Rare and Complex Cardiac Anomalies Associated with 22q11.2 Deletion: An Ultrasonographic Visual Trip from Diagnosis until Delivery (preprint)

The 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder caused by hemizygous microdeletion of the long arm of chromosome 22. It is now known to have a heterogenous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioral phenotypes and psychiatric illness. The purpose of our paper is to present the case of a fetus diagnosed with a rare and complex cardiac malformation (interrupted aortic arch (IAA) type B, large malalignment-type ventricular septal defect (VSD), pulmonary valve dysplasia, aberrant right subclavian artery (ARSA). The result of the genetic testing revealed 22q11.2 deletion and after genetic counselling the patient decided to continue the pregnancy. She was regularly followed until delivery which took place in Germany so that neonatal cardiac surgery could be performed in an experienced center for cardiac malformations. We emphasize on the ultrasound aspects regarding the cardiac anomaly and specific features of 22q11.2DS in a continuous manner from diagnosis until delivery.

Is Modern Medicine in Need of an Overhydration Marker in Kidney Failure? The Accuracy of Available Fluid Overload Markers and the Potential of the New Ones (preprint)

Overhydration (OH) is a common medical problem found in patients with kidney or heart failure, but still a specific marker has not been found. Clinicians today use bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function like NT-pro-BNP, GFR or creatinine levels. New serum markers such as Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are being researched with promising results. The need to discover a more precise marker of overhydration is dire mainly because physical examination is extremely imprecise. Signs and symptoms of fluid overload like edema or gradual increase of body mass are not always present, especially in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation focusing especially on kidney diseases.

Prognostic Significance of Amino Acid and Biogenic Amines Profiling in Chronic Kidney Disease (preprint)

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by LC-MS/MS to determine a metabolic profile of 28 aminoacids (AA) and biogenic amines to test their value as markers of CKD risk and progression. The Kynurenine/Tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient=-0.731, P<0.0001). Models created with Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) containing the metabolic signature showed high goodness of fit and predictability for controls/CKD (R2X:0.73;R2Y:0.92;Q2:0.92) and lower for CDK/ESKD (R2X:0.56;R2Y:0.59;Q2:0.55). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD or CKD/ESKD groups were citrulline (1.67) and tryptophan (1.59), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (P<0.0001), and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (P<0.0001). Plasma concentrations of AA and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

Medical Application of Molecular Hydrogen to Diabetic Kidney Disease: Therapeutic Potential through Improvements in Mitochondrial Function (preprint)

With the rapid increase in diabetes worldwide, the number of patients with diabetic kidney disease (DKD), a complication of diabetes mellitus, is also on the rise. DKD is a major cause of chronic kidney disease progressing to end-stage renal failure; however, current medical treatments for DKD do not achieve satisfactory outcomes. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. H2 was recently shown to exert not only antioxidant, but also anti-inflammatory, cell lethality-regulating, and signal transduction-regulating effects, and is now being applied clinically. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Therefore, we conducted a literature review on animal models and human clinical trials in which H2 showed efficacy against various renal diseases. This literature review and our previous findings collectively suggest that H2 exerts therapeutic effects in patients with DKD by improving mitochondrial function. Future large-scale clinical studies are needed to confirm these findings.

Association between pre-existing conditions and hospitalization, intensive care services and mortality from COVID-19, a cross sectional analysis of an international global health data repository (preprint)

Objective To investigate the association between pre-existing conditions and hospitalization, need for intensive care services (ICU) and mortality due to COVID-19. Methods We used data on all cases recorded in the Global Health Data repository up to the 10th of March 2021 to carry out a cross-sectional analysis of associations between cardiovascular diseases (CVD), hypertension, diabetes, obesity, lung diseases and kidney disease and hospitalization, ICU admission and mortality due to COVID-19. The Global Health repository reported data from 137 countries, but only Brazil, Mexico and Cuba reported more than 10 COVID-19 cases in participants with preexisting conditions. We used multivariable logistic regression to compute adjusted odds ratios (aOR) of the three outcomes for each pre-existing condition in ten-year age groups from 0-9 years and up to 110-120 years. Results The Global Health repository held 25 900 000 records of confirmed cases of COVID-19, of which 2 900 000 cases were from Brazil, Mexico and Cuba. The overall adjusted odds of hospitalization for the selected pre-existing condition were; CVD (OR 1.7, 95%CI 1.7-1.7), hypertension (OR 1.5, 95%CI 1.4-1.5), diabetes (OR 2.2, 95%CI 2.1-2.2), obesity (OR 1.7, 95%CI 1.6-1.7), kidney disease (OR 5.5, 95%CI 5.2-5.7) and lung disease (OR 1.9, 95%CI 1.8-1.9). The overall adjusted odds of ICU admission for each pre-existing condition were; CVD (OR 2.1, 95%CI 1.8-2.4), hypertension (OR 1.3, 95%CI 1.2-1.4), diabetes (OR 1.7, 95%CI 1.5-1.8), obesity (OR 2.2, 95%%CI 2.1-2.4), kidney disease (OR 1.4, 95%CI 1.2-1.7) and lung disease (OR 1.1, 95%CI 0.9-1.3). The overall adjusted odds of mortality for each pre-existing condition were; CVD (OR 1.7, 95%CI 1.6-1.7), hypertension (OR 1.3, 95%CI 1.3-1.4), diabetes (OR 2.0, 95%CI 1.9-2.0), obesity (OR 1.9, 95%CI 1.8-2.0), kidney disease (OR 2.7, 95%CI 2.6-2.9) and lung disease (OR 1.6, 95%CI 1.5-1.7). The odds of each outcome were considerably larger in children and young adults with these preexisting conditions than for adults, especially for kidney disease, CVD, and diabetes. Conclusion This analysis of a global health repository confirms associations between pre-existing diseases and clinical outcomes of COVID-19. The odds of these outcomes are especially elevated in children and young adults with these preexisting conditions.

Phenol-based Chemical Peeling Therapy for Cervico-vaginal Intraepithelial Neoplasia (CIN/VaIN) (preprint)

Objective: This study aimed to validate the use of liquid phenol-based chemical peeling therapy for cervico-vaginal intraepithelial neoplasia (CIN and VaIN), with the goal of circumventing obstetric complications associated with surgical treatment. Methods: A total of 483 eligible women diagnosed with CIN and/or VaIN participated in this study. Participants underwent phenol-based chemical peeling therapy every 4 weeks until disease clearance. Disease clearance was determined by negative Pap tests for four consecutive weeks. HPV genotyping was conducted at the onset of the study and after disease clearance in select cases. Results: Among the 476 participants (excluding those with cancer), the number of treatment sessions until CIN/VaIN clearance ranged from 2 to 49 (median = 7 sessions). Forty-five participants (9.4%) underwent surgical treatments. Seven participants (1.5%) experienced recurrence, presenting with CIN2/VaIN2 or worse lesions; of these, three underwent LEEP, while four repeated the chemical peeling therapy. No obstetrical complications were noted among the 98 pregnancies following this therapy. The findings suggest that phenol-based therapy is safe and effective for CIN, although it requires numerous and lengthy treatments. Factors associated with resistance to this therapy include immune suppression, high-grade lesions, multiple HPV type infection, and direct or passive smoking.

Adverse Drug Events after Kidney Transplantation (preprint)

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk patients with COVID-19 in North West London: aretrospective cohort study using the Discover dataset (preprint)

IntroductionThere is uncertainty regarding how in vitro antibody neutralisation activity translates to the clinical efficacy of sotrovimab against severe acute respiratory syndrome coronavirus 2, although real-world evidence has demonstrated continued effectiveness during both BA.2 and BA.5 predominance. We previously reported descriptive results from the Discover dataset for patients treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per National Health Service (NHS) criteria but who were untreated. This study sought to assess the effectiveness of sotrovimab compared with no early coronavirus disease 2019 (COVID-19) treatment in highest-risk patients with COVID-19. MethodsRetrospective cohort study using the Discover dataset in North West London. Patients had to be non-hospitalised at index, aged [≥]12 years old and meet [≥]1 of the NHS highest-risk criteria for receiving early COVID-19 treatment with sotrovimab. The primary objective was to assess the risk of COVID-19-related hospitalisation and/or COVID-19-related death within 28 days of the observed/imputed treatment date between patients treated with sotrovimab and highest-risk patients who received no early COVID-19 treatment. We also performed subgroup analyses for patients aged <65 and [≥]65 years, patients with renal dysfunction, and by Omicron subvariant prevalence period (BA.1/2 emergence: 1 December 2021-12 February 2022 [period 1]; BA.2 reaching and at its peak: 13 February-31 May 2022 [period 2]; BA.2 falling and BA.4/5 emergence: 1 June-31 July 2022 [period 3]). Inverse probability of treatment weighting based on propensity scores was used to adjust for measured known and likely confounders between the cohorts. Cox proportional hazards models with stabilised weights were performed to assess hazard ratios (HRs). ResultsA total of 599 highest-risk patients treated with sotrovimab and 5,191 untreated highest-risk patients were included. Compared with untreated patients, sotrovimab treatment reduced the risk of COVID-19 hospitalisation or death by 50% (HR=0.50; 95% confidence interval [CI] 0.24, 1.06); however, statistical significance was not reached (p=0.07). In addition, sotrovimab reduced the risk of COVID-19 hospitalisation by 57% (HR=0.43; 95% CI 0.18, 1.00) compared with the untreated group, although also not statistically significant (p=0.051). Among patients aged [≥]65 years and patients with renal disease, sotrovimab treatment was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR=0.11; 95% CI 0.02, 0.82; p=0.03) and 82% (HR=0.18; 95% CI 0.05, 0.62; p=0.007), respectively. In period 1, sotrovimab treatment was associated with a 75% lower risk of COVID-19 hospitalisation or death compared with the untreated group (HR=0.25; 95% CI 0.07, 0.89; p=0.032). In periods 2 and 3, HRs of COVID-19 hospitalisation or death were 0.53 (95% CI 0.14, 2.00; p=0.35) and 0.78 (95% CI 0.23, 2.69; p=0.69), respectively, for the sotrovimab versus untreated groups, but differences were not statistically significant. ConclusionsSotrovimab treatment was associated with a significant reduction in risk of COVID-19 hospitalisation in patients aged [≥]65 years and those with renal disease compared with the untreated cohort. For the overall cohort, the risk of hospitalisation following sotrovimab treatment was also lower compared with the untreated group; however, this did not achieve statistical significance (p=0.051). The risk of hospitalisation and/or death was lower for the sotrovimab-treated cohort across all time periods but did not reach significance for periods 2 and 3.

Safety and Efficacy of Nirmatrelvir/Ritonavir in Advanced Kidney Disease (preprint)

Background: Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ³ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ≥ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Methods: We performed a retrospective cohort study of hospitalized and non-hospitalized patients with a confirmed diagnosis of COVID-19 in Hong Kong, China, for an observation period from 1 January 2022 to 31 December 2022 (during the omicron BA.2 and BA.5 variant wave). Adult COVID-19 patients (age ≥ 18 years) were selected from medical records held by the Hospital Authority of Hong Kong. We included all patients with COVID-19 regardless of disease severity at baseline having chronic kidney disease (CKD) stage 4 or above (i.e with eGFR < 30 ml/min per 1.73m2) with or without dialysis who receive either nirmatrelvir/ritonavir or molnupiravir. Outcomes at day 90 post-treatment of each treatment arm (nirmatrelvir/ritonavir v.s. molnupiravir) were analyzed and compared. All-cause mortality, respiratory outcomes including mechanical ventilation and non-invasive ventilation, cardiovascular events including myocardial infarction and ischemic stroke, and hepatic complications including elevated liver enzymes were analyzed. Time-to-event analysis was performed for the designated outcomes using univariate and multivariate Cox proportional hazard model regression for unadjusted and adjusted hazard ratios (HR).Findings: We included 454 and 5,880 CKD stage 4 or above patients receiving nirmatrelvir/ritonavir and molnupiravir respectively from public clinics and hospitals managed by the Hospital Authority in Hong Kong during the period. At 90 days, 662 (10.4%) patients of the combined cohort experienced all-cause mortality. Nirmatrelvir/ritonavir group had significant lower all-cause mortality than molnupiravir group (6.82% vs 10.7%) with unadjusted HR of 0.67 (95% CI 0.472 - 0.97, p=0.0337*). After adjusting for sex, age, hypertension, diabetes mellitus, history of myocardial infarction and dialysis in multi-variate analysis, nirmatrelvir/ritonavir group was still associated with superior 90-day survival with adjusted HR of 0.60 (95% CI 0.48 - 0.992, p = 0.0452*). Composites of mechanical and non-invasive ventilation rate were similar in nirmatrelvir/ritonavir and molnupiravir groups (0.96% vs 1.10%, p=0.651). Nirmatrelvir/ritonavir group had higher proportion of patients who received non-invasive ventilation (1.10% vs 0.42%, p = 0.0383*) and trended towards fewer patients requiring mechanical ventilation although statistical significance was not reached (0% vs 0.59%, p = 0.996). There were no significant differences in rate of myocardial infarction (0.88% vs 2.14%, p = 0.0844) and ischemic stroke (0.22% vs 0.61%, p = 0.34) between nirmatrelvir/ritonavir and molnupiravir groups. Hepatic impairment, defined by elevated alanine aminotransferase concentration ≥ 2X upper limit of normal (ULN), was present in 1.45% and 0.94% of patients in nirmatrelvir/ritonavir and molnupiravir groups respectively (p=0.523).Interpretation: Nirmatrelvir/ritonavir is safe and efficacious when compared to molnupiravir in patients with advanced kidney disease.Funding: Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong Special Administrative Region, China and Mr. Lee Won Keung Donation Fund.Declaration of Interest: The authors report no conflict of interest.Ethical Approval: The study was approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster. Informed consent from individual patient was waived as the study involved analysis of anonymized data from hospital registry only. The study was performed in compliance with the Declaration of Helsinki.

[Role of Complement in Kidney Diseases - New Aspects]. / Die Rolle des Komplementsystems bei Nierenerkrankungen ­ Neue Aspekte.

Complement is a central part of the immune system. In the human body, complement is responsible for recognition of infectious microbes, for coordinating the adaptive immune response, controlling homeotic reactions and for the non-inflammatory removal of modified self-cells and infectious microbes. Complement is also closely linked to another proteolytic cascade, the coagulation system. Defective activation and altered complement regulation drives pathology of several severe human kidney diseases.This manuscript summarizes the latest developments on the role of complement in kidney diseases, on new complement inhibitors and on recent complement targeting therapies. In particular focusing on diseases (1) atypical Hemolytic Uremic Syndrome, (2) C3 Glomerulopathy, (3) Anti Neutrophil Cytoplasmic Antibody Mediated Vasculitis, (4) IgA Nephropathy, (5) Membranous Glomerulopathy, (6) Systemic Lupus Erythematosus, (7) Transplant rejection and (8) COVID 19 Infection-Triggered Kidney Diseases. More excitement is generated in this field, as more and more complement mediated diseases can be treated. Several complement targeting compounds are approved by the EMA and FDA and an increasing number of new candidates are in late phase clinical trials. In addition, clinical guidelines are developed for Diagnosis and Therapy of complement mediated diseases, new biomarkers are evaluated in clinical studies, and diagnostic guidelines are in development. The recent Covid infections showed a clear link of complement in thrombo inflammation, which ultimately results in kidney damage. These aspects have increased further the focus of complement inhibitors in COVID infections.

Clinical characteristics and outcomes of unvaccinated kidney transplant patients infected with SARS-CoV-2 omicron subvariant BA.5.2 (preprint)

Background  Kidney transplant (KT) recipients, who are chronically immunocompromised, face increased risks due to COVID-19 and lower vaccination rates. Limited knowledge exists regarding the clinical characteristics of unvaccinated KT patients with COVID-19. This study aimed to examine the clinical features and outcomes of unvaccinated KT patients infected with SARS-CoV-2 omicron subvariant BA.5.2.  Methods  The study enrolled 36 unvaccinated KT patients with COVID-19 and compared them to 20 infected control cases without underlying medical conditions. Clinical characteristics, laboratory tests, treatment regimens, and outcomes were analyzed. RT-PCR confirmed SARS-CoV-2 Omicron BA.5.2 subvariant infection.  Results  The KT patients experienced severe disease, with 66.7% classified as severe/critical illness. Dyspnea on admission, lower blood leukocyte and lymphocyte counts, hemoglobin levels, and serum albumin levels were more prevalent in the KT group compared to the control group. Severe/critical illness was associated with factors such as age, diabetes mellitus, lung infection CT score, and elevated levels of D-dimer, IL-6, CRP, Procalcitonin, and ferritin. Blood lymphocyte counts and serum albumin levels were significantly lower in the severe/critical illness group in KT patients. Treatment included discontinuation of anti-metabolic drugs, reduction, or discontinuation of calcineurin inhibitor drugs, antiviral therapy, and early patient-tailored nutritional support. Acute kidney injury was observed in 19.4% of cases, and four patients died during the observation period.  Conclusions  Early diagnosis, personalized treatment regimens, and diligent monitoring are crucial for unvaccinated KT patients with COVID-19. These findings contribute to understanding the clinical characteristics and management of COVID-19 in the KT population.

Assessing the Prevalence of Anemia Post-COVID-19 Infection in Adult Members of a Southeastern U.S. Integrated Healthcare System (preprint)

Background COVID-19 may cause or worsen anemia, leading to fatigue, lower quality of life, increased risk of comorbidities, and significantly associated with worse outcomes in patients hospitalized with COVID-19. Little is known among a community-based population. We aimed to investigate the incidence and risk factors of anemia post-COVID diagnosis in a community-based population. Methods We identified all adult members of KPGA with a confirmed diagnosis of COVID-19 between January 2020 and March 2022 and followed through March 2023. Anemia was defined using hemoglobin (Hgb) labs 180-days (±30-days) and 365-days (±30-days) after COVID-19 diagnosis and sex-specific thresholds. Potential risk factors included demographics and clinical characteristics (defined by diagnosis codes) at the time of COVID-19 diagnosis. Hospitalization with COVID-19 was used as a marker of COVID-19 severity. Logistic regression among individuals not diagnosed with anemia pre-COVID investigated the association between each risk factor and anemia 180- and 365-days post-COVID-19 infection. We stratified fully adjusted model by hospitalization with COVID-19 to assess effect modification. Results We included 3,450 and 3,043 individuals who met the inclusion criteria and had Hgb results available 180- and 365- days post-COVID-19 diagnosis. One-third of our population had anemia 180-days (n=1,100, 32.17%) and 365-days (n=1,007, 33.09%) post-COVID-19, with approximately 11% of the cohort being newly diagnosed cases of anemia. In the fully adjusted models females (vs. males) (OR=1.71, 95% CI: 1.42, 2.06), Black or African American individuals (vs. non-Black individuals) (OR=2.34, 95% CI: 1.98, 2.76), adults diagnosed with kidney disease (OR=1.79, 95% CI: 1.42, 2.25) or diabetes  (OR=1.26, 95% CI: 1.12, 1.64), and adults hospitalized with COVID-19 (OR=1.43, 95% CI: 1.15, 1.78) were more likely to be diagnosed with anemia 365-days after COVID-19 diagnosis. Analyses stratified by hospitalization status showed a possible effect modification between hospitalization status and post-COVID-19 anemia. Discussion Our study showed that one in three people in a community-based population have anemia 180-days and 365-days after their first COVID-19 diagnosis. Anemia can cause fatigue, a lingering symptom of COVID-19 infection. Though more research is needed, ongoing surveillance of COVID-19 patients for anemia may be an important component of management of long COVID-19.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals or no treatment in Scotland (preprint)

Introduction: Severe acute respiratory syndrome coronavirus 2 is constantly evolving. The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe the real-world use of, and clinical outcomes associated with, early COVID-19 treatments among non-hospitalised patients with COVID-19 at highest risk of developing severe disease in Scotland. Methods: Retrospective cohort study of non-hospitalised patients diagnosed with COVID-19 from 1 December 2021 to 25 October 2022, using administrative health data managed by Public Health Scotland and National Records of Scotland. Patients included in the study were aged [≥]18 years, met at least one of the National Health Service highest-risk conditions criteria for early COVID-19 treatment, and had received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of either COVID-19-positive diagnosis or early COVID-19 treatment during the study period. Baseline patient characteristics and acute clinical outcomes in the 28 days following the index date were reported. To protect patient confidentiality, values of [≤]5 were suppressed. Results: A total of 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709 eligible highest-risk untreated). Patients aged [≥]75 years accounted for 6.9% (n=34/492) of the sotrovimab-treated group, 21.0% (n=58/276) of those treated with nirmatrelvir/ritonavir, 16.9% (n=12/71) of those treated with molnupiravir and 13.2% (n=225/1709) of untreated patients. Advanced renal disease was reported for 6.7% (n=33/492) of sotrovimab-treated and 4.7% (n=81/1709) of untreated patients, and five or fewer patients in the nirmatrelvir/ritonavir and molnupiravir cohorts. A high proportion of treated patients did not have a highest-risk condition reported in the database (71.7% for sotrovimab [n=353/492], 85.1% for nirmatrelvir/ritonavir [n=235/276], 85.9% for molnupiravir [n=61/71]). Five or fewer patients in each treated cohort experienced COVID-19-related hospitalisations during the 28-day acute period. For untreated patients, the percentage of COVID-19-related hospitalisations was 3.0% (n=48/1622). All-cause hospitalisations were experienced by 5.3% (n=25/476) of sotrovimab-treated patients, 6.9% (n=12/175) of nirmatrelvir/ritonavir-treated patients and 13.3% (n=216/1622) of untreated patients. Five or fewer patients in the molnupiravir cohort experienced all-cause hospitalisation. There were no deaths within 28 days of index for patients in the treated cohorts. Mortality was 4.3% (n=70/1622) in untreated patients (18.6% [n=13/70] had COVID-19 as the primary cause). In our analyses of outcomes for sotrovimab-treated and untreated patients during BA.1, BA.2 and BA.5 predominance, COVID-19-related hospitalisation rates were consistent, with n[≤]5 for sotrovimab-treated patients in each period. Conclusions: Our findings indicate that sotrovimab was often used amongst patients who were aged <75 years old and had advanced renal disease. Among patients who received early COVID-19 treatment, proportions of all-cause hospitalisation and death within 28 days of treatment were low.

Outcomes of Pediatric End Stage Renal Disease Patients with Moderate To Severe Covid-19 Infection Who Underwent Hemodialysis With Hemoperfusion In A Tertiary Subspecialty Hospital In Metro Manila: A Retrospective Single Center Study (preprint)

BACKGROUND  SARS-COV 2 became a pandemic in the early part of 2020 affecting individuals of all ages. Patients with End Stage Renal Disease who have COVID-19 infection are at higher risk for morbidity and mortality. There are studies on the use of of hemoperfusion in patients with COVID, however, data on its use in the pediatric population are scarce and conflicting.  OBJECTIVE  The objective of this study is to determine the clinical outcomes of pediatric end stage renal disease patients with moderate to severe COVID-19 infection who underwent hemodialysis with hemoperfusion in a tertiary subspecialty hospital in Metro Manila  METHODS  Retrospective cohort study was done. All eligible patients were included in the study. Data collection was conducted through chart review of medical records of ESRD patients <19 years of age admitted at the National Kidney and Transplant Institute from March 1, 2020 to March 1, 2022, presenting with moderate to severe COVID infection. Inflammatory markers and Chest xray were repeated to compare the values from baseline after 1-4 sessions of hemoperfusion. Clinical outcomes were determined in terms of discharge, duration of hospital stay, resolution of symptoms, progression of the severity of COVID infection, and final disposition either death or discharged.  RESULTS  C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Lactate Dehydrogenase (LDH), and Ferritin decreased after 2-3 sessions of hemodialysis with hemoperfusion but the results were not statistically significant. Procalcitonin significantly decreased after the second session (p=0.046). Pneumonia on Chest xray decreased across all sessions. All patients showed clinical resolution of symptoms and were discharged.  CONCLUSION  The combined use of hemodialysis and hemoperfusion can be used as adjunct treatment for moderate to severe COVID infection after maximizing supportive and medical management. Should it be employed, 2-3 sessions are safe to improve the patient’s clinical status.   Keywords: End Stage Renal Disease, COVID-19 infection, hemoperfusion, inflammatory markers

COVID-19 Diagnosis Like an Avalanche Triggers a Series of Adverse Events However Saves a Life in the End (preprint)

Patients diagnosed with cancer are less frequently covered by preventive measures for cardiovascular diseases. The frequent co-occurrence of these diseases makes it necessary to apply parallel diagnostics and cardiological treatment with anti-cancer therapy. Case report: We present a case of a 73-year-old former smoker with hyperlipidemia, type 2 diabetes, and arterial hypertension, after a partial right nephrectomy in 2005 due to kidney cancer, diagnosed with SARS-COV-2 infection in April 2022. Follow-up chest imaging showed a 20 mm focal lesion in the left lung further classified as a small cell neuroendocrine carcinoma. Unexpectedly the patient was hospitalized for ST-segment elevation inferior left ventricular (LV) myocardial infarction treated successfully with coronary angioplasty, however heart failure (HF) with reduced left ventricle ejection fraction was diagnosed. One month later patient required another hospitalization due to the HF decompensation and cardiological treatment was optimized with flozin addition to the standard HF therapy. After cardiological approval chemotherapy was initiated with the cisplatinum-etoposide regimen and continued for 6 months without HF decompensation and significant deterioration of renal function. After that, the patient underwent radical radiotherapy. Follow-up chest computed tomography scans showed regression of the neoplastic lesion. Conclusions: Coincidence of newly recognized cancer and infection might contribute and provoke serious cardiological events . To reduce the risk of cardiovascular complications, early periodic cardiological surveillance and optimal pharmacotherapy are required.

Admission Serum Magnesium Levels Is Associated with Short and Long-Term Clinical Outcomes in COVID-19 Patients.

BACKGROUND: In the face of the global pandemic that the coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. OBJECTIVE: To evaluate the association between serum magnesium (sMg) levels on admission and clinical outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively analyzed all patients admitted to a single tertiary center with a primary de novo diagnosis of COVID-19. Patients were followed for a mean of 10 ± 7 months. Demographic, clinical and laboratory data were collected and compared between five groups of patients according to sMg quintiles on hospital admission. RESULTS: The cohort included 1522 patients (58% male, 69 ± 17 years old). A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, renal dysfunction, higher levels of inflammatory markers and stay in the intensive care unit. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4th quintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p < 0.001 for all). After adjusting for significant clinical parameters indicating severe disease and renal dysfunction, only low sMg state was independently associated with increased mortality (HR = 1.57, p < 0.001). CONCLUSIONS: Both low and high sMg levels were associated with increased mortality in a large cohort of hospitalized COVID-19 patients. However, after correction for renal dysfunction and disease severity, only low sMg maintained its prognostic ability.

Kidney health for all: preparedness for the unexpected in supporting the vulnerable.

As the rate of natural disasters and other devastating events caused by human activities increases, the burden on the health and well-being of those affected by kidney disease has been immeasurable. Health system preparedness, which involves creating a resilient system that is able to deal with the health needs of the entire community during times of unexpected disruptions to usual care, has become globally important. In the wake of the COVID-19 pandemic, there is a heightened awareness of the amplification of negative effects on the renal community. Paradoxically, the complex medical needs of those who have kidney diseases are not met by systems handling crises, often compounded by an acute increase in burden via new patients as a result of the crisis itself. Disruptions in kidney care as a result of unexpected events are becoming more prevalent and likely to increase in the years to come. It is therefore only appropriate that the theme for this year's World Kidney Day will focus on Kidney Health for All: preparedness for the unexpected in supporting the vulnerable.

Use of medicines for covid-19 treatment in patients with loss of kidney function: a narrative review.

Covid-19 has been identified as the cause of acute respiratory disease with interstitial and alveolar pneumonia, but it can affect several organs, such as kidneys, heart, blood, nervous system and digestive tract. The disease-causing agent (Sars-CoV-2) has a binding structure to the angiotensin-converting enzyme 2 (ACE2) receptor, enabling entry into cells that express ACE2, such as the pulmonary alveolar epithelial cells. However, studies also indicate the possibility of damage to renal cells, since these cells express high levels of ACE2. Currently, there is no evidence to indicate a specific treatment for covid-19. Several drugs have been used, and some of them may have their excretion process altered in patients with abnormal kidney function. To date, there are no studies that assist health professionals in adjusting the dose of these drugs. Thus, this study aims to review and discuss the topic, taking into account factors associated with kidney injury in covid-19, as well as pharmacokinetic aspects and dose recommendations of the main drugs used for covid-19.

Covid-19 pandemic: from carnival masks to surgical masks.

Given the high transmissibility of SARS-CoV-2, COVID-19 pandemic has a huge impact on our health system. Even in developed countries, strategic resources soon become insufficient. Although people over 60 and with comorbidities are at greater risk of developing severe forms, younger people may also require precious and scarce care. Hence, the World Health Organization recommend tests - PCR and serological tests - for detecting infected people on a large scale. The most common symptoms are fever, fatigue, dry cough, anorexia, myalgia, and dyspnea, with tomographic pulmonary findings being frequent even in asymptomatic cases. The Brazilian Society of Nephrology has published guidelines for the management of hypertensive, diabetic, dialysis, and transplant patients. In its alerts, care and precautions in dialysis units are also being detailed, both for the health team and for the patients. Although important renal manifestations are not yet evident in the admission of positive cases, recent studies with renal patients and performed in nephrology services are listed here. This pandemic lead us to learn from its progress in order to face new challenges in dialysis clinics, transplant services, and intensive care services.