Patients with COVID-19 Infection and Stroke have Higher than Expected Mortality, Regardless of the Primary Presentation (preprint)

BackgroundCOVID-19 infection is associated with thrombotic events; however, this phenomenon is poorly understood. Few studies have reported the association between COVID-19 and stroke in the hospital setting. MethodsWe retrospectively reviewed and characterized all patients who presented to a single, quaternary medical center between March and December 2020 (N=603). COVID-19 positive patients who developed ischemic or hemorrhagic stroke were included in the analysis (N=66). This cohort was compared with patients who were COVID-19 negative at the time of stroke presentation in the same period (N=537). Statistical significance was evaluated using Pearsons Chi squared test with Yates continuity correction and linear model ANOVA. ResultsSixty-six patients had COVID-19 and Stroke. Of these patients, 22 (33.4%) patients initially presented with stroke and 44 (66.7%) initially presented with COVID-19. Patients who presented with COVID-19 and had a stroke during their hospitalization (COVID-first) had worse outcomes than patients presenting to the hospital with stroke whose COVID test became positive later in the hospitalization (stroke-first). Patients who presented with COVID-19 and had a stroke during their hospitalization had an increased rate of acute renal failure (48.9% vs 19.0%, p=0.021) and need for ventilation (60.0% vs 28.6%, p=0.017). Further, in the COVID-first cohort, the use of heparin prior to the stroke event was not associated with mortality or type of stroke (ischemic or hemorrhagic). ConclusionIn the early pandemic, patients with COVID-19 infection and stroke had a higher mortality rate compared to COVID-19 negative patients with stroke. Among patients with both COVID-19 and stroke, patients presenting with COVID-19 first had worse outcomes than patients presenting with stroke first. The use of heparin prior to the stroke event was not associated with mortality or type of stroke.

Artificial Intelligence (AI) Based Prediction of Mortality, for COVID-19 Patients (preprint)

For severely affected COVID-19 patients, it is crucial to identify high-risk patients and predict survival and need for intensive care (ICU). Most of the proposed models are not well reported making them less reproducible and prone to high risk of bias particularly in presence of imbalance data/class. In this study, the performances of nine machine and deep learning algorithms in combination with two widely used feature selection methods were investigated to predict last status representing mortality, ICU requirement, and ventilation days. Fivefold cross-validation was used for training and validation purposes. To minimize bias, the training and testing sets were split maintaining similar distributions. Only 10 out of 122 features were found to be useful in prediction modelling with Acute kidney injury during hospitalization feature being the most important one. The algorithms performances depend on feature numbers and data pre-processing techniques. LSTM performs the best in predicting last status and ICU requirement with 90%, 92%, 86% and 95% accuracy, sensitivity, specificity, and AUC respectively. DNN performs the best in predicting Ventilation days with 88% accuracy. Considering all the factors and limitations including absence of exact time point of clinical onset, LSTM with carefully selected features can accurately predict last status and ICU requirement. DNN performs the best in predicting Ventilation days. Appropriate machine learning algorithm with carefully selected features and balance data can accurately predict mortality, ICU requirement and ventilation support. Such model can be very useful in emergency and pandemic where prompt and precise

COVID-19-associated acute renal failure in critically ill patients correlates with microthrombosis and renal loss of thrombomodulin (preprint)

Critically ill COVID-19 patients have a high degree of acute kidney injury which develops in up to 85% of patients. We have previously shown that circulating levels of angiopoietin-2 increased in critically ill COVID-19 patients correlated to kidney injury, coagulopathy, and mortality. Furthermore, our experiments showed a causal effect on coagulopathy from angiopoietin-2 binding and inhibition of thrombomodulin mediated anticoagulation. In the current study we hypothesize that renal microthrombi may be a mechanism for reduced renal function in critically ill COVID-19 patients, and that local dysregulation of thrombomodulin and angiopoietin-2 may be involved. To investigate our hypothesis, we utilized postmortem kidney tissue from seven COVID-19 patients treated at the intensive care unit. We evaluated kidney function, thrombosis, tubular injury, fibrosis, glomerulosclerosis, glomerular size as well as renal expression of thrombomodulin and angiopoietin-2. Proximity ligation assay was utilized to evaluate the presence of angiopoietin-2 binding to thrombomodulin. Normal kidney tissue came from the healthy part of six nephrectomies due to cancer. Our experiments show renal thrombosis in 6/7 COVID-19 patients, on average 14.7 (6.9-22.5) thrombi per mm2. Most COVID-19 kidneys had extensive kidney injury, especially tubular necrosis, but also glomerular enlargement, glomerulosclerosis, and tubulointerstitial fibrosis which in some cases most likely resulted from underlying disease. Thrombomodulin expression was reduced in glomeruli and peritubular capillaries in kidneys from COVID-19 patients, whereas no change was found for angiopoietin-2. In summary, our study describes a high degree of acute renal failure, renal microthrombosis, and loss of thrombomodulin in postmortem tissue from critically ill COVID-19 patients.

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury (preprint)

COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

Identification and estimation of mediational effects of longitudinal modified treatment policies (preprint)

We demonstrate a comprehensive semiparametric approach to causal mediation analysis, addressing the complexities inherent in settings with longitudinal and continuous treatments, confounders, and mediators. Our methodology utilizes a nonparametric structural equation model and a cross-fitted sequential regression technique based on doubly robust pseudo-outcomes, yielding an efficient, asymptotically normal estimator without relying on restrictive parametric modeling assumptions. We are motivated by a recent scientific controversy regarding the effects of invasive mechanical ventilation (IMV) on the survival of COVID-19 patients, considering acute kidney injury (AKI) as a mediating factor. We highlight the possibility of "inconsistent mediation," in which the direct and indirect effects of the exposure operate in opposite directions. We discuss the significance of mediation analysis for scientific understanding and its potential utility in treatment decisions.

The Role of Thromboelastography as a Predictor of Acute Kidney Injury in COVID-19 Patients in ICU (preprint)

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

Acute kidney injury outcomes of COVID-19 confirmed patients in a Philippine tertiary hospital: A retrospective study (preprint)

The novel coronavirus (COVID-19) is known to be the fifth pandemic causing massive deaths worldwide. This virus has not only been deeply associated with acute respiratory distress, but also acute kidney injury (AKI). This study describes the baseline characteristics and various outcomes of AKI based on the KDIGO 2012 Clinical Practice Guidelines in patients hospitalized with COVID-19 at a Philippine tertiary hospital. A total of 195 patient records were retrospectively reviewed for the study. Of the 195 patients, 81(42%) patients developed AKI. Significant baseline characteristics included older age (56.28 + 14.12), presence of hypertension (p=0.004), diabetes mellitus (p=0.002), and cardiovascular disease (p=0.003). Also, the use of diuretics, inotropes and antibiotics were more prevalent in patients who developed AKI. Most of the patients who had AKI were categorized as stage 1 (49.38%).  Mechanical ventilation was significantly (p<0.001) more prevalent in patients with AKI (20.99%) compared to patients without AKI (5.26%). There was significantly higher rates (p<0.001) of renal replacement therapy in patients with AKI (30.86%). Lastly, higher mortality rates were observed in patients with AKI (50.62%) versus patients without AKI (12.28%). Our study demonstrated that patients with COVID-19 can develop AKI and tend to have a poorer prognosis.

Renal consequences of the novel coronavirus disease 2019 (COVID-19) and hydrogen sulfide as a potential therapy (preprint)

The novel coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global pandemic which is primarily considered a respiratory illness. However, emerging reports show that the virus exhibits both pulmonary and extra-pulmonary manifestations in humans, with the kidney as a major extra-pulmonary target due to its abundant expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, which facilitate entry of the virus into cells. Acute kidney injury has become prevalent in COVID-19 patients without prior any history of kidney dysfunction. In addition, the virus also worsens kidney conditions and increases mortality of COVID-19 patients with pre-existing chronic kidney disease, renal cancer, diabetic nephropathy, end-stage kidney disease as well as dialysis and kidney transplant patients. In the search for antiviral agents for the treatment of COVID-19, hydrogen sulfide (H2S), the third established member of gasotransmitter family, is emerging as a potential candidate, possessing important therapeutic properties including antiviral, anti-inflammatory, anti-thrombotic and antioxidant properties. A recent clinical study revealed higher serum H2S levels in survivors of COVID-19 pneumonia with reduced interleukin-6 levels compared to fatal cases. In this review, we summarize the global impact of COVID-19 on kidney conditions and discuss the emerging role of H2S as a potential COVID-19 therapy.

Cytokine Storm Fatal Acute Kidney Infection Triggered by COVID-19 (SARS CoV-2) Infection: A Review (preprint)

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

Thrombotic microangiopathy with kidney involvement in a patient with coronavirus disease 2019: A case report and literature review (preprint)

Background and aim: Millions of people worldwide have suffered from coronavirus disease 2019 (COVID-19). COVID-19 can lead to coagulopathy and thrombosis, presenting as pulmonary artery thromboembolism, deep vein thrombosis, and thrombotic microangiopathy (TMA), the latter being a rare finding in affected patients’ kidneys. Prior reports have rarely addressed the pathophysiology, clinical presentations, and therapeutic options in patients with COVID-19-associated TMA. Case presentation: We herein described a case of renal biopsy-proven TMA after COVID-19 in a 36-year-old woman. Initial examination revealed inflammation, acute kidney injury (AKI), anemia, and thrombocytopenia. She was diagnosed with hemolytic uremic syndrome, pulmonary infection, and COVID-19. After treatment, her condition stabilized but remained hemodialysis-dependent after discharge. One week later, she was re-hospitalized, and physical examination showed anemia and bilateral lower extremity edema. Abdominal ultrasound showed increased bilateral kidney echogenicity. Whole-exome sequencing detected an unknown variant of the C3 gene associated with hemolytic uremic syndrome susceptibility type 5/complement C3 deficiency. Kidney biopsy showed renal artery lesions, including small arteriole endothelial swelling, intimal thickening, mucinous degeneration, luminal occlusion, and small arterial wall necrosis. She received plasma exchange and steroids with significant renal function recovery. Conclusion: TMA likely contributed to AKI after COVID-19,thus supporting the notion that TMA plays an important role in the pathogenesis of COVID-19-related kidney injury. When diagnosing and treating COVID-19 patients with abnormal renal function, clinicians should incorporate kidney biopsy and genetic testing for the complement system, identify renal-limited and systemic TMA, and treat accordingly, which can improve patient outcomes.

Connecting the Dots: Systematic Exploration of COVID-19 and Acute Kidney Injury through Meta-Analysis (preprint)

ObjectiveCOVID-19 pandemic is a danger for the whole world. Also, our knowledge about acute kidney injury (AKI) in COVID-19 patients is incomplete. Few studies informed that the problem of AKI is a common complication, but other studies concluded that AKI is only an unusual event during COVID-19 infection. This study using meta-analysis tools aimed to find disease progression and mortality risk in affected population. MethodsWe systematically reviewed the literature on COVID-19 and its association with AKI as per PRISMA guideline. All authors independently performed a literature search until 8th June 2023. We included studies which reported clinical characteristics, incidence of AKI, and the death risk with AKI during COVID-19 infection. FindingsWe have included five studies and all of them reported older age (73-75) and males (67-84.2%) were risk factors for patient illness. COVID-19 patients with AKI had more than five times mortality risk of those without AKI. Diagnosis time after disease onset was 8.5 days (IQR, [4-11]). Fatality time after initial hospital admission was 13.5 days (IQR, 8-17). In non-survivors, systemic inflammation with high temperature, abnormal respiratory rate, acute myocardial injury, and acute respiratory distress syndrome (ARDS) were observed. Abnormal biochemical analytes and immunological markers were observed. ConclusionOur analyses indicate that patients experienced repeated changes in biochemical analytes and immune marker with the progression of the disease. It indicates the requirement of early management and treatment. Further study is required to conclude and to have better knowledge of AKI mechanism with COVID-19 infection.

Acute renal injury in patients with COVID-19, in the critical care unit of a public hospital, Lima-Peru. (preprint)

Objective: To determine the clinical and laboratory characteristics, as well as evaluating the factors associated with mortality in patients with COVID-19 infection and acute kidney injury (AKI) hospitalized in the Intensive Care Unit (ICU) of the Hospital Nacional Arzobispo Loayza. Materials and Methods: Retrospective cohort study, with convenience sampling during the period from April 2020 to March 2021, through the review of medical records data. Inclusion criteria were; patients [≥] 18 years old, with a diagnosis of COVID-19 infection, who were admitted to ICU with normal renal function and developed AKI during their stay in ICU. Exclusion criteria were; patients who developed AKI prior to ICU admission, patients with chronic kidney disease with and without dialysis. Results: A total of 177 medical records that met the inclusion and exclusion criteria were evaluated. The mean age was 57.2+/-13.2 years, 145 (81.4%) were male; comorbidities were: obesity 112(63.3%), arterial hypertension 55 (31.1%) and diabetes mellitus 30(16.9%); the most frequent cause of AKI was hypoperfusion (93%). 83 participants (46.8%) received dialytic support in the intermittent hemodialysis modality. In-hospital mortality was 151 (85.3%) and was higher in the group with stage 3 AKI: 109 (72.2%). The increase in ferritin level (OR: 10.04 (95%CI 4.4-38.46), p<0.001) and APACHE score (OR: 1.75 (95%CI 1.4-2.12), p<0.001), as well as the decrease in PaO2/FiO2 level (OR: 0.85 (95%CI 0.59-0.92), p<0.041, were related to mortality. Conclusions: AKI in ICU patients with COVID-19 infection has a high mortality and the related factors were the increase in APACHE II score and ferritin level, as well as the decrease in PaO2/FiO2 level. Keywords: Acute kidney injury, COVID-19, Intensive care units (MeSH)

Antimicrobial peptides and other potential biomarkers of critical illness in Sars-CoV-2 patients with acute kidney injury (preprint)

Antimicrobial peptides (AMPs) are a complex network of 10-100 amino acid sequence molecules, widely distributed in Nature. Even though more than 300 AMPs have been described in mammals, cathelicidins and defensins remain the most investigated to date. Some publications examined the role of AMPs in COVID-19, but the findings are preliminary and in vivo studies are still lacking. Here, we report the plasma levels of five AMPs (LL-37, -defensin 1, -defensin 3, {beta}-defensin 1 and {beta}-defensin 3) and five cytokines (tumor necrosis factor-, interleukin-1{beta}, interleukin-6, interleukin-10, interferon-gamma and monocyte chemoattractant protein-1), in 15 healthy volunteers, 36 COVID-19 patients without Acute Kidney Injury (AKI) and 17 COVID-19 patients with AKI, since AKI is a well-known marker of worse prognosis in Sars-CoV-2 infections. We found increased levels of -defensin 1, -defensin 3 and {beta}-defensin 3, but not LL-37 or {beta}-defensin 3, in our COVID-19 population, when compared with the healthy controls, in conjunction with higher levels of interleukin-6, interleukin-10, interferon-gamma and monocyte chemoattractant protein-1, putting in evidence that these AMPs and cytokines may have an important role in the systemic inflammatory response and tissue damage that characterizes severe COVID-19.

Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes (preprint)

Background: COronaVIrus Disease 2019 (COVID-19) has been observed to be associated with a hypercoagulable state. Intracardiac thrombosis is a serious complication but has seldom been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis. Methods: COVID-19 inpatients during 2020 were retrospectively identified from the national inpatient sample (NIS) database, and data retrieved regarding clinical characteristics, intracardiac thrombosis, and adverse outcomes. Multivariable logistic regression was performed to identify the clinical factors associated with intracardiac thrombosis and in-hospital mortality and morbidities. Results: A total of 1,683,785 COVID-19 inpatients were identified in 2020 from NIS, with a mean age of 63.8 {+/-} 1.6 years, and 32.2% females. Intracardiac thrombosis was present in 0.001% (1,830) patients. Overall, in-hospital outcomes include all-cause mortality 13.2% (222,695/1,683,785), cardiovascular mortality 3.5%, cardiac arrest 2.6%, acute coronary syndrome (ACS) 4.4%, heart failure 16.1%, stroke 1.3% and acute kidney injury (AKI) 28.3%. The main factors associated with intracardiac thrombosis were a history of congestive heart failure and coagulopathy. Intracardiac thrombosis was independently associated with a higher risk of in-hospital all-cause mortality (OR: 3.32, 95% CI: 2.42-4.54, p<0.001), cardiovascular mortality (OR: 2.95, 95% CI: 1.96-4.44, p<0.001), cardiac arrest (OR: 2.04, 95% CI: 1.22-3.43, p=0.006), ACS (OR: 1.62, 95% CI: 1.17-2.22, p=0.003), stroke (OR: 3.10, 95% CI: 2.11-4.56, p<0.001), and AKI (OR: 2.13 95% CI: 1.68-2.69, p<0.001), but not incident heart failure (p=0.27). Conclusion: Although intracardiac thrombosis is rare in COVID-19 inpatients, its presence was independently associated with higher risks of in-hospital mortality and most morbidities. Prompt investigations and treatments for intracardiac thrombosis are warranted when there is a high index of suspicion and a confirmed diagnosis respectively.

Analysis of nursing diagnoses, interventions, and activities in patients undergoing hemodialysis secondary to COVID-19: a descriptive study / Análise de diagnósticos, intervenções e atividades de enfermagem em pacientes submetidos à hemodiálise secundária à COVID-19: estudo descritivo

OBJETIVO: Analisar os diagnósticos, as intervenções e atividades de enfermagem em pacientes submetidos à hemodiálise secundária à COVID-19. MÉTODO: Estudo descritivo, retrospectivo e de natureza quantitativa. A população do estudo foi representada pelos prontuários de pacientes submetidos à hemodiálise secundária à COVID-19, totalizando cerca de 64 registros. Consultaram-se os dados do instrumento de coleta de dados, bem como dados sociodemográficos, clínicos e indicadores dos diagnósticos de enfermagem. Para análise, utilizou-se da estatística descritiva e inferencial. RESULTADOS: Os principais diagnósticos de enfermagem encontrados foram: risco de infecção, risco de volume de líquidos desequilibrado, déficit no autocuidado para banho/higiene íntima e troca de gases prejudicada. As intervenções e atividades assinaladas foram correspondentes aos diagnósticos traçados. CONCLUSÃO: O estudo possibilitou identificar os principais diagnósticos, as intervenções e atividades de enfermagem em pacientes acometidos pela COVID-19 que desenvolveram lesão renal aguda.

Objective: To analyze nursing diagnoses, interventions, and activities in patients undergoing hemodialysis secondary to COVID-19. METHOD: This is a descriptive, retrospective, and quantitative study. The study population was represented by the medical records of patients undergoing hemodialysis secondary to COVID-19, totaling about 64 records. Data from the data collection instrument, sociodemographic and clinical data, and indicators of nursing diagnoses were consulted. Descriptive and inferential statistics were used for analysis. RESULTS: The main nursing diagnoses found were risk for infection, risk for imbalanced fluid volume, bathing/toileting self-care deficit, and impaired gas exchange. The registered interventions and activities corresponded to the outlined diagnoses. CONCLUSION: The study identified the main diagnoses, interventions, and nursing activities in patients affected by COVID-19 who developed acute kidney injury.

Histopathological findings in renal biopsy of patients with COVID-19 and renal involvement / Hallazgos histopatológicos en biopsia renal de pacientes con COVID-19 y compromiso renal

Introducción. La lesión renal aguda (LRA) en el paciente con COVID-19 ocurre más frecuentemente en presencia de enfermedades crónicas como diabetes, obesidad, hipertensión arterial y enfermedad renal crónica previa, considerándose un fuerte predictor de resultados desfavorables y mortalidad. El propósito de este estudio fue describir las características histopatológicas en biopsias renales de pacientes hospitalizados por COVID-19, que experimentaron algún grado de daño renal durante su hospitalización. Metodología. Se incluyeron 30 pacientes mayores de 18 años, hospitalizados en diferentes centros de atención en Medellín, Colombia, con diagnóstico confirmado de COVID-19, sin antecedente de terapia de reemplazo renal, que durante la infección desarrollaron algún grado de daño renal, y que tuvieran estudio histopatológico de biopsia renal. Se analizaron las características demográficas, formas clínicas de presentación y hallazgos histopatológicos a nivel renal. Resultados. La mayoría de los pacientes eran de sexo masculino (70%). Los antecedentes patológicos más frecuentes fueron la enfermedad renal crónica previa (16,7%), diabetes mellitus (16,7%), trasplante renal (13,3%) y VIH (10%). El 35,7% de los pacientes no tenían ninguna comorbilidad subyacente. La manifestación clínica inicial más frecuente fue la LRA (56,7%). Algunos pacientes tuvieron más de una manifestación clínica inicial. El 100% de los pacientes evaluados tuvieron hallazgos histopatológicos renales, siendo la nefritis tubulointersticial aguda (40%) el más frecuente. Conclusión. Nuestro estudio no descarta una posible asociación del sexo masculino con peores desenlaces en la enfermedad COVID-19. La LRA fue el hallazgo clínico inicial más frecuente. Es posible que los hallazgos histopatológicos del presente estudio puedan ser consecuencia del daño directo a nivel tubulointersticial renal y la mala perfusión renal, dado el estado de choque por la tormenta inflamatoria, el empeoramiento de enfermedades preexistentes, o la superposición clínica con otras entidades. Sin embargo, son necesarios más estudios para dilucidar los mecanismos por los cuales se generan estas lesiones

Acute kidney injury (AKI) in patients with COVID-19 occurs more frequently in the presence of chronic diseases such as diabetes, obesity, hypertension, and previous chronic kidney disease, and is considered a strong predictor of unfavorable outcomes and mortality. The purpose of this study was to describe the histopathological characteristics in kidney biopsies from patients hospitalized for COVID-19, who experienced some degree of kidney damage during their hospitalization. Methodology. We included 30 patients over 18 years of age, hospitalized in different care centers in Medellín, Colombia, with a confirmed diagnosis of COVID-19, without a history of renal replacement therapy, who developed some degree of kidney disease during the infection, and had histopathological study of renal biopsy. Demographic characteristics, clinical manifestations and histopathological findings were analyzed. Results. Most of the patients were male (70%). The most frequent previous pathological findings were chronic kidney disease (16.7%), diabetes mellitus (16.7%), kidney transplant (13.3%) and HIV (10%). 35.7% of the patients did not have any underlying comorbidity. The most frequent initial clinical manifestation was AKI (56.7%). Some patients had more than one initial clinical manifestation. 100% of the patients had renal histopathological findings, with acute tubulointerstitial nephritis (40%) being the most frequent. Conclusion. Our study does not rule out a possible association of the male gender with worse outcomes in COVID-19 disease. AKI was the most common initial clinical finding. It is possible that the histopathological findings of this study may be a consequence of direct damage at the renal tubulointerstitial level and poor renal perfusion due to the inflammatory storm, worsening of pre-existing diseases, or clinical overlap with other entities. However, more studies are needed to elucidate the mechanisms by which these lesions are generated

The Association between COVID-19 Infection and Kidney Damage in a Regional University Hospital.

Background and Objectives: Kidneys are one of the main targets for SARS-CoV-2. Early recognition and precautionary management are essential in COVID-19 patients due to the multiple origins of acute kidney injury and the complexity of chronic kidney disease management. The aims of this research were to investigate the association between COVID-19 infection and renal injury in a regional hospital. Materials and Methods: The data of 601 patients from the Vilnius regional university hospital between 1 January 2020 and 31 March 2021 were collected for this cross-sectional study. Demographic data (gender, age), clinical outcomes (discharge, transfer to another hospital, death), length of stay, diagnoses (chronic kidney disease, acute kidney injury), and laboratory test data (creatinine, urea, C-reactive protein, potassium concentrations) were collected and analyzed statistically. Results: Patients discharged from the hospital were younger (63.18 ± 16.02) than those from the emergency room (75.35 ± 12.41, p < 0.001), transferred to another hospital (72.89 ± 12.06, p = 0.002), or who died (70.87 ± 12.83, p < 0.001). Subsequently, patients who died had lower creatinine levels on the first day than those who survived (185.00 vs. 311.17 µmol/L, p < 0.001), and their hospital stay was longer (Spearman's correlation coefficient = -0.304, p < 0.001). Patients with chronic kidney disease had higher first-day creatinine concentration than patients with acute kidney injury (365.72 ± 311.93 vs. 137.58 ± 93.75, p < 0.001). Patients with acute kidney injury and chronic kidney disease complicated by acute kidney injury died 7.81 and 3.66 times (p < 0.001) more often than patients with chronic kidney disease alone. The mortality rate among patients with acute kidney injury was 7.79 (p < 0.001) times higher than among patients without these diseases. Conclusions: COVID-19 patients who developed acute kidney injury and whose chronic kidney disease was complicated by acute kidney injury had a longer hospital stay and were more likely to die.

Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI. METHODS: PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bioRxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model meta-analysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI. RESULTS: This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group. CONCLUSION: Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.

Serum cystatin C and inflammatory factors related to COVID-19 consequences.

BACKGROUND: Besides impaired respiratory function and immune system, COVID-19 can affect renal function from elevated blood urea nitrogen (BUN) or serum creatinine (sCr) levels to acute kidney injury (AKI) and renal failure. This study aims to investigate the relationship between Cystatin C and other inflammatory factors with the consequences of COVID-19. METHODS: A total of 125 patients with confirmed Covid-19 pneumonia were recruited in this cross-sectional study from March 2021 to May 2022 at Firoozgar educational hospital in Tehran, Iran. Lymphopenia was an absolute lymphocyte count of less than 1.5 × 109/L. AKI was identified as elevated serum Cr concentration or reduced urine output. Pulmonary consequences were evaluated. Mortality was recorded in the hospital one and three months after discharge. The effect of baseline biochemical and inflammatory factors on odds of death was examined. SPSS, version 26, was used for all analyses. P-vale less than 0.05 was considered significant. RESULTS: The highest amount of co-morbidities was attributed to COPD (31%; n = 39), dyslipidemia and hypertension (27%; n = 34 for each) and diabetes (25%; n = 31). The mean baseline cystatin C level was 1.42 ± 0.93 mg/L, baseline creatinine was 1.38 ± 0.86 mg/L, and baseline NLR was 6.17 ± 4.50. Baseline cystatin C level had a direct and highly significant linear relationship with baseline creatinine level of patients (P < 0.001; r: 0.926). ). The average score of the severity of lung involvement was 31.42 ± 10.80. There is a direct and highly significant linear relationship between baseline cystatin C level and lung involvement severity score (r = 0.890, P < 0.001). Cystatin C has a higher diagnostic power in predicting the severity of lung involvement (B = 3.88 ± 1.74, p = 0.026). The mean baseline cystatin C level in patients with AKI was 2.41 ± 1.43 mg/L and significantly higher than patients without AKI (P > 0.001). 34.4% (n = 43) of patients expired in the hospital, and the mean baseline cystatin C level of this group of patients was 1.58 ± 0.90 mg/L which was significantly higher than other patients (1.35 ± 0.94 mg/L, P = 0.002). CONCLUSION: cystatin C and other inflammatory factors such as ferritin, LDH and CRP can help the physician predict the consequences of COVID-19. Timely diagnosis of these factors can help reduce the complications of COVID-19 and better treat this disease. More studies on the consequences of COVID-19 and knowing the related factors will help treat the disease as well as possible.