p<0,01; 0.277, <0,001). Lethality (in-hospital death rate) correlated with respiratory insufficiency and AKI (0.733, 0,617; p<0,0001). We found that age had a reverse correlation with AKI and RI (younger patients were more likely to have a higher prevalence of AKI and RI, p<0,001). It was noticed that AKI correlated with the minimal albumin level (-0,35, p=0,016), minimal lymphocyte count (-0.377, p<0,0001), IL-6 (0.201, p=0,035), ferritin (0.34, p <0,0001), maximal CRP (0.439, p<0,0001). There was a mild correlation between Padua Score and AKI (0,232, p<0,01) and PLRI (0,172, p=0,05).

Conclusions: Early assessment of renal dysfunction could be used as a marker of severe outcomes of COVID-19, especially in the case of comorbidities such as metabolic disorders and cardiovascular events. We suggest using the Padua score, assessment of personal lethality risk index (PLRI), and rise of serum creatinine as additional tools for assessment criteria for hospitalisation.

Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes.

We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury.

Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%).

We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.

Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking.

This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo.

In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing.

MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125.

The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.