Severe disseminated infection by hypermucoviscous Klebsiella pneumoniae successfully treated by intensive therapy with continuous hemodiafiltration using AN69ST: A case report and review of the literature.

Klebsiella pneumoniae (Kpn) is one of the most common gram-negative bacilli causing lung, urinary tract, and biliary tract infections. However, as a distinct entity from classic Kpn, hypervirulent Kpn causing liver abscess, endophthalmitis, and lung abscess with poor prognoses has been reported mainly in East and Southeast Asia since the mid-1980s. Although the definition of hypervirulent Kpn is unclear, the hypermucoviscosity of Kpn is considered an important feature of hypervirulence. We present a case of emphysematous pyelonephritis accompanied by septic shock and acute kidney injury caused by hypermucoviscous Kpn infection that was successfully treated by intensive treatment. A 70-year-old woman with type 2 diabetes mellitus was diagnosed with emphysematous pyelonephritis, and string test-positive Kpn was detected in blood and urine cultures and percutaneous catheter drainage fluid from the renal pelvis. The patient was treated with intensive therapies including antibiotics, ventilator management, and continuous hemodiafiltration (CHDF) using AN69ST, which can absorb cytokines. During the course of treatment, the infection was complicated by pyogenic spondylitis, which was cured by antimicrobial therapy, and the patient was transferred to another hospital for rehabilitation on day 119 after admission. Hypermucoviscous Kpn infection often has a severe course, and it is important to initiate multidisciplinary treatment at an early stage, including rifampicin, which is expected to inhibit the viscosity of hypermucoviscous Kpn. In the current case, immediate CHDF using AN69ST was also considered a life-saving treatment because it improved both volume overload and neutrophil-activated hypercytokinemia.

Interpretations of SARS-CoV-2 IgM and IgG antibody titers in the seroepidemiological study of asymptomatic healthy volunteers.

INTRODUCTION: The usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects. METHODS: From June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins. RESULTS: After setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig. CONCLUSIONS: In SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.

ECG Localization Method Based on Volume Conductor Model and Kalman Filtering.

The 12-lead electrocardiogram was invented more than 100 years ago and is still used as an essential tool in the early detection of heart disease. By estimating the time-varying source of the electrical activity from the potential changes, several types of heart disease can be noninvasively identified. However, most previous studies are based on signal processing, and thus an approach that includes physics modeling would be helpful for source localization problems. This study proposes a localization method for cardiac sources by combining an electrical analysis with a volume conductor model of the human body as a forward problem and a sparse reconstruction method as an inverse problem. Our formulation estimates not only the current source location but also the current direction. For a 12-lead electrocardiogram system, a sensitivity analysis of the localization to cardiac volume, tilted angle, and model inhomogeneity was evaluated. Finally, the estimated source location is corrected by Kalman filter, considering the estimated electrocardiogram source as time-sequence data. For a high signal-to-noise ratio (greater than 20 dB), the dominant error sources were the model inhomogeneity, which is mainly attributable to the high conductivity of the blood in the heart. The average localization error of the electric dipole sources in the heart was 12.6 mm, which is comparable to that in previous studies, where a less detailed anatomical structure was considered. A time-series source localization with Kalman filtering indicated that source mislocalization could be compensated, suggesting the effectiveness of the source estimation using the current direction and location simultaneously. For the electrocardiogram R-wave, the mean distance error was reduced to less than 7.3 mm using the proposed method. Considering the physical properties of the human body with Kalman filtering enables highly accurate estimation of the cardiac electric signal source location and direction. This proposal is also applicable to electrode configuration, such as ECG sensing systems.

Reversal of Enantioselectivity in the Conjugate Addition Reaction of Cyclic Enones with the CuOTf/Azolium Catalytic System.

Hydroxyamide-functionalized azolium salt (NHC•HI 4) was evaluated for dual enantioselective control in a Cu-catalyzed asymmetric conjugate addition (ACA) reaction. This investigation was based on our previously reported ACA reaction catalyzed using CuOTf combined with NHC•AgI complex 1. It was revealed that the stereocontrol of the catalytic ACA reaction depended on the order of the addition of the substrates. Additionally, the chiral NHC ligand precursors, substrates, the relationship between the catalyst ee (eecat) and product ee (eepro), and halogen counter anion were completely evaluated. These results suggested that the catalytic performance of the CuOTf/4 system was comparable with that of the CuOTf/1 system. Furthermore, to gain knowledge of the Cu species generated using CuOTf and NHC ligand precursor, the reaction of CuOTf with 1 was investigated. Although obtaining the corresponding NHC•CuX species failed, the corresponding NHC•AuCl complex 11 could be synthesized by allowing 1 to react with AuCl•SMe2.

Transcriptomic variation among six Arabidopsis thaliana accessions identified several novel genes controlling aluminium tolerance.

Differences in the expression levels of aluminium (Al) tolerance genes are a known determinant of Al tolerance among plant varieties. We combined transcriptomic analysis of six Arabidopsis thaliana accessions with contrasting Al tolerance and a reverse genetic approach to identify Al-tolerance genes responsible for differences in Al tolerance between accession groups. Gene expression variation increased in the signal transduction process under Al stress and in growth-related processes in the absence of stress. Co-expression analysis and promoter single nucleotide polymorphism searching suggested that both trans-acting polymorphisms of Al signal transduction pathway and cis-acting polymorphisms in the promoter sequences caused the variations in gene expression associated with Al tolerance. Compared with the wild type, Al sensitivity increased in T-DNA knockout (KO) lines for five genes, including TARGET OF AVRB OPERATION1 (TAO1) and an unannotated gene (At5g22530). These were identified from 53 Al-inducible genes showing significantly higher expression in tolerant accessions than in sensitive accessions. These results indicate that the difference in transcriptional signalling is partly associated with the natural variation in Al tolerance in Arabidopsis. Our study also demonstrates the feasibility of comparative transcriptome analysis by using natural genetic variation for the identification of genes responsible for Al stress tolerance.

Paravascular inner retinal abnormalities in healthy eyes.

PURPOSE: To investigate the prevalence and characteristics of paravascular inner retinal abnormalities in healthy eyes. MATERIALS AND METHODS: In this prospective observational case series, we included 178 healthy eyes (178 patients) with no ocular diseases. Eyes with co-existing ocular diseases, e.g., epiretinal membrane, glaucoma, or high myopia, were excluded from the current study. The posterior pole and paravascular areas of the temporal arcade vessels were comprehensively examined by dense radial scanning of optical coherence tomography (OCT) with the extended field imaging technique. RESULTS: On fundus photography, no inner retinal abnormalities were detected along the temporal arcade vessels. On OCT sections, paravascular inner retinal abnormalities were seen in 77 (43.3%) eyes. In 71 (39.9%) eyes, inner retinal cystoid or fissure-like spaces that had no connection to the vitreous cavity were seen adjacent to the temporal arcade vessels. Most of these lesions were detected only on several consecutive OCT sections. In four (2.2%) eyes, inner retinal cleavages with openings to the vitreous cavity were seen adjacent to the temporal arcade vessels. These lesions were more frequently detected in the inferior hemisphere and along the major retinal veins. No eyes showed typical broad defects of the inner retinal tissue. There were no significant differences in age, gender, visual acuity, refractive error, or axial length between eyes with or without paravascular inner retinal abnormalities. CONCLUSIONS: Paravascular cystoid or fissure-like spaces were frequently seen in the inner retina of healthy eyes. However, we detected no typical paravascular inner retinal defects in healthy eyes.

ASSOCIATION BETWEEN PARAFOVEAL CAPILLARY NONPERFUSION AND MACULAR FUNCTION IN EYES WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To investigate the parafoveal perfusion status of the superficial and deep capillary layer in eyes with resolved branch retinal vein occlusion, and to study its effects on retinal sensitivity. METHODS: In 27 enrolled eyes (27 patients) with resolved branch retinal vein occlusion, superficial and deep capillaries in the macular area (3- × 3-mm, centered on the fovea) were examined with optical coherence tomography angiography. Retinal sensitivity was examined with fundus-monitored microperimetry. RESULTS: Optical coherence tomography angiography clearly showed the parafoveal superficial and deep capillaries individually. On the affected side of retina, 25 eyes (92.6%) showed capillary nonperfusion; 23 (85.2%) in the superficial layer and 22 (81.5%) in the deep layer. Capillary nonperfusions of both layers frequently overlapped and appeared to be connected with each other. Mean (±SD) retinal sensitivity at the superficial capillary nonperfusion was 19.2 ± 6.3 dB, significantly lower than that at the superficial capillary perfusion (24.4 ± 2.8 dB, P < 0.001). Similarly, mean retinal sensitivity at the deep capillary nonperfusion was 20.8 ± 5.0 dB, significantly lower than that at deep capillary perfusion (24.3 ± 2.8 dB, P = 0.0016). Mean retinal sensitivity with superficial capillary nonperfusion was significantly lower than that with deep capillary nonperfusion (P = 0.0226). CONCLUSION: Optical coherence tomography angiography visualized parafoveal capillary nonperfusion in superficial and deep layers individually in eyes with resolved branch retinal vein occlusion. Retinal sensitivity was significantly reduced at these capillary nonperfusions.

Joint genetic and network analyses identify loci associated with root growth under NaCl stress in Arabidopsis thaliana.

Plants have evolved a series of tolerance mechanisms to saline stress, which perturbs physiological processes throughout the plant. To identify genetic mechanisms associated with salinity tolerance, we performed linkage analysis and genome-wide association study (GWAS) on maintenance of root growth of Arabidopsis thaliana in hydroponic culture with weak and severe NaCl toxicity. The top 200 single-nucleotide polymorphisms (SNPs) determined by GWAS could cumulatively explain approximately 70% of the variation observed at each stress level. The most significant SNPs were linked to the genes of ATP-binding cassette B10 and vacuolar proton ATPase A2. Several known salinity tolerance genes such as potassium channel KAT1 and calcium sensor SOS3 were also linked to SNPs in the top 200. In parallel, we constructed a gene co-expression network to independently verify that particular groups of genes work together to a common purpose. We identify molecular mechanisms to confer salt tolerance from both predictable and novel physiological sources and validate the utility of combined genetic and network analysis. Additionally, our study indicates that the genetic architecture of salt tolerance is responsive to the severity of stress. These gene datasets are a significant information resource for a following exploration of gene function.

Prevalence, characteristics, and pathogenesis of paravascular inner retinal defects associated with epiretinal membranes.

PURPOSE: To investigate the prevalence, detailed characteristics, and pathogenesis of paravascular inner retinal defects (PIRDs) in eyes with epiretinal membranes (ERMs). METHODS: In this prospective observational case series, we included 81 eyes of 81 patients with idiopathic ERMs, without high myopia. The retinal structure surrounding the PIRDs was assessed using sequential thin sectioning of optical coherence tomography. The PIRDs were classified into three grades. Typical defects of the inner retinal tissue were defined as grade 3. Inner retinal cleavages with openings to the vitreous cavity and no apparent defect of the inner retinal tissue were defined as grade 2. Inner retinal cleavages or cystoid spaces with no connection to the vitreous cavity were defined as grade 1. RESULTS: Of 81 eyes with ERMs, 31 (38.3 %) had PIRDs along the temporal arcade vessels (grade 1 in six eyes, grade 2 in four eyes, and grade 3 in 21 eyes). PIRDs were frequently accompanied by broad defects of the inner retinal tissue (grade 3). Although some ERMs directly adhered to the edge of a PIRD or the retinal vessels, PIRDs were often located outside the area of adhesion to the ERM. In some OCT sections, vitreous traction on the inner retina seemed to contribute to the progression of PIRDs. Visual field abnormalities corresponded to the location of the PIRDs in 44.4 % of eyes with grade 3 PIRDs. CONCLUSIONS: Deviation of retinal vessels due to the traction of the ERMs may contribute to the pathogenesis of PIRDs. PIRDs often cause visual field abnormalities corresponding to the location of the defect.

Fungal hemicellulose-degrading enzymes cause physical property changes concomitant with solubilization of cell wall polysaccharides.

MAIN CONCLUSION: Physical properties of wheat coleoptile segments decreased after treatment with hemicellulose-degrading enzymes, indicating that hemicellulosic polysaccharides function to control the strength of primary cell walls. Changes in the physical properties of plant cell walls, a viscoelastic structure, are thought to be one of the growth-limiting factors for plants and one of the infection-affecting factors for fungi. To study the significance of hemicellulosic polysaccharides that form cross-bridges between cellulose microfibrils in controlling cell wall strength in monocot plants, the effects of hemicellulose degradation by recombinant Magnaporthe oryzae xylanase and 1,3-1,4-ß-glucanase, and recombinant Aspergillus oryzae xyloglucanase on the physical properties and polysaccharide solubilization were investigated using wheat (Triticum aestivum L.) coleoptiles. Treatments with xylanase or 1,3-1,4-ß-glucanase significantly decreased the viscosity and elasticity of wheat coleoptile segments. In addition, xyloglucanase treatment slightly decreased the viscoelasticity. Furthermore, 1,3-1,4-ß-glucan polymer was solubilized during hydrolysis with xylanase and xyloglucanase, even though neither enzyme had hydrolytic activity towards 1,3-1,4-ß-glucan. These results suggest that xylan and xyloglucan interact with 1,3-1,4-ß-glucan and that the composites and hemicellulosic polysaccharides form inter-molecular bridges. Degradation of these bridges causes decreases in the physical properties, resulting in increased extensibility of the cell walls. These findings provide a testable model in which wheat coleoptile cell walls are loosened by the degradation of hemicellulosic polysaccharides and hemicellulose-degrading enzymes play a significant role in loosening the walls during fungal infection.

Infection mechanism of biofilm-forming Staphylococcus aureus on indwelling foreign materials in mice.

Indwelling foreign-body infections are a critical medical problem, especially in immunocompromised patients. To examine the pathogenicity of biofilm-forming bacteria settling on foreign materials, mice implanted with plastic discs were infected with Staphylococcus aureus. After opening a wide subcutaneous pocket on the dorsal side of mice with or without temporal leukocytopenia, a plastic sheet was placed in the left subcutaneous space; subsequently, bacteria in a planktonic state were dispersed over the subcutaneous space. Bacterial numbers were examined 7 days after inoculation. In subcutaneous tissue on the right, S. aureus was found only in leukocytopenic mice. Meanwhile, bacteria were detected on the plastic and neighbouring tissue in both leukocytopenic and normal mice; however, colony-forming analysis indicated that leukocytopenic mice possessed significantly more bacteria. Tissue reaction against bacteria was pathologically examined. Invading S. aureus induced severe inflammation. In transient leukocytopenic mice, bacterial microcolonies formed on the plastic as well as in the developed necrotic tissue - both of which were shielded from inflammatory cell infiltration - result in bacteraemia. These results indicate that biofilm-forming S. aureus settling on indwelling foreign material are tolerant against host immunity and assault neighbouring tissue, which may lead to chronic wound infection.

Degradation and synthesis of ß-glucans by a Magnaporthe oryzae endotransglucosylase, a member of the glycoside hydrolase 7 family.

BACKGROUND: Plant pathogens secrete enzymes that degrade plant cell walls to enhance infection and nutrient acquisition. RESULTS: A novel endotransglucosylase catalyzes cleavage and transfer of ß-glucans and decreases the physical strength of plant cell walls. CONCLUSION: Endotransglucosylation causes depolymerization and polymerization of ß-glucans, depending on substrate molecular size. SIGNIFICANCE: Enzymatic degradation of plant cell walls is required for wall loosening, which enhances pathogen invasion. A Magnaporthe oryzae enzyme, which was encoded by the Mocel7B gene, was predicted to act on 1,3-1,4-ß-glucan degradation and transglycosylation reaction of cellotriose after partial purification from a culture filtrate of M. oryzae cells, followed by liquid chromatography-tandem mass spectrometry. A recombinant MoCel7B prepared by overexpression in M. oryzae exhibited endo-typical depolymerization of polysaccharides containing ß-1,4-linkages, in which 1,3-1,4-ß-glucan was the best substrate. When cellooligosaccharides were used as the substrate, the recombinant enzyme generated reaction products with both shorter and longer chain lengths than the substrate. In addition, incorporation of glucose and various oligosaccharides including sulforhodamine-conjugated cellobiose, laminarioligosaccharides, gentiobiose, xylobiose, mannobiose, and xyloglucan nonasaccharide into ß-1,4-linked glucans were observed after incubation with the enzyme. These results indicate that the recombinant enzyme acts as an endotransglucosylase (ETG) that cleaves the glycosidic bond of ß-1,4-glucan as a donor substrate and transfers the cleaved glucan chain to another molecule functioning as an acceptor substrate. Furthermore, ETG treatment caused greater extension of heat-treated wheat coleoptiles. The result suggests that ETG functions to induce wall loosening by cleaving the 1,3-1,4-ß-glucan tethers of plant cell walls. On the other hand, use of cellohexaose as a substrate for ETG resulted in the production of cellulose II with a maximum length (degree of polymerization) of 26 glucose units. Thus, ETG functions to depolymerize and polymerize ß-glucans, depending on the size of the acceptor substrate.

Association between roxadustat use and suppression of thyroid function: a systematic review and meta-analysis.

BACKGROUND: Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function. METHODS: We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term "roxadustat" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool. RESULTS: Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I2 = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia. CONCLUSIONS: Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.

Chiral Van Der Waals Superlattices for Enhanced Spin-Selective Transport and Spin-Dependent Electrocatalytic Performance.

The emergence of the chiral-induced spin-selectivity (CISS) effect offers a new avenue for chiral organic molecules to autonomously manipulate spin configurations, thereby opening up possibilities in spintronics and spin-dependent electrochemical applications. Despite extensive exploration of various chiral systems as spin filters, one often encounters challenges in achieving simultaneously high conductivity and high spin polarization (SP). In this study, a promising chiral van der Waals superlattice, specifically the chiral TiS2 crystal, is synthesized via electrochemical intercalation of chiral molecules into a metallic TiS2 single crystal. Multiple tunneling processes within the highly ordered chiral layered structure of chiral TiS2 superlattices result in an exceptionally high SP exceeding 90%. This remarkable observation of significantly high SP within the linear transport regime is unprecedented. Furthermore, the chiral TiS2 electrode exhibits enhanced catalytic activity for oxygen evolution reaction (OER) due to its remarkable spin-selectivity for triplet oxygen evolution. The OER performance of chiral TiS2 superlattice crystals presented here exhibits superior characteristics to previously reported chiral MoS2 catalysts, with an approximately tenfold increase in current density. The combination of metallic conductivity and high SP sets the stage for the development of a new generation of CISS materials, enabling a wide range of electron spin-based applications.

Lithium-Modified TiO2 Surface by Anodization for Enhanced Protein Adsorption and Cell Adhesion.

Promoting osseointegration is an essential step in improving implant success rates. Lithium has gradually gained popularity for promoting alkaline phosphatase activity and osteogenic gene expression in osteoblasts. The incorporation of lithium into a titanium surface has been reported to change its surface charge, thereby enhancing its biocompatibility. In this study, we applied anodization as a novel approach to immobilizing Li on a titanium surface and evaluated the changes in its surface characteristics. The objective of this study was to determine the effect of Li treatment of titanium on typical proteins, such as albumin, laminin, and fibronectin, in terms of their adsorption level as well as on the attachment of osteoblast cells. Titanium disks were acid-etched by 66 wt % H2SO4 at 120 °C for 90 s and set as the control group. The etched samples were placed in contact with an anode, while a platinum bar served as the counter electrode. Both electrodes were mounted on a custom electrochemical cell filled with 1 M LiCl. The samples were anodized at constant voltages of 1, 3, and 9 V. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results showed no significant differences in the topography. However, the ζ potentials of the 3 V group were higher than those of the control group at a physiological pH of 7.4. Interestingly, the adsorption level of the extracellular matrix protein was mostly enhanced on the 3 V-anodized surface. The number of attached cells on the Li-anodized surfaces increased. The localization of vinculin at the tips of the stretching cytoplasmic projections was observed more frequently in the osteoblasts on the 3 V-anodized surface. Although the optimal concentration or voltage for Li application should be investigated further, this study suggests that anodization could be an effective method to immobilize lithium ions on a titanium surface and that modifying the surface charge characteristics enables a direct protein-to-material interaction with enhanced biological adhesion.

Exploration of the optimal GS-441524 trough concentration for treating COVID-19.

OBJECTIVES: Remdesivir (RDV) is the cornerstone for treating coronavirus disease 2019 (COVID-19). The active metabolite of RDV, GS-441524 (a nucleoside analogue), has high interindividual variability in plasma concentrations; however, its concentration-response relationship is still unclear. This study investigated the target GS-441524 trough concentration for symptom improvement in COVID-19 pneumonia. METHODS: This single-center, retrospective, observational study included Japanese patients (age ≥15 years) with COVID-19 pneumonia who were administered RDV for ≥3 days from May 2020 to August 2021. To determine the cut-off value of GS-441524 trough concentration on Day 3, achievement of the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS) ≤3 after RDV administration was evaluated using the cumulative incidence function (CIF) with the Gray test and time-dependent receiver operating characteristic (ROC) analysis. Multivariate logistic regression analysis was performed to determine factors influencing GS-441524 target trough concentrations. RESULTS: The analysis comprised 59 patients. The CIF revealed that GS-441524 trough concentration ≥70 ng/mL was associated with the achievement of NIAID-OS ≤3 (P = 0.047), which was significant based on the time-dependent ROC analysis. Factors influencing GS-441524 trough concentration ≥70 ng/mL included a decrease in estimated glomerular filtration rate (eGFR) [adjusted odds ratio (aOR) = 0.96, 95% confidence interval (CI) 0.92-0.99; P = 0.027] and BMI ≥25 kg/m2 (aOR = 0.26, 95% CI 0.07-0.86; P = 0.031). CONCLUSION: GS-441524 trough concentration ≥70 ng/mL is a predictor of efficacy in COVID-19 pneumonia. The presence of lower eGFR or BMI ≥25 kg/m2 was associated with achieving GS-441524 trough concentration ≥70 ng/mL.